Maturation of the human medial efferent reflex revisited.
Past work applying otoacoustic emissions to gauge maturational status of the medial olivocochlear (MOC) reflex in human newborns has produced mixed results. The present study revisits the question while considering the dual nature of the 2f(1) - f(2) distortion product otoacoustic emission (DPOAE) and expanding measures of medial efferent function. Subjects included premature and term-born neonates, 6-month-old infants and young adults. The MOC reflex was elicited with contralateral acoustic stimulation (CAS) while shifts in amplitude and phase of the DPOAE, and its distortion and reflection components, were monitored. Overall, CAS-elicited reductions in DPOAE level did not differ among age groups. For all ages, the MOC reflex was strongest at frequencies below 1.5 kHz, and the reflection component of the DPOAE was most affected, showing maximally reduced amplitude and shallower phase slope when contralateral noise was presented. Results suggest that the MOC reflex likely reaches maturation prior to full-term birth. However, prematurely born neonates show markedly more episodes of CAS-induced DPOAE level enhancement. This may be due to more intrusive component mixing in this age group or disruptions in the formation of the MOC pathway or synapse in the most premature neonates.


Access to and use of unauthorised online HIV self-tests by internet-using French-speaking men who have sex with men.
Although not authorised in France, HIV self-tests are easily available online. The authors questioned French-speaking internet-using men who have sex with men (MSM) concerning their access to and use of such tests. Online questionnaire on sex websites and gay and HIV community websites. A multivariate logistic regression for rare events was used to identify factors associated with accessing self-tests. 9169 MSM completed the questionnaire. 2748 (30%) were aware of online self-tests, but only 82 of those aware and not already HIV positive (3.5%) declared having accessed one and only 69 using it. In the multivariate model, living one's sex-life with men in absolute secrecy (odds ratio (OR)=3.90, 95% CI 1.73 to 8.76), knowing of the tests via a sex partner (OR=3.42, CI 1.39 to 8.41) or an internet search engine (OR=2.18, CI 1.26 to 3.74) but not through the general (OR=0.21, CI 0.11 to 0.42) or the gay press (OR=0.34, CI 0.16 to 0.73), having unprotected anal intercourse with a casual partner in the preceding year (OR=1.90, CI 1.17 to 3.06), using self-tests for other diseases (OR=2.66, CI 1.43 to 4.90), using poppers (OR=2.23, CI 1.35 to 3.67) and doping products (OR=3.53, CI 1.55 to 8) in the preceding year, having done a traditional HIV test but not in the preceding year (OR=1.93, CI 1.14 to 3.32), never having had suicidal thoughts (OR=0.54, CI 0.32 to 0.90) and living in the provinces (OR=1.80, CI 1.01 to 3.25) were all independently associated with accessing self-tests. Although readiness to admit use of unauthorised medical products may have influenced results, few MSM aware of the existence of self-tests actually declared having accessed one. Accessing the self-test was independently associated with both living one's sex-life with men in total secrecy and having had unprotected anal intercourse in the last 12 months, indicating that autonomous self-testing may reduce barriers to testing for this vulnerable population.


Hepatic Legionella pneumophila Infection in an Infant With Severe Combined Immunodeficiency.
Rare cases of extrapulmonary involvement in Legionella spp. infections have been described, mostly in immunocompromised adults. We report a case of a 2-month old male with reticular dysgenesis variant of severe combined immune deficiency with multiple liver lesions. Core-needle biopsies of one liver lesion demonstrated Gram-negative bacilli and a broad-spectrum polymerase chain reaction assay detected Legionella pneumophila.


Impact of One-Health framework on vaccination cost-effectiveness: A case study of rabies in Ethiopia.
Livestock losses due to rabies and health and the corresponding benefits of controlling the disease are not often considered when the cost-effectiveness of rabies control is evaluated. In this research, assessed the benefits of applying a One Health perspective that includes these losses to the case of canine rabies vaccination in Ethiopia. We constructed a dynamic epidemiological model of rabies transmission. The model was fit to district-specific data on human rabies exposures and canine demography for two districts with distinct agro-ecologies. The epidemiological model was coupled with human and livestock economic outcomes to predict the health and economic impacts under a range of vaccination scenarios. The model indicates that human exposures, human deaths, and rabies-related livestock losses would decrease monotonically with increasing vaccination coverage. In the rural district, all vaccination scenarios were found to be cost-saving compared to the status quo of no vaccination, as more money could be saved by preventing livestock losses than would be required to fund the vaccination campaigns. Vaccination coverages of 70% and 80% were identified as most likely to provide the greatest net health benefits at the WHO cost-effectiveness threshold over a period of 5 years, in urban and rural districts respectively. Shorter time frames led to recommendations for higher coverage in both districts, as did even a minor threat of rabies re-introduction. Exclusion of rabies-related livestock losses reduced the optimal vaccination coverage for the rural district to 50%. This study demonstrated the importance of including all economic consequences of zoonotic disease into control decisions. Analyses that include cattle and other rabies-susceptible livestock are likely better suited to many rural communities in Africa wishing to maximize the benefits of canine vaccination.


Arterial thrombosis in unusual sites: A practical review.
While cardiovascular disease is common, occasionally hematologists and other practitioners will encounter patients with arterial thrombosis/infarction in unusual sites, without clear cause or obvious diagnostic and treatment paradigms. Contrary to the more commonly encountered cerebrovascular accident and cardiovascular disorders, the various infarctions outlined in this review have unique presentations, pathophysiology, workup, and treatments that all hematologists should be aware of. This review outlines the current literature on arterial thrombosis, with consideration given to anatomic sources and hypercoagulable associations, while focusing on the epidemiology, pathophysiology, provoking factors, and current recommended treatments for intracardiac thrombus, primary aortic mural thrombus, visceral infarctions, and cryptogenic limb ischemia to provide a useful and practical review for the practitioner.


[Follow-up discussion on restructuring the medical-service system].
The Japan Tuberculosis Society organized symposia on restructuring the medical-service system at the 84th and 86th annual meetings. These symposia clarified the following issues and concerns. It is becoming difficult to maintain tuberculosis beds in wards in many areas, since beds required for tuberculosis are declining due to the decreasing incidence of tuberculosis and shortened hospitalization periods. The extremely poor profitability of medical practices has caused closure of tuberculosis wards. A highly urbanized area may have a shortage of tuberculosis beds, while some rural areas have the problem of poor access to hospitalization. Aging of tuberculosis patients causes an increase in the number of patients with serious complications that are sometimes difficult to treat within a prefectural jurisdiction. Infection control for multi-drug resistant tuberculosis needs to be solid. To address these issues and challenges, it will be necessary to restructure the medical-service system for tuberculosis. The Prevention Guideline addressed in May 2011 by the Ministry of Health, Labour, and Welfare mentions that the medical-service system should seek to ensure enough tuberculosis beds and to realize patient-centered medical service. The future directions should be 1) ensuring a core hospital for tuberculosis treatment at the prefectural level, 2) ensuring a principal hospital for treating tuberculosis patients with serious complications in an area, 3) ensuring the treatment environment is suitable to individual patient conditions, 4) formulating a regional coordination mechanism with a core hospital at the center in each area, and 5) achieving complete infection control. This symposium was organized based on discussions in the previous symposia to present points necessary to realize the future medical-service system described in the Prevention Guideline. When constructing a new hospital or renovating a ward, attention must be paid to infection control and amenities for tuberculosis patients whose hospitalization is often longer than patients of other diseases. There is no official standard for a facility with tuberculosis beds at this moment. Professor Atsuo Kakehi, a hospital architectural expert, discussed the points in a draft of the standard he proposed in his report. Aging of tuberculosis patients increases the number of patients with serious complications. Ensuring medical service for such patients is a major challenge. The new National Hospital Organization Hokkaido Medical Center was built in March 2010 with tuberculosis wards. Dr. Arisu Kamada reported on infection control and medical practice for patients with serious complications in a general hospital. Psychiatric diseases including senile dementia are among the largest problems among tuberculosis complications. The National Hospital Organization Kamo Psychiatric Center, which has model beds for tuberculosis, produced successful outcomes by collaborating with the National Hospital Organization Higashihiroshima Medical Center tuberculosis hospital. Dr. Masahiro Nomura reported on the implementation of DOT and regional collaboration as well as medical practice in his hospital. An important point in the National Guideline is regional collaboration. Dr. Tadatoshi Suruda from the National Hospital Organization Wakayama National Hospital discussed the status and outcomes from their regional collaboration system in Wakayama Prefecture, the top runner in this area. Thanks to solid presentation from the speakers and thoughtful comments from the floor, the symposium was very useful for promoting patient-centered medical service, a keyword in the National Guideline. 1. Environment of hospital beds for treating TB patients: Atsuo KAKEHI (Department of Architectural Design, School of Architecture, Kogakuin University) It is becoming more difficult to configure wards since the number of tuberculosis beds is decreasing. It is therefore necessary to mix general beds and tuberculosis beds in one ward, making it necessary to develop criteria for designing facilities as part of a general ward for isolated space. This paper describes the current care environment of tuberculosis patients and the draft guidelines for a more appropriate hospital environment. 2. Treatment to complications in the patients in the tuberculosis hospital: Arisu KAMADA (National Hospital Organization Hokkaido Medical Center) Recently, many patients with tuberculosis, especially the elderly, have been exhibiting various complications. It is often difficult to treat complications at a tuberculosis hospital, especially at the old sanatorium hospital. Our hospital is both a tuberculosis hospital and a general hospital in which various complications can be treated. However, such general hospitals are very rare in Japan. Many patients passed away immediately after transferring to a tuberculosis hospital due to inadequate treatment of complications. To avoid repeating such tragedies, continuing treatment of complications without transferring to a tuberculosis hospital should be considered. Kamo Psychiatric Center has eight model beds for tuberculosis patients with psychiatric diseases. We retrospectively studied 71 cases of hospital DOTS from 2006 to 2011. There were 33 dementia cases and 30 schizophrenia cases. The standard regimens (A or B) were performed for 68 of the 71 cases. The median duration of hospitalization was six months. Some schizophrenia cases taking antipsychotic medications experienced worse mental symptoms when they started tuberculosis treatment. 4. Medical collaboration for tuberculosis patients' care in region: Tadatoshi SURUDA (National Hospital Organization Wakayama National Hospital) Complete medical collaboration for tuberculosis patients' care is possible by close cooperation utilizing coordination tools such as the regional critical path among TB hospitals, other medical facilities, welfare organizations, and health centers that function as a coordinator in an area. TB hospitals and health centers, both major role players in the collaboration scheme, should maintain good ties and share responsibilities. Through establishing close collaboration, medical service for TB patients will be a part of primary practice. It is expected to raise TB awareness among general medical staff and result in early case detection in the area.


Enhancing Production of Pinene in Escherichia coli by Using a Combination of Tolerance, Evolution, and Modular Co-culture Engineering.
α-Pinene is a natural and active monoterpene, which is widely used as a flavoring agent and in fragrances, pharmaceuticals, and biofuels. Although it has been successfully produced by genetically engineered microorganisms, the production level of pinene is much lower than that of hemiterpene (isoprene) and sesquiterpenes (farnesene) to date. We first improved pinene tolerance to 2.0% and pinene production by adaptive laboratory evolution after atmospheric and room temperature plasma (ARTP) mutagenesis and overexpression of the efflux pump to obtain the pinene tolerant strain Escherichia coli YZFP, which is resistant to fosmidomycin. Through error-prone PCR and DNA shuffling, we isolated an Abies grandis geranyl pyrophosphate synthase variant that outperformed the wild-type enzyme. To balance the expression of multiple genes, a tunable intergenic region (TIGR) was inserted between A. grandis GPPSD90G/L175P and Pinus taeda Pt1Q457L . In an effort to improve the production, an E. coli-E. coli modular co-culture system was engineered to modularize the heterologous mevalonate (MEV) pathway and the TIGR-mediated gene cluster of A. grandis GPPSD90G/L175P and P. taeda Pt1Q457L . Specifically, the MEV pathway and the TIGR-mediated gene cluster were integrated into the chromosome of the pinene tolerance strain E. coli YZFP and then evolved to a higher gene copy number by chemically induced chromosomal evolution, respectively. The best E. coli-E. coli co-culture system of fermentation was found to improve pinene production by 1.9-fold compared to the mono-culture approach. The E. coli-E. coli modular co-culture system of whole-cell biocatalysis further improved pinene production to 166.5 mg/L.


Tumor ablation by endoscopic Nd:YAG laser.
Nd:YAG laser ablation of tumors of the gastrointestinal tract is reviewed. Techniques used and problems encountered in the ablation of obstructive tumors is discussed and illustrative cases of esophageal and rectal tumor treatment with laser using a lumen guide are presented. The improvement in quality and dignity of life for patients receiving laser ablation therapy for obstructing tumors of the esophagus and colon is demonstrated.


Seizures induced by intraventricular microinjection of ionized cobalt in the rat--a new experimental model of epilepsy.
A new animal model for epilepsy was successfully produced by microinjection of cobaltous chloride into the lateral cerebral ventricle of the rat. The median convulsive dose (CD50) and the median lethal dose (LD50) of CoCl2 was 0.45 microM/10 microliters (0.27-0.77 microM/10 microliters) and 1.07 microM/10 microliters (0.73-1.57 microM/10 microliters), respectively. The behavioral changes, electrocorticogram (ECoG), and the action of 5 classical anticonvulsants were studied using this new model. Seizures induced by cobaltous chloride are clinically similar to those produced by systemic administration of kainic acid and amygdala kindling. These are characterized by staring spells, wet dog shakes, mild convulsive movements, and stereotyped convulsions. ECoG findings demonstrated a unique epileptic burst during the wet dog shakes. Generalized epileptiform discharges were seen during typical seizures. The burst of spikes first occurred in the opposite temporal and frontal regions; and then became generalized. Among the 5 anticonvulsants studied, phenobarbital (30 mg/kg) and nitrazepam (3 mg/kg) completely antagonized the seizures; carbamazepine showed a moderate effect; and phenytoin as well as sodium valproate showed little effect. It is postulated that the seizures induced by cobaltous chloride may originate in the limbic system; and that cobalt ions are responsible for the seizure-inducing action. The mechanism remains to be investigated.


Pegloticase for treating refractory chronic gout.
Gout is a metabolic disorder of excess uric acid accumulation that manifests clinically as inflammatory arthritis, chronic arthropathy and the formation of deposits of uric acid known as tophi. A primary objective of gout management is to reduce the excess urate burden by regular use of drugs that reduce serum urate levels. Conventional urate-lowering drugs available in the U.S. are allopurinol, febuxostat and probenecid. Some patients are intolerant to or unresponsive to urate-lowering therapies and, therefore, are said to have refractory gout. Recently, a polyethylene glycol-conjugated uricase, pegloticase, was approved for treating refractory gout. In recent clinical trials, pegloticase normalized plasma urate levels, reduced the size of tophi, and improved functional status and quality of life in patients with refractory disease. Immunogenicity to pegloticase is associated with loss of urate-lowering response and the risk of infusion reactions. Pegloticase is effective in treating hyperuricemia and the clinical manifestations of gout in patients who cannot be adequately managed with conventional therapy.


ARID1A Deficiency Impairs the DNA Damage Checkpoint and Sensitizes Cells to PARP Inhibitors.
ARID1A, SWI/SNF chromatin remodeling complex subunit, is a recently identified tumor suppressor that is mutated in a broad spectrum of human cancers. Thus, it is of fundamental clinical importance to understand its molecular functions and determine whether ARID1A deficiency can be exploited therapeutically. In this article, we report a key function of ARID1A in regulating the DNA damage checkpoint. ARID1A is recruited to DNA double-strand breaks (DSB) via its interaction with the upstream DNA damage checkpoint kinase ATR. At the molecular level, ARID1A facilitates efficient processing of DSB to single-strand ends and sustains DNA damage signaling. Importantly, ARID1A deficiency sensitizes cancer cells to PARP inhibitors in vitro and in vivo, providing a potential therapeutic strategy for patients with ARID1A-mutant tumors. ARID1A has been identified as one of the most frequently mutated genes across human cancers. Our data suggest that clinical utility of PARP inhibitors might be extended beyond patients with BRCA mutations to a larger group of patients with ARID1A-mutant tumors, which may exhibit therapeutic vulnerability to PARP inhibitors.


[Signaling and metabolic predispositions linked to the colorectal cancer].
The setting up and the progression of the colorectal cancer (CCR) follow a sequence of events that are spatio-temporally rigorously orchestrated. The failures that specifically target the signaling pathways responsible for the cancerization of the colorectal mucosa have been well described and among these it seems that a dysregulation of the Wnt/β-catenin pathway is involved in the triggering of near 90 % of the cases. It has been also described that several risk factors linked to metabolic disorders (feeding, insulin resistance, metabolic syndrome, etc.) predispose individuals to CCR but no rational explanations were given. We propose that, since it is implicated in the control of the insulin pathway among other actions, the nutritional sensor O-GlcNAcylation may be the element linking these metabolic disorders to CCR.


A cluster of patients with a chronic mononucleosis-like syndrome. Is Epstein-Barr virus the cause?
A cluster of 134 patients who had undergone Epstein-Barr virus (EBV) serological testing because of suspected chronic EBV syndrome was investigated in Nevada. Fifteen case-patients were identified who had severe, persistent fatigue of undetermined etiology for more than two months. When compared with the remaining 119 patients who had less severe illnesses and with 30 age-, sex-, and race-matched control-persons, these 15 patients had significantly higher antibody titers against various components of EBV and against cytomegalovirus and herpes simplex and measles viruses. Epstein-Barr virus serology could not reliably differentiate individual case-patients from the others, and the reproducibility of the tests within and among laboratories was poor. As a group, the case-patients appear to have had a syndrome that is characterized by chronic fatigue, fever, sore throat, and lymphadenopathy. The relationship of this fatigue syndrome to EBV is unclear; further studies are needed to determine its etiology.


A Study on Protecting Patients' Privacy of Obstetric and Gynecologic Nurses.
This study aims to determine obstetric and gynecologic (OBGY) nurses' perception and performance propecting patients' privacy, and to contribute to develop educational program and improve the quality of nursing care. 206 OBGY nurses in 6 hospitals using an electronic medical record or an order communicating system were chosen by convenience sampling and agreed to participate in the study. The questionnaire, explored 4 domains of privacy: direct nursing, linked business, patient information management, communication with relatives. Perception and performance of protecting patient privacy averaged 4.29 (of 5) and 3.55 (of 5), respectively. Most nurses (94.2%) recognized the importance of protecting patient privacy, 80.1% received patient privacy education. There was a distinct difference between the perception and performance of protecting patient privacy of nurses. Performance of protecting patient privacy had a positive correlation with perception. Proper performance of protecting privacy protection requires improving perception of each nurse on the patient privacy, and various efforts should be made to minimize the affect from external factors such as hospital environment. It is needed to educate nurses for patient privacy. It is also needed for medical organizations to improve their policies and facilities to ease the performance for privacy protection.


[Aberrant heterotopic salivary gland in a lateral neck cyst].
An extra aberrant salivary gland located in a branchial cyst is presented. The branchial cysts are usually the result of a transformation disturbance of the branchial clefts and arches, or are cystic changes of the lymph nodes. The above finding can possibly be interpreted if we suppose that an aberrant salivary gland located in a lymph node can develop a cyst. The theory that branchial cysts originate from lymph nodes is encouraged by our case. This theory can also support the existence of unusual tumours in the neck, e.g. adenolymphomas. The content of these cysts can be easily approximately estimated via computed tomography.


[Results of 10-year use of complex treatment of choroidal melanoma stage T2 with brachytherapy and transpupillary thermotherapy].
We studied the results of complex treatment of choroidal melanoma (CM) using Ru-106+Rh- 106 brachytherapy (BT) combined with transpupillary thermotherapy (TTT). 70 patients (70 eyes) with CM prominence ranged from 2.5 till 10.8 mm (mean 6.5+0.24 mm) were enrolled into the study. Follow-up was 6-120 months, median 47 months. TTT (810 microm) was carried out 24-48 hours later ophthalmic applicator suturing. Absolute or partial regression was achieved in 69 patients (99%) from 6.4+0.24 mm till 2.4+1.9 mm. In 1 case treatment was not effective. In 1 patient enucleation was performed due to secondary glaucoma. Dissemination with liver metastases was observed in 3 patients. Kaplan-Meier analysis showed 5 year eye preservation as high as 99%, absence of metastases--94%, survival rate without recurrence--91%, total efficacy (patients without negative results)--89%. Thus complex treatment (BT + TTT) of CM compared with monotherapy BT showed to have better local outcomes (including eye preservation) and it does not reduce survival rate even in patients with stage T2 (less than 10 mm).


A review of plant-based compounds and medicinal plants effective on atherosclerosis.
Atherosclerosis is one of the most important cardiovascular diseases that involve vessels through the development of fatty streaks and plaques. Plant-based compounds can help treat or prevent atherosclerosis through affecting the involved factors. The main purpose of this review article is to investigate and introduce medicinal plants and their potential activities regarding antioxidant properties, effective on lipids level and development of plaque, atherosclerosis, and progression of atherosclerosis as well as the development of cardiovascular disease and ischemia. To search for the relevant articles indexed in Information Sciences Institute, PubMed, Scientific Information Database, IranMedex, and Scopus between 1980 and 2013, with further emphasis on those indexed from 2004 to 2015, we used these search terms: atherosclerosis, antioxidant, cholesterol, inflammation, and the medicinal plants below. Then, the articles with inclusion criteria were used in the final analysis of the findings. Plant-based active compounds, including phenols, flavonoids, and antioxidants, can be effective on atherosclerosis predisposing factors and hence in preventing this disease and associated harmful complications, especially through reducing cholesterol, preventing increase in free radicals, and ultimately decreasing vascular plaque and vascular resistance. Hence, medicinal plants can contribute to treating atherosclerosis and preventing its progression through reducing cholesterolemia, free radicals, inflammation, vascular resistance, and certain enzymes. They, alone or in combination with hypocholesterolemic drugs, can therefore be useful for patients with hyperlipidemia and its complications.


The efficacy of sodium channel blockers to prevent phencyclidine-induced cognitive dysfunction in the rat: potential for novel treatments for schizophrenia.
Sodium channel inhibition is a well precedented mechanism used to treat epilepsy and other hyperexcitability disorders. The established sodium channel blocker and broad-spectrum anticonvulsant lamotrigine is also effective in the treatment of bipolar disorder and has been evaluated in patients with schizophrenia. Double-blind placebo-controlled clinical trials found that the drug has potential to reduce cognitive symptoms of the disorder. However, because of compound-related side-effects and the need for dose titration, a conclusive evaluation of the drug's efficacy in patients with schizophrenia has not been possible. (5R)-5-(4-{[(2-Fluorophenyl)methyl]oxy}phenyl)-l-prolinamide (GSK2) and (2R,5R)-2-(4-{[(2-fluorophenyl)methyl]oxy}phenyl)-7-methyl-1,7-diazaspiro[4.4]nonan-6-one (GSK3) are two new structurally diverse sodium channel blockers with potent anticonvulsant activity. In this series of studies in the rat, we compared the efficacy of the two new molecules to prevent a cognitive deficit induced by the N-methyl-d-aspartic acid receptor antagonist phencyclidine (PCP) in the reversal-learning paradigm in the rat. We also explored the effects of the drugs to prevent brain activation and neurochemical effects of PCP. We found that, like lamotrigine, both GSK2 and GSK3 were able to prevent the deficit in reversal learning produced by PCP, thus confirming their potential in the treatment of cognitive symptoms of schizophrenia. However, higher doses than those required for anticonvulsant efficacy of the drugs were needed for activity in the reversal-learning model, suggesting a lower therapeutic window relative to mechanism-dependent central side effects for this indication.


Consumption of food away from home in Bangladesh: Do rich households spend more?
While consumption of food away from home (FAFH) is an established phenomenon among households in the developed countries, FAFH is a growing phenomenon in many middle-income and rapidly growing developing countries. Although, studies are available on the factors affecting consumption of FAFH in developed countries, there is a paucity of such studies in developing countries. This study examines households' choice of and expenditures on FAFH. We used information from Bangladeshi households and applied a double-hurdle regression model estimation procedure. Findings show that, in general, rich households are spending proportionately less on FAFH and, over time, the trend is continuing. Although households with female members who work in the non-farm sector are more likely to consume FAFH, educated household heads and spouses, and particularly urban households are less likely to consume and spend on FAFH. As the problem of food adulteration by dishonest sellers is rampant in Bangladesh, perhaps it discourages rich, urban and households headed by educated heads and spouses to consume and spend more on FAFH. Based on the findings, some points of interventions are also prescribed in this study.


Changes in Structure and Function of the Back Muscles in Low Back Pain: Different Time Points, Observations, and Mechanisms.
Spinal health depends on optimal back muscle performance, and this is determined by muscle structure and function. There has been substantial research evaluating the differences in structure and function of many back muscles, including the multifidus and erector spinae, but with considerable variation in results. Many studies have shown atrophy, fat infiltration, and connective tissue accumulation in back muscles, particularly deep fibers of the multifidus, but the results are not uniform. In terms of function, results are also somewhat inconsistent, often reporting lower multifidus activation and augmented recruitment of more superficial components of the multifidus and erector spinae, but, again, with variation between studies. A major recent observation has been the identification of time-dependent differences in features of back muscle adaptation, from acute to subacute/recurrent to chronic states of the condition. Further, these adaptations have been shown to be explained by different time-dependent mechanisms. This has substantial impact on the rationale for rehabilitation approaches. The aim of this commentary was to review and consolidate the breadth of research investigating adaptation in back muscle structure and function, to consider explanations for some of the variation between studies, and to propose how this model can be used to guide rehabilitation in a manner that is tailored to individual patients and to underlying mechanisms. J Orthop Sports Phys Ther 2019;49(6):464-476. doi:10.2519/jospt.2019.8827.


α-N-Linked glycopeptides: conformational analysis and bioactivity as lectin ligands.
Natural N-glycosylation involves a β-anomeric linkage connecting the sugar to one asparagine residue of the protein. We herein report NMR- and modelling-based data on glycomimetics containing α-glycosidic linkages. The bioactivity of α-Gal-containing glycopeptides has been documented by revealing binding to two plant lectins, i.e. a potent β-trefoil toxin (Viscum album agglutinin) and β-sandwich lectin (Erythrina corallodendron agglutinin), by NMR protocols. Docking provided insights into the 3D structures of the resulting complexes. These results provide the basis to introduce α-substituted neoglycopeptides to the toolbox of scaffold for the design of potent lectin inhibitors.


Manipulative therapies for infantile colic.
Infantile colic is a common disorder, affecting around one in six families, and in 2001 was reported to cost the UK National Health Service in excess of £65 million per year (Morris 2001). Although it usually remits by six months of age, there is some evidence of longer-term sequelae for both children and parents.Manipulative therapies, such as chiropractic and osteopathy, have been suggested as interventions to reduce the severity of symptoms. To evaluate the results of studies designed to address efficacy or effectiveness of manipulative therapies (specifically, chiropractic, osteopathy and cranial manipulation) for infantile colic in infants less than six months of age. We searched following databases: CENTRAL (2012, Issue 4), MEDLINE (1948 to April Week 3 2012), EMBASE (1980 to 2012 Week 17), CINAHL (1938 to April 2012), PsycINFO (1806 to April 2012), Science Citation Index (1970 to April 2012), Social Science Citation Index (1970 to April 2012), Conference Proceedings Citation Index - Science (1990 to April 2012) and Conference Proceedings Citation Index - Social Science & Humanities (1970 to April 2012). We also searched all available years of LILACS, PEDro, ZETOC, WorldCat, TROVE, DART-Europe, ClinicalTrials.gov and ICTRP (May 2012), and contacted over 90 chiropractic and osteopathic institutions around the world. In addition, we searched CentreWatch, NRR Archive and UKCRN in December 2010. Randomised trials evaluating the effect of chiropractic, osteopathy or cranial osteopathy alone or in conjunction with other interventions for the treatment of infantile colic. In pairs, five of the review authors (a) assessed the eligibility of studies against the inclusion criteria, (b) extracted data from the included studies and (c) assessed the risk of bias for all included studies. Each article or study was assessed independently by two review authors. One review author entered the data into Review Manager software and the team's statistician (PP) reviewed the chosen analytical settings. We identified six studies for inclusion in our review, representing a total of 325 infants. There were three further studies that we could not find information about and we identified three other ongoing studies. Of the six included studies, five were suggestive of a beneficial effect and one found no evidence that manipulative therapies had any beneficial effect on the natural course of infantile colic. Tests for heterogeneity imply that there may be some underlying difference between this study and the other five.Five studies measured daily hours of crying and these data were combined, suggesting that manipulative therapies had a significant effect on infant colic - reducing average crying time by one hour and 12 minutes per day (mean difference (MD) -1.20; 95% confidence interval (CI) -1.89 to -0.51). This conclusion is sustained even when considering only studies with a low risk of selection bias (sequence generation and allocation concealment) (MD -1.24; 95% CI -2.16 to -0.33); those with a low risk of attrition bias (MD -1.95; 95% CI -2.96 to -0.94), or only those studies that have been published in the peer-reviewed literature (MD -1.01; 95% CI -1.78 to -0.24). However, when combining only those studies with a low risk of performance bias (parental 'blinding'), the improvement in daily crying hours was not statistically significant (MD -0.57; 95% CI -2.24 to 1.09).One study considered whether the reduction in crying time was clinically significant. This found that a greater proportion of parents of infants receiving a manipulative therapy reported clinically significant improvements than did parents of those receiving no treatment (reduction in crying to less than two hours: odds ratio (OR) 6.33; 95% CI 1.54 to 26.00; more than 30% reduction in crying: OR 3.70; 95% CI 1.15 to 11.86).Analysis of data from three studies that measured 'full recovery' from colic as reported by parents found that manipulative therapies did not result in significantly higher proportions of parents reporting recovery (OR 11.12; 95% CI 0.46 to 267.52).One study measured infant sleeping time and found manipulative therapy resulted in statistically significant improvement (MD 1.17; 95% CI 0.22 to 2.12).The quality of the studies was variable. There was a generally low risk of selection bias but only two of the six studies were evaluated as being at low risk of performance bias, three at low risk of detection bias and one at low risk of attrition bias.One of the studies recorded adverse events and none were encountered. However, with only a sample of 325 infants, we have too few data to reach any definitive conclusions about safety. The studies included in this meta-analysis were generally small and methodologically prone to bias, which makes it impossible to arrive at a definitive conclusion about the effectiveness of manipulative therapies for infantile colic.The majority of the included trials appeared to indicate that the parents of infants receiving manipulative therapies reported fewer hours crying per day than parents whose infants did not, based on contemporaneous crying diaries, and this difference was statistically significant. The trials also indicate that a greater proportion of those parents reported improvements that were clinically significant. However, most studies had a high risk of performance bias due to the fact that the assessors (parents) were not blind to who had received the intervention. When combining only those trials with a low risk of such performance bias, the results did not reach statistical significance. Further research is required where those assessing the treatment outcomes do not know whether or not the infant has received a manipulative therapy.There are inadequate data to reach any definitive conclusions about the safety of these interventions.


Hydrodynamic effects in the measurement of interparticle forces in nematic colloids.
We propose improved measurement methods of interparticle force between nematic colloids. Although various methods have been utilized for the force measurement, the comparison between the forces obtained by different methods has not been reported. In the frequently used method called the "free-release" method, the hydrodynamic interaction between moving particles has a serious influence on the measurement. In this study we modified those measurement methods by taking the long-ranged hydrodynamic interaction into account. The evaluated forces have been compared with that obtained by the dual beam "optical trap" method, which is free from the hydrodynamic effect. The agreement between them is quantitatively fairly good.


Differentiation from precursors in athymic nude mouse bone marrow of unusual spontaneously cytolytic cells showing anti-self-H-2 specificity and bearing T cell markers.
We describe an in vitro limiting dilution culture system that supports growth and differentiation of nylon wool nonadherent bone marrow cells from athymic nude mice. Cells were seeded at low cell numbers (5-120 cells per 20-microliter microculture well) in the absence of added filler or feeder cells but in the presence of conditioned medium. Microwells positive for growth appeared to contain a single clone of cells that adhered together to form a tight cluster referred to here as a colony. A fraction of colonies contained cells that expressed an unusual spontaneous cytolytic activity. They lysed syngeneic or semisyngeneic Con A blast or tumor cell targets but seldom lysed H-2-incompatible Con A blast or tumor target cells, even in a lectin-facilitated assay. A large fraction of colonies contained lymphoid cells that expressed the T cell markers Thy-1 and Lyt-1. Colonies expressing spontaneous cytolytic activity and also containing cells with Thy-1+ and/or Lyt-1+ markers could be grown from nylon wool nonadherent nude marrow cells depleted rigorously by cell sorting of cells expressing either of these markers. Expression of Thy-1 and spontaneous cytolytic activity in a particular colony was significantly correlated. Short-term lines established from cytolytic colonies with T cell markers maintained both characteristics. The cytolytic effector cells observed in these cultures may represent an early stage in the development of the T cell repertoire.


Low Back Pain.
This article provides an overview of evaluating and treating low back pain in the outpatient setting. As most cases of acute low back pain have a favorable prognosis, current guidelines on imaging studies recommend conservative treatment for 6 weeks prior to obtaining an MRI if no red flags are present. Of these red flags, a prior history of cancer is the strongest risk factor for a malignant etiology and requires urgent evaluation with MRI. Management of acute low back pain is mainly conservative with oral non-narcotic analgesics and mobilization as the initial recommendations. For patients with radiculopathy, epidural steroids may result in short-term pain relief, but long-term effects are still unclear. A systematic, evidence-based approach to the patient with low back pain is key to providing safe and cost-efficient care.


Non-oxidative ethanol metabolism in human hepatic cells in vitro: Involvement of uridine diphospho-glucuronosyltransferase 1A9 in ethylglucuronide production.
Ethanol is the most frequently psychoactive substance used in the world, leading to major public health problems with several millions of deaths attributed to alcohol consumption each year. Metabolism of ethanol occurs mainly in the liver via the predominant oxidative metabolism pathway involving phase I enzymes including alcohol dehydrogenases (ADH), cytochrome P450 (CYP) 2E1 and catalase. In a lesser extent, an alternative non-oxidative pathway also contributes to the metabolism of ethanol, which involves the uridine diphospho-glucuronosyltransferase (UGT) and sulfotransferase (SULT) phase II enzymes. Using liquid chromatography-high resolution mass spectrometry, ethylglucuronide (EtG) and ethylsulfate (EtS) produced respectively by UGT and SULT conjugation and detected in various biological samples are direct markers of alcohol consumption. We report herein the efficient non-oxidative metabolic pathway of ethanol in human differentiated HepaRG cells compared to primary human hepatocytes (HH). We showed dose- and time-dependent production of EtS and EtG after ethanol (25 or 50 mM) treatment in culture media of differentiated HepaRG cells and HH and a significant induction of CYP2E1 mRNA expression upon acute ethanol exposure in HepaRG cells. These differentiated hepatoma cells thus represent a suitable in vitro human liver cell model to explore ethanol metabolism and more particularly EtG and EtS production. In addition, using recombinant HepG2 cells expressing different UGT1A genes, we found that UGT1A9 was the major UGT involved in ethanol glucuronidation.


Upper GI training of young surgeons: a reality full of hurdles. An international survey.
Anecdotal evidence suggests that the training of young surgeons in Upper GI is not homogeneous across the world. This survey aimed to investigate the different training programs and the level of satisfaction of young surgeons with their surgical and scientific education pathway. A multiple-choice and single best answer format questionnaire was sent to 36 Upper GI chairs from international referral centres and then forwarded to young surgeons (attending physician less than 40 years old). The same questionnaire containing 5 main topics (demographics, residency, fellowship, academic research and activities, manual skill improvement) was posted online on a Surveymonkey website. San Luigi University Hospital, Orbassano (Turin), Italy; Tertiary University Hospital. Fourteen replies were received from colleagues in 36 referral centres (39% response rate) and 65 voluntary answers from the survey monkey platform. During residency training, only 43% of residents had a specific training in upper GI tract surgery, which was characterized by a small number of interventions performed both with trainer scrubbed and unscrubbed. Fellowship programmes were undertaken by 49% of participants and 64% spent this training period abroad. Operative experience was reported by nearly all respondents with only 27% performing > 10 gastrectomies and only 11% performing > 10 oesophagectomies with the trainer scrubbed. The majority attended less than 10 meetings (58%), and 70% of them published less than 5 papers. The present survey reveals that the young surgeons of the twenty-first century face many hurdles during their surgical training. Overall, the surgical education settings are limited for both practical and scientific training for upper GI trainees. As a result, it is not possible to train in upper GI surgery to a level of competent independent practice.


A top-down saliency model with goal relevance.
Most visual saliency models that integrate top-down factors process task and context information using machine learning techniques. Although these methods have been successful in improving prediction accuracy for human attention, they require significant training data and are unable to provide an understanding of what makes information relevant to a task such that it will attract gaze. This means that we still lack a general theory for the interaction between task and attention or eye movements. Recently, Tanner and Itti (2017) proposed the theory of goal relevance to explain what makes information relevant to goals. In this work, we record eye movements of 80 participants who each played one of four variants of a Mario video game and construct a combined saliency model using features from three sources: bottom-up, learned top-down, and goal relevance. We use this model to predict the eye behavior and find that the addition of goal relevance significantly improves the Normalized Scanpath Saliency score of the model from 4.35 to 5.82 (p < 1 × 10-100).


Risk of acute arterial events associated with treatment of inflammatory bowel diseases: nationwide French cohort study.
Patients with IBD are at increased risk of acute arterial events. Antitumour necrosis factor (TNF) agents and thiopurines may, via their anti-inflammatory properties, lower the risk of acute arterial events. The aim of this study was to assess the impact of thiopurines and anti-TNFs on the risk of acute arterial events in patients with IBD. Patients aged 18 years or older and affiliated to the French national health insurance with a diagnosis of IBD were followed up from 1 April 2010 until 31 December 2014. The risks of acute arterial events (including ischaemic heart disease, cerebrovascular disease and peripheral artery disease) were compared between thiopurines and anti-TNFs exposed and unexposed patients with marginal structural Cox proportional hazard models adjusting for baseline and time-varying demographics, medications, traditional cardiovascular risk factors, comorbidities and IBD disease activity. Among 177 827 patients with IBD (96 111 (54%) women, mean age at cohort entry 46.2 years (SD 16.3), 90 205 (50.7%) with Crohn's disease (CD)), 4145 incident acute arterial events occurred (incidence rates: 5.4 per 1000 person-years). Compared with unexposed patients, exposure to anti-TNFs (HR 0.79, 95% CI 0.66 to 0.95), but not to thiopurines (HR 0.93, 95% CI 0.82 to 1.05), was associated with a decreased risk of acute arterial events. The magnitude in risk reduction was highest in men with CD exposed to anti-TNFs (HR 0.54, 95% CI 0.40 to 0.72). Exposure to anti-TNFs is associated with a decreased risk of acute arterial events in patients with IBD, particularly in men with CD.


KLF1-null neonates display hydrops fetalis and a deranged erythroid transcriptome.
We describe a case of severe neonatal anemia with kernicterus caused by compound heterozygosity for null mutations in KLF1, each inherited from asymptomatic parents. One of the mutations is novel. This is the first described case of a KLF1-null human. The phenotype of severe nonspherocytic hemolytic anemia, jaundice, hepatosplenomegaly, and marked erythroblastosis is more severe than that present in congenital dyserythropoietic anemia type IV as a result of dominant mutations in the second zinc-finger of KLF1. There was a very high level of HbF expression into childhood (>70%), consistent with a key role for KLF1 in human hemoglobin switching. We performed RNA-seq on circulating erythroblasts and found that human KLF1 acts like mouse Klf1 to coordinate expression of many genes required to build a red cell including those encoding globins, cytoskeletal components, AHSP, heme synthesis enzymes, cell-cycle regulators, and blood group antigens. We identify novel KLF1 target genes including KIF23 and KIF11 which are required for proper cytokinesis. We also identify new roles for KLF1 in autophagy, global transcriptional control, and RNA splicing. We suggest loss of KLF1 should be considered in otherwise unexplained cases of severe neonatal NSHA or hydrops fetalis.


Elucidation of Hosts, Native Distribution, and Habitat of the Coffee Berry Borer (Hypothenemus hampei) Using Herbaria and Other Museum Collections.
The coffee berry borer (Hypothenemus hampei) is the most damaging insect pest of global coffee production. Despite its importance, our knowledge on the insect's natural habitat, range, and wild host species remains poorly known. Using archival sources (mainly herbaria but also other museum collections), we surveyed 18,667 predominantly wild-collected herbarium specimens mostly from Africa, Madagascar, and Asia for coffee berry borer occurrence. A total of 72 incidences were confirmed for presence of the coffee berry borer, with identifications assisted by micro-CT for SEM. Of the 72 positive infestations, all were from tropical African coffee (Coffea) species, of which 32 were from wild (non-cultivated) plants. Of the 32 wild occurrences, 30 were found in C. canephora (robusta coffee), 1 in C. liberica (Liberica coffee), and 1 in C. arabica (Arabica coffee). Our herbarium survey confirms literature and anecdotal reports that the coffee berry borer is indigenous to tropical Africa, and that coffee species, and particularly robusta coffee, are important hosts. We identify the wetter type of Guineo-Congolian forest as either the preferred or exclusive native habitat of the coffee berry borer. Other than coffee, we find no evidence of other naturally occurring hosts. Characters of infestation (e.g., hole position on coffee fruits) infers a certain degree of specificity between the coffee berry borer and its host.


It's about Time: Ossification Center Formation in C57BL/6 Mice from E12⁻E16.
The establishment of precise, high-resolution temporal sequences for morphogenetic events in laboratory mice remains a vexing issue in developmental biology. Mouse embryos collected at the same period of gestation, even those from the same litter, show wide variation in individual levels of progress along their developmental trajectory. Therefore, age at harvest does not provide sufficient information about developmental progress to serve as the basis for forming samples for the study of rapidly or near-simultaneously occurring events such as the sequence of ossification center formation. Here, we generate two measures of individual developmental progress (developmental age) for a large sample of mouse embryos using crown⁻rump lengths that measures size, and limbstaging ages produced by the embryonic Mouse Ontogenetic Staging System (eMOSS) that measure shape. Using these measures, we establish fine-grained sequences of ossification center appearance for mouse embryos. The two measures of developmental progress generate slightly different sequences of ossification center formation demonstrating that despite their tight correlation throughout the developmental period, size and shape are aspects of form that are at least partially dissociated in development.


Radiofrequency Ablation of Papillary Thyroid Microcarcinoma: A 10-Year Follow-Up Study.
To investigate the efficacy and safety of radiofrequency ablation (RFA) for papillary thyroid microcarcinoma (PTMC) after > 10 years of follow-up. This study included five patients who underwent RFA to treat PTMCs (five lesions, mean diameter 0.5 cm, range 0.4-0.7 cm) between November 2006 and December 2009. The inclusion criteria were histopathologically confirmed PTMCs, a single PTMC lesion without extrathyroidal extension, no metastasis, and ineligibility or refusal to undergo surgery. RFA was performed by a single radiologist using a radiofrequency generator and an internally cooled electrode. We retrospectively analyzed the procedure-induced complications, serial changes in ablated tumors, recurrence, and local as well as lymph node metastasis based on data obtained from medical records and radiological images. The mean follow-up period was 130.6 months (range 121-159 months). Three patients underwent a single RFA session, and two patients underwent two RFA sessions. We observed no procedure-induced complications. Three tumors completely disappeared after ablation, and ablation of the other two tumors resulted in the formation of a small scar that showed long-term stability (mean duration 16.8 months, range 12-27 months). At the last follow-up, no patient showed recurrence or lymph node metastasis, and serum thyroglobulin levels were within normal limits in all patients. RFA may be effective and safe to treat low-risk PTMC in patients who refuse or are ineligible for surgery.


[Economic efficiency of renal denervation in patients with resistant hypertension: results of Markov modeling].
Aim of this study was to evaluate the cost-effectiveness of renal denervation (RD) in resistant arterial hypertension (AH) in Russia. Modeling of Markov conducted economic impact of RD on the Russian population of patients with resistant hypertension in combination with optimal medical therapy (OMT) compared with OMT using a model developed by American researchers based on the results of international research. The model contains data on Russian mortality, and costs of major complications of hypertension. The simulation results showed a significant reduction in relative risk reduction of adverse outcomes in patients with resistant hypertension for 10 years (risk of stroke is reduced by 30%, myocardial infarction - 32%). RD saves 0.9 years of quality-adjusted life (QALY) by an average of 1 patient with resistant hypertension. Costs for 1 year stored in the application of quality of life amounted to RD 203 791.6 rubles. Which is below the 1 gross domestic product and therefore indicates the feasibility of this method in Russia.


Persistence of Vibrio cholerae in inter epidemic period--preliminary observations on analysis of water.
Out of the 61 water samples collected from hand pumps and wells from cholera endemic areas of Varanasi City, Vibrio cholerae non 01 was detected in only one sample. However, seven (18.9 per cent) samples out of 37 samples of river water were positive for V. cholerae non 01. None of the samples showed Vibrio cholerae. These observations indicate transmission and dilution of Vibrio cholerae bacillus in environment.


Arginase inhibition ameliorates adipose tissue inflammation in mice with diet-induced obesity.
This study examined whether oral administration of an arginase inhibitor regulates adipose tissue macrophage infiltration and inflammation in mice with high fat diet (HFD)-induced obesity. Male C57BL/6 mice (n = 30) were randomly assigned to control (CTL, n = 10), HFD only (n = 10), and HFD with arginase inhibitor N(ω)-hydroxy-nor-l-arginine (HFD with nor-NOHA, n = 10) groups. Plasma and mRNA levels of cytokines in epididymal adipose tissues (EAT), macrophage infiltration into EAT, and macrophage phenotype polarization were measured in the animals after 12 weeks. Additionally, the effects of nor-NOHA on adipose tissue macrophage infiltration and mRNA expression of cytokines were measured in co-cultured 3T3-L1 adipocytes and RAW 264.7 macrophages. Macrophage infiltration into the adipocytes was significantly suppressed by nor-NOHA treatment in adipocyte/macrophage co-culture system and mice with HFD-induced obesity. Pro-inflammatory cytokines, including monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), were significantly downregulated, and the anti-inflammatory cytokine IL-10 was significantly upregulated in nor-NOHA-treated co-cultured cells. In the mice with HFD-induced obesity, plasma and mRNA levels of MCP-1 significantly reduced after supplementation with nor-NOHA. In addition, oral supplement of nor-NOHA modified M1/M2 phenotype ratio in the EAT. Oral supplementation of an arginase inhibitor, nor-NOHA, altered M1/M2 macrophage phenotype and macrophage infiltration into HFD-induced obese adipose tissue, thereby improved adipose tissue inflammatory response. These results may indicate that arginase inhibition ameliorates obesity-induced adipose tissue inflammation.


How accurately do nurses perceive patients' needs? A comparison of general and psychiatric settings.
This paper examines to what extent nurses' perceptions of patients' needs correspond to the patients' views of their own needs. A questionnaire was designed to assess patients' emotional and physical needs in general medical wards and in acute psychiatric wards. Sixty patients, 30 psychiatric and 30 general, together with their 'key' nurses, took part in the study. Results indicate that, despite there being no evidence of appreciable disagreement between the 'average' psychiatric nurse and the 'average' psychiatric patient, there is little evidence that individual nurses and their patients, whether psychiatric or general, agree. The nurses' inability to perceive patients' needs on an individual basis is consistent with other studies which suggest that nurses use stereotypes when perceiving patients' needs. Implications for nursing care are discussed.


Development of a Patient-Derived Xenograft Model Using Brain Tumor Stem Cell Systems to Study Cancer.
Patient-derived xenograft (PDX) models provide an excellent platform to understand cancer initiation and development in vivo. In the context of brain tumor initiating cells (BTICs), PDX models allow for characterization of tumor formation, growth, and recurrence, in a clinically relevant in vivo system. Here, we detail procedures to harvest, culture, characterize, and orthotopically inject human BTICs derived from patient samples.


Estrogen receptor-related receptor alpha: a mediator of estrogen response in bone.
Estrogen receptor-related receptor-alpha (ERRalpha) is an orphan nuclear receptor with sequence homology to the estrogen receptors, ERalpha/beta, but it does not bind estrogen. However, several recent studies suggest that ERRalpha not only plays a functional role in osteoblasts but also impinges on the estrogen axis in bone, as it does in at least certain other estrogen target tissues. We summarize here data on ERRalpha and its cellular and molecular modes of action that have broad implications for considering the potential role of this orphan receptor as a new therapeutic target in osteopenic disorders such as osteoporosis as well as other estrogen-responsive conditions.


A review on thermal and catalytic pyrolysis of plastic solid waste (PSW).
Plastic plays an important role in our daily lives due to its versatility, light weight and low production cost. Plastics became essential in many sectors such as construction, medical, engineering applications, automotive, aerospace, etc. In addition, economic growth and development also increased our demand and dependency on plastics which leads to its accumulation in landfills imposing risk on human health, animals and cause environmental pollution problems such as ground water contamination, sanitary related issues, etc. Hence, a sustainable and an efficient plastic waste treatment is essential to avoid such issues. Pyrolysis is a thermo-chemical plastic waste treatment technique which can solve such pollution problems, as well as, recover valuable energy and products such as oil and gas. Pyrolysis of plastic solid waste (PSW) has gained importance due to having better advantages towards environmental pollution and reduction of carbon footprint of plastic products by minimizing the emissions of carbon monoxide and carbon dioxide compared to combustion and gasification. This paper presents the existing techniques of pyrolysis, the parameters which affect the products yield and selectivity and identify major research gaps in this technology. The influence of different catalysts on the process as well as review and comparative assessment of pyrolysis with other thermal and catalytic plastic treatment methods, is also presented.


Attitudes and Knowledge of Healthcare Professionals Regarding Organ Donation. A Survey of the Saolta University Health Care Group.
Organ donation saves lives and healthcare professionals (HCPs) play a vital role in that process. Therefore, the purpose of this study was to assess the attitudes and level of knowledge of HCPs regarding organ donation. An online anonymous self-administered questionnaire containing 40 questions on organ donation using google forms was created. The survey was distributed to HCPs working in the Saolta University Health Care Group. A hundred and thirty-nine responses were received giving a response rate of 11.8%. HCPs willingness to donate their organs was at 93% compared to 97% willing to receive a transplant. More HCPs understood or had knowledge of the term donation after brain death (64%) than donation after circulatory death (49%). HCPs working in intensive care knew more about the management of brain dead donors than other specialties (p<0.0001). Over 60% of HCPs when asked either disagreed or strongly disagreed with the adequacy of training in organ donation and transplant. Overall, HCPs surveyed had positive attitudes towards organ donation but there was a lack of knowledge particularly among non-intensive care professionals. This study highlights the need to increase awareness along with implementation of educational programmes among HCPs regarding organ donation and transplant.


Clinical practice in perioperative monitoring in adult cardiac surgery: is there a standard of care? Results from an national survey.
This study was to investigate and define what is considered as a current clinical practice in hemodynamic monitoring and vasoactive medication use after cardiac surgery in Italy. A 33-item questionnaire was sent to all intensive care units (ICUs) admitting patients after cardiac surgery. 71 out of 92 identified centers (77.2 %) returned a completed questionnaire. Electrocardiogram, invasive blood pressure, central venous pressure, pulse oximetry, diuresis, body temperature and blood gas analysis were identified as routinely used hemodynamic monitoring, whereas advanced monitoring was performed with pulmonary artery catheter or echocardiography. Crystalloids were the fluids of choice for volume replacement (86.8 % of Centers). To guide volume management, central venous pressure (26.7 %) and invasive blood pressure (19.7 %) were the most frequently used parameters. Dobutamine was the first choice for treatment of left heart dysfunction (40 %) and epinephrine was the first choice for right heart dysfunction (26.8 %). Half of the Centers had an internal protocol for vasoactive drugs administration. Intra-aortic balloon pump and extra-corporeal membrane oxygenation were widely available among Cardiothoracic ICUs. Angiotensin-converting enzyme inhibitors were suspended in 28 % of the Centers. The survey shows what is considered as standard monitoring in Italian Cardiac ICUs. Standard, routinely used monitoring consists of ECG, SpO2, etCO2, invasive BP, CVP, diuresis, body temperature, and BGA. It also shows that there is large variability among the various Centers regarding hemodynamic monitoring of fluid therapy and inotropes administration. Further research is required to better standardize and define the indicators to improve the standards of intensive care after cardiac surgery among Italian cardiac ICUs.


A Case Report of Tension Hydrothorax Incited by Bowel Perforation.
We report the case of a 34-year-old man who developed cardiac arrest due to tension hydrothorax from colonic perforation. Tension hydrothorax, an entity characterized by pleural effusion leading to mediastinal compression, has not been reported in association with intraabdominal inflammation. Our patient developed respiratory insufficiency after repair of colonic perforation, followed by respiratory failure and cardiac arrest. Transthoracic echocardiography provided rapid diagnosis during decompensation and prompted a lifesaving thoracostomy. Clinicians should consider tension hydrothorax as a rare cause of hemodynamic collapse, even in the absence of liver failure, and use bedside tools like transthoracic echocardiography to facilitate diagnosis and intervention.


Betulinic acid inhibits the proliferation of human laryngeal carcinoma cells through reactive oxygen species-mediate mitochondrial apoptotic pathway.
Betulinic acid (BA), a natural pentacyclic triterpene, was extracted from the white birch tree, Triphyophyllum peltatum and the jujube tree. In a variety of human cancer cell lines, this substance displays anticancer properties. In this study, we examined how BA works to inhibit human laryngeal cancer growth. We discovered that BA minimally exhibited cytotoxicity in normal cells (human normal cell line GES-1), while remarkably inhibiting viability of AMC-HN-8, TU212, HEp-2 and M4e cells in a concentration-dependent manner. In AMC-HN-8 cancer cells, BA induced apoptosis, activated caspase-3/9/PARP, significantly reduced mitochondrial membrane potential (MMP), increased the expression of cytochrome C in the cytoplasm, transported Bax to the mitochondria, increased the production of reactive oxygen species (ROS), and the ROS scavenger N-acetylcysteine can reduce apoptosis. All data showed that BA triggered apoptosis via the mitochondrial pathway, in which ROS production was likely involved. The findings support the development of BA as a viable drug for the treatment of human laryngeal carcinoma.


A genetic locus essential for formate-dependent growth of Bradyrhizobium japonicum.
A genetic locus essential for the formate-dependent growth of Bradyrhizobium japonicum was isolated by complementation of ethyl methanesulfonate-induced mutants with a cosmid gene library of B. japonicum DNA. Three related cosmids containing 18.7 kilobase pairs of B. japonicum DNA in common were identified as being able to restore formate-dependent growth capability to mutants lacking either ribulosebisphosphate carboxylase or both ribulosebisphosphate carboxylase and phosphoribulokinase activities. To further localize the complementing gene(s), a series of four deletions spanning a total of 16.1 kilobase pairs were introduced into the B. japonicum chromosome. Each resulting deletion mutant lacked formate dehydrogenase activity and lacked ribulosebisphosphate carboxylase activity and immunologically detectable protein. Three of the four also lacked phosphoribulokinase activity. Two other mutants in which the deletion-bearing recombinant plasmid had integrated into the chromosome also lacked ribulosebisphosphate carboxylase activity and protein and phosphoribulokinase activities. The genetic locus defined by these mutants could contain the structural genes for these enzymes or a regulatory gene(s) controlling their expression or both.


[Episodes with goose bumps caused by anti-LGI-1 encephalitis].
Anti-LGI-1 encephalitis is a type of autoimmune encephalopathy, where antibodies react against the cell surface protein leucine-rich glioma inactivated protein 1 (LGI-1). It presents with a subacute confusion, changes in behaviour, short-term memory deficits and seizures. A piloerectile semiology is common, which has been described as reflecting insular ictal activity. Patients may have temporal lobe abnormalities on brain MRI and EEG. More than half of the patients with limbic encephalitis associated with anti-LGI1 antibodies have hyponatremia. The diagnosis of anti-LGI-1 encephalitis can be made by the detection of antibodies against LGI-1 in serum and/or cerebrospinal fluid. Prompt diagnosis and treatment are important to avoid long-term disability. This case report describes a man with episodes of goose bumps and mild confusion caused by anti-LGI-1 encephalitis.


American Society of Clinical Oncology Strategic Plan for Increasing Racial and Ethnic Diversity in the Oncology Workforce.
In December 2016, the American Society of Clinical Oncology (ASCO) Board of Directors approved the ASCO Strategic Plan to Increase Racial and Ethnic Diversity in the Oncology Workforce. Developed through a multistakeholder effort led by the ASCO Health Disparities Committee, the purpose of the plan is to guide the formal efforts of ASCO in this area over the next three years (2017 to 2020). There are three primary goals: (1) to establish a longitudinal pathway for increasing workforce diversity, (2) to enhance ASCO leadership diversity, and (3) to integrate a focus on diversity across ASCO programs and policies. Improving quality cancer care in the United States requires the recruitment of oncology professionals from diverse backgrounds. The ASCO Strategic Plan to Increase Racial and Ethnic Diversity in the Oncology Workforce is designed to enhance existing programs and create new opportunities that will move us closer to the vision of achieving an oncology workforce that reflects the demographics of the US population it serves.


Denosumab-related osteonecrosis of the jaw: A retrospective study.
Osteonecrosis of the jaw is a very delicate side effect of Denosumab. The aim of this retrospective study was to assess the occurrence rate of Denosumab-related osteonecrosis of the jaw (DRONJ) at the Cancer Institute of Lorraine (ICL) and to highlight necrosis risk factors. To that purpose, we analyzed the medical records of 249 consecutive patients treated with Denosumab at the ICL during the past 5 years. Patients who received orofacial radiotherapy or a previous treatment with a bisphosphonate were excluded. The P-value was set at .005. A total of 141 patients treated at the ICL between January 2010 and December 2015 were included. All patients were treated with XGEVA® . Of the 141 patients included in the study, 10 developed DRONJ. The incidence of DRONJ increases with the duration of follow-up as follows: 3% at 1 year, 7% at 2 years, and 8% from 30 months on. No risk factor for necrosis could be identified except the realization of prior dental extraction (P = .025). Our results raise important questions about the dental management of these patients, in particular, concerning the healing period between dental extractions and the initiation of Denosumab.


Superoxide generation from nNOS splice variants and its potential involvement in redox signal regulation.
We previously demonstrated different spacial expression profiles of the neuronal nitric oxide (NO) synthase (nNOS) splice variants nNOS-µ and nNOS-α in the brain; however, their exact functions are not fully understood. Here, we used electron paramagnetic resonance to compare the electron-uncoupling reactions of recombinant nNOS-µ and nNOS-α that generate reactive oxygen species (ROS), in this case superoxide. nNOS-µ generated 44% of the amount of superoxide that nNOS-α generated. We also evaluated the ROS production in HEK293 cells stably expressing nNOS-α and nNOS-µ by investigating these electron-uncoupling reactions as induced by calcium ionophore A23187. A23187 treatment induced greater ROS production in HEK293 cells expressing nNOS-α than those expressing nNOS-µ. Also, immunocytochemical analysis revealed that A23187-treated cells expressing nNOS-α produced more 8-nitroguanosine 3',5'-cyclic monophosphate, a second messenger in NO/ROS redox signaling, than did the cells expressing nNOS-µ. Molecular evolutionary analysis revealed that the ratio of nonsynonymous sites to synonymous sites for the nNOS-µ-specific region was higher than that for the complete gene, indicating that this region has fewer functional constraints than does the complete gene. These observations shed light on the physiological relevance of the nNOS-µ variant and may improve understanding of nNOS-dependent NO/ROS redox signaling and its pathophysiological consequences in neuronal systems.


Identification of long noncoding RNA RP11-89K21.1 and RP11-357H14.17 as prognostic signature of endometrial carcinoma via integrated bioinformatics analysis.
Endometrial carcinoma (EC) is one of the most common malignant tumors in gynecology. The potential functions and mechanisms of long noncoding RNAs (lncRNAs) in the occurrence and progression of EC remains unclear. It's meaningful to explore lncRNAs signature for providing prognostic value of EC. The differentially expressed lncRNAs and their prognostic values in EC were investigated based on The Cancer Genome Atlas (TCGA) database; the transcriptional factors (TFs), the competing endogenous RNA (ceRNA) mechanism, functional regulatory network and immune infiltration of RP11-89K21.1 and RP11-357H14.17 were further explored by various bioinformatics tools and databases. We firstly identified high expression of RP11-89K21.1 and RP11-357H14.17 were closely associated with shorten overall survival (OS) and poor prognosis in patients with EC. We also elucidated the networks of transcription factor and co-expression genes associated with RP11-89K21.1 and RP11-357H14.17. Furthermore, the ceRNA network mechanism was successfully constructed through 2 lncRNAs (RP11-89K21.1 and RP11-357H14.17), 11 miRNAs and 183 mRNAs. Functional enrichment analysis revealed that the targeting genes of RP11-89K21.1 and RP11-357H14.17 were strongly associated with microRNAs in cancer, vessel development, growth regulation, growth factor and cell differentiation, and involved in pathways including pathways in cancer, microRNAs in cancer and apoptotic signaling pathway. We demonstrated for the first time that RP11-89K21.1 and RP11-357H14.17 may play crucial roles in the occurrence, development and malignant biological behavior of EC, and can be regarded as potential prognostic biomarkers for EC.


Texture analysis and classification with tree-structured wavelet transform.
A multiresolution approach based on a modified wavelet transform called the tree-structured wavelet transform or wavelet packets is proposed. The development of this transform is motivated by the observation that a large class of natural textures can be modeled as quasi-periodic signals whose dominant frequencies are located in the middle frequency channels. With the transform, it is possible to zoom into any desired frequency channels for further decomposition. In contrast, the conventional pyramid-structured wavelet transform performs further decomposition in low-frequency channels. A progressive texture classification algorithm which is not only computationally attractive but also has excellent performance is developed. The performance of the present method is compared with that of several other methods.


Wait-and-see policy in clinical stage I non-seminomatous germ cell tumors of the testis.
Thirty-three patients with a non-seminomatous germ cell tumor of the testis in clinical stage I were treated only by orchidectomy. The very careful follow-up--with tumor marker assays every 3 weeks, chest X-rays every 6 weeks and CT-scans of the lungs and retroperitoneum every 3 months--revealed metastases in 7 of the patients (21%). All these relapses were diagnosed within 6 months of the orchidectomy. Para-aortic node metastases were found in 5 of the 7 patients, with additional inguinal node metastases in 1 and additional lung metastases in 1; 2 patients had only lung metastases. Six of the 7 patients with a relapse were given chemotherapy (PVB); 1 patient refused chemotherapy. In view of residual disease a surgical excision was performed; it revealed necrosis as well as mature teratoma. All 33 patients are still alive, the post-orchidectomy follow-up period being 12-38 months.


Constituents from Apium graveolens and their anti-inflammatory effects.
A phthalide glycoside, (3R, 4R)-4-O-β-D-glucopyranosyl-senkyunolide (1), and a megastigmane glycoside, (6S, 7R)-3-oxo-megastigma-4, 8-dien-7-O-β-D-glucoside (2), along with two known aglycones (3-4), were isolated from the 70% EtOH extract of fresh whole grass of Apium graveolens L. Their structures were elucidated by extensive spectroscopic analysis. All of these compounds were tested for their inhibitory effects on nitric oxide (NO) production in the RAW 264.7 macrophages. Among them, compounds 3 and 4 showed potent inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages, with IC50 values of 24.0 ± 2.1 μM and 28.6 ± 2.4 μM, respectively.


The Association Between Occlusal Status and the Soft and Hard Tissue Conditions Around Single-Unit Dental Implants.
The occlusal status of single-unit dental implants were evaluated using traditional and computerized methods. The type of occlusal contact in maximum intercuspation and the presence of occlusal contacts on the implant during eccentric movements were recorded. A digital sensor was used for computerized analysis of occlusion. Forty-four patients with 74 implants were included. Twenty-nine implants (39%) presented with "heavy" occlusal contacts, 40 implants (54.1%) presented with "light" contacts, and 5 implants (6.8%) presented with "no contact." No statistically significant association was found between the occlusal status and any of the soft and hard tissue condition variables (P > .05).


[Mathematical algorithm for evaluation of the human cardio-respiratory homeostatic function].
Mathematical algorithm of the cardiorespiratory homeostasis was determined by oxygen demand (VO2) and carbon dioxide production (VCO2) during maximal physical loading on the bicycle ergometer; calculated and measured parameters of the physical capacity were compared in experiments with long-term (110- to 240-d) isolation of human subjects. Aerobic capacity was evaluated during incremental physical testing in the sitting position on bicycle Elema-Siemens 380-B. The following parameters were measured: peak (maximal loading) heart rate (HRpeak) and VO2, work time, and VO2 at 15 points on the Borg load scale, total aerobic test time and some others. Analysis of the homeostatic function of the cardiorespiratory system with the integral H = (h(u)du failed to state statistically reliable differences (p > 0.05) before and after isolation in group-1; however, it evidenced an increased homeostatic ability (p < 0.05) in group-2 and a decreased homeostatic ability in group-3 after isolation. Hence, the proposed mathematical algorithm showed a good agreement with the aerobic capacity parameters measured using classic methods. There was a high correlation (p < 0.05) between the homeostatic function and aerobic capacity in the groups of subjects and, therefore, determination of the cardiorespiratory homeostatic function can be considered an additional evaluative criterion.


Cyclic deformation fatigue behaviour of Ti6Al4V thermochemically nitrided for articular prostheses.
Titanium and its alloys have many attractive properties including high specific strength, low density, and excellent corrosion resistance. Titanium and the Ti6Al4V alloy have long been recognized as materials with high biocompatibility. These properties have led to the use of these materials in biomedical applications. Despite these advantages, the lack of good wear resistance makes the use of titanium and Ti6Al4V difficult in some biomedical applications, for example, articulating components of prostheses. To overcome this limitation, nitriding has been investigated as a surface-hardening method for titanium. Although nitriding greatly improves the wear resistance, this method reduces the fatigue strength. Low cycle fatigue performance in air of nitrided Ti6Al4V at different deformation amplitudes has been studied. Results show a reduction of low cycle fatigue life of up to 10% compared to the non-treated material. Studies suggest it is not related to the titanium nitride surface layer, but to microstructural changes caused by the high temperature treatment. (Journal of Applied Biomaterial & Biomechanics 2003; 1: 43-7).


Automatic Segmentation of Epidermis and Hair Follicles in Optical Coherence Tomography Images of Normal Skin by Convolutional Neural Networks.
Optical coherence tomography (OCT) is a well-established bedside imaging modality that allows analysis of skin structures in a non-invasive way. Automated OCT analysis of skin layers is of great relevance to study dermatological diseases. In this paper, an approach to detect the epidermal layer along with the follicular structures in healthy human OCT images is presented. To the best of the authors' knowledge, the approach presented in this paper is the only epidermis detection algorithm that segments the pilosebaceous unit, which is of importance in the progression of several skin disorders such as folliculitis, acne, lupus erythematosus, and basal cell carcinoma. The proposed approach is composed of two main stages. The first stage is a Convolutional Neural Network based on U-Net architecture. The second stage is a robust post-processing composed by a Savitzky-Golay filter and Fourier Domain Filtering to fully define the borders belonging to the hair follicles. After validation, an average Dice of 0.83 ± 0.06 and a thickness error of 10.25 μm is obtained on 270 human skin OCT images. Based on these results, the proposed method outperforms other state-of-the-art methods for epidermis segmentation. It demonstrates that the proposed image segmentation method successfully detects the epidermal region in a fully automatic way in addition to defining the follicular skin structures as main novelty.


Effect of subleathal concentrtion of imidacloprid on the histology of heart, liver and kidney in Labeo rohitr.
Randomly selected 500 fingerlings of Labeo rohita were collected from fish seed hatchery Muzaffar Garh. Six groups of 40 fish each were exposed to subleathal concentration of Imidacloprid (120 mg L-1) under short-term (2, 4 and 8 days) and long term (16, 32 and 64 days) conditions to assess the effect of this most extensively used insecticide on the heart, liver and kidney of economically most important fresh water fish, L. rohita, in Pakistan. Separate control groups were used for each Imidacloprid treatment. No drastic histopathological changes were observed in heart structure following short and long term treatment with Imidacloprid. Exposure of liver to Imidacloprid resulted in severe degenerative changes, which were directly related to exposure time. Wrinkling of hepatocyte cell membrane, hepatocyte necrosis and degeneration, dislocation of nucleus, dilation of blood sinusoid and pycnosis of hepatic nuclei were the visible changes in liver histology in various experimental treatments. Comparison of treated and untreated kidney of L. rohita revealed wide Bowman's space, renal tubular lumen enlargement, necrosis and inflammation of cells. Our results are the pioneer report indicating that imidacloprid can act as strong toxic agent for L. rohita.


[Radioimmunological analysis in assessing the function of the hypothalamo-neurohypophyseal system in patients with hypothalamic syndromes].
Assessment of vasopressin by radioimmunoassay has shown an increase in its blood concentration and a disturbed reaction of the vasopressinergic structures of the hypothalamus to metoclopramide, furosemide, insulin hypoglycemia, and exercise. Functional tests with the dopaminergic drug bromocriptine and antiserotoninergic drug cyproheptadine help to make an individual choice of the most effective drug for therapy of the hypothalamic syndrome of neuroendocrine-metabolic type. The patients can be divided into sensitive to either the first or the second drug of both which is important for adequate pathogenetic therapy.


Basal cell carcinoma and melanocytic nevus in the same lesion.
We report a case of basal cell carcinoma and intradermal melanocytic nevus in the same lesion. A review of the literature indicates that the simultaneous occurrence of two or more neoplasms in one specimen is a relatively infrequent finding. The pathogenesis of simultaneously occurring neoplasms remains the subject of speculation. Based on currently available evidence, we believe that the coexistence of lesions in this particular patient is most likely coincidental.


Early interaction in autism spectrum disorder: Mothers' and children's behaviours during joint engagement.
More knowledge about the interaction between young children with autism spectrum disorder and their parents is one way to improve intervention. This study aims to investigate the behaviours of mothers and children with autism spectrum disorder during joint engagement, with a focus on pacing or rate (i.e., incidences per minute) of their behaviours when being in this state. Video recordings of 10 min of free-play between 58 children (2-4 years) diagnosed with childhood autism and their mothers were used to examine rate of mothers' and children's behaviours (i.e., toy introduction, toy expansion, positive affect, and language) during joint engagement, the association between rate of mothers and children's behaviours, the relation between rate of mothers' behaviours and time in joint engagement, and how child factors might be associated with the latter. Mothers(m) and children(c) showed similar rate of positive affect (Mm = 0.6/Mc = 0.5) and toy expansion (Mm = 0.7/Mc = 0.7) per minute, whereas mothers talked almost three times more than their children (Mm = 10.2/Mc = 3.8). In contrast, mothers introduced fewer toys compared to the children (Mm = 0.7/Mc = 1.2). Rate of mothers' toy introduction, toy expansion, and positive affect was inversely related to time in joint engagement (Regression coefficient = -70.7 to -48.5, p = .006 to .024). Rates of mothers' and children's behaviours were associated (Spearman rank order coefficient = .53 to .29, p < .001 to .03), but neither rate of children's behaviours nor mental age was associated with the observed relation between rate of these maternal behaviours and time in joint engagement. Time in joint engagement was related to rate of mothers' behaviours and children's mental age but not to rate of children's behaviours in this study. Thus, intervention teaching parents of young children with autism strategies designed to increase time in joint engagement may be vital. The complex nature of the interaction between mother and child behaviours in promoting joint engagement warrants further elucidation.


Variations of Candida albicans electrophoretic karyotypes.
We previously described 14 rare spontaneous morphological mutants of Candida albicans that were associated with chromosomal aberrations (E. P. Rustchenko-Bulgac, F. Sherman, and J. B. Hicks, J. Bacteriol. 172:1276-1283, 1990). Improved conditions for separation of chromosomes, as well as hybridization probes, were used to investigate the variation of karyotypes of clinical isolates and additional morphological mutants. All 23 newly analyzed morphological mutants, representing frequently occurring and highly unstable colonial forms, had a variety of altered karyotypes. All chromosomal changes were similar to those previously observed in mutants m1 to m14. In this study, I particularly noted that the most frequent changes involved the long chromosome VIII, which carries ribosomal DNA cistrons. Two rates of instability were uncovered by analyzing the progenies from two highly unstable mutants. An unstable mutant proved to be able to continuously produce a large number of altered karyotypes that could result in a wide variety of different phenotypes. Furthermore, all four independent clinical isolates, FC18, C9, 3153A, and WO-1, common laboratory strains, revealed different electrophoretic karyotypes and distinct colonial morphologies on a synthetic medium, similar to spontaneous mutants. The differences of electrophoretic karyotypes observed among clinical isolates resembled the changes found among different kinds of spontaneous morphological mutants. These findings contribute to the understanding of natural karyotypic variability and are in agreement with the hypothesis that chromosomal alterations observed spontaneously under laboratory conditions provide this amictic species with genetic variability in nature.


Coalescence times, life history traits and conservation concerns: An example from four coastal shark species from the Indo-Pacific.
Dispersal abilities play a crucial role in shaping the extent of population genetic structure, with more mobile species being panmictic over large geographical ranges and less mobile ones organized in metapopulations exchanging migrants to different degrees. In turn, population structure directly influences the coalescence pattern of the sampled lineages, but the consequences on the estimated variation of the effective population size (Ne ) over time obtained by means of unstructured demographic models remain poorly understood. However, this knowledge is crucial for biologically interpreting the observed Ne trajectory and further devising conservation strategies in endangered species. Here we investigated the demographic history of four shark species (Carharhinus melanopterus, Carharhinus limbatus, Carharhinus amblyrhynchos, Galeocerdo cuvier) with different degrees of endangered status and life history traits related to dispersal distributed in the Indo-Pacific and sampled off New Caledonia. We compared several evolutionary scenarios representing both structured (metapopulation) and unstructured models and then inferred the Ne variation through time. By performing extensive coalescent simulations, we provided a general framework relating the underlying population structure and the observed Ne dynamics. On this basis, we concluded that the recent decline observed in three out of the four considered species when assuming unstructured demographic models can be explained by the presence of population structure. Furthermore, we also demonstrated the limits of the inferences based on the sole site frequency spectrum and warn that statistics based on linkage disequilibrium will be needed to exclude recent demographic events affecting meta-populations.


Marijuana use does not affect weight loss or complication rate after bariatric surgery.
Marijuana use has been legalized in several states. It is unclear if marijuana use affects weight loss outcomes or complication rates following bariatric surgery. The purpose of this study was to determine if patients who use marijuana had higher complication rates or lower weight loss compared with non-users. All patients at a single institution who underwent primary bariatric surgery between July 2015 and July 2020 at a single institution after the legalization of marijuana within the jurisdiction were included. Data regarding marijuana use, weight and complications were abstracted retrospectively. Differences between groups were evaluated with Wilcoxon Rank-Sum tests and Fisher Freeman Halton test. Trends for marijuana use over time was evaluated with simple linear regression on summary data. 1107 patients met inclusion criteria. 798 (73.3%) were never users, 225 (19.4%) were previous users, and 84 (7.2%) were active users. The proportion of active users and previous users increased over time, with significantly more prior marijuana use reported in more recent years (p = 0.014). Active users had significantly higher pre-procedural BMIs than never users: 48.7 vs. 46.3 (p = 0.03). Any marijuana use (active and previous users) was associated with higher preoperative weight compared to never: 136.4 kg vs. 130.6 kg (p = 0.001). Overall complication rate was low in all groups, and there was no difference in the rates of any complications. Active and previous users tended to lose less weight than never users, but this was not statistically significant (p = 0.17). Active and prior marijuana users tend to have higher BMIs on presentation, but use was not associated with complications or percent weight loss. The incidence of patient reported marijuana use is increasing in the study population. More studies on the effects of marijuana use in this patient population are warranted.


Parameters associated with short- and midterm survival in bridging to lung transplantation with extracorporeal membrane oxygenation.
Patients with terminal lung failure may be bridged to lung transplantation (LTX) by extracorporeal membrane oxygenation (ECMO). With the present shortage of donor organs and the high level of invasiveness of ECMO treatment, appropriate selection criteria for bridge to transplant need to be defined. We report retrospective data from 26 patients on ECMO listed for LTX. Seven patients were successfully transplanted (LTX-s). Six patients survived until transplantation, but died intra- or post-operatively (LTX-ns). Thirteen patients died before transplantation (Fail). There was no difference between LTX-s and the 19 overall non-survivors (NS) prior to ECMO initiation with regard to demographic data or ventilator parameters except for higher PaO2 /FiO2 in the LTX-s. Time on ECMO pre-LTX did not differ in the LTX-s and LTX-ns groups. SOFA score was lower in LTX-s when compared to LTX-ns before ECMO (p = 0.0155), during bridging (p = 0.028), and right before transplantation (p = 0.0038). Maximal bilirubin during bridging and bilirubin prior to transplantation was markedly elevated in the LTX-ns group [4.2 (2.4-4.7) vs. 1.1 (0.8-2.0) mg/dL; p = 0.0266 and 1.6 (1.2-3.0) vs. 0.5 (0.5-0.5) mg/dL; p = 0.0047). Bridging to LTX is a challenging but viable option for selected patients. Special consideration should be given to hepatic function.


Liver Injury Increases the Incidence of HCC following AAV Gene Therapy in Mice.
Adeno-associated virus (AAV) integrates into host genomes at low frequency, but when integration occurs in oncogenic hotspots it can cause hepatocellular carcinoma (HCC). Given the possibility of recombinant AAV (rAAV) integration leading to HCC, common causes of liver inflammation like non-alcoholic fatty liver disease (NAFLD) may increase the risk of rAAV-induced HCC. A rAAV targeting the oncogenic mouse Rian locus was used, and as expected led to HCC in all mice infected as neonates, likely due to growth-related hepatocyte proliferation in young mice. Mice infected with rAAV as adults did not develop HCC unless they were fed a diet leading to NAFLD, with increased inflammation and hepatocyte proliferation. Female mice were less susceptible to rAAV-induced HCC, and male mice with NAFLD treated with estrogen exhibited less inflammation and immune exhaustion associated with oncogenesis compared to those without estrogen. Adult NAFLD mice infected with a non-targeted control rAAV also developed HCC, though only half as frequently as those exposed to the Rian targeted rAAV. This study shows that adult mice exposed to rAAV gene therapy in the context of chronic liver disease developed HCC at high frequency, and thus warrants further study in humans given the high prevalence of NAFLD in the population.


Intimate partner sexual and physical violence among women in Togo, West Africa: prevalence, associated factors, and the specific role of HIV infection.
A substantial proportion of newly diagnosed HIV infections in sub-Saharan Africa occur within serodiscordant cohabiting heterosexual couples. Intimate partner violence is a major concern for couple-oriented HIV preventive approaches. This study aimed at estimating the prevalence and associated factors of intimate partner physical and sexual violence among HIV-infected and -uninfected women in Togo. We also described the severity and consequences of this violence as well as care-seeking behaviors of women exposed to intimate partner violence. A cross-sectional survey was conducted between May and July 2011 within Sylvanus Olympio University Hospital in Lomé. HIV-infected women attending HIV care and uninfected women attending postnatal care and/or children immunization visits were interviewed. Intimate partner physical and sexual violence and controlling behaviors were assessed using an adapted version of the WHO Multi-country study on Women's Health and Life Events questionnaire. Overall, 150 HIV-uninfected and 304 HIV-infected women accepted to be interviewed. The prevalence rates of lifetime physical and sexual violence among HIV-infected women were significantly higher than among uninfected women (63.1 vs. 39.3%, p<0.01 and 69.7 vs. 35.3%, p<0.01, respectively). Forty-two percent of the women reported having ever had physical injuries as a consequence of intimate partner violence. Among injured women, only one-third had ever disclosed real causes of injuries to medical staff and none of them had been referred to local organizations to receive appropriate psychological support. Regardless of HIV status and after adjustment on potential confounders, the risk of intimate partner physical and sexual violence was strongly and significantly associated with male partner multi-partnership and early start of sexual life. Among uninfected women, physical violence was significantly associated with gender submissive attitudes. The prevalence rates of both lifetime physical and sexual violence were very high among HIV-uninfected women and even higher among HIV-infected women recruited in health facilities in this West African country. Screening for intimate partner violence should be systematic in health-care settings, and specifically within HIV care services. At a time of increased investments in couple-oriented HIV prevention interventions, further longitudinal research to better understanding of HIV-serodiscordant couple dynamics in terms of intimate partner violence is needed.