Mitochondrial dysfunction in inherited renal disease and acute kidney injury

Nature Reviews Nephrology

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The challenging diagnosis of non-community-acquired pneumonia in non-mechanically ventilated subjects: Value of microbiological investigation

Respiratory Care

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Number of comorbidities negatively influence psychological outcomes of the elderly following hip fracture in Taiwan

Journal of Aging and Health

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Effects of optimism and gratitude on physical activity, biomarkers, and readmissions after an acute coronary syndrome

Circulation: Cardiovascular Quality and Outcomes

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Epidemiology of lawnmower-related injuries in children: A ten year review

The American Journal of Surgery

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Tracheal ultrasonography and ultrasonographic lung sliding for confirming endotracheal tube placement: faster? reliable?

The American Journal of Emergency Medicine

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Aneurysm rupture from blunt abdominal trauma after endovascular repair

Vascular

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Laboratory prediction of primary postpartum haemorrhage: A comparative cohort study

BMC Pregnancy and Childbirth

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Identifying the broken heart: Predictors of mortality and morbidity in suspected blunt cardiac injury

The American Journal of Surgery

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Prevention of post-traumatic stress disorder after trauma: Current evidence and future directions

Current Psychiatry Reports

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Impact of length of stay for first psychiatric admissions on the ratio of readmissions in subsequent years in a large Brazilian catchment area

Social Psychiatry and Psychiatric Epidemiology

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Usability of the Massachusetts prescription drug monitoring program in the emergency department: a mixed methods study

Academic Emergency Medicine

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Manipulation and reduction of paediatric fractures of the distal radius and forearm using intranasal diamorphine and 50% oxygen and nitrous oxide in the emergency department: a 2.5-year study

The Bone & Joint Journal

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Diagnostic performance of isolated orbital CT scan for assessment of globe rupture in acute blunt facial trauma

Injury

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Bladder injury and success rates following retropubic mid-urethral sling: TVT EXACT vs. TVT

European Journal of Obstetrics & Gynecology and Reproductive Biology

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Modeling the influence of Twitter in reducing and increasing the spread of influenza epidemics

A more realistic mathematical influenza model including dynamics of Twitter, which may reduce and increase the spread of influenza, is introduced. The basic reproductive number is derived and the stability of the steady states is proved. The existence of Hopf bifurcation are also demonstrated by analyzing the associated characteristic equation. Furthermore, numerical simulations and sensitivity analysis of relevant parameters are also carried out. Our results show that the impact posed by the negative information of Twitter is not significant than the impact posed by the positive information of Twitter on influenza while the impact posed by the negative information of Twitter on the influenza virus is still extraordinary.Mathematics Subject Classification: 92D25.

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Detection of fraudulent financial statements using the hybrid data mining approach

The purpose of this study is to construct a valid and rigorous fraudulent financial statement detection model. The research objects are companies which experienced both fraudulent and non-fraudulent financial statements between the years 2002 and 2013. In the first stage, two decision tree algorithms, including the classification and regression trees (CART) and the Chi squared automatic interaction detector (CHAID) are applied in the selection of major variables. The second stage combines CART, CHAID, Bayesian belief network, support vector machine and artificial neural network in order to construct fraudulent financial statement detection models. According to the results, the detection performance of the CHAID–CART model is the most effective, with an overall accuracy of 87.97 % (the FFS detection accuracy is 92.69 %).

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A tumoral mass (local recurrence of renal cell carcinoma) causing massive intraabdominal bleeding after blunt abdominal trauma.

A tumoral mass (local recurrence of renal cell carcinoma) causing massive intraabdominal bleeding after blunt abdominal trauma.

Int J Surg Case Rep. 2016 Jan 16;20:57-59

Authors: Yıldız İ, Koca YS, Okur K, Barut İ

Abstract
BACKGROUND: Solid organ injury after abdominal trauma is a common condition, however, injury of the local recurrent tumoral masses following abdominal trauma is rare. The injuries and bleeding in recurrent tumors tend to be highly serious since they are more fragile. The bleedings caused by renal cell carcinomas and by the traumatic laceration of their recurrence commonly occur in the retroperitoneum. In this report, we present a 55-year-old female patient who underwent emergency surgery due to intraabdominal bleeding and bleeding was from the recurrence of a renal cell carcinomas.
PRESENTATION OF CASE: The 55-year-old female patient was admitted to the emergency service with intraabdominal bleeding. Physical examination revealed tenderness in the right lower quadrant, particularly in the traumatic area. Ultrasonography and computed tomography revealed diffuse intraabdominal fluid and a ruptured bleeding mass was excised. Pathological analysis indicated that the mass was isolated local recurrence of renal cell carcinoma.
DISCUSSION: Solid organ injury caused by blunt abdominal trauma may be accompanied by tumoral laceration; however, minor bleeding may occur in cases with blunt trauma, coexistence of blunt abdominal trauma with local recurrence and massive bleeding is extremely rare. Control of bleeding is more challenging in tumoral tissues compared to normal tissues. The bleeding intraabdominal area rather than the retroperitoneal area, and this condition was attributed to the peritoneal tear caused by the trauma.
CONCLUSION: Local recurrent tumoral masses may be the source of the intraabdominal massive bleeding after blunt trauma.

PMID: 26812671 [PubMed - as supplied by publisher]

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Two-stage surgical resection of an atypical teratoid rhabdoid tumor occupying the infratentorial and supratentorial compartment in children under two years: Report of two cases.

Two-stage surgical resection of an atypical teratoid rhabdoid tumor occupying the infratentorial and supratentorial compartment in children under two years: Report of two cases.

Int J Surg Case Rep. 2016 Jan 16;20:49-52

Authors: Foreman PM, Madura CJ, Johnston JM, Rocque BG

Abstract
INTRODUCTION: Atypical teratoid rhabdoid tumors are highly malignant neoplasms that present in young children and can grow to a large size. Maximal safe surgical resection is a mainstay of treatment.
PRESENTATION OF CASES: Two cases of children under the age of two with large tumors involving the supratentorial and infratentorial compartments are presented. A two-staged operative approach combining a standard suboccipital approach to the fourth ventricle followed by an infratentorial, supracerebellar approach was utilized for resection.
DISCUSSION: Maximal safe surgical resection of large tumors in young children is challenging. A staged approach is presented that affords maximal tumor resection while minimizing perioperative morbidity.
CONCLUSION: A staged operative approach appears safe and efficacious when resecting large tumors from both the infratentorial and supratentorial compartments in children less than two years of age.

PMID: 26812670 [PubMed - as supplied by publisher]

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Retroperitoneal mass presenting as recurrent inguinal hernia: A case report.

Retroperitoneal mass presenting as recurrent inguinal hernia: A case report.

Int J Surg Case Rep. 2016 Jan 14;20:46-48

Authors: Tardu A, Yagci MA, Karagul S, Ertugrul I, Kayaalp C

Abstract
INTRODUCTION: Retroperitoneal masses presenting as an inguinal hernia are rare conditions.
PRESENTATION OF CASE: A 53 year old male admitted with the symptoms of weight loss, abdominal discomfort and left sided recurrent inguinal hernia. Physical examination demonstrated an abdominal mass in the left flank and an irreducible, painless scrotal mass. He had a history of left sided inguinal hernia surgery six years ago. Computed tomography revealed a large enhancing left sided retroperitoneal mass invading the colon, pancreas and kidney and it was going down towards the left scrotum. Unblock tumor resection including the neighboring organs (left kidney, left colon, distal pancreas with spleen) was performed. Scrotal extension of the tumor was also excised and the inguinal canal was repaired primarily. Histopathology of the mass was myxoid-liposarcoma. The patient has disease free, without hernia recurrence but poor in renal function after twenty months follow-up.
DISCUSSION: Large retroperitoneal tumors may grow towards the inguinal region and they can mimic an inguinal hernia. An irreducible, painless and hard scrotal mass should be considered from this perspective.

PMID: 26812669 [PubMed - as supplied by publisher]

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Atypical breasts cancers.

Atypical breasts cancers.

Int J Surg Case Rep. 2016 Jan 16;20:41-45

Authors: Wright L, Ng CE, Fasih T

Abstract
INTRODUCTION: With increasing incidence of breast cancers there are now a larger number of cases diagnosed with rare malignancies. These can be diagnostic dilemmas and management strategy can be different by various breast multi-disciplinary teams (MDT). We aim to discuss the evidence-based approach for management of these atypical breast cancers which were identified in patients from a single breast screening unit.
METHOD: Patient with unusual breast malignancies (all types except invasive ductal and lobular) treated under the care of a single surgeon were identified during the breast multi-disciplinary discussion from 2011 to 2015. The histology and management of these cases were reviewed and literature search of electronic databases via PubMed and the search engines Google/Google Scholar was performed. Emphasis on keywords based on the histology type was used to limit search. Search was focused on the diagnosis, management and prognosis of these unusual breast cancers.
CONCLUSION: This series aims to focus on the evidence-based management of these rare breast malignancies; the diagnosis of which is crucial as it affects the overall treatment and prognosis.

PMID: 26812668 [PubMed - as supplied by publisher]

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Primary lumbar hernia: A rarely encountered hernia.

Primary lumbar hernia: A rarely encountered hernia.

Int J Surg Case Rep. 2015 Oct 30;20:53-56

Authors: Sundaramurthy S, Suresh HB, Anirudh AV, Prakash Rozario A

Abstract
INTRODUCTION: Lumbar hernia is an uncommon abdominal wall hernia, making its diagnosis and management a challenge to the treating surgeon. Presentation may be misleading and diagnosis often missed. An imaging study forms an indispensable aid in the diagnosis and surgery is the only treatment option.
PRESENTATION OF CASE: A 42 year old male presented with history of pain in lower back of 4 years duration and was being treated symptomatically over 4 years with analgesics and physiotherapy. He had noticed a swelling over the left side of his mid-back and consequently on examination was found to have a primary acquired lumbar hernia arising from the deep superior lumbar triangle of Grynfelt. Diagnosis was confirmed by Computed Tomographic imaging.
DISCUSSION: A lumbar hernia may be primary or secondary with only about 300 cases of primary lumbar hernia reported in literature. Lumbar hernias manifest through two possible defects in the posterior abdominal wall, the superior being more common. Management remains surgical with various techniques emerging over the years. The patient at our center underwent an open sublay mesh repair with excellent outcome.
CONCLUSION: A surgeon may encounter a primary lumbar hernia perhaps once in his lifetime making it an interesting surgical challenge. Sound anatomical knowledge and adequate imaging are indispensable. Inspite of advances in minimally invasive surgery, it cannot be universally applied to patients with lumbar hernia and management requires a more tailored approach.

PMID: 26812667 [PubMed - as supplied by publisher]

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Parallel Stitching of 2D Materials

Diverse parallel stitched 2D heterostructures, including metal–semiconductor, semiconductor–semiconductor, and insulator–semiconductor are synthesized directly through selective "sowing" of aromatic molecules as the seeds in the chemical vapor deposition (CVD) method. The methodology enables the large-scale fabrication of lateral heterostructures, which offers tremendous potential for its application in integrated circuits.

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Fluorescence nanoprobe for single bacterium tracking: Functionalization of silver nanoparticles with tryptophan to probe the nanoparticle accumulation with single cell resolution

Analyst, 2016, Accepted Manuscript
DOI: 10.1039/C5AN02358K, Paper

Radovan J Dojcilovic, Jelena D Pajovic, Dusan K. Bozanic, Vesna Vodnik, Suzana Dimitrijevic-Brankovic, Aleksandar R. Milosavljevic, Slavka Kascakova, Matthieu Refregiers, Vladimir Djokovic
The investigation of the interaction of silver nanoparticles andlive bacteria cells is of particular importance for understanding and controlling of their bactericidal properties. In this study,the process of internalization of...
The content of this RSS Feed (c) The Royal Society of Chemistry

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Analysis of sinonasal anatomical variations associated with maxillary sinus fungal balls.

Analysis of sinonasal anatomical variations associated with maxillary sinus fungal balls.

Auris Nasus Larynx. 2016 Jan 22;

Authors: Shin JM, Baek BJ, Byun JY, Jun YJ, Lee JY

Abstract
OBJECTIVE: The pathogenesis of MSFB development remains unclear, but it has been suggested that poor sinus ventilation is associated with disease development; such a ventilation is influenced by anatomical variation of the paranasal sinuses. Thus, we sought to determine whether sinonasal anatomical variations were associated with MSFB development.
METHODS: Thirty-one patients with MSFB and 28 gender-matched control patients were included in the present study. The presence or absence of Haller cells and a concha bullosa were scored, and the angle of septal deviation and the minimal and maximal lengths of the infundibulum were measured on preoperative computed tomography images.
RESULTS: In the MSFB group, both a concha bullosa (61.3% vs. 28.6%, p=0.006) and Haller cells (41.9% vs. 30.4%) were present at higher frequencies than in the control group, although the between-group difference in Haller cell occurrence was not statistically significant (p=0.348). In addition, MSFB patients had a significantly lower mean infundibular width (3.23±0.69mm vs. 3.99±1.17mm, p<0.001) and a longer infundibular length (9.71±1.43mm vs. 8.23±1.72mm, p<0.001) than controls.
CONCLUSIONS: Sinonasal anatomical variations, especially the presence of a concha bullosa, and/or a narrow and long infundibulum, may play roles in the development of maxillary sinus fungal balls (MSFBs).

PMID: 26811302 [PubMed - as supplied by publisher]

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Limits of application of initiated chemiluminescence in monitoring of oncological process of mucous membrane of mouth and larynx.

Limits of application of initiated chemiluminescence in monitoring of oncological process of mucous membrane of mouth and larynx.

Luminescence. 2016 Jan 25;

Authors: Oliynyk I

Abstract
Investigation into the limits of application of chemiluminescence (CL) methods in oncology still attracts the attention of researchers. In the present work we analyze the screening and monitoring of oncological processes (OP) in the mucous membrane of the mouth and larynx by initiated CL (ICL). Chemiluminescence has already been used by stomatologists to define the start of OP, but methods that reflect the metabolic changes in organism under cancer diagnostics still have not found their place. This work presents results of ICL on blood serum (BS) of patients with oncological diseases at different stages of medical treatment compared with those of healthy people. We found an essential metabolic difference only in types of OP that are characterized by two maxima on chemiluminograms. These OP represent only 12.81% of groups of patients with oncological diseases. The possibility to apply ICL methods to monitor operation quality and control medical treatment at different stages when the two ICL maxima are present is established. At present, the chemiluminograms with the two maxima are mostly informative, but this does not exclude the quantitative analysis of other ICL kinetic methods and is encouraging for their investigation. Any OP introduces changes in organism function and these should be reflected in the ICL. Copyright © 2016 John Wiley & Sons, Ltd.

PMID: 26809216 [PubMed - as supplied by publisher]

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Case 223: Arytenoid Dislocation.

Related Articles

Case 223: Arytenoid Dislocation.

Radiology. 2015 Nov;277(2):607-11

Authors: Oppenheimer AG, Gulati V, Kirsch J, Alemar GO

Abstract
A 71-year-old man with a history of atrial fibrillation refractory to medical therapy and lung cancer status after left upper lobectomy presented to our hospital for elective cardioversion and rate control with tikosyn. Overnight, the patient became unresponsive and was found to be in a state of cardiogenic shock. A code was called, and he was stabilized after cardioversion and bedside intubation. His stay in the intensive care unit was complicated by ventilator-associated pneumonia. The patient subsequently underwent multiple failed extubation attempts, requiring two additional reintubations. He was finally extubated 18 days after his initial admission to the intensive care unit. After he was discharged, he reported a hoarse voice and was only able to whisper. His voice varied in timbre and volume, and it became hoarser with use. Otolaryngology evaluation, including laryngoscopy and video stroboscopy, showed immobility of the right vocal cord. He was referred for speech therapy, and a computed tomographic (CT) examination of the neck was ordered.

PMID: 26492026 [PubMed - indexed for MEDLINE]

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Increased B Cell ADAM10 in Allergic Patients and Th2 Prone Mice.

Related Articles

Increased B Cell ADAM10 in Allergic Patients and Th2 Prone Mice.

PLoS One. 2015;10(5):e0124331

Authors: Cooley LF, Martin RK, Zellner HB, Irani AM, Uram-Tuculescu C, El Shikh ME, Conrad DH

Abstract
ADAM10, as the sheddase of the low affinity IgE receptor (CD23), promotes IgE production and thus is a unique target for attenuating allergic disease. Herein, we describe that B cell levels of ADAM10, specifically, are increased in allergic patients and Th2 prone WT mouse strains (Balb/c and A/J). While T cell help augments ADAM10 expression, Balb WT B cells exhibit increased ADAM10 in the naïve state and even more dramatically increased ADAM10 after anti-CD40/IL4 stimulation compared C57 (Th1 prone) WT B cells. Furthermore, ADAM17 and TNF are reduced in allergic patients and Th2 prone mouse strains (Balb/c and A/J) compared to Th1 prone controls. To further understand this regulation, ADAM17 and TNF were studied in C57Bl/6 and Balb/c mice deficient in ADAM10. C57-ADAM10B-/- were more adept at increasing ADAM17 levels and thus TNF cleavage resulting in excess follicular TNF levels and abnormal secondary lymphoid tissue architecture not noted in Balb-ADAM10B-/-. Moreover, the level of B cell ADAM10 as well as Th context is critical for determining IgE production potential. Using a murine house dust mite airway hypersensitivity model, we describe that high B cell ADAM10 level in a Th2 context (Balb/c WT) is optimal for disease induction including bronchoconstriction, goblet cell metaplasia, mucus, inflammatory cellular infiltration, and IgE production. Balb/c mice deficient in B cell ADAM10 have attenuated lung and airway symptoms compared to Balb WT and are actually most similar to C57 WT (Th1 prone). C57-ADAM10B-/- have even further reduced symptomology. Taken together, it is critical to consider both innate B cell levels of ADAM10 and ADAM17 as well as Th context when determining host susceptibility to allergic disease. High B cell ADAM10 and low ADAM17 levels would help diagnostically in predicting Th2 disease susceptibility; and, we provide support for the use ADAM10 inhibitors in treating Th2 disease.

PMID: 25933166 [PubMed - indexed for MEDLINE]

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Cyr61/CCN1 overexpression induces epithelial-mesenchymal transition leading to laryngeal tumor invasion and metastasis and poor prognosis.

Related Articles

Cyr61/CCN1 overexpression induces epithelial-mesenchymal transition leading to laryngeal tumor invasion and metastasis and poor prognosis.

Asian Pac J Cancer Prev. 2015;16(7):2659-64

Authors: Liu Y, Zhou YD, Xiao YL, Li MH, Wang Y, Kan X, Li QY, Lu JG, Jin DJ

Abstract
BACKGROUND: To examine the expression of cysteine-rich 61 (Cyr61/CCN1) protein in laryngeal squamous- cell carcinoma (LSCC) tissues, and its relationship with the tumor epithelial-mesenchymal transition (EMT), invasion, metastasis, and prognosis.
MATERIALS AND METHODS: Immunohistochemistry was used to detect the expressions of Cyr61, Vimentin (Vim), and E-cadherin (E-cad) in 88 cases of LSCC tissues and 30 cases of tumor-adjacent normal tissues. Vim and E-cad were used as mesenchymal and epithelial markers, respectively, to determine the relationship between Cyr61 expression and the EMT of LSCC cells. In addition, clinical and histopathological data were combined to analyze the relationship between the positive-expression rates of Cyr61, Vim and E-cad and LSCC invasion, metastasis and prognosis.
RESULTS: In LSCC tissues, Vim expression rate was significantly higher than that of the tumor-adjacent tissues, whereas E-cad expression rate was significantly lower than that of the tumor-adjacent tissues. The Vim expression rate was significantly higher in stages T3 and T4 than in stages T1 and T2 LSCC tissues, whereas E-cad expression rate was significantly lower in stages T3 and T4 than in stages T1 and T2 LSCC tissues. Compared to the group without lymph node metastasis, the Vim expression rate was significantly higher and the E-cad expression rate was significantly lower in the group with lymph node metastasis. The expression rate of Cyr61 was significantly higher in LSCC tissues than in the tumor-adjacent normal tissues. In addition, the Cyr61 expression rate was higher in stages T3 and T4 than in stages T1 and T2 LSCC, and higher in the group with lymph node metastasis than in the group without lymph node metastasis. The Vim expression rate was significantly higher in the Cyr61 positive group than in the Cyr61 negative group, whereas the E-cad expression rate was significantly higher in the Cyr61 negative group than in the Cyr61 positive group. Survival analysis indicated that survival rates of Cyr61 positive, Vim positive and E-cad negative groups were significantly lower than that of Cyr61 negative, Vim negative and E-cad positive groups, respectively.
CONCLUSIONS: Cyr61 expression is closely associated with LSCC invasion and lymph node metastasis. Overexpression of Cyr61 may induce EMT and therefore leads to LSCC invasion and metastasis and poor prognosis. Cyr61 may become a new maker for clinical prediction of LSCC invasion and metastasis and a new target for LSCC treatment.

PMID: 25854342 [PubMed - indexed for MEDLINE]

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Speech-like rhythm in a voiced and voiceless orangutan call.

Related Articles

Speech-like rhythm in a voiced and voiceless orangutan call.

PLoS One. 2015;10(1):e116136

Authors: Lameira AR, Hardus ME, Bartlett AM, Shumaker RW, Wich SA, Menken SB

Abstract
The evolutionary origins of speech remain obscure. Recently, it was proposed that speech derived from monkey facial signals which exhibit a speech-like rhythm of ∼5 open-close lip cycles per second. In monkeys, these signals may also be vocalized, offering a plausible evolutionary stepping stone towards speech. Three essential predictions remain, however, to be tested to assess this hypothesis' validity; (i) Great apes, our closest relatives, should likewise produce 5Hz-rhythm signals, (ii) speech-like rhythm should involve calls articulatorily similar to consonants and vowels given that speech rhythm is the direct product of stringing together these two basic elements, and (iii) speech-like rhythm should be experience-based. Via cinematic analyses we demonstrate that an ex-entertainment orangutan produces two calls at a speech-like rhythm, coined "clicks" and "faux-speech." Like voiceless consonants, clicks required no vocal fold action, but did involve independent manoeuvring over lips and tongue. In parallel to vowels, faux-speech showed harmonic and formant modulations, implying vocal fold and supralaryngeal action. This rhythm was several times faster than orangutan chewing rates, as observed in monkeys and humans. Critically, this rhythm was seven-fold faster, and contextually distinct, than any other known rhythmic calls described to date in the largest database of the orangutan repertoire ever assembled. The first two predictions advanced by this study are validated and, based on parsimony and exclusion of potential alternative explanations, initial support is given to the third prediction. Irrespectively of the putative origins of these calls and underlying mechanisms, our findings demonstrate irrevocably that great apes are not respiratorily, articulatorilly, or neurologically constrained for the production of consonant- and vowel-like calls at speech rhythm. Orangutan clicks and faux-speech confirm the importance of rhythmic speech antecedents within the primate lineage, and highlight potential articulatory homologies between great ape calls and human consonants and vowels.

PMID: 25569211 [PubMed - indexed for MEDLINE]

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Comparison of the result of consolidative technique otoplasty and incisionless otoplasty in the repairs of prominent ears.

Comparison of the result of consolidative technique otoplasty and incisionless otoplasty in the repairs of prominent ears.

Eur Arch Otorhinolaryngol. 2016 Jan 25;

Authors: Temel M, Şamil Kahraman Ş, Berber Ö, Çevik C, Akoğlu E

Abstract
We aimed to compare the long-term results of complications of consolidative technique otoplasty (CTO) and incisionless otoplasty (IO). The study consists of 156 patients who were operated between 2006 and 2015. According to surgical techniques, these patients were divided into two groups as IO group and CTO group. The distance between the head and the ear was assessed by measuring the four points preoperatively and postoperatively (SUP: most superior helical point, SCA: superior conchal attachment, ICA: inferior conchal attachment, and lobule). Early and late postoperative complications, operative time were recorded. 128 ears in IO group, 163 ears in CTO group were prominent. When postoperative SUP, SCA, ICA, lobule values for right and left ears in both groups were statistically evaluated, it was found that CTO technique has led to significantly greater improvement compared to the IO technique (p < 0.001). The success rate in IO technique and CTO technique was 72 and 96 %, respectively. Early complications were similar in both groups. The late period complication determined much more frequently was seen in the IO group. Concerning operative time, it was identified as significantly lower in the IO group (p < 0.001). The early-term outcomes of both techniques were similar; however, the complication rates due to suture material and needed for revision in IO technique were higher whereas CTO technique was more permanent with lower complication risks.

PMID: 26810363 [PubMed - as supplied by publisher]

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SATB1 expression is correlated with β-catenin associated epithelial-mesenchymal transition in colorectal cancer.

SATB1 expression is correlated with β-catenin associated epithelial-mesenchymal transition in colorectal cancer.

Cancer Biol Ther. 2016 Jan 25;:0

Authors: Lv JH, Wang F, Wang Y, Shen MH, Wang X, Zhou XJ

Abstract
SATB1, a global gene regulator, has been implicated in the growth and metastasis of multiple cancers, including colorectal cancer. While the understanding about the role of SATB1 in CRC remains limited. The aim of our study is to investigate the expression of SATB1 in CRC, and the relationship between SATB1 expression pattern and clinicopathological variables. A further aim is to analyse the correlation between SATB1 expression and epithelial-mesenchymal transition in CRC. Immunohistochemical expression of SATB1, β-catenin, E-cadherin, CK20, Vimentin, SMA, and desmin were assessed in a cohort of 200 patients using tissue microarrays. SATB1 was expressed in 133 (66.5%) CRC primary lesions, 14 (28%) adjacent colorectal mucosa specimens, and 60 (75%) corresponding lymph node metastases. The expression level of SATB1 was significantly higher in lymph node metastases than in CRC primary lesions and normal mucosa (P = 0.000). High expression of SATB1 in CRC was strongly correlated with poor differentiation of tumor tissues (P = 0.000). High expression of SATB1 was significantly correlated with aberrant expression of β-catenin (P = 0.0005), low expression of E-cadherin (P = 0.000) and CK20 (P = 0.000) and with high expression of Vimentin (P = 0.001). No SMA or desmin protein was expressed in the CRC cells. Our results suggested that high expression of SATB1 is significantly correlated with poor differentiation of CRC. SATB1 might promote the epithelial-mesenchymal transition by increasing the aberrant expression of β-catenin.

PMID: 26810818 [PubMed - as supplied by publisher]

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EBI-907, a novel BRAF(V600E) inhibitor, has potent oral anti-tumor activity and a broad kinase selectivity profile.

EBI-907, a novel BRAF(V600E) inhibitor, has potent oral anti-tumor activity and a broad kinase selectivity profile.

Cancer Biol Ther. 2016 Jan 25;:0

Authors: Zhang J, Lu B, Liu D, Shen R, Yan Y, Yang L, Zhang M, Zhang L, Cao G, Cao H, Fu B, Gong A, Sun Q, Wan H, Zhang L, Tao W, Cao J

Abstract
The oncogenic mutation of BRAF (V600E) has been found in approximately 8% of all human cancers, including more than 60% of melanoma and 10% of colorectal cancers. The clinical proof of concept in treating BRAF(V600E)-driving melanoma patients with the BRAF inhibitors has been well established. We have sought to identify and develop novel BRAF(V600E) inhibitors with more favorable profiles. Our chemistry effort has led to the discovery of EBI-907 as a novel BRAF(V600E) inhibitor with potent anti-tumor activity in vitro and in vivo. In a LanthaScreen BRAF(V600E) kinase assay, EBI-907 showed an IC50 of 4.8 nM, which is >10-fold more potent than Vemurafenib (IC50 = 58.5 nM). In addition, EBI-907 showed a broader kinase selectivity profile, with potent activity against a number of important oncogenic kinases including FGFR1-3, RET, c-Kit, and PDGFRb. Concomitant with such properties, EBI-907 exhibits potent and selective cytotoxicity against a broader range of BRAF(V600E)-dependent cell lines including certain colorectal cancer cell lines with innate resistance to Vemurafenib. In BRAF(V600E)-dependent human Colo-205 and A375 tumor xenograft mouse models, EBI-907 caused a marked tumor regression in a dose-dependent manner, with superior efficacy to Vemurafenib. Our results also showed that combination with EGFR or MEK inhibitor enhanced the potency of EBI-907 in cell lines with innate or acquired resistance to BRAF inhibition alone. Our findings present EBI-907 as a potent and promising BRAF inhibitor, which might be useful in broader indications.

PMID: 26810733 [PubMed - as supplied by publisher]

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A novel multi-CDK inhibitor P1446A-05 restricts melanoma growth and produces synergistic effects in combination with MAPK pathway inhibitors.

A novel multi-CDK inhibitor P1446A-05 restricts melanoma growth and produces synergistic effects in combination with MAPK pathway inhibitors.

Cancer Biol Ther. 2016 Jan 25;:0

Authors: Eliades P, Miller DM, Miao B, Kumar R, Taylor M, Buch S, Srinivasa SP, Flaherty KT, Tsao H

Abstract
Nearly 100% of melanomas have a defect in the p16(INK4A):cyclin D-CDK4/6:RB pathway, leading to abnormal cell cycle control and unregulated cellular proliferation. Here, we report that P1446A-05, a novel multi-CDK inhibitor has significant inhibitory activity against cutaneous and uveal melanoma. Mechanistic studies revealed that P1446A-05 inhibits phosphorylation targets of CDK members, and induces cell cycle arrest and apoptosis irrespective of melanoma genotype or phenotype. Additionally, we show preclinical evidence that P1446A-05 can synergize with other small molecule inhibitors previously studied in melanoma. Collectively, these data demonstrate that targeting cell cycle and transcriptional CDKs with a small molecule multi-CDK inhibitor is a viable approach for developing novel anti-melanoma therapeutics.

PMID: 26810603 [PubMed - as supplied by publisher]

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Lymphocytic Esophagitis With CD4 T-cell-predominant Intraepithelial Lymphocytes and Primary Esophageal Motility Abnormalities: A Potential Novel Clinicopathologic Entity.

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Lymphocytic Esophagitis With CD4 T-cell-predominant Intraepithelial Lymphocytes and Primary Esophageal Motility Abnormalities: A Potential Novel Clinicopathologic Entity.

Am J Surg Pathol. 2015 Nov;39(11):1558-67

Authors: Xue Y, Suriawinata A, Liu X, Li Z, Gabbard S, Rothstein R, Lacy B, Lisovsky M

Abstract
Lymphocytic esophagitis (LE) is an uncommon poorly defined histologic pattern. Its significance is largely unknown. The goal of our study was to characterize LE clinically, histologically, and immunophenotypically. Biopsies of 45 patients with LE and no intraepithelial granulocytes were selected throughout a 36-month period during routine diagnostic work. After reevaluation, complete absence of intraepithelial granulocytes was confirmed in 21 patients (LE-NG group), and few granulocytes were found in 24 patients (LE-FG). The control group consisted of 28 patients with active esophagitis consistent with reflux and overtly increased intraepithelial lymphocytes (REIL). The ratio of CD4:CD8 intraepithelial lymphocytes (IEL)>1 indicated predominance of CD4 IEL; the ratio ≤1 indicated predominance of CD8 IEL. Dysphagia was the primary complaint in 71%, 54%, and 39% of the patients with LE-NG, LE-FG, and REIL, respectively (P=0.04, LE-NG vs. REIL). Importantly, primary esophageal motility abnormalities were found in 10/11 (91%) tested LE-NG patients, 6/10 (60%) LE-FG patients, and 6/11 (54%) REIL patients. CD4 IELs were predominant in 81%, 50%, and 39% of LE-NG, LE-FG, and REIL cases, respectively (P=0.004, LE-NG vs. REIL), and in 90%, 83%, and 88% of the cases with primary motility abnormalities from the same groups. The prevalence of primary motility abnormalities was significantly higher in patients with CD4-predominant esophagitis than in patients with CD8-predominant esophagitis from all groups (21/24 [83%] vs. 2/8 [25%], P=0.005). A distinctive type of LE with predominance of CD4 IEL is associated with primary motility abnormalities suggesting a diagnostic utility of evaluating CD4 and CD8 subpopulations of T cells in LE.

PMID: 26379147 [PubMed - indexed for MEDLINE]

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Self-medication of achalasia with cannabis, complicated by a cannabis use disorder.

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Self-medication of achalasia with cannabis, complicated by a cannabis use disorder.

World J Gastroenterol. 2015 May 28;21(20):6381-3

Authors: Luquiens A, Lourenco N, Benyamina A, Aubin HJ

Abstract
Achalasia is a rare esophagus motility disorder. Medical, endoscopic and surgical treatments are available, but all endorse high relapse rates. No data has been published to date reporting a therapeutic effect of cannabis use neither in achalasia nor on its influence on manometric measurements. We report the case of a patient diagnosed with achalasia. He could benefit from a large panel of therapeutic interventions, but none of them was effective over the time. He first used cannabis at age 20 and identified benefits regarding achalasia symptoms. He maintained regular moderate cannabis use for 9 years, with minimal digestive inconvenience. A manometry performed without cannabis premedication was realized at age 26 and still found a cardiospasm. Cannabis use could explain the gap between functional symptoms assessment and manometry measurement. Further investigations are warranted to explore a therapeutic effect of cannabis in achalasia and possible influence on outcome measurements.

PMID: 26034374 [PubMed - indexed for MEDLINE]

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Idiopathic pulmonary fibrosis: the turning point is now!

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Idiopathic pulmonary fibrosis: the turning point is now!

Swiss Med Wkly. 2015;145:w14139

Authors: Funke M, Geiser T

Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with poor survival. Recent studies have improved understanding of IPF and new discoveries have led to novel treatment options, which now have become available for patients. In face of the newly available therapies we present an update on the pathophysiology and epidemiology of IPF. We discuss the typical clinical findings and elaborate diagnostic procedures according to current guidelines and our daily practice approach. The role of biomarkers will briefly be outlined. Finally, we discuss novel antifibrotic treatment options for IPF (pirfenidone, nintedanib) and the management of patients regarding to comorbidities and complications. Both pirfenidone and nintedanib were shown to reduce the progression of IPF and therefore represent novel therapeutic strategies in this so far untreatable chronic lung disease.

PMID: 26024356 [PubMed - indexed for MEDLINE]

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Irsogladine maleate and rabeprazole in non-erosive reflux disease: A double-blind, placebo-controlled study.

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Irsogladine maleate and rabeprazole in non-erosive reflux disease: A double-blind, placebo-controlled study.

World J Gastroenterol. 2015 Apr 28;21(16):5023-31

Authors: Suzuki T, Matsushima M, Masui A, Tsuda S, Imai J, Nakamura J, Tsukune Y, Uchida T, Yuhara H, Igarashi M, Koike J, Mine T

Abstract
AIM: To evaluate the efficacy of adding irsogladine maleate (IM) to proton-pump inhibitor (PPI) therapy in non-erosive reflux disease (NERD) treatment.
METHODS: One hundred patients with NERD were recruited and randomized to receive rabeprazole plus IM (group I) or rabeprazole plus placebo (group P). The efficacy of the treatment was assessed using the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG) and the short form (SF)-36 quality of life questionnaires after four weeks of treatment. We also assessed whether patients with NERD with minimal changes (grade M) had different responses to the therapies compared with patients who did not have minimal changes (grade N).
RESULTS: Group I and group P showed significant improvements in their FSSG scores after the treatment (from 17.9 ± 7.9 to 9.0 ± 7.6, and from 17.7 ± 7.3 to 11.2 ± 7.9, respectively, P = 0.0001), but there was no statistically significant difference between the FSSG scores in group I and those in group P. Subgroup analysis showed that significant improvements in the FSSG scores occurred in the patients in group I who had NERD grade N (modified Los Angeles classification) (7.8 ± 7.4 vs 12.5 ± 9.8, P = 0.041). The SF-36 scores for patients with NERD grade N who had received IM and rabeprazole were significantly improved in relation to their vitality and mental health scores.
CONCLUSION: The addition of IM to rabeprazole significantly improves gastroesophageal reflux disease symptoms and the quality of the lives of patients with NERD grade N.

PMID: 25945018 [PubMed - indexed for MEDLINE]

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Pathophysiology of functional heartburn based on Rome III criteria in Japanese patients.

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Pathophysiology of functional heartburn based on Rome III criteria in Japanese patients.

World J Gastroenterol. 2015 Apr 28;21(16):5009-16

Authors: Tamura Y, Funaki Y, Izawa S, Iida A, Yamaguchi Y, Adachi K, Ogasawara N, Sasaki M, Kaneko H, Kasugai K

Abstract
AIM: To investigate the pathophysiology of functional heartburn (FH) in Japanese patients.
METHODS: A total of 111 patients with proton pump inhibitor (PPI)-refractory non-erosive gastroesophageal reflux disease underwent intraesophageal pressure testing and 24-h multichannel intraluminal impedance-pH (24MII-pH) testing. The patients also completed several questionnaires while they were receiving the PPI treatment, including the questionnaire for the diagnosis of reflux disease (QUEST), the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), the gastrointestinal symptoms rating scale (GSRS), SF-36, and the Cornell Medical Index (CMI). The subjects were classified into FH and endoscopy-negative reflux disease (ENRD) groups based on the Rome III criteria.
RESULTS: Thirty-three patients with esophageal motility disorder were excluded from this study, while 22 patients with abnormal esophageal acid exposure time (pH-POS) and 34 with hypersensitive esophagus (HE) were included in the ENRD group. The FH group included 22 patients with no reflux involvement. Sex, age, and body mass index did not differ significantly between the groups. The mean SF-36 values were < 50 (normal) for all scales in these groups, with no significant differences. The GSRS scores in these groups were not different and showed overlap with other gastrointestinal symptoms. The QUEST and the FSSG scores did not differ significantly between the groups. Neuroticism was diagnosed using the CMI questionnaire in 17 of the 78 included subjects within the pH-POS (n = 4), HE (n = 8), and FH (n = 5) groups, with no significant differences.
CONCLUSION: Clinical characteristics of the FH and PPI-refractory ENRD groups were similar. Therefore, esophageal function should be examined via manometry and 24MII-pH testing to differentiate between them.

PMID: 25945016 [PubMed - indexed for MEDLINE]

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Anxiety and depression in patients with gastroesophageal reflux disease and their effect on quality of life.

Related Articles

Anxiety and depression in patients with gastroesophageal reflux disease and their effect on quality of life.

World J Gastroenterol. 2015 Apr 14;21(14):4302-9

Authors: Yang XJ, Jiang HM, Hou XH, Song J

Abstract
AIM: To explore the role of psychological factors in gastroesophageal reflux disease (GERD) and their effect on quality of life (QoL) of GERD patients.
METHODS: A total of 279 consecutive patients with typical symptoms and 100 healthy controls were enrolled in the study. All of the participants were evaluated with the Zung Self-Rating Anxiety Scale (ZSAS), the Zung Self-Rating Depression Scale (ZSDS) and the SF-36 questionnaire. The scores for anxiety, depression and QoL of the two groups were analyzed. The correlation between psychological factors and QoL was also analyzed.
RESULTS: Compared with healthy controls (34.70 ± 8.00), the scores of ZSAS in the non-erosive reflux disease (NERD) group (48.27 ± 10.34) and the reflux esophagitis (RE) group (45.38 ± 10.27) were significantly higher (P < 0.001). The mean ZSAS score of the NERD group was significantly higher than that of the RE group (P = 0.01). Compared with healthy controls (37.61 ± 8.44), the mean ZSDS scores were significantly higher in the NERD group (49.65 ± 11.09, P < 0.001) and the RE group (46.76 ± 11.83, P < 0.001). All dimensions of the SF-36 form were negatively correlated with the SAS and SDS scores in patients with NERD and RE (P < 0.05). According to the SF-36 form, vitality, mental health and social functioning were significantly correlated with symptoms of depression in patients with NERD and RE. General health was obviously affected by symptoms of depression in patients with NERD (P < 0.05).
CONCLUSION: Anxiety and depression may play an important role in the occurrence of GERD and especially that of NERD. The QoL of patients with GERD is reduced by anxiety and depression.

PMID: 25892882 [PubMed - indexed for MEDLINE]

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Dysphagia: current reality and scope of the problem.

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Dysphagia: current reality and scope of the problem.

Nat Rev Gastroenterol Hepatol. 2015 May;12(5):259-70

Authors: Clavé P, Shaker R

Abstract
Dysphagia is a symptom of swallowing dysfunction that occurs between the mouth and the stomach. Although oropharyngeal dysphagia is a highly prevalent condition (occurring in up to 50% of elderly people and 50% of patients with neurological conditions) and is associated with aspiration, severe nutritional and respiratory complications and even death, most patients are not diagnosed and do not receive any treatment. By contrast, oesophageal dysphagia is less prevalent and less severe, but with better recognized symptoms caused by diseases affecting the enteric nervous system and/or oesophageal muscular layers. Recognition of the clinical relevance and complications of oesophageal and oropharyngeal dysphagia is growing among health-care professionals in many fields. In addition, the emergence of new methods to screen and assess swallow function at both the oropharynx and oesophagus, and marked advances in understanding the pathophysiology of these conditions, is paving the way for a new era of intensive research and active therapeutic strategies for affected patients. Indeed, a unified field of deglutology is developing, with new professional profiles to cover the needs of all patients with dysphagia in a nonfragmented way.

PMID: 25850008 [PubMed - indexed for MEDLINE]

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Future Oncology; +24 new citations

24 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

Future Oncology

These pubmed results were generated on 2016/01/27

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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Percutaneous perirenal thrombin injection for the treatment of acute hemorrhage after renal biopsy.

Percutaneous perirenal thrombin injection for the treatment of acute hemorrhage after renal biopsy.

Diagn Interv Radiol. 2016 Jan 26;

Authors: Mafeld S, McNeill M, Haslam P

Abstract
Percutaneous renal biopsy is a valuable diagnostic approach. While commonly safe, it is not without risk and the most feared vascular complications include hemorrhage, pseudoaneurysm, and arterio-venous fistula formation. We report a case of acute hemorrhage after renal biopsy that was immediately identified by ultrasonography and successfully treated with percutaneous perirenal thrombin injection. This technique may prove a useful addition to the armamentarium of any operator performing renal biopsies.

PMID: 26809832 [PubMed - as supplied by publisher]

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Severe symptomatic intracranial internal carotid artery stenosis treated with intracranial stenting: a single center study with 58 patients.

Severe symptomatic intracranial internal carotid artery stenosis treated with intracranial stenting: a single center study with 58 patients.

Diagn Interv Radiol. 2016 Jan 26;

Authors: Wang ZL, Gao BL, Li TX, Cai DY, Zhu LF, Xue JY, Bai WX, Li ZS

Abstract
PURPOSE: We aimed to investigate the safety and effectiveness of intracranial stenting in a population with severe (≥70%) symptomatic intracranial internal carotid artery (ICA) atherosclerotic stenosis.
METHODS: Fifty-eight patients with severe intracranial ICA atherosclerotic stenosis were prospectively enrolled. The baseline data, cerebral angiography, success rate, perioperative complications, clinical and imaging follow-up were prospectively analyzed.
RESULTS: All patients had successful intracranial stenting (100%), and the mean degree of stenosis was improved from 84.3%±7.5% to 23.5%±5.1% after the stent procedure. During the 30-day perioperative period, only one patient (1.7%) had ischemic stroke. Seven patients (12.1%) had headache and dysphoria. Thirty-six patients (62.1%) had clinical follow-up for 6-68 months after stenting. Five female patients (13.9%) had ipsilateral stroke including one death, but no disabling stroke, while three other patients (8.3%) had ipsilateral temporary ischemic attack (TIA). The recurrent stroke rate was higher in patients presenting with stroke (4/17, 23.5%) than in patients presenting with TIA (1/19, 5.3%), with no statistical significance (P = 0.33). Thirteen patients (22.4%) had imaging follow-up of 5-12 months following stenting, five of whom (38.5%) had in-stent restenosis.
CONCLUSION: Intracranial stenting for patients with intracranial ICA atherosclerotic stenosis has a low perioperative stroke rate and decent outcome on long-term follow-up, despite a relatively high in-stent restenosis rate.

PMID: 26809831 [PubMed - as supplied by publisher]

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ABR thresholds in infants born with CLP and OME and infants with OME.

ABR thresholds in infants born with CLP and OME and infants with OME.

Int J Pediatr Otorhinolaryngol. 2016 Feb;81:21-5

Authors: Sundman H, Flynn T, Tengroth B, Lohmander A

Abstract
OBJECTIVES: The aim of this study was to investigate and compare auditory brainstem response (ABR) thresholds related to otitis media with effusion (OME) in infants with and without cleft palate and/or lip (CP±L).
METHODS: Forty-seven infants with CP±L and 67 infants with OME participated in the study. Hearing thresholds of ears of infants with OME were compared between groups and within the group with CP±L.
RESULTS: Infants with CP±L and OME presented with similar hearing thresholds as infants with OME and not CP±L. Within the cleft group, infants with isolated cleft palate and OME demonstrated significantly higher hearing thresholds than infants with unilateral cleft lip and palate and OME.
CONCLUSION: A high prevalence of infants with CP±L present with OME early in life. Hearing thresholds of these infants are similar to infants without CP±L, but with OME. The ear status and hearing thresholds of infants with CP±L needs to be monitored to be able to provide the best access to hearing in order to fully allow speech and language development.

PMID: 26810283 [PubMed - in process]

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Assessing the physical environment related to cycling and walking

Background: Walking and cycling are accessible and inexpensive forms of physical activity, which can be easily integrated in daily routines of life. Socio-ecological models are used to study the influencing factors of these behaviors, and highlight the importance of physical environmental elements, in combination with the individual and psychosocial elements. However, assessing the physical environment remains challenging. Purpose: To give an overview of methods that can be used to assess the physical environment in relation with walking and cycling. Approach: Both objective (e.g. audit tools, geographic information systems and global positioning systems) and subjective (e.g. questionnaires, interviews, focus groups, photo-voice, walk- and bike-along interviews and photographs) measurement methods are discussed. These measurement tools and their applications, advantages and limitations are discussed. Findings: From this chapter, it can be concluded that there are a number of instruments which can be used to assess the physical environment. At this moment, there is no method that can be considered as the gold standard. Depending on the aim of the study and the recourses available, one specific method or a combination of methods will be most appropriate. Implications: Practitioners, researchers and policy makers are informed about the possibilities on how to assess the physical environment, and more importantly, this will ensure that there is more insight on how the physical environmental should be created, in order that people will be more involved in walking and cycling for transport.

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The effect of tape on ankle joint landing kinematics in subjects with chronic ankle instability

Background: Chronic ankle instability is a frequently reported residual pathology as a result of an initial ankle sprain. Although tape is a commonly used treatment modality, the precise working mechanism remains unclear. Objective: To evaluate the effect of taping on ankle joint landing kinematics during a jump landing protocol in subjects with chronic ankle instability. Design: Repeated measures. Setting: Laboratory setting. Participants: Twenty-eight subjects with chronic ankle instability (10 men and 18 women, age = 22.3 ± 3.0 years, height = 1.73 ± 0.10m, body mass = 71.0 ± 10.6kg, FADI = 88.2 ± 7.2%, FADI- S = 69.0 ± 9.6%) participated in this study, characterized by an initial ankle sprain prohibiting sports participation for at least 3 weeks, episodes of "giving way", repetitive ankle sprains, feelings of instability and weakness around the ankle joint. Interventions: The taping procedure consisted of a double figure-of-6 and a medial heel lock. Main Outcome Measurements: Unilateral ankle joint 3D kinematics were registered with an eight-camera optoelectronic setup during a forward and side jump with and without tape. After each task, difficulty level and subjective instability at the ankle was documented using a visual analogue scale. Statistical parametric mapping was used to assess the intervention effect of tape on mean joint angles over the entire impact phase from 200ms prior to 200ms post landing (normalized to 100% with touch down at 50%). Results: For both the forward and side jump, a less plantar flexed position (respectively from 25%-55%, and 45%-53%), a more everted position (respectively from 30%-45%, and 30%- 55%), and a less abducted position (respectively from 0%-15%, and 5%-22%) were found for the taped condition (p < 0.05). The subjective instability level significantly decreased (p < 0.05) when taped, whereas perceived difficulty level was not influenced. Conclusions: The taping protocol significantly altered ankle joint kinematics and improved the subjective stability level in subjects with chronic ankle instability.

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Depression or anxiety in adult twins is associated with asthma diagnosis but not with offspring asthma

Abstract

Background

Asthma is common in both children and adults in the Western world, just like anxiety and depression. While some research has revealed that these diseases might share important environmental and pathophysiological aspects, the exact mechanisms still remain unclear.

Objective

To study the correlation firstly between depression or anxiety and asthma diagnosis in adult twins, and secondly the association between parental depression or anxiety and offspring asthma in children of twins.

Methods

In total, 24,685 adult twins aged 20-47 years were interviewed or completed a web-based questionnaire and their children were identified through the Multi-Generation Register. Asthma diagnosis was obtained from the Patient Register and the Prescribed Drug Register. Assessment of depression and anxiety was obtained from questionnaires using Center for Epidemiologic Studies Depression Scale (CES-D), Major Depression and Generalized Anxiety Disorder (GAD) from DSM-IV. The association between depression or anxiety and asthma was analyzed with logistic regression adjusting for confounders in twins and offspring. To address genetic and familial environmental confounding we performed a co-twin analysis using disease-discordant twin pairs.

Results

We found an association between asthma and CES-D, major depression and GAD, e.g. adjusted OR for major depression and register-based asthma 1.56(1.36-1.79). Most of the point estimates remained in the co-twin control analysis, indicating that the association was likely not due to genetic or familial environmental factors. There was no association between parental depression and/or anxiety and asthma diagnosis in the offspring which implies lack of genetic confounding.

Conclusions

We found an association between own asthma diagnosis and anxiety or depression, but not with offspring asthma. Our results indicate that the associations were not due to confounding from genes or environment shared by the twins.

This article is protected by copyright. All rights reserved.

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Evaluation of golimumab for the treatment of patients with active rheumatoid arthritis.

Evaluation of golimumab for the treatment of patients with active rheumatoid arthritis.

Expert Opin Drug Metab Toxicol. 2016 Jan 25;

Authors: Tanaka Y, Senoo A, Fujii H, Baker D

Abstract
INTRODUCTION: Golimumab is a human anti-TNF monoclonal antibody that was derived from human antibody-transgenic mice. Golimumab demonstrated meaningful clinical benefit and tolerable safety in patients with active rheumatoid arthritis (RA) who were methotrexate (MTX)-naïve, or who inadequately responded to MTX or who had previously been treated with a TNF inhibitor. Areas covered: This review summarizes published data on the clinical efficacy and safety for golimumab (including its pharmacodynamic and pharmacokinetic characteristics) from multiple global phase 3 and Japanese phase 2/3 clinical trials. In the long term extension of three Phase 3 studies with subcutaneous golimumab the reported retention rate is high. Expert opinion: Golimumab binds TNF with high affinity and can be delivered subcutaneously every 4 weeks. Like other IgG1 antibodies, FcR functions suggests that antibody dependent cellular cytotoxicity is observed but the contribution of cell lysis to efficacy is unclear. Although anti-TNFα agents made it possible to achieve clinical remission in RA patients, there is still an unmet need to develop treatments that will enable them to discontinue all RA medication and maintain drug-free remission.

PMID: 26811250 [PubMed - as supplied by publisher]

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Pharmacokinetics of drugs in adult living donor liver transplant patients: regulatory factors and observations based on studies in animals and humans.

Pharmacokinetics of drugs in adult living donor liver transplant patients: regulatory factors and observations based on studies in animals and humans.

Expert Opin Drug Metab Toxicol. 2016 Jan 26;

Authors: Li M, Zhao Y, Humar A, Tevar AD, Hughes C, Venkataramanan R

Abstract
INTRODUCTION: Limited information is available on the pharmacokinetics of drugs in the donors and recipients following adult living donor liver transplantation (LDLT). Given that both the donors and recipients receive multiple drug therapies, it is important to assess the pharmacokinetics of drugs used. Areas covered: Pathophysiological changes that occur post-surgery and regulatory factors that may influence pharmacokinetics of drugs, especially hepatic drug metabolism and transport in both LDLT donors and the recipients are discussed. Pharmacokinetic data in animals with partial hepatectomy are presented. Clinical pharmacokinetic data of certain drugs in LDLT recipients are further reviewed. Expert opinion: It takes up to six months for the liver volume to return to normal after LDLT surgery. In the LDLT recipients, drug exposure generally is higher with lower clearance during early period post-transplant; lower initial dosages of immunosuppressants are used than deceased donor liver transplant recipients during the first six months post-transplantation. In animals, the activities of hepatic drug metabolizing enzymes and transporters are known to be altered differentially during liver regeneration. Future studies on actual hepatic function with reference to drug metabolism and transport, and the biliary secretory function in both LDLT patient populations are required.

PMID: 26809188 [PubMed - as supplied by publisher]

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