Promotion of endocytosis efficiency through an ATP-independent mechanism at rat calyx of held terminals

Abstract

Neurotransmission relies on membrane endocytosis to maintain vesicle supply and membrane stability. Endocytosis has been generally recognized as a major ATP-dependent function, which efficiently retrieves more membrane at elevated neuronal activity when ATP consumption within nerve terminals drastically increases. This paradox raises an interesting question whether increased activity recruits ATP-independent mechanism(s) to accelerate endocytosis while preserving ATP availability for other tasks. To address this issue, we studied ATP requirement in three typical forms of endocytosis at the rat calyx of Held terminals by whole-cell membrane capacitance measurements. At room temperature, blocking ATP hydrolysis effectively abolished slow endocytosis and rapid endocytosis, but only partially inhibited excess endocytosis following intense stimulation. The ATP-independent endocytosis occurred at calyces from postnatal 8–15 days, suggesting its existence before and after hearing onset. This endocytosis was not affected by reduction of exocytosis using the light chain of botulinum toxin C, or by block of clathrin-coat maturation. It was abolished by EGTA, which preferentially blocked endocytosis of retrievable membrane pre-existing at surface, and impaired by oxidation of cholesterol and inhibition of neutral sphingomyelinase. ATP-independent endocytosis became more significant at 34–35°C, and recovered membrane by an amount that on average was close to exocytosis. Our results suggest that activity and temperature recruit ATP-independent endocytosis of pre-existing membrane, in addition to ATP-dependent endocytosis, to efficiently retrieve membrane at nerve terminals. This less understood endocytosis represents a non-canonical mechanism regulated by lipids such as cholesterol and sphingomyelinase.

This article is protected by copyright. All rights reserved

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Deficiency of filaggrin regulates endogenous cysteine protease activity, leading to impaired skin barrier function

Summary

Background

Atopic dermatitis (AD) is a common inflammatory skin disorder, characterized by skin barrier defects and enhanced allergen priming. Null mutations in the filaggrin gene (FLG) are strongly associated with moderate to severe AD, but the pathways linking barrier dysfunction and cutaneous inflammation are still largely unknown.

Aim

To assess alteration of endogenous cysteine protease activity in FLG-deficient keratinocytes, and to determine whether the alteration in cysteine protease activity affects epidermal barrier function and associated gene and protein expression.

Methods

We established a stable FLG knockdown cell line, and reconstructed epidermal equivalents in vitro. Barrier function of the reconstructed epidermis, the barrier-associated genes and proteins, and the activity of endogenous cysteine proteases were tested. Inhibitors of cysteine proteases were used to further evaluate the role of endogenous cysteine proteases in epidermal barrier function.

Results

FLG knockdown induced impaired epidermal barrier function. Microarray, western blotting and fluorescence staining showed reduced expression of K10, ZO-1, E-cadherin, claudin-1 and occludin in FLG knockdown keratinocytes. Compared with cysteine protease activity in control cells, protease activity was dramatically enhanced in FLG knockdown keratinocytes. Furthermore, administration of cysteine protease inhibitors significantly recovered expression of K10 and tight junction proteins, and the barrier defect induced by FLG deficiency.

Conclusions

This is the first observation of elevated endogenous cysteine protease activity in FLG-deficient keratinocytes, which may play an important role in impaired barrier function in AD skin. Modulation of cysteine protease activity might be a novel therapeutic approach for AD treatment.

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Skin involvement as the first symptom of rapidly progressive ALK-positive systemic anaplastic large cell lymphoma

Summary

Systemic anaplastic large cell lymphomas (sALCLs) comprise a heterogeneous group of relatively rare T-cell non-Hodgkin lymphomas that are characterized by CD30 expression. Anaplastic lymphoma kinase (ALK)-positive ALCL is a type of sALCL that commonly involves lymph nodes and extranodal sites. Skin involvement usually presents as tumours, nodules and ulcers. We describe an unusual case of ALK-positive ALCL in an 11-year-old Chinese boy, who initially presented with skin eruption with rapid progression and poor prognosis. This case emphasizes the value of clinical factors to predict the prognosis of ALK-positive sALCL, and we recommend close collaboration between dermatologists, pathologists and haematologists/oncologists to assure the correct diagnosis and treatment.

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A recent-onset ulcerated nodular plaque on the scalp

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Preclinical pilot study monitoring topical drug penetration and dermal bioavailability of a peptidase inhibitor from different galenic formulations into pig dermis, using cutaneous microdialysis

Summary

Background

Cutaneous microdialysis (CM) is an ex vivo technique that allows study of tissue chemistry, including bioavailability of actual tissue concentration of unbound drug in the interstitial fluid of the body.

Aim

To test the penetration and dermal bioavailability of galenic formulations of the small-molecule IP10.C8, a dual-protease inhibitor of the dipeptidyl peptidase and aminopeptidase families.

Methods

Using CM, we tested the penetration and dermal bioavailability of IP10.C8 into the dermis and subcutis of pigs, and determined the tissue concentration of IP10.C8 enzymatically, using an enzyme activity assay (substrate Gly-Pro-pNA) and high performance liquid chromatography.

Results

Dermal bioavailability was enhanced by using microemulsion or the addition of the penetration enhancer oleic acid to a hydroxyethylcellulose (HEC) gel formulation. Dermal bioavailability was also enhanced when galenic formulations were prepared with higher pH (7.5 vs. 6.5) or higher drug concentration (5% vs. 1%) in HEC gel.

Conclusion

It seems possible, using CM for topical skin penetration testing in anaesthetized domestic pigs, to test the bioavailability of newly designed drugs. However, the experimental time is limited due to the anaesthesia, and is dependent on drug recovery. Validation of this technique for routine use is challenging, and more experiments are needed to validate this preclinical set-up.

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Topical capsaicin 8% for the treatment of neuropathic itch conditions

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Integration of reflectance confocal microscopy into clinical practice for the management of lentigo maligna

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Actinic keratosis. Or maybe not?

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Systematic review of the diagnosis of scabies in therapeutic trials

Summary

Human scabies (infestation with the mite Sarcoptes scabiei var hominis) causes a significant disease burden worldwide, yet there are no agreed diagnostic guidelines. We aimed to determine whether a consistent approach to diagnosing scabies has been used for published scabies therapeutic trials. The data sources used were the MEDLINE, Embase and Cochrane databases, from 1946 to 29 August 2013. Eligible studies were trials of therapeutic interventions against scabies in human subjects, published in English, enrolling patients with scabies, and using various therapeutic interventions. Language was a limitation of this study as some relevant trials published in languages other than English may have been excluded. Each study was reviewed by two independent authors, who assessed the clinical examination and testing approaches used for scabies diagnosis in the included studies. We found that of 71 included trials, 40 (56%) specified which clinical findings were used for diagnosis, which were predominantly rash, rash distribution, pruritus and mite burrows. Parasitological testing was used in 63% of trials (n = 45) and was used more frequently in clinic-based than in field studies. Nearly one-quarter of trials (24%, n = 17) did not define the diagnostic method used. Overall, the diagnostic approaches were poorly described, prohibiting accurate comparison of existing studies. This review further supports the need for consensus diagnostic guidelines for scabies.

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Deficiency of filaggrin regulates endogenous cysteine protease activity, leading to impaired skin barrier function

Summary

Background

Atopic dermatitis (AD) is a common inflammatory skin disorder, characterized by skin barrier defects and enhanced allergen priming. Null mutations in the filaggrin gene (FLG) are strongly associated with moderate to severe AD, but the pathways linking barrier dysfunction and cutaneous inflammation are still largely unknown.

Aim

To assess alteration of endogenous cysteine protease activity in FLG-deficient keratinocytes, and to determine whether the alteration in cysteine protease activity affects epidermal barrier function and associated gene and protein expression.

Methods

We established a stable FLG knockdown cell line, and reconstructed epidermal equivalents in vitro. Barrier function of the reconstructed epidermis, the barrier-associated genes and proteins, and the activity of endogenous cysteine proteases were tested. Inhibitors of cysteine proteases were used to further evaluate the role of endogenous cysteine proteases in epidermal barrier function.

Results

FLG knockdown induced impaired epidermal barrier function. Microarray, western blotting and fluorescence staining showed reduced expression of K10, ZO-1, E-cadherin, claudin-1 and occludin in FLG knockdown keratinocytes. Compared with cysteine protease activity in control cells, protease activity was dramatically enhanced in FLG knockdown keratinocytes. Furthermore, administration of cysteine protease inhibitors significantly recovered expression of K10 and tight junction proteins, and the barrier defect induced by FLG deficiency.

Conclusions

This is the first observation of elevated endogenous cysteine protease activity in FLG-deficient keratinocytes, which may play an important role in impaired barrier function in AD skin. Modulation of cysteine protease activity might be a novel therapeutic approach for AD treatment.

http://ift.tt/2rbsPNj

Skin involvement as the first symptom of rapidly progressive ALK-positive systemic anaplastic large cell lymphoma

Summary

Systemic anaplastic large cell lymphomas (sALCLs) comprise a heterogeneous group of relatively rare T-cell non-Hodgkin lymphomas that are characterized by CD30 expression. Anaplastic lymphoma kinase (ALK)-positive ALCL is a type of sALCL that commonly involves lymph nodes and extranodal sites. Skin involvement usually presents as tumours, nodules and ulcers. We describe an unusual case of ALK-positive ALCL in an 11-year-old Chinese boy, who initially presented with skin eruption with rapid progression and poor prognosis. This case emphasizes the value of clinical factors to predict the prognosis of ALK-positive sALCL, and we recommend close collaboration between dermatologists, pathologists and haematologists/oncologists to assure the correct diagnosis and treatment.

http://ift.tt/2qqTokh

A recent-onset ulcerated nodular plaque on the scalp

http://ift.tt/2rbL7Ou

Preclinical pilot study monitoring topical drug penetration and dermal bioavailability of a peptidase inhibitor from different galenic formulations into pig dermis, using cutaneous microdialysis

Summary

Background

Cutaneous microdialysis (CM) is an ex vivo technique that allows study of tissue chemistry, including bioavailability of actual tissue concentration of unbound drug in the interstitial fluid of the body.

Aim

To test the penetration and dermal bioavailability of galenic formulations of the small-molecule IP10.C8, a dual-protease inhibitor of the dipeptidyl peptidase and aminopeptidase families.

Methods

Using CM, we tested the penetration and dermal bioavailability of IP10.C8 into the dermis and subcutis of pigs, and determined the tissue concentration of IP10.C8 enzymatically, using an enzyme activity assay (substrate Gly-Pro-pNA) and high performance liquid chromatography.

Results

Dermal bioavailability was enhanced by using microemulsion or the addition of the penetration enhancer oleic acid to a hydroxyethylcellulose (HEC) gel formulation. Dermal bioavailability was also enhanced when galenic formulations were prepared with higher pH (7.5 vs. 6.5) or higher drug concentration (5% vs. 1%) in HEC gel.

Conclusion

It seems possible, using CM for topical skin penetration testing in anaesthetized domestic pigs, to test the bioavailability of newly designed drugs. However, the experimental time is limited due to the anaesthesia, and is dependent on drug recovery. Validation of this technique for routine use is challenging, and more experiments are needed to validate this preclinical set-up.

http://ift.tt/2qr8eHJ

Topical capsaicin 8% for the treatment of neuropathic itch conditions

http://ift.tt/2rbzTt3

Integration of reflectance confocal microscopy into clinical practice for the management of lentigo maligna

http://ift.tt/2qraG0B

Actinic keratosis. Or maybe not?

http://ift.tt/2rbuNwU

Systematic review of the diagnosis of scabies in therapeutic trials

Summary

Human scabies (infestation with the mite Sarcoptes scabiei var hominis) causes a significant disease burden worldwide, yet there are no agreed diagnostic guidelines. We aimed to determine whether a consistent approach to diagnosing scabies has been used for published scabies therapeutic trials. The data sources used were the MEDLINE, Embase and Cochrane databases, from 1946 to 29 August 2013. Eligible studies were trials of therapeutic interventions against scabies in human subjects, published in English, enrolling patients with scabies, and using various therapeutic interventions. Language was a limitation of this study as some relevant trials published in languages other than English may have been excluded. Each study was reviewed by two independent authors, who assessed the clinical examination and testing approaches used for scabies diagnosis in the included studies. We found that of 71 included trials, 40 (56%) specified which clinical findings were used for diagnosis, which were predominantly rash, rash distribution, pruritus and mite burrows. Parasitological testing was used in 63% of trials (n = 45) and was used more frequently in clinic-based than in field studies. Nearly one-quarter of trials (24%, n = 17) did not define the diagnostic method used. Overall, the diagnostic approaches were poorly described, prohibiting accurate comparison of existing studies. This review further supports the need for consensus diagnostic guidelines for scabies.

http://ift.tt/2qqStAm

XIST RNA ISH as a Tool for Resolving Specimen Contamination Events

Abstract

The large number of manual steps involved in processing tissue creates many opportunities for specimen cross-contamination and carry-over defects, which may have serious medicolegal ramifications.¹ In one study extraneous tissue was identified in 0.6% of slides, causing severe diagnostic difficulties in 0.4% of cases.¹ As these events are not fully preventable, a quick, reliable, easily accessible method to resolve suspected contamination events is crucial.

This article is protected by copyright. All rights reserved.

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Osteolytic lesions: osteitis fibrosa cystica in the setting of severe primary hyperparathyroidism

A 58-year-old female patient presented with several weeks history of significant bilateral knee pain. Initial knee radiographs demonstrated lucencies of the bony cortex while extensive osteolytic lesions on a routine chest radiograph were suggestive of multiple myeloma or bony metastases. Biochemical investigation revealed primary hyperparathyroidism with renal insufficiency. A parathyroid adenoma was demonstrated on a neck ultrasound and sestamibi scan and subsequently confirmed by histology. We illustrate a case of primary hyperparathyroidism with osteitis fibrosa cystica and brown tumours which were initially mistaken for malignant disease.

http://ift.tt/2reh5f4

Streptococcus bovis prosthetic valve endocarditis associated with silent colonic carcinoma

A 75-year-old woman was admitted to our hospital with a 3-month history of fever. Of note, she had a bioprosthetic mitral valve replacement 1 year prior to admission. Streptococcus bovis was isolated from three sets of blood cultures. An echocardiogram showed a flickering mass attached to the bioprosthesis. Her blood culture became sterile by the fourth day of ceftriaxone therapy. In spite of the absence of gastrointestinal symptoms, screening colonoscopy revealed an invasive colonic adenocarcinoma. The association linking S. bovis endocarditis and colonic tumours is well recognised. However, despite early reports of this association by Klein et al in 1979, a large number of practising physicians remain unaware of this phenomenon. This lack of awareness results in lost opportunities for early diagnosis and, consequently, improved outcome in such patients. Our report emphasises this association in an area with a low incidence of S. bovis endocarditis.

http://ift.tt/2schtYC

Ichthyosis linearis circumflexa with bamboo hair: challenges in the diagnosis and management

A 15-year-old boy had persistent and refractory erythroderma since early childhood. His parents noticed polycyclic skin lesions and hair fragility around the age of 5 years. He was treated by a local untrained practitioner for more than 3 years without any significant improvement, and he developed weight gain, thinning of skin, muscle weakness and growth retardation. He was evaluated in 2015 and found to have iatrogenic Cushing's disease with severe skeletal complications and pituitary-adrenal-gonadal suppression, which persisted despite gradual withdrawal of steroids.

http://ift.tt/2reqdA5

A rare case of bilateral lens dislocations

Description

A 39-year-old man presented to our hospital following transfer from a rural site with an acute right eye anterior lens dislocation following a traumatic blow to the head. He had been hit 7 days prior and had suffered gradual vision loss in the right eye since then. Visual acuity was counting fingers at 1 m in his right eye and perception of light in his left eye. He had an intraocular pressure (IOP) of 50 mm Hg in his right eye on arrival. He had a CT head non-contrast performed. The axial (figure 1) and sagittal (figures 2 and 3) slices demonstrated a right eye anterior lens dislocation and a left eye posterior lens dislocation. The left eye had been injured 3 years prior and the patient had not sought treatment for it at the time. On examination, the left eye was found to...

http://ift.tt/2scqikX

Osteolytic lesions: osteitis fibrosa cystica in the setting of severe primary hyperparathyroidism

A 58-year-old female patient presented with several weeks history of significant bilateral knee pain. Initial knee radiographs demonstrated lucencies of the bony cortex while extensive osteolytic lesions on a routine chest radiograph were suggestive of multiple myeloma or bony metastases. Biochemical investigation revealed primary hyperparathyroidism with renal insufficiency. A parathyroid adenoma was demonstrated on a neck ultrasound and sestamibi scan and subsequently confirmed by histology. We illustrate a case of primary hyperparathyroidism with osteitis fibrosa cystica and brown tumours which were initially mistaken for malignant disease.

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Streptococcus bovis prosthetic valve endocarditis associated with silent colonic carcinoma

A 75-year-old woman was admitted to our hospital with a 3-month history of fever. Of note, she had a bioprosthetic mitral valve replacement 1 year prior to admission. Streptococcus bovis was isolated from three sets of blood cultures. An echocardiogram showed a flickering mass attached to the bioprosthesis. Her blood culture became sterile by the fourth day of ceftriaxone therapy. In spite of the absence of gastrointestinal symptoms, screening colonoscopy revealed an invasive colonic adenocarcinoma. The association linking S. bovis endocarditis and colonic tumours is well recognised. However, despite early reports of this association by Klein et al in 1979, a large number of practising physicians remain unaware of this phenomenon. This lack of awareness results in lost opportunities for early diagnosis and, consequently, improved outcome in such patients. Our report emphasises this association in an area with a low incidence of S. bovis endocarditis.

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Ichthyosis linearis circumflexa with bamboo hair: challenges in the diagnosis and management

A 15-year-old boy had persistent and refractory erythroderma since early childhood. His parents noticed polycyclic skin lesions and hair fragility around the age of 5 years. He was treated by a local untrained practitioner for more than 3 years without any significant improvement, and he developed weight gain, thinning of skin, muscle weakness and growth retardation. He was evaluated in 2015 and found to have iatrogenic Cushing's disease with severe skeletal complications and pituitary-adrenal-gonadal suppression, which persisted despite gradual withdrawal of steroids.

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A rare case of bilateral lens dislocations

Description

A 39-year-old man presented to our hospital following transfer from a rural site with an acute right eye anterior lens dislocation following a traumatic blow to the head. He had been hit 7 days prior and had suffered gradual vision loss in the right eye since then. Visual acuity was counting fingers at 1 m in his right eye and perception of light in his left eye. He had an intraocular pressure (IOP) of 50 mm Hg in his right eye on arrival. He had a CT head non-contrast performed. The axial (figure 1) and sagittal (figures 2 and 3) slices demonstrated a right eye anterior lens dislocation and a left eye posterior lens dislocation. The left eye had been injured 3 years prior and the patient had not sought treatment for it at the time. On examination, the left eye was found to...

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Long Noncoding RNAs as Biomarkers in Cancer

Long noncoding RNAs (lncRNAs) are a relatively well-characterized class of noncoding RNA (ncRNA) molecules, involved in the regulation of various cell processes, including transcription, intracellular trafficking, and chromosome remodeling. Their deregulation has been associated with the development and progression of various cancer types, the fact which makes them suitable as biomarkers for cancer diagnosis and prognosis. In recent years, detection of cancer-associated lncRNAs in body fluids of cancer patients has proven itself as an especially valuable method to effectively diagnose cancer. Cancer diagnosis and prognosis employing circulating lncRNAs are preferential when compared to classical biopsies of tumor tissues, especially due to their noninvasiveness, and have great potential for routine usage in clinical practice. Thus, this review focuses on summarizing the perspectives of lncRNAs as biomarkers in cancer, based on evaluating their expression profiles determined in body fluids of cancer patients.

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MUSHA: MUltifunctional Smart HAnds project

MUSHA – MUltifunctional Smart HAnds: new technological insight for mini-invasive surgical tools and artificial anthropomorphic hands is a new Italian project, aiming to extend the capabilities of surgical tools, building on the PRISMA HANDs.

"MUSHA aims at creating future generations of bio-inspired tools and advanced bio-aware manipulation paradigms toward breakthrough mini-invasive surgical instruments and android robotic hands.

Bio-inspired mechanical design will address the reduction of tools weight and dimension by limiting the number of actuators while preserving dexterity and manipulation capabilities. Fiber optic sensor will be suitably integrated to measure the contact forces exchanged with the environment and the temperature of the touched materials. Finally, an integrated framework merging vision and touch information in reasoning to carry out complex manipulation tasks will be developed. MUSHA arises from the need to replicate human manipulation capabilities in various fields where robotics can help to improve life. This includes unstructured environments in which a humanoid robot must replace the human being or parts of the body to address daily-life tasks, but also minimally invasive robotic surgery where the surgeon is unable to use hands to manipulate organs and tissues while feeling its anatomy, consistency and temperature. In both cases, the lack of knowledge on object or tissue textures, due to missing tactile and temperature information, entails a loss of performance

in task execution as well as wrong decisions. Moreover, the study of smart correlation patterns between perception and action, inspired by the observation of humans, will enhance the performance of planning and control strategies. MUSHA will integrate contributions from: surgeons, on tool requirements definition and on testing in mechanical simulators and surgical settings; electronic engineers, on the development, design and integration of fiber optic sensors; robotic engineers, on mechanical design, on vison-force control development from the observation of human sensory-motor coordination and on testing on robotic manipulation. The synergy of the different competences is the key point to accomplish MUSHA objectives."

Source: MUSHA project site

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Novel dermoscopic findings in mudi-chood disease – a case report

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Novel dermoscopic findings in mudi-chood disease – a case report

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Title Page/Sections Editors

Publication date: July 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1860, Issue 7





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Sometimes pain originating from a non-odontogenic pathologic condition is mistaken as endodontic illness, leading to misdiagnosis.

http://ift.tt/2rwk2rY

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

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Subclinical hypothyroidism (SCH) has been associated with atherosclerosis and increased risk of ischemic stroke.

http://ift.tt/2qtlyHk

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

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Sometimes pain originating from a non-odontogenic pathologic condition is mistaken as endodontic illness, leading to misdiagnosis.

http://ift.tt/2rwk2rY

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

http://ift.tt/2qqMPyc

Subclinical hypothyroidism (SCH) has been associated with atherosclerosis and increased risk of ischemic stroke.

http://ift.tt/2qtlyHk

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

http://ift.tt/2rbCMKr

Sometimes pain originating from a non-odontogenic pathologic condition is mistaken as endodontic illness, leading to misdiagnosis.

http://otorhinolaryngology-crete.blogspot.com/2017/05/adenoid-cystic-carcinoma-of-maxillary.html

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Subclinical hypothyroidism (SCH) has been associated with atherosclerosis and increased risk of ischemic stroke.

http://otorhinolaryngology-crete.blogspot.com/2017/05/subclinical-hypothyroidism-and-risk-of.html

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Mutational status predicts the risk of thromboembolic events in lung adenocarcinoma

Precision medicine promises to improve prognosis of patients affected by untreatable diseases. Patients with lung cancer (especially lung adenocarcinoma) bear an increased risk of VTE. Mutations in the EGFR an...

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Instant velocity and consistency of emitted cloud change by the different levels of canister filling with Metered Dose Inhalers (MDIs), but not with Soft Mist Inhalers (SMIs): a bench study

Inhalation is the preferred route for respiratory drug delivery, but several factors contribute to the variability of the respirable dose fraction. Instant velocity and the dynamic characteristics of the dropl...

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Ultrafast dynamic contrast-enhanced mri of the breast using compressed sensing: breast cancer diagnosis based on separate visualization of breast arteries and veins

Purpose

To evaluate the feasibility of ultrafast dynamic contrast-enhanced (UF-DCE) magnetic resonance imaging (MRI) with compressed sensing (CS) for the separate identification of breast arteries/veins and perform temporal evaluations of breast arteries and veins with a focus on the association with ipsilateral cancers.

Materials and Methods

Our Institutional Review Board approved this study with retrospective design. Twenty-five female patients who underwent UF-DCE MRI at 3T were included. UF-DCE MRI consisting of 20 continuous frames was acquired using a prototype 3D gradient-echo volumetric interpolated breath-hold sequence including a CS reconstruction: temporal resolution, 3.65 sec/frame; spatial resolution, 0.9 × 1.3 × 2.5 mm. Two readers analyzed 19 maximum intensity projection images reconstructed from subtracted images, separately identified breast arteries/veins and the earliest frame in which they were respectively visualized, and calculated the time interval between arterial and venous visualization (A-V interval) for each breast.

Results

In total, 49 breasts including 31 lesions (breast cancer, 16; benign lesion, 15) were identified. In 39 of the 49 breasts (breasts with cancers, 16; breasts with benign lesions, 10; breasts with no lesions, 13), both breast arteries and veins were separately identified. The A-V intervals for breasts with cancers were significantly shorter than those for breasts with benign lesions (P = 0.043) and no lesions (P = 0.007).

Conclusion

UF-DCE MRI using CS enables the separate identification of breast arteries/veins. Temporal evaluations calculating the time interval between arterial and venous visualization might be helpful in the differentiation of ipsilateral breast cancers from benign lesions.

Level of Evidence: 3

J. Magn. Reson. Imaging 2017.

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Combined Angiography and Late Gadolinium Enhancement Acquisition to Improve Assessment of Pulmonary Vein Isolation for Atrial Fibrillation

Purpose

To develop a Shared K-space (SharK) magnetic resonance imaging (MRI) sequence that combines angiographic and late gadolinium enhancement (LGE) acquisitions to improve atrial wall segmentation and scar identification, and to develop a novel visualization method that quantifies scar encirclement of pulmonary veins postablation treatment for atrial fibrillation.

Materials and Methods

A SharK sequence was developed and used at 3T to image the left atrium in 11 patients postcryoballoon ablation. The effects of sharing k-space between the angiographic and LGE acquisitions on the accuracy of scar were assessed. The left atrial wall was segmented and points about each pulmonary vein (PV) ostia were projected onto a bullseye to quantitatively compare PV encirclement. The parameters used to quantify encirclement were varied to perform a sensitivity analysis.

Results

Compared to using a complete set of k-space, total atrial scar differences were significant only when sharing >75% k-space (P = 0.014), and 90% sensitivity and specificity for identifying scar was achieved when sharing 50% k-space. In patients, the right PVs showed more intersubject variance in encirclement compared to the left PVs. A 100° anteroinferior portion of the left PVs was always encircled, while the superior segments of both right PVs was ablated in only 6/11 patients.

Conclusion

A SharK sequence was developed to combine angiographic and LGE imaging for atrial wall segmentation and scar identification. The PV bullseye quantifies and localizes encirclement about the PVs. The left PVs showed a higher amount of scar encirclement and less variability compared to the right PVs.

Level of Evidence

2

Technical Efficacy

Stage 1J. Magn. Reson. Imaging 2017;00:000–000.

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Hassall's corpuscles in the fine-needle aspiration cytology of pediatric ectopic thymic tissue

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Ψ Multiple eccrine spiradenomas with a zosteriform pattern—Report of a rare case diagnosed on fine needle aspiration cytology

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Biphasic axillary synovial sarcoma diagnosed by preoperative fine-needle aspiration cytology

Synovial sarcoma (SS) is a soft-tissue sarcoma which usually occurs in lower extremities. Less than 20 cases of SS located in shoulder or axillary region have been reported, and these studies describe histopathological features. We report a case of axillary SS diagnosed by fine-needle aspiration cytology, immunocytochemistry, and molecular techniques performed on cytology smears. A 48-year-old woman presented with a palpable and well-defined axillary mass which measured 4 cm. On-site smears showed high cellularity with spindle cells, and a mesenchymal tumor was suspected. Definitive cytological analysis showed cells with ovoid- or comma-shaped nuclei arranged in loose sheets and fascicles, associated with naked nuclei and isolated cells. Mitotic count was 2 mitoses/HPF. Immunocytochemical studies showed vimentin and focal CK AE1-AE3 positivity. A PCR was performed and the specific translocation t(X;18) was detected. The lesion was excised and the diagnosis of biphasic SS was confirmed. The identification of SS on cytology specimens is difficult and differential diagnosis is broad. Complementary studies are necessary and they can be performed on FNA smears or cell blocks.

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Upper urinary tract washings outperform voided urine specimens to detect upper tract high-grade urothelial carcinoma

Background

Cytological examination of voided urine (VU) can reliably diagnose high-grade urothelial carcinoma (HGUC) of the lower urinary tract, but its value in the diagnosis of upper tract HGUC (UTHGUC) is less well-established. To clarify the utility of VU in the setting of UTHGUC, we examined urinary specimens from patients with UTHGUC on follow-up surgical pathology.

Methods

52 VU specimens (47 patients) with subsequent biopsy-proven UTHGUC were identified over a 12-year period; 32 had a corresponding upper tract urinary washing (UW) specimen. Patients with concurrent bladder HGUC were excluded. The diagnoses of VU specimens were tabulated and compared to those of UW specimens.

Results

Three UW specimens had a less severe diagnosis, 8 had the same diagnosis, and 21 had a more severe diagnosis than the corresponding VU specimen from the same patient. Significantly more UW specimens demonstrated high-risk features as compared with VU specimens (P = .003). In specimens with atypia, a definitive diagnosis of HGUC was made significantly more often on UW vs. VU specimens (P = .003).

Conclusions

Among patients with confirmed UTHGUC, 50% of preceding VU specimens demonstrated high-grade features compared to almost 90% of UW specimens. Though VU cytology shows atypia in the majority of cases, it performs inferiorly to UW for the detection of UTHGUC.

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The global state of psoriasis disease epidemiology: a workshop report

Summary

The International Psoriasis Council, a global nonprofit organization dedicated to innovation across the full spectrum of psoriasis, led a symposium to discuss the current state of psoriasis epidemiology and to introduce the vision and development of a Global Psoriasis Atlas. The symposium was held on 9 September 2015 at the 45th annual meeting of the European Society for Dermatological Research, Rotterdam, the Netherlands. Collectively, these presentations highlighted challenges associated with assessing psoriasis epidemiology and emphasized the urgent need for an authoritative resource to clarify psoriasis disease burden on a global scale.

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The global state of psoriasis disease epidemiology: a workshop report

Summary

The International Psoriasis Council, a global nonprofit organization dedicated to innovation across the full spectrum of psoriasis, led a symposium to discuss the current state of psoriasis epidemiology and to introduce the vision and development of a Global Psoriasis Atlas. The symposium was held on 9 September 2015 at the 45th annual meeting of the European Society for Dermatological Research, Rotterdam, the Netherlands. Collectively, these presentations highlighted challenges associated with assessing psoriasis epidemiology and emphasized the urgent need for an authoritative resource to clarify psoriasis disease burden on a global scale.

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BacterioFiles 295 - Fly Ferries Fungus Feebleness

This episode: Fungus-eating flies transfer viruses that help make fungi less harmful to plants!

(7.8 MB, 8.5 minutes)

Show notes: 

...

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Atenolol Versus Propranolol for Treatment of Infantile Hemangiomas During the Proliferative Phase: A Retrospective Noninferiority Study

Abstract

Background/Objectives

The nonselective beta-blocker propranolol is the current criterion standard for treatment of infantile hemangiomas (IHs) and the first therapy that the U.S. Food and Drug Administration has approved for the condition, but concern about adverse effects, such as bronchospasm, hypoglycemia, and sleep disturbances, has sparked interest in the use of alternative agents such as the selective β1 antagonist atenolol. Our aim was to compare the efficacy and adverse effect profiles of atenolol with those of propranolol in the treatment of IHs in a retrospective noninferiority trial.

Methods

Twenty-seven children with IHs treated with atenolol according to the Cleveland Clinic foundation's standardized clinical assessment and management plan (SCAMP) met inclusion criteria and were compared with a matched group of 53 children with IHs treated with propranolol. Three reviewers assessed response to therapy using a modified version of the previously validated Hemangioma Activity Score (HAS).

Results

The mean change in HAS was −2.94 ± 1.20 for patients treated with atenolol and −2.96 ± 1.42 for those treated with propranolol. There was no statistically significant difference in pre- and posttreatment modified HAS scores between the two groups (p = 0.60). There was no significant difference in the overall rate of adverse effects (p = 0.10), although 11% of patients treated with propranolol experienced reactive airway symptoms, whereas this was not seen in any of the patients treated with atenolol.

Conclusion

Our study supports previous findings that atenolol is at least as effective as propranolol for treatment of IHs and poses less risk of bronchospasm. Our SCAMP proposes guidelines for dosing and monitoring parameters.

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Atenolol Versus Propranolol for Treatment of Infantile Hemangiomas During the Proliferative Phase: A Retrospective Noninferiority Study

Abstract

Background/Objectives

The nonselective beta-blocker propranolol is the current criterion standard for treatment of infantile hemangiomas (IHs) and the first therapy that the U.S. Food and Drug Administration has approved for the condition, but concern about adverse effects, such as bronchospasm, hypoglycemia, and sleep disturbances, has sparked interest in the use of alternative agents such as the selective β1 antagonist atenolol. Our aim was to compare the efficacy and adverse effect profiles of atenolol with those of propranolol in the treatment of IHs in a retrospective noninferiority trial.

Methods

Twenty-seven children with IHs treated with atenolol according to the Cleveland Clinic foundation's standardized clinical assessment and management plan (SCAMP) met inclusion criteria and were compared with a matched group of 53 children with IHs treated with propranolol. Three reviewers assessed response to therapy using a modified version of the previously validated Hemangioma Activity Score (HAS).

Results

The mean change in HAS was −2.94 ± 1.20 for patients treated with atenolol and −2.96 ± 1.42 for those treated with propranolol. There was no statistically significant difference in pre- and posttreatment modified HAS scores between the two groups (p = 0.60). There was no significant difference in the overall rate of adverse effects (p = 0.10), although 11% of patients treated with propranolol experienced reactive airway symptoms, whereas this was not seen in any of the patients treated with atenolol.

Conclusion

Our study supports previous findings that atenolol is at least as effective as propranolol for treatment of IHs and poses less risk of bronchospasm. Our SCAMP proposes guidelines for dosing and monitoring parameters.

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Simplified clinical algorithm for identifying patients eligible for immediate initiation of antiretroviral therapy for HIV (SLATE): protocol for a randomised evaluation

Introduction

African countries are rapidly adopting guidelines to offer antiretroviral therapy (ART) to all HIV-infected individuals, regardless of CD4 count. For this policy of 'treat all' to succeed, millions of new patients must be initiated on ART as efficiently as possible. Studies have documented high losses of treatment-eligible patients from care before they receive their first dose of antiretrovirals (ARVs), due in part to a cumbersome, resource-intensive process for treatment initiation, requiring multiple clinic visits over a several-week period.

Methods and analysis

The Simplified Algorithm for Treatment Eligibility (SLATE) study is an individually randomised evaluation of a simplified clinical algorithm for clinicians to reliably determine a patient's eligibility for immediate ART initiation without waiting for laboratory results or additional clinic visits. SLATE will enrol and randomise (1:1) 960 adult, HIV-positive patients who present for HIV testing or care and are not yet on ART in South Africa and Kenya. Patients randomised to the standard arm will receive routine, standard of care ART initiation from clinic staff. Patients randomised to the intervention arm will be administered a symptom report, medical history, brief physical exam and readiness assessment. Patients who have positive (satisfactory) results for all four components of SLATE will be dispensed ARVs immediately, at the same clinic visit. Patients who have any negative results will be referred for further clinical investigation, counselling, tests or other services prior to being dispensed ARVs. After the initial visit, follow-up will be by passive medical record review. The primary outcomes will be ART initiation ≤28 days and retention in care 8 months after study enrolment.

Ethics and dissemination

Ethics approval has been provided by the Boston University Institutional Review Board, the University of the Witwatersrand Human Research Ethics Committee (Medical) and the KEMRI Scientific and Ethics Review Unit. Results will be published in peer-reviewed journals and made widely available through presentations and briefing documents.

Trial registration

NCT02891135

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DJC Suppresses Advanced Glycation End Products-Induced JAK-STAT Signaling and ROS in Mesangial Cells

The antidiabetic properties and anti-inflammatory effects of Danzhi Jiangtang Capsules (DJC) have been demonstrated in clinical and laboratory experiments. In this study, we explored whether DJC can ameliorate advanced glycation end products- (AGEs-) mediated cell injury and the precise mechanisms of DJC in treating diabetic nephropathy (DN). Western blot analysis was employed to assess the expressions of iNOS, COX2, and SOCS and the phosphorylation of JAK2, STAT1, and STAT3 in glomerular mesangial cells (GMCs) after treatment with DJC. TNF-α, IL-6, and MCP-1 were determined using double-antibody sandwich ELISA. ROS and NADPH oxidase activity were measured by DCFH-DA assay and lucigenin-enhanced chemiluminescence, respectively. DJC significantly reversed the AGEs-induced expression of COX2 and iNOS. Moreover, DJC inhibited the AGEs-induced JAK2-STAT1/STAT3 activation, resulting in the inhibition of inflammatory cytokines such as IL-6, MCP-1, and TNF-α in a concentration-dependent manner. The ability of DJC to suppress STAT activation was also verified by the observation that DJC significantly increased the SOCS3 protein level. DJC reversed the AGEs-induced accumulation of ROS and NADPH oxidase activity, thus confirming that DJC possesses antioxidant activity. The results suggest that the anti-inflammatory effects of DJC in GMCs may be due to its ability to suppress the JAK2-STAT1/STAT3 cascades and reduce ROS production.

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Editorial: Grappling with mother, newborn and child health (MNCH) issues in a continentbeset by non-communicable and infecious diseases

No Abstract

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Renal histoarchitectural changes in nevirapine therapy: possible role of kolaviron and vitamin C in an experimental animal model

Background: There is paucity of literature regarding the nephrotoxicity of antiretroviral drugs and its interaction with plantbased adjuvants. This study investigates the attenuating effect of kolaviron in nevirapine- therapy on the histological structure of the kidneys of adult male Sprague-Dawley rats.

Objective: To determine the attenuating influence of anti-oxidant status of kolaviron on the kidneys of experimental animals following nevirapine administration.

Methods: Forty eight pathogen-free adult male Sprague-Dawley rats were used for this study. The animals were divided into 8 groups (A-H) with 6 animals in each group. Group A was given normal saline as the control; group B was given nevirapine; group C was given kolaviron; group D was given vitamin C; group E was given nevirapine and kolaviron; group F was given nevirapine and vitamin C; Group G was given nevirapine and kolaviron (kolaviron withdrawn after day 28) and group H was given corn oil. The experiment lasted 56 days after which the animals were sacrificed, blood samples were collected through cardiac puncture for serum analysis and the kidneys were harvested and prepared for H& E histological examination.

Results: Nevirapine caused histoarchitectural damage in the glomerular apparatus with resultant increase in kidney/body weight ratio (p<0.001). Adjuvant treatment with kolaviron attenuated these nephrotoxic effects. Serum anti-oxidant enzyme (SOD and CAT) activities were significantly reduced in kolaviron and vitamin C treated animals, whereas in the nevirapine group these parameters were significantly elevated (P<0.05). However, co-administration of nevirapine and vitamin C did not improve the histoarchitecture of the kidney.

Conclusion: Adjuvant treatment with kolaviron (an anti-oxidant) for 56 days appears to attenuate the nephrotoxicity of nevirapine in this model.

Keywords: Kidney, histoarchitecture, kolaviron, antiretroviral drugs

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Where there is no doctor: can volunteer community health workers in rural Uganda provide integrated community case management?

Introduction: Integrated community case management (iCCM) involves assessment and treatment of common childhood illnesses by community health workers (CHWs). Evaluation of a new Ugandan iCCM program is needed.

Objectives: The objectives of this study were to assess if iCCM by lay volunteer CHWs is feasible and if iCCM would increase proportions of children treated for fever, pneumonia, and diarrhoea in rural Uganda.

Methods: This pre/post study used a quasi-experimental design and non-intervention comparison community. CHWs were selected, trained, and equipped to assess and treat children under five years with signs of the three illnesses. Evaluation included CHW-patient encounter record review plus analysis of pre/post household surveys.

Results: 196 iCCM-trained CHWs reported 6,276 sick child assessments (45% fever, 46% pneumonia, 9% diarrhoea). 93% of cases were managed according to algorithm recommendations. Absolute proportions of children receiving treatment significantly increased post-intervention: antimalarial for fever (+24% intervention versus +4% control) and oral rehydration salts/zinc for diarrhoea (+14% intervention versus +1% control).

Conclusion: In our limited-resource, rural Ugandan setting, iCCM involving lay CHWs was feasible and significantly increased the proportion of young children treated for malaria and diarrhoea.

Keywords: Uganda; maternal health; child health; community health worker; integrated community case management

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Proportion and factors associated with low fifth minute Apgar score among singleton newborn babies in Gondar University referral hospital; North West Ethiopia

Background: New born babies with low Apgar scores are at an increased risk of perinatal morbidity and mortality.

Objective: To assess proportion and factors associated with low 5^th minute Apgar Apgar score among singleton newborn babies in Gondar University referral hospital; North West Ethiopia.

Methods: A cross-sectional study was conducted on singleton 261 live births from March - May, 2013. Data was collected from mother/newborn index using a structured and pre-tested questionnaire. It was then cleaned, coded and entered using EPI INFO version 3.4.3, then analyzed with IBM SPSS statistics versions 20.0. Logistic regression was used to identify significant variables with low 5^th minute Apgar score.

Result: The proportion of low 5^th minute Apgar score in this study was 13.8%. Factors that were significantly associated with low 5^th minute Apgar score were: non-vertex fetal presentation, prolonged labor, presence of meconium stained liquor, induced/ augmented labor and low birth weight.

Conclusion: Mainly obstetric factors contribute to low Apgar score. Improving labor management through implementing regular use of partograph, 1:1 midwife-client ratio and advanced electronic fetal monitoring technology is recommended.

Keywords: Apgar score, Gondar University referral hospital

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Delivery practices, hygiene, birth attendance and neonatal infections in Karamoja, Uganda: a community-based study

Background: Drawing attention to home birth conditions and subsequent neonatal infections is a key starting point to reducing neonatal morbidity which are a main cause of mortality in sub-Saharan Africa.

Objectives: To determine the proportion of respiratory, ophthalmic, and diarrhoeal infections in neonates; the proportion of mothers of neonates, following clean delivery practices; and to explore existing community practices during delivery and the neonatal period.

Methods: A descriptive, cross-sectional, exploratory study, including 10 questionnaires and five Key-Informant interviews, in rural Karamoja, Uganda.

Results: Post-delivery razor blade and string use was 90%, but clean delivery surface use only 30%, while 90% obtained bathing water for neonates from boreholes. No mothers washed hands after latrine-related activities compared with 83% for food-related activities. None delivered in health centres or with skilled birth attendants. Respiratory infections occurred in eight neonates, compared to two ophthalmic infections, and no diarrhoea.

Conclusion: Use of clean delivery surfaces needs to be improved as well as washing after latrine-related activities. Diarrhoea was far less common than expected. Since rural Mother-Infant pairs spend the majority of their post-delivery time around the homestead, hygiene impacts neonatal infections to a large degree, possibly even more so than delivery practices.

Keywords: Neonatal, birth, delivery, clean delivery kit (CDK), clean delivery practices, infection, diarrhoea, ophthalmic, respiratory, hygiene, traditional birth attendant (TBA), home, rural, community, Nakaale, Nakapiripirit, Karamoja, Uganda

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Quorum sensing inhibitory activity of sub-inhibitory concentrations of β-lactams

Introduction: The virulence factors of Pseudomonas aeruginosa are under the control of quorum sensing (QS) signals. Hence, interference with QS prevents its pathogenesis.

Objective: The aim of the present research is to assess the influence of some β-lactam antibiotics on cell communication and the release of different virulence factors.

Methods: The minimal inhibitory concentrations of ceftazidime, cefepime and imipenem were evaluated by microbroth dilution method. The effect of sub-inhibitory concentration of the tested antibiotics on QS signals was investigated using reporter strain assay. In addition, different virulence factors (elastase, protease, pyocyanin and hemolysin) were estimated in the presence of their sub-inhibitory concentrations.

Results: Low concentrations of ceftazidime, cefepime and imipenem caused significant elimination of the QS signals 3OHC12- HSL and C4-HSL up to 1/20 MIC. Furthermore, low concentrations of the tested antimicrobials suppressed virulence factors elastase and hemolysin. Moreover, 1/20 of their MICs reduced elastase, protease, pyocyanin and hemolysin.

Conclusion: Utilization of β-lactam antibiotics at low concentrations could be an effective approach for prevention and treatment of P. aeruginosa infection.

Keywords: Quorum sensing inhibition, β-lactams, Pseudomonas aeruginosa

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How weight during pregnancy influences the association between pre-pregnancy body mass index and types of delivery and birth: a comparison of urban and rural areas

Background: Women in study areas suffered from the problems of caesarean delivery (CD), low birth weight (LBW), and macrosomia.

Objective: To investigate how gestational weight gain (GWG) influences the effect of the pre-pregnancy body mass index (BMI) on the risks of CD, LBW, and macrosomia in urban and rural areas in a city of Iran.

Methods: We used 767 and 612 eligible subjects from the public health care centers in urban and rural areas respectively.

Results: The risk of CD increased from 74% to 2.62-fold in urban and from 62% to 2.15-fold in rural areas, and the risk of macrosomia increased from 58% to 2.35-fold in urban and from 47% to 96% in rural areas, among obese women compared to normal weight women who gained above median GWG. The risk of LBW increased from 38% to 92% in urban and from 49% to 97% in rural areas among lean women compared to normal weight women who gained below median GWG.

Conclusion: These findings strongly support the need to reform adequate pre-pregnancy weight and GWG against the risks of CD and macrosomia among overweight and obese women, and against the risk of LBW among lean women in both areas.

Keywords: Body mass index, gestational weight gain, caesarean delivery, low birth weight, macrosomia

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Sonographic assessment of petroleum-induced hepatotoxicity in Nigerians: does biochemical assessment underestimate liver damage?

Background: Exposure to petroleum products has been shown to have significant adverse effects on the liver which can manifest either as morphological or physiological changes.

Objectives: The aim of the study was to assess the effects of chronic exposure to some petroleum products on the liver of exposed workers using sonography and to determine whether biochemical assessments underestimated hepatotoxicity.

Methods: Abdominal ultrasound was performed on 415 exposed workers in order to evaluate liver echogenicity and size. Also, biochemical assessment of the liver was done to evaluate its function

Results: Statistically significant increase in the liver parenchymal echogenicity and the liver size was seen in the exposed workers compared with control (p ≤ 0.05). These increased as the exposure duration increased. It was also noted that out of 16.87% (N=70) exposed workers with abnormal liver echopattern, only 2.65% (N=11) had alanine aminotransferase above the reference range.

Conclusion: The study revealed evidence of ultrasound detectable hepatotoxicity among the exposed subjects. Sonography appeared to detect petroleum products-induced hepatic toxicity more than biochemical assays suggesting that biochemical assessment may have underestimated toxicity.

Keywords: Petroleum Products, Exposure, Hepatotoxicity, Sonography, Biochemical assessment, Nigeria

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Geophagy as risk behaviour for gastrointestinal nematode infections among pregnant women attending antenatal clinics in a humid tropical zone of Nigeria

Background: Geophagy is wide spread among pregnant women in Ebonyi State, Nigeria.

Objective: The aim of this study was to assess intestinal nematode infections among geophagous pregnant women in Southern Ebonyi State, Nigeria.

Methods: Pregnant women were aged 17-45 years at gestational ages of ≥ 14 to 24 weeks on hospital enrolment were sampled. Data on geophagy was collected using structured questionnaire. Gastrointestinal nematode status of the participants was determined by stool analyses. Soil types ingested were examined for intestinal nematode ova / larvae.

Results: The prevalence of geophagy (46.4%) was associated with socio-demographic characteristics. Ascaris lumbricoides and hookworm were associated with geophagy while Trichuris trichiura and Strongyloides stercoralis had no association. Prevalence of A. lumbricoides, T. trichiura and S. stercoralis differed significantly (p<0.05) between geophagous and non-geophagous women. The soil types consumed had eggs / larvae of A. lumbricoides and T. trichiura. Geophagy is a risk behaviour directly associated with A. lumbricoides, hookworm, T. trichiura, and to a lesser extent S. stercoralis infection among pregnant women.

Conclusion: Sensitization and mass education of pregnant women on the dangers of geophagy is needed. Furthermore, deworming of pregnant women should be integrated into the healthcare delivery system of the State.

Keywords: Geophagy, gastrointestinal nematode, pregnant women, humid tropics

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Sexual risk behavior among HIV-positive persons in Jamaica

Background: HIV/AIDS remains a global public health challenge, especially in sub-Saharan Africa and the Caribbean. Sexual risk behaviors among HIV-positive persons place their partners at risk for HIV transmission and other sexually transmitted infections. Stopping transmission acts among HIV-positive people is crucial in reversing HIV incidence.

Objective: This study aimed to assess the prevalence and predictors of sexual risk behaviors among HIV-positive individuals in clinical care in Northwestern Jamaica.

Methods: A cross-sectional survey of 118 (33 males and 85 females) HIV-positive individuals was used to assess demographic and health characteristics, HIV/AIDS knowledge, attitudes, and beliefs and sexual risk behaviors.

Results: About 12% of the study population stated that they had unprotected anal or vaginal sex without disclosing their HIV status. Participants who agreed that condoms reduce the risk of HIV transmission were 13.1 times more likely to use condoms during their last sexual encounters(95% CI: 2.1-79.0) than those who disagreed. About 75% of participants reported using a condom every time they had sexual intercourse in the past year, while 25% used condoms irregularly. Participants who had unprotected anal or vaginal sex without disclosing their status were less likely to have used condoms during the last sexual encounter (OR=0.1; 95% CI: 0.02-0.5).

Conclusion: The prevalence of unsafe sex remains high among sexually active people living with HIV/AIDS in Jamaica. Study participants who engaged in unprotected sex without disclosing their HIV-positive status potentially place their partners at risk for HIV transmission and other sexually transmitted infections. The study findings highlight the need to promote safe sexual behaviors and a positive social environment for people living with HIV/AIDS in Jamaica.

Keywords: HIV-seropositivity, sexual behavior, Jamaica, anti-retroviral therapy, condom use

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Evaluation of the mobile phone electromagnetic radiation on serum iron parameters in rats

Background: Electromagnetic fields (EMF) created by mobile phones during communication have harmful effects on different organs.

Objectives: It was aimed to investigate the effects of an EMF created by a mobile phone on serum iron level, ferritin, unsaturated iron binding capacity and total iron binding capacity within a rat experiment model.

Methods: A total of 32 male Wistar albino rats were randomly divided into the control, sham, mobile phone speech (2h/day) and stand by (12 h/day) groups. The speech and stand by groups were subjected to the EMF for a total of 10 weeks.

Results: No statistically significant difference was observed between the serum iron and ferritin values of the rats in the speech and stand by groups than the control and sham groups (p>0.05). The unsaturated iron binding capacity and total iron capacity values of the rats in the speech and stand by groups were significantly lower in comparison to the control group (p<0.01).

Conclusion: It was found that exposure to EMF created by mobile phones affected unsaturated iron binding capacity and total iron binding capacity negatively.

Keywords: cellular phone, electromagnetic fields, ferritin, serum iron

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Diversities in timing of sexual debut among Nigerian youths aged 15-24 years: parametric and non-parametric survival analysis approach

Objective: This study examined gender, generational, cultural and social diversities in timing of sexual debut among Nigerian youths and determined factors influencing the timings.

Methods: We extracted data of respondents aged 15-24 years from 2012 Nigeria nationally representative data. The outcome of interest was time at sexual debut while predictors included residence, marital status, zones, education, religion, age at first marriage. Data was censored, cox proportional hazard and generalized gamma models were used to model age at sexual debut with p=0.05.

Results: The median survival time of sexual debut was 19 years, female youths were twice as likely to begin sexual activities than their male counterparts, HR=1.99, 1.87-2.11 while uneducated youths were more than twice likely to have earlier sexual debut than those with higher education, HR=2.19, 1.95-2.25. Likelihood of having had sexual debut was about 30% higher among those aged 20-24 years than those aged 15-19 years, HR=1.27, 1.19-1.36.

Conclusion: Females from poor households mostly in rural areas with no education and who married early in life were more likely to have earlier sexual debut. Both teenagers and young adults are on different trajectories of sexual debut but both urgently need sexual and reproductive health education to delay sexual debut.

Keywords: Sexual debut, survival analysis, Nigeria, generalised gamma, wealth

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Willingness by people living with HIV/AIDS to utilize HIV services provided by Village Health team workers in Kalungu district, central Uganda

Background: Less than one quarter of people in need have access to HIV services in Uganda. This study assessed willingness of people living with HIV/AIDS (PLWHAs) to utilize HIV services provided by Village Health Teams (VHTs) in Kalungu district, central Uganda.

Methods: A cross-sectional study conducted in two health facilities providing anti-retroviral therapy enrolled 312 PLWHAs. Pre-tested semi-structured questionnaires were administered to participants at household level. A forward fitting logistic regression model computed the predictors of willingness of PLWHAs to utilize services provided by VHTs.

Results: Overall, 49% were willing to utilize HIV services provided by VHTs increasing to 75.6% if the VHT member was HIV positive. PLWHAs who resided in urban areas were more likely to utilize HIV services provided by VHTs (AOR 0.24, 95%CI 0.06-0.87). Barriers to utilizing HIV services provided by VHTs were: income level > 40 USD (AOR 6.43 95%CI 1.19-34.68), being a business person (AOR 8.71 95%CI 1.23-61.72), peasant (AOR 7.95 95%CI 1.37-46.19), lack of encouragement from: peers (AOR 6.33 95%CI 1.43-28.09), spouses (AOR 4.93 95%CI 1.23-19.82) and community leader (AOR 9.67 95%CI 3.35-27.92).

Conclusion: Social support could improve willingness by PLWHAs to utilize HIV services provided by VHTs for increased access to HIV services by PLWHA.

Keywords: Willingness by people living with HIV/AIDS to utilize HIV services provided by Village Health Team workers in Kalungu district, central Uganda

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Developmental screening: predictors of follow-up adherence in primary health care

Background: The importance of early identification for infants and young children with developmental delays is well established. Poor follow-up on referrals, however, undermines the effectiveness of early intervention programmes.

Objectives: To identify factors, including text message reminders, that influence follow-up adherence for early intervention after developmental screening in primary health care. A secondary objective surveyed reasons for follow-up default.

Methods: The PEDS tools were used to screen 247 high-risk children. A risk assessment questionnaire was completed with caregivers whose children were referred for speech-language and/or occupational therapy (n=106, 43%). A quasi-experimental correlational study was employed to identify risk factors for defaulting on appointments. A thematic analysis of telephonic interviews was also employed to determine reasons for follow-up defaults.

Results: Follow-up adherence was 17%. Participants who were never married, divorced or widowed were 2.88 times more likely to attend a follow-up appointment than those who were married or living together (95%, CI 0.97-8.63). Text message reminders did not improve follow-up. More than half (58%) of participants who defaulted on appontments could be reached for telephonic interviews. Interviews showed that 87% of participants were unconcerned about their child's development. Other reasons for defaulting were employment, logistical issues, other responsibilities and forgetfulness.

Conclusion: Follow-up adherence for early intervention services following a positive primary health care screen was poor. Increased awareness and education regarding the importance of development for educational success is needed.

Keywords: Developmental screening, follow-up return rate, occupational therapy, PEDS tools, primary health care, speech-language therapy, text message reminders

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Hydroxyurea therapy in adult Nigerian sickle cell disease: a monocentric survey on pattern of use, clinical effects and patient’s compliance

Background: The clinical prospects of hydroxyurea therapy in the management of sickle cell disease (SCD) require evaluation in the Nigerian setting to develop indigenous guidelines. This survey examines the pattern of hydroxyurea therapy, its clinico-haematologic benefits and safety profile in Nigerian SCD subjects.

Methods: A cross sectional pilot survey was carried out among 60 adult SCD subjects over 3 months. Data on clinical phenotypes, relevant haematological parameters and details of hydroxyurea therapy were obtained using a structured questionnaire through an interview process and case file review.

Results: The median age was 30 years. Thirty-four (56.7%) of the subjects are aware of hydroxyurea therapy in SCD. Twenty-four (40%) SCD patients had previously used hydroxyurea. Only 4 subjects were fully compliant. Reasons for non-complianceincluded poor knowledge and lack of funds. In particular, hydroxyurea reduced leucocyte count and increased mean red cell volume (MCV) in compliant subjects.

Conclusion: Hydroxyurea use is low among Nigerian SCD subjects despite its proven efficacy/clinical prospects in the developed nations. Large scale multicenter studies and clinical trials are needed to form a basis for developing standard local treatment protocol for its use.

Keywords: Hydroxyurea therapy, Nigerian sickle cell disease, pattern of use, clinical effects, patient's compliance

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Cytotoxicity testing of aqueous extract of bitter leaf (Vernonia amygdalina Del) and sniper 1000EC (2,3 dichlorovinyl dimethyl phosphate) using the Alium cepa test

Background: The unrefined nature of the herbal preparations from Vernonia amygdalina (VA) and toxicity potentials of Sniper may both have severe consequences on the biochemical and genetic systems.

Objectives: To assess the microscopic and macroscopic effects of these substances.

Methods: VA leafs and Sniper were prepared and dissolved in distilled water to give different concentrations. Series of baseline tests were carried out to establish concentration range for root growth. Series of twelve onion bulbs of three per series was prepared, with a series of three onion bulbs serving as control. Chromosomal aberrations were statistically analysed using chisquared test. Root bundle mean length was obtained after 96 hours and EC₅₀ values at 95% confidence interval was determined from a plot of root length against sample concentrations using Microsoft Excel software.

Results: Total cytotoxic effect was induced by 2% sniper and 70% VA. EC₅₀ for VA and sniper were 33.07 and 0.346 respectively. The two substances induced chromosomal aberrations and the effect was concentration dependent.

Conclusion: There are risks of these widely used substances for therapeutic and environmental purposes.

Keywords: Chromosomal aberrations, Sniper 1000EC, Vernonia amygdalina, toxicity

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Investigation of the relationship between structural empowerment and organizational commitment of nurses in Zanjan hospitals

Background: The demanding nature of nursing work environments signals longstanding and growing concerns about nurses' health and job satisfaction and the provision of quality care. Specifically in health care settings, nurse leaders play an essential role in creating supportive work environments to avert these negative trends and increase nurse job satisfaction.

Objective: The purpose of this study was to examine the relationship between structural empowerment and organizational commitment of nurses.

Methods: 491 nurses working in Zanjan hospitals participated in this descriptive-correlational study in 2010. Tools for data collection were Meyer and Allen's organizational commitment questionnaire and "Conditions for Work Effectiveness Questionnaire-II" (CWEQ-II). Data was analyzed by SPSS16. The statistical tests such as variance analysis, t-test, pearson correlation coefficient and linear regression were used for data analysis.

Results: According to the findings, the perception of nurses working in hospitals on "Structural Empowerment" was moderate (15.98±3.29). Nurses believed "opportunity" as the most important element in structural empowerment with the score of 3.18 ±0.79. Nurses working in non-academic hospitals and in non-teaching hospitals had higher organizational commitment than others. There was a significant relationship between structural empowerment and organizational commitment.

Conclusion: Generally, structural empowerment (relatively strong) correlates with nurses' organizational commitment. We concluded that a high structural empowerment increases the organizational commitment of nurses.

Keywords: Structural empowerment, organizational commitment, nurses, Zanjan

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Contextual determinants of adolescent mortality in South Africa

Objectives: South Africa has a large adolescent population (approximately 20% of the total population). The survival and development of these individuals are a priority among parents and the government. In an effort to better understand the factors contributing to adolescent mortality in South Africa, this study examined the effect of household and community factors on adolescent death.

Methods: The study used data from Census 2001. Multilevel modelling was used to study the impact of community and household factors on adolescent mortality. A multivariate binary logistic 2- level model was developed. Odds ratios were produced and, statistically significant values (p<0.05) were discussed. There were 41,261 reported adolescent deaths from census data.

Results: This study found that having a few household assets, six or more people living in a residence, and high racial diversity is associated with increased odds of adolescent mortality in South Africa in 2001.

Conclusions: Socio-economic status of the household and racial diversity within communities is likely to increase adolescent mortality in South Africa. However, there is need to examine the role of other community characteristics, such as number of schools, health facilities and employment opportunities in order to create a holistic profile of the contextual determinants of adolescent mortality in the country.

Keywords: Adolescent mortality, South Africa

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Distribution of symptoms of post-stroke depression in relation to some characteristics of the vulnerable patients in socio-cultural context

Objective: To determine the distribution of symptoms of post-stroke depression (PSD) in relation to some predisposing factors in an African population.

Relevance: Environment is a key determinant of behavior, and varied socio-cultural contexts must have implications for modifiable characteristics (age, duration of the stroke, marital status, type of employment, gender, the location of cerebral lesion and complications) of individuals vulnerable to PSD, which may be targeted to enhance recovery.

Method: This was a cross-sectional observational study of 50 (22 females and 28 males) stroke survivors (mean age=54.76±8.79 years), at the physiotherapy department, the University of Nigeria teaching hospital, Enugu, selected using convenience sampling technique. Data were collected using Becks Depression Inventory and analyzed using Z-score, Chi-square test and univariate logistic regression, at p<0.05.

Results: PSD was more prevalent in females (45.45%); young(100%); middle-age(60%) adults(27-36/47-56 years respectively); living with spouse (45%); left cerebral lesions (40.74%); complications(45%); cold case >3 years(47.05%); self-employed and unemployed (66.67%), respectively. Age was significantly associated with depression (χ² =4.92,df=1,p=0.03), and was related to the risk of PSD (3.7[1.1-12.0], p=0.03, φ = +0.31, φ²=0.1).

Conclusion: Age could be a risk factor for PSD, which was more prevalent in the elderly than young/middle-age adults, female gender, left cerebral lesion, complications, cold case; those living with a spouse, self-employed and unemployed.

Keywords: Symptoms of post-stroke depression, modifiable characteristics of the vulnerable patients, African socio-cultural context

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Oxidative stress and histopathological changes induced by methylthiophanate, a systemic fungicide, in blood, liver and kidney of adult rats

Background: Methyl-thiophanate (MT), a fungicide largely used in agriculture throughout the world including Tunisia, protects many vegetables, fruits and field crops against a wide spectrum of fungal diseases. Oxidative stress has been proposed as a possible mechanism involved in MT toxicity on non-target organism.

Methods: In the present study, the effect of MT injected intraperitoneally to adult rats at 300 or 500 mg/kg of body weight was studied on blood, liver and kidney.

Results: Our results showed 3 days after MT injection, a significant decrease in hemoglobin and hematocrit values. A disruption in total white blood cells and platelets also occurred. Accordingly, an increased in malondialdehyde, H²O² and advanced oxidation protein levels in liver and kidney were noted with the two doses. A significant change in plasma biomarkers and organ enzymatic and non-enzymatic activities were observed after MT treatment. The modifications in biochemical parameters were substantiated by histopathological data.

Conclusion: These data confirmed the pro-oxidant effects of this fungicide. Accordingly, care must be taken to avoid mammalian and human exposure to MT.

Keywords: Methyl-thiophanate, white blood cells, red blood cells, liver, kidney

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Direct Sulfonamidation of Primary and Secondary Benzylic Alcohols Catalyzed by a Boronic Acid/Oxalic Acid System

The direct sulfonamidation of primary and secondary benzylic aclohols catalyzed by a 1,2,3,4-tetrafluorophenylboronic acid/oxalic acid co-catalytic system has been examined. The reaction proceeds in mild conditions with readily available starting materials and has been shown to be gram-scalable without significant decrease of yield. Both primary and secondary benzylic alcohols were evaluated and afforded the desired sulfonamide products with good to excellent yields

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Assembly of [2]rotaxanes in water

Two [2]rotaxanes are assembled in water from modular subunits relying on Cu(I)-catalyzed azide-alkyne "click" chemistry. For this purpose, 2,6-substituted naphthalene axles with solubilizing oligoethylene glycol (OEG) chains (n = 1 - 5), and propargyl termination are synthesized and examined for their propensity to form inclusion complexes with a dicationic Diederich-type cyclophane host. The dependence of pseudo-rotaxane formation on the linking chemistry between naphthalene core and OEG chain, and in the case of ester linkers on different spacer lengths is analyzed by titration experiments. In addition the inclusion complexes of two [2]rotaxanes were trapped using a water-soluble azide-functionalized stopper. Repetitive chromatography finally enabled the isolation of both mechanically interlocked [2]rotaxanes.

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A case of ulcerative colitis with squamous cell carcinomas and multiple foci of squamous dysplasia

Squamous cell carcinoma (SqCC) in ulcerative colitis (UC) is rare. A 38 year-old Japanese woman, who suffered from left-sided UC for 18 years, underwent total colectomy due to SqCCs in the rectum and the sigmoid colon. They were well differentiated SqCC, and metastasis was found in the paracolic lymph nodes. Multiple small foci of squamous dysplasia (SD) were noted in the rectal mucosa. Glandular dysplasia was not found. TP53 was not detected in SD. Approximately 40% of cells were immunostained with TP53 in SqCC, however no mutation was found in TP53 gene. Human papilloma virus and Epstein Barr virus were negative in SD and SqCCs. The patient is free of the disease at one and half years after surgery and chemotherapy. SD may be a precursor of SqCC. It appeared that TP53 does not play a vital role in the development of SqCCs in the current case. Careful attention should be paid to SD in UC patients. Viral infection may need to be examined. The pathogenesis of SqCC in patients of UC needs to be elucidated.

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Cost of elective percutaneous coronary intervention in Malaysia: a multicentre cross-sectional costing study

Objectives

Limitations in the quality and access of cost data from low-income and middle-income countries constrain the implementation of economic evaluations. With the increasing prevalence of coronary artery disease in Malaysia, cost information is vital for cardiac service expansion. We aim to calculate the hospitalisation cost of percutaneous coronary intervention (PCI), using a data collection method customised to local setting of limited data availability.

Design

This is a cross-sectional costing study from the perspective of healthcare providers, using top-down approach, from January to June 2014. Cost items under each unit of analysis involved in the provision of PCI service were identified, valuated and calculated to produce unit cost estimates.

Setting

Five public cardiac centres participated. All the centres provide full-fledged cardiology services. They are also the tertiary referral centres of their respective regions.

Participants

The cost was calculated for elective PCI procedure in each centre. PCI conducted for urgent/emergent indication or for patients with shock and haemodynamic instability were excluded.

Primary and secondary outcome measures

The outcome measures of interest were the unit costs at the two units of analysis, namely cardiac ward admission and cardiac catheterisation utilisation, which made up the total hospitalisation cost.

Results

The average hospitalisation cost ranged between RM11 471 (US$3186) and RM14 465 (US$4018). PCI consumables were the dominant cost item at all centres. The centre with daycare establishment recorded the lowest admission cost and total hospitalisation cost.

Conclusions

Comprehensive results from all centres enable comparison at the levels of cost items, unit of analysis and total costs. This generates important information on cost variations between centres, thus providing valuable guidance for service planning. Alternative procurement practices for PCI consumables may deliver cost reduction. For countries with limited data availability, costing method tailored based on country setting can be used for the purpose of economic evaluations.

Registration

Malaysian MOH Medical Research and Ethics Committee (ID: NMRR-13-1403-18234 IIR).

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Extracardiac Imaging of Infective Endocarditis

Abstract

Purpose of Review

This review analyzes recent studies evaluating the diagnostic and therapeutic impacts of systematic extracardiac imaging techniques in patients with suspected or proven infective endocarditis.

Recent Findings

Extracardiac imaging techniques are more and more frequently used to establish infective endocarditis (IE) diagnosis in doubtful situations. They also help in evaluating the risk-benefit balance of therapeutic strategies and particularly valvular surgery which is performed in approximately 50% of patients. Latest research underlines the high frequency of asymptomatic lesions found, and a different advantage-disadvantage profile for each of these techniques.

Summary

Extracardiac imaging techniques are helpful in doubtful situations and may be considered in other situations. Their interest for improving patients' prognosis remains to be established.

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Computer-assisted orthognathic surgery: evaluation of mandible registration accuracy and report of the first clinical cases of navigated sagittal split ramus osteotomy

Intraoperative navigation is a helpful tool in complex anatomical regions or procedures. The mobility of the mandible in relation to the skull base limits the use of navigation tools on the lower jaw if the reference device is installed on the forehead. A new workflow that allows navigation-assisted sagittal split osteotomy in orthognathic surgery using a separate non-invasive mandibular registration technique has been developed. An evaluation of accuracy in different anatomical regions and with different registration techniques was performed on skull models and skulls with movable mandibles.

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The effects of alpha 1-adrenoceptor blockade and angiotensin converting enzyme inhibition on central and brachial blood pressure and vascular reactivity: the doxazosin–ramipril study

Abstract

We aimed to study whether inhibition of the renin–angiotensin–aldosterone system has effects on vascular structure and function beyond the effects on blood pressure reduction alone. Patients with mild-to-moderate hypertension (n = 61, age 54 ± 12 years, 34% women) received the angiotensin converting enzyme inhibitor ramipril 10 mg or the alpha 1-adrenoceptor blocker doxazosin 8 mg double-blind for 12 weeks. Aortic blood pressure, pulse wave velocity, and augmentation index were assessed by applanation tonometry. Endothelial function was studied by forearm post-ischemic flow mediated vasodilatation and by pulse wave analysis with beta 2-adrenoceptor agonist stimulation. Skin microvascular reactivity was assessed by laser Doppler fluxmetry and iontophoresis. Treatment with doxazosin or ramipril reduced aortic and brachial blood pressures (all P < 0.001), with greater reductions in aortic than brachial systolic blood pressures (P = 0.021) and aortic/brachial pulse pressure ratio (P = 0.005). Compared to doxazosin, ramipril reduced carotid-femoral and carotid-radial pulse wave velocity (both P < 0.05). Forearm endothelial dependent and independent vasodilatation, assessed by post-ischemic flow mediated vasodilatation and glyceryl trinitrate, and by pulse wave analysis remained unchanged by both doxazosin and ramipril. In addition, skin microvascular endothelial dependent (acetylcholine) and independent vasodilatation (sodium nitroprusside) remained unchanged. In conclusion, ramipril reduced indices of aortic stiffness, suggesting that angiotensin converting enzyme inhibitor therapy may have effects beyond blood pressure reduction. However, treatment did not appear to influence endothelial function. Evidence of endothelial dysfunction and its possible improvement by antihypertensive treatment might require more advanced hypertension.

This study is registered at ClinicalTrials.gov (NCT02901977) and at EudraCT (# 2007-000631-25).

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Platelet reactivity and clinical outcomes in patients using CYP3A4-metabolized statins with clopidogrel in percutaneous coronary intervention

Abstract

Statins are primarily metabolized by cytochrome P450 3A4 (CYP3A4), which reduces clopidogrel to its active metabolite. Recent studies suggest that CYP3A4-metabolized statins attenuate clopidogrel's anti-aggregatory effect on platelets. We aimed to assess the impact of concomitant CYP3A4-metabolized statin and clopidogrel use on antiplatelet activity and clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). We enrolled 1187 patients from the HOST–ASSURE trial with platelet reactivity unit (PRU) values at both baseline and 1 month. Patients were assigned to the CYP3A4-metabolized statin group (group A, n = 725) or non-CYP3A4-metabolized statin group (group B, n = 462) according to type of statin used. Co-primary outcomes were the differences between PRU at baseline and 1 month and the composite of cardiovascular death, recurrent myocardial infarction, stent thrombosis, revascularization, and cerebrovascular accident. We found that follow-up PRU values did not change in group A and decreased significantly in group B (mean difference: −15 ± 79, p < 0.001) in both the crude and matched cohorts. Patients with a high PRU value at baseline, irrespective of statin type, had a significant reduction in mean PRU difference (group A, −62 ± 78, p < 0.001; group B, −59 ± 69, p < 0.001) in both the crude and matched cohorts. The composite of clinical events did not differ between groups in either cohort. CYP3A4-metabolized statins slightly inhibit the antiplatelet activity of clopidogrel during dual antiplatelet therapy. However, they do not inhibit clopidogrel's antiplatelet effect in patients with high platelet reactivity or increase clinical events in patients following PCI.

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Hidroalcoholic extract from Nerium oleander L. (Apocynaceae) elicits arrhythmogenic activity

Publication date: Available online 28 May 2017
Source:Journal of Ethnopharmacology
Author(s): Ana Flávia Machado Botelho, Artur Santos-Miranda, Humberto Cavalcante Joca, Cláudio Roberto Scabelo Mattoso, Maira Souza de Oliveira, Felipe Pierezan, Jader Santos Cruz, Benito Soto-Blanco, Marília Martins Melo
Ethnopharmacological relevanceNerium oleander L. (OLE) has been used medicinally and is reported to possess a wide range of pharmacological activities. OLE effects are caused by different cardiac glycosides (CG), primarily oleandrin, found within the plant. CG can potentially impair sodium-potassium ATPase (NKA) pump activity and cause positive inotropic effects on the heart.Aim of the studyThe aim of this study was to investigate the potential arrhythmogenic effects of hydroalcoholic extracts from N. oleander (OLE).Materials and methodsOLE hydroalcoholic extracts were obtained from N. oleander leaves and analyzed by HPLC. In vivo experiments with guinea pigs consisted if oral administration of water, 150mg/kg and 300mg/kg OLE extract. Clinical signs and ECG analysis were evaluated. Sample tissues from the heart were processed for histopathological and ultra-structural analysis. Autonomic effects were assessed through pharmacological blockade and ECG monitoring. In vitro experiments were conducted with isolated ventricular myocytes from adult mice. The effects of OLE extract on cardiac excitability, Na⁺/K⁺ pump current and global Ca²⁺ transients were evaluated.ResultsOur results demonstrated that OLE hydroalcoholic extract elicited severe cardiac arrhythmias that can lead to death with minimal tissue damage. In vitro experiments suggest that OLE causes electromechanical disturbances in the heart due to inhibition of Na⁺/K⁺ pump, mitochondrial swelling, and modulation of the sarco(endo)plasmic Ca²⁺ ATPase without interfering with the autonomic nervous system. Thus, arrhythmias and electrical conduction disturbances promoted by OLE are mainly associated with impaired cardiomyocyte dysfunction, rather than anatomical tissue remodeling and/or autonomic modulation.ConclusionOur data revealed the potential cardiotoxicity and positive inotropic effect of OLE and its important role in modulation of electrophysiology in cardiomyocytes.

Graphical abstract

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Suitability of functional evaluation embedded in serious game rehabilitation exercises to assess motor development across lifespan

Publication date: September 2017
Source:Gait & Posture, Volume 57
Author(s): B. Bonnechère, V. Sholukha, L. Omelina, M. Van Vooren, B. Jansen, S. Van Sint Jan
The aim of this study was to determine if the results of activities performed using specially developed serious games for physical rehabilitation could be used as an indicator of the natural maturation and decline of motor control in healthy participants. Eighty-one participants (19 children (5–15 years old), 40 adults (18–65 years old) and 22 aged subjects (60–88 years old) participated in this study. Motions performed were recorded using the Kinect sensor. Three different exercises embedded in the games were used to assess upper limb, trunk and lower limb control. The trial duration and accuracy, measures of gross motor function and fine motor control, respectively, were computed for each participant. ANOVA tests shows statistically significant differences between the three groups for duration (53±15, 27±10 and 119±30s for children, adults and elderly subjects respectively) and accuracy (87±5, 89±10 and 70±8% for children, adults and elderly subjects respectively). The slopes of the curves that approximated the evolution of the performance over various ages are coherent with previous studies about motor control development and physiological decline. The proposed solution, i.e. serious games rehabilitation exercises coupled to motion analysis, seems to be an interesting tool to assess global motor function. Further studies are needed to study the influence of pathologies on the studied parameters.



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