Medicine

Keeping in pace with the new Biomedical Waste Management Rules: What we need to know! Publication date: Available online 15 April 2019 Source: Medical Journal Armed Forces India Author(s): Gurpreet Singh Bhalla, Kuntal Bandyopadhyay, Kavita Sahai Abstract Biomedical Waste Management Rules were first implemented in our country on 20th July 1998. Thereafter, the rules have undergone periodic updates and amendments in the years 2003 and 2011. Latest Biomedical Waste Management Rules, 2016, and (Amendment) Rules, 2018, were an update and simplification of BMW disposal as compared with the previous version, keeping in pace with the changes in the requirements of the health-care setup. Although exhaustive, numerous medical devices/products/kits did not find any mention even in the latest amendment of the rules. Thus, this article aims to bring out the key points to be known by all health-care workers and the gray areas which require clarification and inclusion in the rules for a completeness of the said rules.

Hemophagocytic lymphohistiocytosis in a child with chronic granulomatous disease: A rare complication of a rare disorder Publication date: Available online 15 April 2019 Source: Medical Journal Armed Forces India Author(s): Gitanjali Jain, Suprita Kalra, Saurabh Sharma, Gautam Kumar Vasnik, Rakesh Gupta Abstract Chronic Granulomatous Disease (CGD) is a primary immunodeficiency disorder (PID) of phagocytic cells resulting in failure to eradicate catalase positive microorganisms like Staphylococci and fungal infections; due to deficiency or malfunction of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase subunits in phagocytic leucocytes. We illustrate here one such case; a six year old girl who was admitted in our hospital with history of prolonged fever, non resolving bilateral otitis media and recurrent pneumonia. She was evaluated for an underlying PID and was found to have CGD based on Nitro blue Tetrazolium (NBT) Slide Test and flow cytometric Dihydrorhodamine (DHR) assay. The child was symptomatic despite initial treatment with first-line followed by second-line antibiotics. During the course of current systemic infection, she also developed infection-associated secondary Hemophagocytic Lympho Histiocytosis (HLH) as suggested by her clinical and laboratory parameters. Despite a thorough search, no microorganism could be isolated and so she was treated with empircal antibiotic therapy comprising of meropenem, linezolid and an antifungal. Fever resolved with gradual improvement of laboratory parameters and finally spontaneous resolution of HLH. We conclude that a high index of suspicion for PID is required in a child with recurrent infections. Identification of underlying infectious agent should be attempted to start targeted antimicrobial therapy; both to prevent as well as cure infection associated secondary HLH.

Endothelial corneal transplants: indications, clinical profile and surgical outcomes in a tertiary care hospital Publication date: Available online 15 April 2019 Source: Medical Journal Armed Forces India Author(s): Vijay Kumar Sharma, Santosh Kumar, Sagarika Patyal, Hemant S. Trehan, Arun Kumar Yadav, K. Raji, Anirudh Singh Abstract Background Endothelial keratoplasties have become the surgical procedure of choice over full thickness penetrating keratoplasty for corneal decompensation because of endothelial dysfunction. Methods A retrospective data review was performed from February 2016 to April 2017 for all the patients who underwent endothelial keratoplasty in a tertiary care center for Indian Armed Forces. Results A total of 161 corneal transplants were performed; endothelial keratoplasties accounted for 34 (21.1%) transplants. Most common indication was pseudophakic/aphakic bullous keratopathy followed by Ahmed glaucoma valve–related corneal decompensation and Fuchs' corneal dystrophy, respectively. Mean preoperative corneal thickness was 845.96 ± 106.9 microns. Mean lenticule thickness was 131.55 ± 42.47 microns with microkeratome for descemet stripping automated endothelial keratoplasty (DSAEK) and 174 ± 70.4 microns manually for descemet stripping endothelial keratoplasty (DSEK). Mean preoperative best-corrected visual acuity (BCVA) was 1.65 LogMAR (Snellen equivalent in meters 2/60 approx) which significantly improved to 0.82 LogMAR (Snellen equivalent in meters 6/36 approx) after surgery. In the DSAEK group, BCVA improved from 1.61 to 0.7 LogMAR, whereas in the DSEK group, the visual acuity improved from 1.7 to 0.94 LogMAR at one-month postoperative period. Postoperatively, two patients had graft detachment and had to undergo repeat DSAEK. Conclusion Study results suggest the similar trends in our tertiary care hospital as in other most advanced ophthalmic centers around the world for adoption of newer techniques of lamellar corneal transplants and their outcomes.

Clinical manifestation and images of a patient having cardiovascular involvement in myxoedema coma Publication date: Available online 15 April 2019 Source: Medical Journal Armed Forces India Author(s): Vishesh Verma, Anil S. Menon, Ajay Bahadur, Ajeet Sikarwar Abstract Myxoedema coma is an endocrine emergency characterised by diminished sensorium associated with features of severe hypothyroidism. The disease carries a high mortality of 30%–60 %. The cardiac manifestation of the disease consists of bradycardia, hypotension, pericardial effusion and certain echocardiographic changes such as heart block and features of hypothermia. Here, we report a case of myxoedema coma with characteristic cardiac manifestations. These manifestations revert promptly on starting treatment, and achieving a eumetabolic status as was demonstrated in this patient.

Comparison of electrosurgery by electrodessication versus cryotherapy by liquid nitrogen spray technique in the treatment of plantar warts Publication date: Available online 15 April 2019 Source: Medical Journal Armed Forces India Author(s): Sehdev Singh, Shekhar Neema Abstract Background Warts or verrucae are benign proliferations of the skin and mucosa resulting from infection with papilloma viruses. Warts form a small subset of patients attending skin out-patient department (OPD), out of which the plantar warts are one of the common presentation. The present study is an attempt to compare two modalities of treatment that is electrosurgery and cryotherapy in patients with plantar warts. There are no studies available where comparison of complications between two modalities has been done in plantar warts thus making it one of unique studies of its kind. Methods A prospective, comparative study was conducted over a period of 6 years. After exclusion criteria, one hundred forty-seven male patients having plantar warts were included in the study. Selection of patients suffering from warts subjected to treatment was done by simple random selection. After treatment, 39 patients were lost to follow-up, and finally 48 patients treated by electrosurgery and 60 by cryotherapy were compared and analysed statistically for response to treatment and incidence of complications. Results The overall clearance rate was 75% in electrosurgery versus 73.3% in cryotherapy patients. The pain, delayed wound healing and scarring were observed significantly in more patients treated with electrosurgery than cryotherapy. In our study, recurrence at 24 weeks was observed in 21.9% of the electrosurgery patients which was slightly higher than cryotherapy, where it was 16.6%. Conclusion This study highlighted that cryotherapy is quick, safe and comparatively painless procedure with less complications with success almost similar to electrosurgery making it more suitable for plantar warts.

Food poisoning outbreak in a religious mass gathering Publication date: Available online 5 April 2019 Source: Medical Journal Armed Forces India Author(s): Swati Bajaj, Puja Dudeja Abstract Background Food poisoning outbreaks are commonly seen in mass social events where food is prepared under temporary arrangements. This study reports a food poisoning outbreak in a city of western Maharashtra, India, where around 4000 people had consumed food during a religious community lunch and reported sick to the nearby hospital with complaints of diarrhea, abdominal cramps, fever with chills, and vomiting. Methods This was a retrospective–prospective study. Investigation of the food poisoning outbreak was conducted to identify the causes and recommend preventive measures. Interview method was used to elicit food history from the affected and non-affected persons. Inspection of the cooking area was conducted to find the likely source of contamination. Results A total of 291 patients reported sick after consumption of meal at a religious mass gathering. The range of incubation period was from 10 hours to 40 hours. Predominant features were diarrhea (100%), abdominal cramps (89%), fever with chills (81%), and vomiting (28.5%). Maximum relative risk of 14.89 was seen for green gram (moong dal) with 95% confidence interval of 2.16–102.6. Keeping the incubation period and clinical profile in view, the likely organisms are enteropathogenic Escherichia coli or Salmonella spp. Conclusion Maintaining food safety during mass gatherings is a major challenge for public health authorities. The Food Safety and Standards Act (2006) in India brings the food consumed during religious gatherings such as 'prasad' and 'langar' under its purview and comprehensively addresses this issue.

Rapid in-situ hybridization and immunohistochemistry: a pilot comparative study of two rapid diagnostic techniques for establishing monoclonality in plasma cell dyscrasias Publication date: Available online 5 April 2019 Source: Medical Journal Armed Forces India Author(s): Arijit Sen, Divya Gupta, Rajat Jagani Abstract Background Light chain restriction needs to be established on the paraffin embedded tissue in certain types of plasma cell dyscrasias when serum levels of monoclonal immunoglobulins and light chain assays in the urine and serum may be normal. Rapid-in-situ-hybridisation (RISH) is thought to be a superior to immunohistochemistry (IHC) for kappa and lambda staining due to brighter and crisp staining without any background. Methods Fifty cases were included in this pilot study. Serum light chain restriction status of the case was taken as gold standard. The results of standard IHC for kappa and lambda immunoglobulins on the bone marrow biopsy of these cases was compared with RISH performed by the two commercially available kits. The results of the two methods were compared for sensitivity, need to repeat the test and background staining. Results The study found that in IHC first run sensitivity was 58% which improved to 88% after the second run. For RISH the sensitivity was 100%. Conclusion Rapid-in-situ-hybridisation (RISH) is a superior technique to IHC for detecting kappa and lambda light chain in plasma cells. The test is as labour intensive and time consuming as the routine IHC but has no background staining with more bright and crisp staining quality.

Bilateral ptosis: An unusual presentation of mid brain tuberculoma Publication date: Available online 2 April 2019 Source: Medical Journal Armed Forces India Author(s): J. Sankar, S.S. Majumdar, Manish Unniyal, Harmanpreet Singh, Atul Khullar, Kishore Kumar Abstract Central nervous system tuberculoma can have different clinical manifestations like headache, seizures, papilledema or other signs of raised intracranial pressure depending up on the site and number of tuberculoma. We report a case of 56 year old female reported with history of bilateral asymmetric ptosis of one month duration,with no other neurological defecit. Magnetic resonance imaging (MRI) brain revealed well defined ring enhancing lesion in the medial aspect of left hemi midbrain with diffuse disproportionate perilessional edema. Contrast Enhanced Computed Tomogram (CECT) of chest and abdomen revealed features of disseminated tuberculosis. She was diagnosed as a case of disseminated tuberculosis and started on antitubercular therapy with steroids and the ptosis almost resolved after 01 month of antitubercular therapy. Our case report is unique in the sense that only few cases of midbrain tuberculoma causing occulomotor abnormalities are reported in literature.

Primary pulmonary Hodgkin's lymphoma with pulmonary histoplasmosis Publication date: Available online 2 April 2019 Source: Medical Journal Armed Forces India Author(s): G.S. Chowdhary, Ritu Mehta, Rahul Tyagi Abstract Primary pulmonary Hodgkins lymphoma is a rare and enigmatic neoplasm commonly seen in females. The aim of this case report is to emphasize that pulmonary lymphoma should be considered as a differential diagnosis in a young patient presenting with a lung mass and B symptoms. Extensive clinical details, imaging should be done to rule out the secondary involvement of lung by other lymphomas.

Correlation between cerebral co-oximetry (rSO2) and outcomes in traumatic brain injury cases: A prospective, observational study Publication date: April 2019 Source: Medical Journal Armed Forces India, Volume 75, Issue 2 Author(s): Mathews Jacob, M.N. Kale, Shahabaz Hasnain Abstract Background Traumatic brain injury (TBI) is known to be an important reason for the increase in disabilities and deaths worldwide. Studies have demonstrated that brain tissue oxygen (PO2) monitoring reduces mortality significantly but is a invasive method of monitoring. Therefore, there is a need to monitor cerebral ischemia in TBI by noninvasive methods. The study aims to correlate cerebral co-oximetry and possible outcomes in patients with TBI. Methods The study included 78 patients with TBI admitted in intensive care unit (ICU) with glascow coma scale (GCS) of 8 or less than 8. Near-infrared spectroscopy monitor is applied to the patients immediately after admission to ICU; readings are noted every 4 hours up to first 48 hours, and outcomes studied as survival or neurological deficit are noted at 28 days. Results A total of 12 (15.4%) deaths were seen in this study. Survived patients were further divided into good recovery 33 (42.3%), moderate disability 21(26.9%), major disability 8 (10.3%), and persistent vegetative state 4 (5.1%). The rSO2 values in surviving patients were ranging from mean of 60.74% (standard deviation [SD] 4.38) to a mean of 64.98% (SD 5.01), and the mean rSO2 values in patients who died were ranging from a mean of 52.17% (SD 4.11) to a mean of 37.17% (SD 12.48). Lower rSO2 values were correlating significantly with worse neurological outcome or death by using two independent sample t-test (p < 0.001). Conclusion Cerebral co-oximetry is a simple noninvasive method for predicting the outcomes in TBI and can be used to guide the management of these patients.

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

6948891480

alsfakia@gmail.com

NanoEthics

World Community; and Remarks on our Own Behalf

Models of Anticipation Within the Responsible Research and Innovation Framework: the Two RRI Approaches and the Challenge of Human Rights Abstract Anticipation is one of the main goals of new governance models, such as Responsible Research and Innovation. However, there is not a single mode of anticipation in this model. Two approaches can be addressed within the RRI framework: a socio-empirical one, which tends to underline the role of the democratic processes, aimed at identifying values on which governance needs to be anchored (bottom-up); and a normative one, which stresses the role of EU goals (among which are fundamental rights) as 'normative anchor points' in governance (top-down). These two approaches also address two different models of anticipation: one based on the construction of shared pathways for reflexivity on the purposes of innovation (visions), the other based on the progressive implementation of constitutional goals in risk assessment and management tools. However, both can be deemed partially unsatisfactory from the standpoint of human rights since one puts individual rights in the middle of the 'values lottery' where any participatory process ultimately leads; the other can be inadequate since fundamental rights are balanced alongside other goals and thus can be (totally or partially) sacrificed, exposing the system to possible adverse court decisions. The normative framework of human rights can help to counterbalance both models aimed at maximising inclusion and those aimed at pursuing constitutional normative principles at the basis of technologically advanced societies, strengthening their dimension of anticipation according to a rights-based perspective.

Lessons from the European Regulation 1223 of 2009, on Cosmetics: Expectations Versus Reality Abstract The aim of this paper is to conduct an analysis of the application of the specific rules of nanotechnology incorporated in Regulation No. 1223/2009 of the European Parliament and of the Council of 30 November 2009 on cosmetic products. It has been ten years since the European Commission had issued its proposal to start the co-decision procedure to create Regulation 1223 of 2009. Although it has been praised for noting the regulatory difference of nanomaterials over the rest of the chemicals, what has been the efficacy of the standard? It is concluded that despite what it meant, the regulation has encountered technical obstacles, thus rendering the objectives relating to nanotechnology that were proposed from the European Commission unfulfilled. This finding is inferred through legal dogmatic methodologies and the identification of nanomaterials that have not been expressly approved. Nevertheless, products incorporating nanomaterials still circulate in the European market. The precepts about nanotechnology in the regulation should be reviewed because technical inconsistencies should be avoided in future regulations or applicable regulations in contexts other than Europe. Such inconsistencies exist with respect to the high level of protection of human health that should be ensured and the provisions intended to protect consumer safety. For instance, the catalog of nanomaterials in circulation does not indicate the materials that have been approved or their toxicological profiles. To date, no comparison studies have been presented between the expectations and legislative objectives set as embodied in the regulation and debated in the European Parliament involving the actual efficacy of this regulation.

Nation-Building and the Governance of Emerging Technologies: the Case of Nanotechnology in India Abstract Emerging technologies like nanotechnologies are governed in different ways around the world. This article draws attention to an important element that can help to explain the emergence of this diversity in governance practices: the role of nanotechnology in nation-building. By investigating the relation between nanotechnology and the nation in India, the article demonstrates that various particularities of the Indian governance of nanotechnology can be explained by the relation between science, technology, and nation-building. The article discusses four instances in which the governance of nanotechnology in India is informed by the role science and technology has in nation-building: the historical image of India as a country that can attain modernity and development by engaging with modern science and technology supported the government's decision to free funds for nanotechnology research; the view of India as a country that cannot rely on foreign assistance to get access to the latest technologies reinforced the strategy to pro-actively pursue nanotechnology research and development itself; the historical use of science and technology as crucial elements in overcoming deeply rooted societal divisions enabled the science-centered way in which nanotechnology was governed; and the Indian ambition to become a global superpower informed the governance of nanotechnology as an object of international competition. The governance of nanotechnology in turn defines 'Indianness' in a post-liberalization world.

Development and Pilot Testing of an Evidence-Based Training Module for Integrating Social and Ethical Implications into the Lab Abstract In this project, we (1) explore perceptions of the social and ethical implications (SEI) of nanotechnology among US scientists who work at the nanoscale, and (2) develop and pilot test an online training module to foster consideration of social and ethical implications in the lab. To meet our first goal, we drew qualitative insights from open-ended survey data collected from scientists affiliated with the National Nanotechnology Infrastructure Network. Our data suggest that while the survey participants responded positively to the idea that consideration of SEI should be a part of the work they do, there was confusion about whether SEI refers to lab safety, research integrity, or something more. This is something we sought to address in the online training module that we developed based on that qualitative data and on feedback collected from experts in nanoethics and lab management. We then pilot tested the module with undergraduate students studying nanotechnology in the National Science Foundation's Research Experiences for Undergraduates (REU) program and with scientists registered to use a National Nanotechnology Coordinated Infrastructure-funded microelectronics research lab. The undergraduate data suggested that students appreciated the SEI training but wished professors and scientists would begin integrating the ideas therein into coursework and mentoring. The scientist data suggested that the module increased understanding of "social and ethical implications," increased the perceived need to implement SEI into workplace routines, and, interestingly, heightened perceptions of risk associated with the scientists' own work. The practical and theoretical implications of this work are discussed.

Improving Responsibility, Responsible Improvements

Responsibility and Human Enhancement

Rethinking Human Enhancement: Social Enhancement and Emergent Technologies

Giving Voice to Patients: Developing a Discussion Method to Involve Patients in Translational Research Abstract Biomedical research policy in recent years has often tried to make such research more 'translational', aiming to facilitate the transfer of insights from research and development (R&D) to health care for the benefit of future users. Involving patients in deliberations about and design of biomedical research may increase the quality of R&D and of resulting innovations and thus contribute to translation. However, patient involvement in biomedical research is not an easy feat. This paper discusses the development of a method for involving patients in (translational) biomedical research aiming to address its main challenges. After reviewing the potential challenges of patient involvement, we formulate three requirements for any method to meaningfully involve patients in (translational) biomedical research. It should enable patients (1) to put forward their experiential knowledge, (2) to develop a rich view of what an envisioned innovation might look like and do, and (3) to connect their experiential knowledge with the envisioned innovation. We then describe how we developed the card-based discussion method 'Voice of patients', and discuss to what extent the method, when used in four focus groups, satisfied these requirements. We conclude that the method is quite successful in mobilising patients' experiential knowledge, in stimulating their imaginaries of the innovation under discussion and to some extent also in connecting these two. More work is needed to translate patients' considerations into recommendations relevant to researchers' activities. It also seems wise to broaden the audience for patients' considerations to other actors working on a specific innovation.

Responsible Research and Innovation and the Governance of Human Enhancement Abstract This article aims to explore the debate on human enhancement (HE) from the perspective of the evolutions of responsibility paradigms, and in particular from the perspective of the so-called Responsible Research and Innovation (RRI) approach. The aim is not to explore the arguments pro or contra the ethical legitimacy and/or technical feasibility of human enhancement, but rather exploring if, and how, the RRI perspective can shape the debate on human enhancement (and vice versa). In particular, the human enhancement debate will be read through the lenses of four main responsibility paradigms that we sketch by examining both, the historical and conceptual evolution of the responsibility idea and the dynamics of its ascription. In order to provide a useful scheme for interpreting human enhancement, RRI will be characterised as a distinctive responsibility model that can subsequently be used to frame the debate on HE with a particular emphasis on its normative implications, as well as on its social and political significance.

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

6948891480

alsfakia@gmail.com

Surgical and Radiologic Anatomy

Arch of cricoid cartilage anatomical variation: morphological and radiological aspects Abstract The cricoid cartilage serves as an anatomical reference for several surgical procedures for access to the airway. Additionally, it serves as an attachment point for muscles that move the vocal folds. We present a case where the cricoid cartilage arch is divided into distinct superior and inferior arches, with a fibrous membrane between them. We did not find any similar description to this case in the literature, which makes it unique to date. This type of variation is important knowledge for clinicians and surgeons during airway management in the anterior neck region. The presence of this variation could induce an error during a palpation of the thyroid and cricoid cartilages, realized in clinical examination and surgical or emergency procedures.

Using the zygomatic arch as a reference line for clinical applications and anthropological studies Abstract Purpose The Frankfurt line is the most frequently and widely used reference line in cephalometric analysis, but has shortcomings including the difficulty of landmark identification. This study investigated using the superior border of the zygomatic arch as a new external bony landmark, including measuring the angle between the new reference line and the Frankfurt line. Methods Facial computed tomography scans were obtained from 170 patients (100 males and 70 females) hospitalized at Konkuk University Chungju Hospital. After three-dimensional reconstruction, the locations of the porion and the inferior orbital rim and the superior border of the zygomatic arch were identified twice by two observers using software. A horizontal line parallel to the superior border of the zygomatic arch was established. The angle between the Frankfurt line and new reference line was then measured on each side. Results There was no significant intraobserver or interobserver bias. The angle between the Frankfurt line and the superior border of the zygomatic arch was 4.5° ± 2.5° (mean ± SD), and it was somewhat larger in females than males, but the difference was not statistically significant. Conclusions This study demonstrated the good reproducibility of the location of the superior border of the zygomatic arch and found that the angle between the new reference line and the Frankfurt line is relatively constant. The superior border of the zygomatic arch therefore has potential as an alternative reference line to the Frankfurt line in specific clinical applications and anthropological studies, since it is a more accessible bony landmark on the external skull.

Multiple muscular abnormalities in a fetal cadaver with CHARGE syndrome Abstract The CHARGE syndrome characterized by coloboma, heart defects, atresia of the choanae, retarded growth, genitourinary hypoplasia, and ear anomalies is one of the rare syndromes. Although certain clinical issues (scapular winging, sloping shoulder, Sprengel's deformity, kyphosis and scoliosis) which could be related to abnormalities in musculoskeletal structures of the neck and shoulder have been identified in CHARGE syndrome, data on details of muscle anomalies seem to be quite limited in the literature. In this case report, bilateral multiple muscular abnormalities (agenesis of the trapezius, presence of the rhombo-atloid muscle, and presence of the bipartite rhomboid minor with superficial and deep parts) was presented in a fetus cadaver with atypical CHARGE syndrome to attract the attention of clinicians for definitive diagnoses and surgical reconstruction of the shoulders deformity such as scapular winging and Sprengel's deformity. By considering the previous studies, we propose that the absence of the trapezius, as well as the other muscle abnormalities around the neck and shoulder, should be revised as being a component of CHARGE syndrome.

Differences in the strain applied to Achilles tendon fibers when the subtalar joint is overpronated: a simulation study Abstract Purpose The purpose of this study was to investigate the strain applied to each of the tendon fiber bundles of the medial head of the gastrocnemius (MG), the lateral head of the gastrocnemius (LG), and the soleus muscle (Sol) that compose the Achilles tendon (AT) when the subtalar joint is pronated and supinated. Methods Three AT twist types (least, moderate, extreme) were investigated. Using the MicroScribe system, the AT and the talocrural and subtalar joints were digitized to reconstruct three-dimensional models. Using this system, subtalar joint rotations in the pronation (20°) and supination (20°) directions were simulated, and the degrees of strain (%) on each tendon were calculated. Results For all twist types, when the subtalar joint was pronated, MG, LG, and Sol stretched, and when supinated, MG, LG, and Sol shortened. In particular, the least and severe twist types had large degrees of strain of Sol when the subtalar joint was pronated, and furthermore, each tendon fiber composing Sol had different degrees of strain. Conclusions The study results suggest that the degree of strain applied within the AT with subtalar joint pronation is not constant, and that, especially in least and extreme twist types, the risk of developing AT disorders may increase.

The diaphragma sellae, diaphragm opening, and subdiaphragmatic cistern: an anatomical study using magnetic resonance imaging Abstract Purpose Few studies have explored the detailed morphology of the diaphragma sellae (DS), diaphragm opening (DO) or stoma, and subdiaphragmatic cistern (SDC) using neuroimages. The aim of the present study was to characterize these structures using magnetic resonance imaging. Methods Thin-sliced, sagittal and coronal T2-weighted imaging was performed for a total of 84 outpatients. Results The DS, DO, SDC, and relevant structures were consistently delineated in all patients. In 66% of patients, all three structures appeared to be highly variable, and were classifiable as six distinct morphological types. In 4% of patients, the DS presented as a complete sheet lacking a discernible DO. In addition, 30% of the patients presented with undiscernible SDCs. In the coronal sections of 11% of patients, the pituitary glands extended laterally, reaching or extending beyond the center line on the sectional image of the cavernous internal carotid artery. Conclusions Thin-sliced, sagittal, and coronal T2-weighted sequences are useful for delineating the DS, DO, and SDC. Morphological variation of these structures among individuals may considerably influence the direction of pituitary tumor expansion.

Unusual and multiple variations of head and neck veins: a case report Abstract We report an unusual and multiple variation involving the right head and neck veins which were found during routine dissection in a 50-year-old male cadaver, facial vein draining into both external and internal jugular veins, fenestration in external jugular vein transmitting the supraclavicular nerve trunk, the anterior division of the retromandibular vein draining into anterior jugular vein and the absence of the common facial vein. The knowledge about these variations is important during various surgical and diagnostic procedures involving head and neck region.

An undescribed venous pathway intervening between the olfactory fossa and nasal vestibule Abstract Purpose A curvilinear pathway intervening between the olfactory fossa and nasal vestibule has not been well documented. Therefore, the aim of this study was to examine its structure using magnetic resonance imaging (MRI). Methods In total, 84 patients underwent thin-sliced, contrast MRI. Among these patients, 31 underwent additional thin-sliced, sagittal T2-weighted imaging. Results A curvilinear pathway intervening between the olfactory fossa and nasal vestibule was delineated on sagittal and coronal imaging in 98% and 82% of patients, respectively. All of these pathways demonstrated communication with the lower limit of the superior sagittal sinus (SSS) or fine venous channels connecting to the SSS in the vicinity of the crista galli. The pathway was identified in the parasagittal regions on both sides with varying lengths, diameters, and curvatures. In 94% of the patients who underwent sagittal T2-weighted imaging, the pathways appeared as linear high-intensity signals. Most pathways were delineated as a single channel coursing extracranially adjacent to the olfactory fossa. In 38% of the patients, post-contrast sagittal images showed variable filling defects between the olfactory bulb and floor of the olfactory fossa, furthermore traversing the venous pathway. Additionally, in 73% of the patients, post-contrast images identified diploic venous channels, variably in the nasal bone and communicating with the venous pathway. Conclusions A curvilinear pathway intervening between the olfactory fossa and nasal vestibule is a consistent venous structure and may function as an extracranial route of cerebrospinal fluid drainage.

Complete bilateral Tessier's facial cleft number 5: surgical strategy for a rare case report Abstract The oro-ocular cleft number 5 according to the Tessier classification is one of the rarest facial clefts and few cases have been reported in the literature. Although the detailed structure of rare craniofacial clefts is well established, the cause of these pathological conditions is not. There are no existing guidelines for the management of this particular kind of cleft. We describe the case of a 19-month-old girl with a complete bilateral facial cleft. We describe the surgical steps taken to achieve the primary correction of the soft tissue deformation. Embryologic development and radiological approach are discussed, as are also the psychological and social aspects of severe facial deformities.

Anatomical variations of anterior ethmoidal artery and their significance in endoscopic sinus surgery: a systematic review Abstract Purpose Anterior ethmoidal artery (AEA) is at risk of injury in endoscopic sinus surgery due to its location. The aim of this review was to assess the anatomical variations of AEA and their significance. Methods A literature search was performed on PUBMED, SCOPUS AND EMBASE. The following keywords were used: ethmoidal artery; anterior ethmoidal artery; anterior ethmoidal canal; ethmoid sinus; ethmoid roof; skull base. The search was conducted over a period of 6 months between October 2016 and April 2017. Results 105 articles were retrieved. 76 articles which were either case reports or unrelated topics were excluded. Out of the 29 full text articles retrieved, 16 articles were selected; 3 were cadaveric dissection, 5 combined cadaveric dissection and computed tomography (CT) and the rest were of CT studies. All studies were of level III evidence and a total of 1985 arteries were studied. Its position at the skull base was influenced by the presence of supraorbital ethmoid cell (SOEC) and length of the lateral lamella of cribriform plate (LLCP). Inter population morphological variations contribute to the anatomical variations. Conclusions The average diameter of AEA was 0.80 mm and the intranasal length was 5.82 mm. 79.2% was found between the second and third lamellae, 12.0% in the third lamella, 6% posterior to third lamella and 1.2% in the second lamella. Extra precaution should be taken in the presence of a well-pneumatized SOEC and a long LLCP as AEA tends to run freely below skull base.

Anatomy of the pterygopalatine fossa: an innovative metrical assessment based on 3D segmentation on head CT-scan Abstract Purpose The pterygopalatine fossa is an important anatomical structure for several surgical and anaesthesiologic procedures; yet, very few data are available about its size. This study aims at providing a metrical assessment of pterygopalatine fossa through an innovative 3D segmentation procedure on head CT-scans. Methods CT-scans from 100 patients (50 males and 50 females) aged between 18 and 85 years were chosen for the study. Right and left pterygopalatine fossae were segmented through ITK-SNAP open source software. Height and volume were calculated on the acquired 3D models. In addition, anterior–posterior nasal spine distance, upper facial height (nasion–prosthion) and biorbital breadth (ectoconchion–ectoconchion) were measured as well. Statistically significant differences of height and volume according to sex and side were assessed through two-way ANOVA test: sexually dimorphic measurements were further assessed through one-way ANCOVA test using the three cranial measurements as covariates (p < 0.05). Results On average pterygopalatine fossa height was 24.1 ± 3.5 mm in males, and 22.8 ± 3.4 mm in females, whereas volume was 0.930 ± 0.181 cm3 in males and 0.817 ± 0.157 cm3 in females, with statistically significant differences according to sex (p < 0.05), but not to side (p > 0.05); interaction was negligible for both the measurements. ANCOVA test verified that sexual dimorphism of both measurements is independent from general cranial size (p < 0.05). Conclusions The present study highlighted the sexual dimorphism of pterygopalatine fossa: results may improve the knowledge of this anatomical structure difficult to explore, but crucial in several fields of clinics and surgery.

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

6948891480

alsfakia@gmail.com

Microbiology

Chromium(VI) reduction in Streptomyces sp. M7 mediated by a novel Old Yellow Enzyme Abstract Old Yellow Enzymes play key roles in several cellular processes and have become an important family of enzymes with biotechnological potential. One of the major challenges of biotechnology consists of the bioremediation of co-polluted soils with organic and inorganic compounds. In co-contaminated areas, chromium normally exists in its more toxic and carcinogenic form Cr(VI). Microorganisms can reduce this metal to the insoluble and less toxic Cr(III). Streptomyces sp. M7 is a strain able to efficiently bioremediate polluted soils with γ-hexachlorocyclohexane and Cr(VI). The complete degradation pathway for γ-hexachlorocyclohexane was recently elucidated in this strain. In the present work, we confirmed the ability of Streptomyces sp. M7 to eliminate a high percentage of Cr(VI) from a synthetic culture medium. After a transcriptional study in the presence of Cr(VI), we also report the molecular cloning of a gene coding for an Old Yellow Enzyme with chromate reductase activity. Our results suggest that the elimination of Cr(VI) by Streptomyces sp. M7 is directly related to the activity of this Old Yellow Enzyme. The importance of our work is in identifying for the first time an Old Yellow Enzyme with chromate reductase activity in Streptomyces and Actinobacteria. Finding this enzyme helps understand chromium homeostasis in Streptomyces sp. M7, in addition to opening a new research window related to Old Yellow Enzymes from Actinobacteria.

Advancing biomarkers for anaerobic o -xylene biodegradation via metagenomic analysis of a methanogenic consortium Abstract Quantifying functional biomarker genes and their transcripts provides critical lines of evidence for contaminant biodegradation; however, accurate quantification depends on qPCR primers that contain no, or minimal, mismatches with the target gene. Developing accurate assays has been particularly challenging for genes encoding fumarate-adding enzymes (FAE) due to the high level of genetic diversity in this gene family. In this study, metagenomics applied to a field-derived, o-xylene-degrading methanogenic consortium revealed genes encoding FAE that would not be accurately quantifiable by any previously available PCR assays. Sequencing indicated that a gene similar to the napthylmethylsuccinate synthase gene (nmsA) was most abundant, although benzylsuccinate synthase genes (bssA) also were present along with genes encoding alkylsuccinate synthase (assA). Upregulation of the nmsA-like gene was observed during o-xylene degradation. Protein homology modeling indicated that mutations in the active site, relative to a BssA that acts on toluene, increase binding site volume and accessibility, potentially to accommodate the relatively larger o-xylene. The new nmsA-like gene was also detected at substantial concentrations at field sites with a history of xylene contamination.

Role of β-oxidation and de novo fatty acid synthesis in the production of rhamnolipids and polyhydroxyalkanoates by Pseudomonas aeruginosa Abstract Pseudomonas aeruginosa are ubiquitous γ-proteobacteria capable of producing the biosurfactant rhamnolipids (RL) and the polymer polyhydroxyalkanoate (PHA). RL are glycolipids with high biotechnological potential, whereas PHA is used for the production of biodegradable plastics. It has been proposed that the β-oxidation pathway provides intermediates for RL biosynthesis, even when using a non-fatty acid carbon source for growth, while an intermediate of de novo fatty acid biosynthesis (FASII) pathway [(R)-3-hydroxyacyl-ACP] is used for PHA biosynthesis. The aim of this work is to study the inter-relationship of the RL and PHA biosynthetic pathways in a culture medium with a non-fatty acid carbon source, focusing on the role of FASII and β-oxidation in supplying the substrates for the first step in RL and PHA synthesis, carried out by the RhlA and PhaG enzymes, respectively. The PHA synthases (PhaC1 and PhaC2) are only able to use CoA-linked 3-hydroxy acids and the PhaG enzyme catalyzes the conversion of (R)-3-hydroxyacyl-ACP to (R)-3-hydroxyacyl-CoA, the substrate of PhaC1 and PhaC2. RhlA in turn catalyzes the synthesis of the RL precursor 3-(3-hydroxyalkanoyloxy) alkanoic acids (HAA) by the dimerization of two 3-hydroxyalkanoic acid molecules (that have been shown to be also (R)-3-hydroxyacyl-ACP). In this work, we show that RhlA can produce both RL and PHA precursors (presumably CoA-linked HAA), that the blockage of carbon flux through β-oxidation pathway does not decrease RL titer, and that the enoyl-CoA hydratase RhlY and enoyl-CoA hydratase/isomerase RhlZ produce the main fatty acids precursor of RL using as substrate also a FASII intermediate (presumably (S)-3-hydroxyacyl-CoA).

Biological agents for 2,4-dichlorophenoxyacetic acid herbicide degradation Abstract Phenoxy herbicides are the most widely used family of herbicides worldwide. The dichlorophenoxyacetic acid (2,4-D) is extensively used as a weed killer on cereal crops and pastures. This herbicide is highly water-soluble, and even after a long period of disuse, considerable amounts of both 2,4-D and its main product of degradation, 2,4 dichlorophenol (2,4-DCP), might be found in nature. Biological decomposition of pesticides is an expressive and effective way for the removal of these compounds from the environment. The role of bacteria as well as the enzymes and genes that regulate the 2,4-D degradation has been widely studied, but the 2,4-D degradation by fungi, especially regarding the ability of white-rot basidiomycetes as agent for its bioconversion, has been not extensively considered. This review discusses the current knowledge about the biochemical mechanisms of 2,4-D biodegradation, focused on the role of white-rot fungi in this process. Finally, the cultivation conditions and medium composition for the growth of 2,4-D-degrading microorganisms are also addressed.

Enhancing the atypical esterase promiscuity of the γ-lactamase Sspg from Sulfolobus solfataricus by substrate screening Abstract Promiscuous enzymes can be modified by protein engineering, which enables the catalysis of non-native substrates. γ-lactamase Sspg from Sulfolobus solfataricus is an enzyme with high activity, high stability, and pronounced tolerance of high concentrations of the γ-lactam substrate. These characteristics suggest Sspg as a robust enzymatic catalyst for the preparation of optically pure γ-lactam. This study investigated the modification of this enzyme to expand its application toward resolving chiral esters. γ-Lactamase-esterase conversion was performed by employing a three-step method: initial sequence alignment, followed by substrate screening, and protein engineering based on the obtained substrate-enzyme docking results. This process of fine-tuning of chemical groups on substrates has been termed "substrate screening." Steric hindrance and chemical reactivity of the substrate are major concerns during this step, since both are determining factors for the enzyme-substrate interaction. By employing this three-step method, γ-lactamase Sspg was successfully converted into an esterase with high enantioselectivity towards phenylglycidate substrates (E value > 300). However, since both wild-type Sspg and Sspg mutants did not hydrolyze para-nitrophenyl substrates (pNPs), this esterase activity was termed "atypical esterase activity." The γ-lactamase activity and stability of the Sspg mutants were not severely compromised. The proposed method can be applied to find novel multi-functional enzyme catalysts within existing enzyme pools.

Mutations in AraR leading to constitutive of arabinolytic genes in Aspergillus niger under derepressing conditions Abstract The AraR transcription factor of Aspergillus niger encodes a Zn(II)2Cys6 transcription factor required for the induction of genes encoding arabinolytic enzymes. One of the target genes of AraR is abfA, encoding an arabinofuranosidase. The expression of abfA as well as other L-arabinose-induced genes in A. niger requires the presence of L-arabinose or its derivative L-arabitol as an inducer to activate AraR-dependant gene expression. In this study, mutants were isolated that express L-arabinose-induced genes independently of the presence of an inducer under derepressing conditions. To obtain these mutants, a reporter strain was constructed in a ΔcreA background containing the L-arabinose-responsive promoter (PabfA) fused to the acetamidase (amdS) gene. Spores of the ΔcreA PabfA-amdS reporter strain were UV-mutagenized and mutants were obtained by their ability to grow on acetamide without the presence of inducer. From a total of 164 mutants, 15 mutants were identified to contain transacting mutations resulting in high arabinofuranosidase activity in the medium after growth under non-inducing conditions. Sequencing of the araR gene of the 15 constitutive mutants revealed that 14 mutants carried a mutation in AraR. Some mutations were found more than once and in total nine different point mutations were identified in AraR. The AraRN806I point mutation was reintroduced into a parental strain and confirmed that this point mutation leads to inducer-independent expression of AraR target genes. The inducer independent of L-arabinose-induced genes in the AraRN806I mutant was found to be sensitive to carbon catabolite repression, indicating that the CreA-mediated carbon catabolite repression is dominant over the AraRN806I mutant allele. These mutations in AraR provide new opportunities to improve arabinase production in industrial fungal strains.

Quantification of outer membrane vesicles: a potential tool to compare response in Pseudomonas putida KT2440 to stress caused by alkanols Abstract The bacterial release of outer membrane vesicles (OMVs) is an important physiological mechanism of Gram-negative bacteria playing numerous key roles. One function of the release of OMVs is related to an increase in surface hydrophobicity. This phenomenon initiates biofilm formation, making bacteria more tolerant to environmental stressors. Recently, it was qualitatively shown for Pseudomonas putida that vesicle formation plays a crucial role in multiple stress responses. Yet, no quantification of OMVs for certain stress scenarios has been conducted. In this study, it is shown that the quantification of OMVs can serve as a simple and feasible tool, which allows a comparison of vesicle yields for different experimental setups, cell densities, and environmental stressors. Moreover, the obtained results provide insight to the underlying mechanism of vesicle formation as it was observed that n-alkanols, with a chain length of C7 and longer, caused a distinct and steep increase in vesiculation (12–19-fold), compared to shorter chain n-alkanols (2–4-fold increase).

High-level production of N-terminal pro-brain natriuretic peptide, as a calibrant of heart failure diagnosis, in Escherichia coli Abstract Heart failure (HF) is a coronary disease that affects people worldwide and has a high mortality rate. N-terminal pro-brain natriuretic peptide (NT-proBNP) has been proven to be a useful and accurate biomarker for diagnosing systolic HF. Here, we report a strategy for the high-level production of recombinant (r)NT-proBNP in Escherichia coli. An Fh8 tag with six histidines was fused to the N terminus of NT-proBNP along with the recognition site of tobacco etch virus (TEV) protease; the 6HFh8-NT-proBNP fusion peptide was expressed in flask cultures of E. coli in almost completely soluble form. The peptide was purified by HisTrap affinity chromatography, and the N-terminal tag was cleaved by TEV protease. After a second round of HisTrap affinity chromatography to remove the TEV protease and N-terminal tag, rNT-proBNP was isolated with high purity (≥ 98%) by carboxymethyl cation exchange chromatography. The final yield of purified rNT-proBNP (97.5 mg/l of bacterial culture; 3.25 mg/g of wet cell) was 55-fold higher than that reported in previous studies (0.5–1.75 mg/l of bacterial culture). Furthermore, the high cell density E. coli fed-batch culture enabled high-level production of rNT-proBNP in the order of grams per liter. The purified rNT-proBNP was detected by enzyme-linked immunosorbent assay and chemiluminescence enzyme immunoassay using commercial monoclonal antibodies recognizing different epitopes, showing a linear dose-response relationship in the range of tested concentrations (slope = 3.58 and r2 = 0.995). These results demonstrate the efficiency of our process for mass producing (gram-to-liter level) rNT-proBNP with acceptable analytical performance.

The antitumor antibiotic rebeccamycin—challenges and advanced approaches in production processes Abstract Rebeccamycin is an antibiotic and antitumor substance isolated from the filamentous bacterium Lentzea aerocolonigenes. After its discovery, investigations of rebeccamycin focused on elucidating its structure, biological activity, and biosynthetic pathway. For potential medical application, a sufficient drug supply has to be ensured, meaning that the production process of rebeccamycin plays a major role. In addition to the natural production of rebeccamycin in L. aerocolonigenes, where the complex cell morphology is an important factor for a sufficient production, rebeccamycin can also be heterologously produced or chemically synthesized. Each of these production processes has its own challenges, and first approaches to production often lead to low final product concentrations, which is why process optimizations are performed. This review provides an overview of the production of rebeccamycin and the different approaches used for rebeccamycin formation including process optimizations.

Identification of genes involved in shea butter biosynthesis from Vitellaria paradoxa fruits through transcriptomics and functional heterologous expression Abstract Shea tree (Vitellaria paradoxa) is one economically important plant species that mainly distributes in West Africa. Shea butter extracted from shea fruit kernels can be used as valuable products in the food and cosmetic industries. The most valuable composition in shea butter was one kind of triacylglycerol (TAG), 1,3-distearoyl-2-oleoyl-glycerol (SOS, C18:0–C18:1–C18:0). However, shea butter production is limited and little is known about the genetic information of shea tree. In this study, we tried to reveal genetic information of shea tree and identified shea TAG biosynthetic genes for future shea butter production in yeast cell factories. First, we measured lipid content, lipid composition, and TAG composition of seven shea fruits at different ripe stages. Then, we performed transcriptome analysis on two shea fruits containing obviously different levels of SOS and revealed a list of TAG biosynthetic genes potentially involved in TAG biosynthesis. In total, 4 glycerol-3-phosphate acyltransferase (GPAT) genes, 8 lysophospholipid acyltransferase (LPAT) genes, and 11 diacylglycerol acyltransferase (DGAT) genes in TAG biosynthetic pathway were predicted from the assembled transcriptome and 14 of them were cloned from shea fruit cDNA. Furthermore, the heterologous expression of these 14 potential GPAT, LPAT, and DGAT genes in Saccharomyces cerevisiae changed yeast fatty acid and lipid profiles, suggesting that they functioned in S. cerevisiae. Moreover, two shea DGAT genes, VpDGAT1 and VpDGAT7, were identified as functional DGATs in shea tree, showing they might be useful for shea butter (SOS) production in yeast cell factories.

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

6948891480

alsfakia@gmail.com

Contemporary Psychotherapy

In Memoriam: Abraham W. Wolf, Ph.D.

David H. Rosmarin: Spirituality, Religion, Cognitive-Behavioral Therapy: A Guide for Clinicians

David A. Treleaven, Trauma-Sensitive Mindfulness: Practices for Safe and Transformative Healing

Comparing Metacognition and Mentalization and Their Implications for Psychotherapy for Individuals with Psychosis Abstract Over the past couple of decades, researchers have investigated the relationship between psychosis and social cognitive deficits and how these deficits might be targets for psychosocial treatments. Two important constructs related to social cognition are metacognition and mentalization, which have been developed into distinct therapeutic models for individuals with psychosis. Though metacognition and mentalization are conceptually similar, this review aims to provide a clearer delineation of each term by reviewing the definition and the application to the treatment of individuals with psychosis. We examined key theoretical papers, case studies, and clinical trials on mentalization and metacognition. Metacognition and mentalization share much in common though subtle conceptual distinction reveal key differences theoretically that have therapeutic implications. While emerging from divergent intellectual traditions, mentalization and metacognition complement one another and more trials are needed to examine the technical differences between these therapeutic approaches and the possibilities for both theoretical and technical integration.

Successful Treatment of Halitophobia with Cognitive Behavioural Therapy: A Case Study Abstract Halitophobia is a condition characterized by an excessive preoccupation with the belief of having halitosis. Cognitive Behavioural Therapy (CBT) was successfully used to treat a man in his 20 s who presented with important anxiety, avoidance and safety behaviours, isolation, and depressed mood. Progressive in-vivo exposure to fearful situations with the systematic prevention of avoidance and safety behaviours resulted in a significant improvement in the patient's anxiety and depression levels. This case suggests that CBT techniques, usually performed in anxiety disorders and in obsessive–compulsive disorder, can be adapted to halitophobia.

Expanding the Conceptualization of Outcome and Clinical Effectiveness Abstract There is a need for studies that advance our knowledge of therapist effectiveness, expanding the definition of what constitutes therapeutic success. In the present study, four aspects of clinical outcome were analyzed using a sample of highly experienced psychotherapists (mean years of experience as therapy practitioners = 30) who also serve as clinical teachers. The four aspects were: (1) overall change in different outcome domains, including long-term outcome; (2) outcome with clinically distressed clients (i.e. clients above the level of clinical disturbance at pretreatment); (3) level of drop-out; and (4) the degree to which clients re-entered treatment during the follow-up period. Participants were 48 clients treated by 18 therapists. Treatments were open-ended, 'therapy as usual', mostly within the setting of independent private practice. Outcome measurements included the OQ-45.2 and IIP-64, with repeated measurements during therapy and extended long-term follow up (up to 3.5 years). Cohen's d effect sizes and multilevel growth trajectories were estimated for patient change in symptomatic and interpersonal distress. The findings indicate that these therapists obtain very good outcomes overall, particularly with clients above cut-off for clinical disturbance. Moreover, there was a high level of maintenance and increase of treatment gains over time. No clients dropped out. Overall, the findings suggest that a sample of highly experienced therapists obtains particularly good outcomes as defined in more comprehensive terms than what is typical in psychotherapy research. Implications for the understanding of therapeutic success and clinical expertise are discussed.

Family-Based Treatment for Pediatric Obesity: Case Study of an Adaptation for a Non-Psychiatric Adolescent Population Abstract Pediatric overweight and obesity, a highly prevalent condition posing risks extending into adulthood, is considered a major public health concern. Findings from the pediatric obesity treatment literature support the efficacy of parental involvement across multiple formats. Family-based treatment is an outpatient intervention for adolescents with eating disorders that enlists parents as the primary agents of symptom management during the acute stages of illness, titrating down their involvement as severity of the disorder decreases. We adapted family-based treatment for pediatric obesity, modifying the original model to recognize that children and adolescents with obesity do not exhibit the developmental regression seen in eating disorders and to reflect the non-psychiatric nature of obesity. Thus, family-based treatment for pediatric obesity modulates the degree of parental involvement as a function of chronological developmental stage, not severity of the condition. To illustrate the implementation of this treatment, we present a case report of a 15 year old with an 8 year history of overweight and a greater than 30-pound weight gain prior to treatment. Through this case study, the three phases of family-based treatment for pediatric obesity and 6 month post treatment follow-up results are presented through the lens of response from this adolescent and her family. We present this case report to illustrate the implementation of the intervention's adolescent module, and the potential impact of the approach in the treatment of adolescents with obesity and their families.

The Relationships Between Client Resistance and Attachment to Therapist in Psychotherapy Abstract Through the lens of contemporary views on client resistance and attachment theory, which underpins the role of security in psychotherapy, the present study examines the relation between client resistance and client attachment to therapist. Forty-six clients and 19 therapists in long-term psychotherapy completed the Client Attachment to Therapist Scale and a therapist-reported questionnaire for client resistance, respectively, in three different times including the therapist's summer holidays, so as to take into consideration the role of the therapist's temporary absence as a real relationship component. Results indicate that resistance is negatively associated with clients' secure attachment to their therapists, while it is positively associated with insecure attachment patterns. Also, holidays in psychotherapy were found to intervene in the interrelation between client's resistive behaviors and attachment security. These preliminary findings indicate the interpersonal and statelike character of client resistance, a conceptual shift that augments clinical work as clients and their resistances are seen in more benevolent terms.

Cognitive Behavioural Therapy for Mild-to-Moderate Transdiagnostic Emotional Dysregulation Abstract Recent research has found that emotional dysregulation is a transdiagnostic feature across a range of common mental health difficulties and within the general population. However, existing treatment for emotional dysregulation is typically long-term, intensive or focused on personality constructs. The aims of this paper are to (1) present a transdiagnostic cognitive model of emotional dysregulation (2) present a short-term cognitive behavioural therapy intervention for mild-to-moderate presentations of emotional dysregulation.

Valued Living Before and After CBT Abstract Whether and to what degree psychotherapy leads to changes in patients' value-based actions is not well documented. In this study we examined whether cognitive behavioral therapy, without explicit values work, enhanced value-oriented action. We also explored the role of change in valued action for subsequent life satisfaction and continued change after therapy. Additionally, data on the reliability and validity of the Valued Living Questionnaire (VLQ) are reported. We analyzed the pre-, post-, and 6-month-follow-up-data of 3687 patients of a university psychotherapy outpatient clinic, most of which suffered from reliably diagnosed anxiety and mood disorders. Questionnaires included the VLQ (with 10 items each on the "importance" and "consistency" of values), symptom scales (Beck Depression Inventory; Brief Symptom Inventory), and the Satisfaction with Life Scale. Over the course of therapy significant improvements in value-oriented action were found (d = .34), especially in treatment responders (d = .51). Increase of value-oriented action significantly explained satisfaction with life at end of treatment, even after controlling for symptom reduction. Temporally preceding improvement on the VLQ predicted further symptom reduction until follow-up. Data indicate that psychotherapy positively affects valued living, even when it is not explicitly targeted in treatment. Valued living may have a role in the course and maintenance of therapeutic change.

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

6948891480

alsfakia@gmail.com

Advances in Therapy

Correction to: Safety and Efficacy of Ripasudil in Japanese Patients with Glaucoma or Ocular Hypertension: 3-month Interim Analysis of ROCK-J, a Post-Marketing Surveillance Study In the original publication values in the results section are incorrect. Errors were also identified in Fig. 5

Correction to: A Relative Cost of Control Analysis of Once-Weekly Semaglutide Versus Exenatide Extended-Release and Dulaglutide for Bringing Patients to HbA1c and Weight Loss Treatment Targets in the USA The article "A Relative Cost of Control Analysis of Once-Weekly Semaglutide Versus Exenatide Extended-Release and Dulaglutide for Bringing Patients to HbA1c and Weight Loss Treatment Targets in the USA", written by Pierre Johansen, Barnaby Hunt, Neeraj N. Iyer, Tam Dang-Tan, Richard F. Pollock was originally published electronically on the publisher's internet portal (currently SpringerLink) on November 27, 2018 without Open Access.

Reporting Clinical Trial Results of Phytomedicines in Acute Rhinosinusitis: Letter to the Editor Regarding Gottschlich S, Röschmann K, Candler H. Adv Ther (2018); 35:1023–1034. doi: 10.1007/s12325-018-0736-7

Response Letter Addressing Letter to the Editor Regarding Gottschlich S, Röschmann K, Candler H. Adv Ther (2018); 35:1023–1034. doi:10.1007/s12325-018-0736-7

Efficacy of Chondroitin Sulfate in Patients with Knee Osteoarthritis: A Comprehensive Meta-Analysis Exploring Inconsistencies in Randomized, Placebo-Controlled Trials Abstract Introduction There are some controversies about treatment modalities in osteoarthritis (OA), including chondroitin sulfate (CS). The objective of this study was to determine whether CS is effective at alleviating pain and improving function in patients with knee OA and to identify the factors that explain inconsistencies in clinical trial results. Methods We conducted a systematic review of randomized, placebo-controlled trials, searching the databases Medline, Cochrane central register for controlled trials and Scopus. Random effects meta-analysis was then performed, using tau2 and I2 statistics to assess heterogeneity. The pain and Lequesne index (LI) scores were expressed as standardized mean differences (SMDs), with a 95% confidence interval (CI). Heterogeneity was explored by stratifying the analyses according to pre-specified study-level characteristics and assessing the sources of funnel plot asymmetry. Results The inclusion criteria yielded 18 trials. Overall, CS significantly but inconsistently reduced pain (SMD: − 0.63; 95% CI: − 0.91, − 0.35; I2 = 94%) and improved function (SMD: − 0.82; 95% CI: − 1.31, − 0.33; I2 = 95%). When limiting the analysis to studies with a low risk of bias, the pharmaceutical grade CS of IBSA origin showed a greater reduction in pain (SMD: − 0.25; 95% CI: − 0.34, − 0.16; I2 = 75%) and function (SMD: − 0.33; 95% CI: − 0.47, − 0.20; I2 = 53%, p = 0.07) compared with the other preparations (SMDPain: − 0.08; 95% CI: − 0.19, + 0.02; I2 = 20%; SMDFunction: − 0.18; 95% CI: − 0.36, +0.01; I2 = 0%). Assessing funnel plot asymmetry in the studies with a low risk of bias, we found strong correlations between the treatment effects and study size (pain: rS = 0.93; LI: rS = 0.86; p < 0.05). Ultimately, there was no residual heterogeneity in the CS effects when the smallest studies were removed from the analyses. Conclusion This new meta-analysis suggests that CS provides a moderate benefit for pain and has a large effect on function in knee OA, however with large inconsistency. The risks of bias, brand and study size were the factors explaining heterogeneity among the clinical trial results.

Appropriate Titration of Basal Insulin in Type 2 Diabetes and the Potential Role of the Pharmacist Abstract A substantial proportion of patients with suboptimal control of their type 2 diabetes experience delays in treatment intensification. Additionally, patients often experience overuse of basal insulin, commonly referred to as "over-basalization," whereby basal insulin continues to be uptitrated in order to meet targets, when addition of a mealtime bolus insulin dose may be a more appropriate option. In order to overcome these challenges, there is a need to develop the capacity of allied healthcare professionals to provide appropriate support to these patients, such as during initiation or titration of basal insulin. Pharmacists play an integral role in healthcare delivery, with patients seeing their pharmacist, on average, seven times more often than their primary care physician. This places pharmacists in a unique position to provide diabetes education and care, which may help patients avoid clinical inertia. Nevertheless, the management of the disease with basal insulin is becoming increasingly complex, with growing numbers of treatment options (such as recent second-generation longer-acting basal insulin formulations) and frequently updated titration algorithms. The two most common titration schedules specify either increasing doses by a set amount every 2–3 days or a treat-to-target strategy. Neither schedule has been shown to be superior, and the decision to use one or the other should be based on a discussion between the clinician and patient after assessment of mental and physical acumen, comfort of both parties, and follow-up plans. This review article discusses basal insulin therapy options and titration algorithms from the unique perspective of the pharmacist in order to help ensure that optimal antidiabetes therapy is initiated, appropriately titrated, and maintained. Funding: Sanofi US, Inc.

Assessing the Role of Anti rh-GAA in Modulating Response to ERT in a Late-Onset Pompe Disease Cohort from the Italian GSDII Study Group Abstract Introduction Patients with late-onset Pompe disease (LOPD) receiving enzyme replacement therapy (ERT) may develop IgG antibodies against alglucosidase alpha (anti-rhGAA) in the first 3 months of treatment. The exact role of these antibodies in modulating efficacy of ERT in this group of patients is still not fully understood. To assess whether anti rh-GAA antibodies interfere with ERT efficacy, we studied a large Italian cohort of LOPD patients. Methods We analyzed clinical findings and performed serial measurements of IgG anti rh-GAA antibody titers from 64 LOPD patients treated with ERT. The first examination (T0) was completed on average at 17.56 months after starting ERT, while the follow-up (T1) was collected on average at 38.5 months. Differences in T0–T1 delta of the six-minute walking test (6MWT), MRC sum score (MRC), gait, stairs and chair performance (GSGC) and forced vital capacity (FVC) were considered and then related to the antibody titers. Results Almost 22% of the patients never developed antibodies against GAA, while 78.1% had a positive titer (31.2% patients developed a low titer, 43.8% a medium titer and 3.1% a high titer). No statistical significance was found in relating the T0–T1 delta differences and antibody titers, except for MRC sum score values in a subgroup of patients treated < 36 months, in which those with a null antibody titer showed a greater clinical improvement than patients with a positive titer. Conclusion Our results confirm that in a large cohort of LOPD patients, anti rh-GAA antibody generation did not significantly affect either clinical outcome or ERT efficacy. However, in the first 36 months of treatment, a possible interference of low-medium antibody titers with the clinical status could be present. Therefore, a careful and regular evaluation of antibody titers, especially in cases with evidence of clinical decline despite ERT, should be performed.

Pharmacological Treatment for Non-alcoholic Fatty Liver Disease Abstract Non-alcoholic fatty liver disease (NAFLD) has become the most frequently encountered chronic liver disease. NAFLD is associated with increased liver-related morbidity and mortality, but also contributes to cardiovascular disease, diabetes and non-liver-related malignancy. Non-alcoholic steatohepatitis (NASH) is considered the more severe subtype of NAFLD that drives most of these adverse outcomes. Lifestyle modification and associated weight loss can improve NASH but are not always sufficient and sustained results are difficult to obtain. There is hence an urgent need for pharmacological treatment. In this review we discuss some of the concepts and challenges in the development of pharmacological treatment. We also briefly summarise what can be achieved with some of the drugs that are currently available for other indications but have demonstrated benefit in the treatment of NASH. Finally we present an overview of some of the main drugs or types of drugs, mainly based on their mode of action, that are now being developed specifically to treat NASH and that might soon result in the availability of drugs licensed for NASH.

Economic Burden of Illness Among Commercially Insured Patients with Systemic Sclerosis with Interstitial Lung Disease in the USA: A Claims Data Analysis Abstract Introduction Interstitial lung disease (ILD) is a common manifestation of scleroderma/systemic sclerosis (SSc). However, the direct and indirect economic burdens of SSc-ILD remain unclear. This study assessed and compared healthcare resource utilization (HRU), direct healthcare costs, work loss, and indirect costs between patients with SSc-ILD and matched controls with neither SSc nor ILD in the USA. Methods Data were obtained from a large US commercial claims database (2005–2015). Patients (at least 18 years old) had at least one SSc diagnosis in the inpatient (IP) or emergency room (ER) setting or at least two SSc diagnoses in another setting, and at least one diagnosis of ILD in the IP or ER setting or at least two diagnoses of ILD in another setting. Controls with neither SSc nor ILD were matched 5:1 to patients with SSc-ILD. Comparisons were conducted using Wilcoxon signed-rank and McNemar's tests and adjusted odds ratios (ORs) and incidence rate ratios (IRRs). Results A total of 479 SSc-ILD patients and 2395 matched controls were included (52 SSc-ILD patients and 260 matched controls for work loss and indirect cost analyses). Patients with SSc-ILD had significantly higher HRU and costs, IP admissions (adjusted IRR = 5.6), IP hospitalization days (adjusted IRR = 12.0), ER visits (adjusted IRR = 2.8), OP visits (adjusted IRR = 3.1), and days of work loss (adjusted IRR = 4.5). The adjusted difference in annual direct healthcare costs was $28,632 (SSc-ILD, $33,195; controls, $4562) and that in indirect costs was $4735 (SSc-ILD, $5640; controls, $906) (all p < 0.0001). Conclusion SSc-ILD patients had significantly higher HRU, work loss, and direct and indirect costs compared to matched controls with neither SSc nor ILD. Funding Boehringer Ingelheim Pharmaceuticals, Inc.

Bloating and Abdominal Distension: Clinical Approach and Management Abstract Functional abdominal bloating and distension (FABD) are common gastrointestinal complaints, encountered on a daily basis by gastroenterologists and healthcare providers. Functional abdominal bloating is a subjective sensation that is commonly associated with an objective abdominal distension. FABD may be diagnosed as a single entity (the sole or cardinal complaint) or may overlap with other functional gastrointestinal disorders such as functional constipation, irritable bowel syndrome, and functional dyspepsia. The pathophysiology of FABD is not completely understood. Proposed underlying mechanisms include visceral hypersensitivity, behavioral induced abnormal abdominal wall-phrenic reflexes, the effect of poorly absorbed fermentable carbohydrates, and microbiome alterations. Management includes behavioral therapy, dietary interventions, microbiome modulation, and medical therapy. This review presents the current knowledge on the pathophysiology, evaluation, and management of FABD.

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

6948891480

alsfakia@gmail.com