Langerhans cells proliferation in ectopic micronodular thymoma with lymphoid stroma: a case report.
Ectopic micronodular thymoma (MNT) is a rare tumor. We described a 76-year-old woman, who was referred to our institutional for a mass in the left cervical region. The Magnetic Resonance Imaging (MRI) scan showed a 3.7 cm × 1.7 cm × 2.0 cm mass. The neoplasm was composed of epithelial tumor cells arranged in a micronodular growth pattern set in a stroma showing lymphoid hyperplasia with germinal centers. Immunohistochemical studies showed that the neoplastic epithelial cells were reactive for AE1/AE3, CK5/6, P63, and the lymphoid component to be of mixed B- and immature T-cell lineage. Langerhans cells were confirmed within epithelial nodules for the first time with langerin, S-100, CD1a expression. We report a case of cervical ectopic MNT to emphasize the langerhans cells proliferation and the histopathologic features and differential diagnosis of the rare lesion to promote a better and broader understanding of this less understood subject.


How can we identify patients with delirium in the emergency department?: A review of available screening and diagnostic tools.
Delirium is a widespread and serious but under-recognized problem. Increasing evidence argues that emergency health care providers need to assess the mental status of the patient as the "sixth vital sign". A simple, sensitive, time-efficient, and cost-effective tool is needed to identify delirium in patients in the emergency department (ED); however, a stand-alone measurement has not yet been established despite previous studies partly because the differential diagnosis of dementia and delirium superimposed on dementia (DSD) is too difficult to achieve using a single indicator. To fill up the gap, multiple aspects of a case should be assessed including inattention and arousal. For instance, we proposed the 100 countdown test as an effective means of detecting inattention. Further dedicated studies are warranted to shed light on the pathophysiology and better management of dementia, delirium and/or "altered mental status". We reviewed herein the clinical questions and controversies concerning delirium in an ED setting.


Atg19 mediates a dual interaction cargo sorting mechanism in selective autophagy.
Autophagy is a catabolic membrane-trafficking mechanism conserved in all eukaryotic cells. In addition to the nonselective transport of bulk cytosol, autophagy is responsible for efficient delivery of the vacuolar enzyme Ape1 precursor (prApe1) in the budding yeast Saccharomyces cerevisiae, suggesting the presence of a prApe1 sorting machinery. Sequential interactions between Atg19-Atg11 and Atg19-Atg8 pairs are thought responsible for targeting prApe1 to the vesicle formation site, the preautophagosomal structure (PAS), and loading it into transport vesicles, respectively. However, the different patterns of prApe1 transport defect seen in the atg11Delta and atg19Delta strains seem to be incompatible with this model. Here we report that prApe1 could not be targeted to the PAS and failed to be delivered into the vacuole in atg8Delta atg11Delta double knockout cells regardless of the nutrient conditions. We postulate that Atg19 mediates a dual interaction prApe1-sorting mechanism through independent, instead of sequential, interactions with Atg11 and Atg8. In addition, to efficiently deliver prApe1 to the vacuole, a proper interaction between Atg11 and Atg9 is indispensable. We speculate that Atg11 may elicit a cargo-loading signal and induce Atg9 shuttling to a specific PAS site, where Atg9 relays the signal and recruits other Atg proteins to induce vesicle formation.


Profile of Tabriz Older People Health Survey (TOPS-2019): a representative community-based cross-sectional study.
Population aging and its consequences are a substantial global concern. The growth in the number of older people is one of the most important factors increasing the burden of non-communicable diseases (NCDs) on society. The Tabriz Older People Health Survey aimed to understand the socio-demographics, health-related behaviors, and health profile of older adults. This cross-sectional study was conducted on a representative sample of 1362 community-dwelling older adults in Tabriz, the most populated city in northwest Iran. The study used probability proportionate to size sampling and the data collection was undertaken in each participants' place of residence from July 2019 to January 2020. Trained interviewers administered the questionnaire, which measured each participant's socio-demographics, health-related behaviors, and health profile. The sample of 1362 participants consisted of 56.4% women and 54.4% were young older people (60-69 years old). Almost half of the sample were completely illiterate. There was no daily walking in 13.3% of the sample, with women reporting a more sedentary lifestyle than men. Almost 10% of the participants (n = 135, 9.9%) were current smokers, which was higher among men (20.9% vs. 1.5%) and women made up over 88% of those living alone. In terms of sleep quality score (men: 4.63 ± 2.70, women: 5.97 ± 2.93), anxiety (men: 5.79 ± 4.70, women: 7.59 ± 5.51), depression (men: 9.54 ± 3.20, women: 10.63 ± 3.09), and social support (men: 23.65 ± 4.50, women: 22.69 ± 4.77), men were significantly better than women. There were also significant sex differences between women and men in the prevalence of diabetes (31.6% vs. 19.5%) and hypertension (86.5% vs. 73.4%). Furthermore, overall hypertension was the most common underlying disease (81.0%). Older women were significantly worse off than older men, in terms of social and disability-related, as well as having a higher burden from several NCDs. The results of this study might help regional health policymakers to identify targets for improving the health status among community-housed geriatrics.


Transcriptomic Analysis of Aedes aegypti Innate Immune System in Response to Ingestion of Chikungunya Virus.
Aedes aegypti (L.) is the primary vector of emergent mosquito-borne viruses, including chikungunya, dengue, yellow fever, and Zika viruses. To understand how these viruses interact with their mosquito vectors, an analysis of the innate immune system response was conducted. The innate immune system is a conserved evolutionary defense strategy and is the dominant immune system response found in invertebrates and vertebrates, as well as plants. RNA-sequencing analysis was performed to compare target transcriptomes of two Florida Ae. aegypti strains in response to chikungunya virus infection. We analyzed a strain collected from a field population in Key West, Florida, and a laboratory strain originating from Orlando. A total of 1835 transcripts were significantly expressed at different levels between the two Florida strains of Ae. aegypti. Gene Ontology analysis placed these genes into 12 categories of biological processes, including 856 transcripts (up/down regulated) with more than 1.8-fold (p-adj (p-adjust value) ≤ 0.01). Transcriptomic analysis and q-PCR data indicated that the members of the AaeCECH genes are important for chikungunya infection response in Ae. aegypti. These immune-related enzymes that the chikungunya virus infection induces may inform molecular-based strategies for interruption of arbovirus transmission by mosquitoes.


Altered expression of caveolin-1 in the colon of patients with Hirschsprung's disease.
The pathogenesis of Hirschsprung's disease-associated enterocolitis (HAEC) is unclear. Caveolin-1 (Cav-1) regulates the functions of different nitric oxide synthase (NOS) isoforms, which play critical roles in inflammation and intestinal epithelial barrier function. We designed this study to investigate the hypothesis that Cav-1 expression is altered in the bowel of patients with Hirschsprung's disease (HSCR). HSCR tissue specimens (n = 10) were collected at the time of pull-through surgery and control samples were obtained at the time of colostomy closure in patients with imperforate anus (n = 10). qRT-PCR analysis was undertaken to quantify Cav-1 gene expression, and Western blot analysis was undertaken to determine Cav-1 protein quantification. Immunolabelling of Cav-1 proteins was visualized using confocal microscopy. qRT-PCR and Western blot analysis revealed that Cav-1 was significantly downregulated in the aganglionic and ganglionic colon of patients with HSCR compared to controls (p < 0.01). Confocal microscopy revealed a markedly decreased expression of Cav-1 in colonic epithelium of aganglionic and ganglionic bowel of patients with HSCR compared to controls. To our knowledge, this is the first report of significantly decreased Cav-1 expression in patients with HSCR. Decreased expression of Cav-1 in the bowel of HSCR may increase susceptibility to HAEC in HSCR.


Cultural Influences on Toddlers' Prosocial Behavior: How Maternal Task Assignment Relates to Helping Others.
This cross-cultural study investigates how maternal task assignment relates to toddlers' requested behavior and helping between 18 and 30 months. One hundred seven mother-child dyads were assessed in three different cultural contexts (rural Brazil, urban Germany, and urban Brazil). Brazilian mothers showed assertive scaffolding (serious and insistent requesting), whereas German mothers employed deliberate scaffolding (asking, pleading, and giving explanations). Assertive scaffolding related to toddlers' requested behavior in all samples. Importantly, assertive scaffolding was associated with toddlers' helping in rural Brazil, whereas mothers' deliberate scaffolding related to toddlers' helping behavior in urban Germany. These findings highlight the role of caregivers' socialization practices for the early ontogeny of helping behavior and suggest culture-specific developmental pathways along the lines of interpersonal responsibility and personal choice.


Comparison of short-term functional outcomes following unilateral and bilateral lung volume reduction surgery.
To compare short-term functional outcomes following unilateral and bilateral lung volume reduction surgery (LVRS) performed in patients with advanced emphysema. LVRS was performed unilaterally in 32 patients and bilaterally in 119 patients. Pulmonary function testing and 6-min walk test (6MWT) were performed preoperatively and repeated at 3 to 6 months postoperatively. Bilateral LVRS was associated with increased in-hospital mortality (10% vs 0%, p<0.05) and a higher incidence of postoperative respiratory failure (12.6% vs 0%; p<0.05) compared with unilateral LVRS. There was no significant difference in duration of air leaks between unilateral and bilateral groups, but the mean hospital stay was significantly longer following bilateral LVRS (21.1+/-32.0 days vs 14.2+/-14.0 days; p<0.05). Preoperatively, there was no significant difference between the unilateral and bilateral groups with respect to FEV1, FVC, residual volume, or 6MWT distance. However, for all of these parameters, the magnitude of improvement was significantly greater following bilateral LVRS. Notably, the magnitude of improvement in each parameter following unilateral LVRS exceeded half that following bilateral LVRS, suggesting that functional outcomes after the unilateral procedure were disproportionate to the amount of tissue resected. Serial functional assessment of seven patients undergoing staged unilateral procedures (two unilateral procedures separated in time by at least 3 months) demonstrated somewhat unpredictable responses; failure to achieve a favorable response to the initial procedure did not necessarily portend a similar outcome with the contralateral side, and vise versa. Bilateral LVRS produces a greater magnitude of short-term functional improvement than does the unilateral procedure and should be considered the procedure of choice for most patients. Unilateral LVRS should be reserved for patients in whom factors contraindicating entrance into one hemithorax exist.


Modeling Human Bone Marrow Failure Syndromes Using Pluripotent Stem Cells and Genome Engineering.
The combination of epigenetic reprogramming with advanced genome editing technologies opened a new avenue to study disease mechanisms, particularly of disorders with depleted target tissue. Bone marrow failure syndromes (BMFS) typically present with a marked reduction of peripheral blood cells due to a destroyed or dysfunctional bone marrow compartment. Somatic and germline mutations have been etiologically linked to many cases of BMFS. However, without the ability to study primary patient material, the exact pathogenesis for many entities remained fragmentary. Capturing the pathological genotype in induced pluripotent stem cells (iPSCs) allows studying potential developmental defects leading to a particular phenotype. The lack of hematopoietic stem and progenitor cells in these patients can also be overcome by differentiating patient-derived iPSCs into hematopoietic lineages. With fast growing genome editing techniques, such as CRISPR/Cas9, correction of disease-causing mutations in iPSCs or introduction of mutations in cells from healthy individuals enable comparative studies that may identify other genetic or epigenetic events contributing to a specific disease phenotype. In this review, we present recent progresses in disease modeling of inherited and acquired BMFS using reprogramming and genome editing techniques. We also discuss the challenges and potential shortcomings of iPSC-based models for hematological diseases.


Letter to the Editor: "Rosai Dorfman: Rare Cause of Cervical Lymphadenopathy".
We read with great interest the article by Kobayashi KE et al. published in 2023 entitled: "Presentation of external ear Rosai-Dorfman disease with laryngeal involvement" and wish to reconnoiter Rosai-Dorfman Disease's (RDD) clinical entities and the possible implications from the perspective of otology.


Safety of carpal tunnel release with a short incision. A cadaver study.
The standard long incision technique for carpal tunnel release causes inevitable damage to skin sensation, the inter-thenar plexus and especially the distal branches of the palmar cutaneous branch of the median nerve (PCM), and may cause long-term disabling pain and scar tenderness. There are many variations in the distal branches of the median nerve at the wrist. Anatomic studies of this region also have important clinical implications to prevent injury to important anatomic structures. The purpose of this study was to evaluate the short-incision carpal tunnel release in cadavers. Several important anatomic structures, with possible anatomic variations, pass through the carpal tunnel, and blind percutaneous transection of the transverse ligament seems to be a high risk procedure. Sixty hands from 40 fresh cadavers were evaluated. Both the transverse ligament and the distal third of the deep forearm fascia were released using a Smillie knife. At the end of each procedure, the hand was explored for injury to tendinous and neurovascular structures of the wrist. In all cases the release of the carpal tunnel and the distal third of the forearm fascia was found to be complete. The superficial palmar arterial arch, flexor tendons, ulnar nerve and vessels, digital nerves, median nerve and its recurrent accessory branches, the flexor tendons, and even the subcutaneous tissue over the transverse ligament were damaged in no instance. Guyon's canal was entered in 6 (10%) hands without damage to its components. The distal branches from the ulnar side of the palmar cutaneous branch of the median nerve (PCM) were injured in 8 (13.6%) hands, an injury that is almost unavoidable with the classic open technique.


CircRAPGEF5 Promotes the Proliferation and Metastasis of Lung Adenocarcinoma through the miR-1236-3p/ZEB1 Axis and Serves as a Potential Biomarker.
Lung adenocarcinoma (LAD) is a common malignancy; however, its underlying molecular mechanism is unclear. Circular RNAs (circRNAs) serve as significant cancer regulators. The overexpression of circRAPGEF5 in LAD tissues and cells indicated that it may be involved in promoting LAD progression. Analysis of 61 LAD tissues revealed that circRAPGEF5 was related to lymph node metastasis. Functionally, circRAPGEF5 promoted the proliferation, migration, invasion, and epithelial-mesenchymal transition of LAD cells in vitro and promoted LAD cells growth in vivo. Mechanistically, dual-luciferase reporter assays confirmed direct interaction of circRAPGEF5, miR-1236-3p, and ZEB1. miR-1236-3p was upregulated and ZEB1 expression reduced after circRAPGEF5 knockdown, and the proliferation, migration, and invasion of LAD cells was inhibited. circRAPGEF5 was significantly overexpressed in LAD cell exosomes, and co-culture experiments showed that exosomal circRAPGEF5 enhanced the metastatic ability of LAD cells. Further experiments found that serum exosomal circRAPGEF5 was overexpressed in LAD; moreover, the area under the receiver operator characteristic curve of exosomal circRAPGEF5 was superior to that of serum carcinoembryonic antigen (CEA). Jointly detected serum exosomal circRAPGEF5 and serum CEA had better diagnostic performance than when detected individually. Thus, exosomal circRAPGEF5 could promote the proliferation and metastasis of LAD via the miR-1236-3p/ZEB1 axis and serum exosomal circRAPGEF5 may serve as a promising biomarker for LAD.


The placement and treatment of thoracolumbar spine fractures. An algorithmic approach.
Advances in imaging techniques and surgical instrumentation systems have made the selection of appropriate treatment for thoracolumbar fractures difficult. A review of the literature and personal cases have led to the development of a series of algorithms for patient care. Fracture patterns with recommended therapeutic approaches are presented and discussed.


Identifying the special needs of children with Type 1 diabetes in the school setting. An overview of parents' perceptions.
The aims of this observational study were to identify the special needs of children with Type 1 diabetes in schools from the parents' point of view and the difficulties experienced with full integration, and to define a series of interventions which may improve the situation. Parents of children aged 3-18 years with Type 1 diabetes were eligible. Those who agreed to participate completed a self-reporting questionnaire which determined the effects of the disease on children, parents and school personnel, and addressed aspects including children's integration, glycaemic control, insulin administration, meals, sports, trips and attitudes of teachers and school colleagues to their disease. A total of 499 questionnaires were completed and validated. Median age of children was 11.5 years (95% CI 7.8-15.2). Only 34% of parents believed that teachers could recognize the symptoms of a mild hypoglycaemic episode. Seventeen per cent of parents experienced problems at their schools when they informed staff about their children's disease, 5% were finally not accepted and 8% were forced to change school. In some cases, they had to modify glucose monitoring (9%) and treatment administration (16%) because of a lack of cooperation from the school. Training sessions on Type 1 diabetes, an increase in the number of nurses, better availability of resources from diabetic associations to schools and improved communication between school personnel and parents were identified as key factors that may improve the full integration of the diabetic child in this setting.


Staining procedures for the endocrine cells of the upper gastrointestinal mucosa: light-electron microscopic correlation for the gastrin-producing cell.
Although histochemical, immunohistochemical, and electron microscopic methods have led to the identification of a large variety of endocrine cells in the upper gastrointestinal mucosa, no conventional light microscopic technique capable of the simultaneous identification of these cells has been reported. Such a staining method would be of considerable value to the pathologist as the malfunction of the endocrine cells of the gut, which produce numerous digestive hormones and biogenic amines, is closely related to a number of clinical conditions afflicting man. In this work, after testing three different polychrome staining methods, it has been concluded that a slightly modified Herlant's tetrachrome in tissues fixed in Zenker-formol is the procedure of choice. This method allows the distinction of several different cell types in the upper gastrointestinal mucosa of man and dog and permits the easy identification of the gastrin-producing cells on a routine basis. This identification has been confirmed in the case of two patients with gastrin cell hyperplasia, seen by both light and electron microscopy. Herlant's tetrachrome has proven valuable in the screening of human as well as experimental gastrointestinal tissues and it has been found to be very suitable for recognizing gastrin-producing cell hyperplasias. The usefulness of this method is expected to increase with the establishment of further correlations between the light and electron microscopy of the endocrine cells of the gut.


[Computer tomography in diagnosis of mental disorders].
The article includes a review of literature discussing the results of CT (computed tomography) usage with psychiatric patients and a range of recommendations for using this diagnostic method in psychiatry. Recommended indications for ordering a CT scan for psychiatric patients have ranged from narrow guidelines (only patients with focal neurological findings) to a broad spectrum, including any of the following: confusion and/or dementia of unknown cause, a first episode of a psychosis of unknown etiology, a movement disorder of unknown etiology, a diagnosis of anorexia nervosa, prolonged catatonia, and a first episode of major affective disorder or personality change after 50.


Emissions of polychlorinated dibenzo-p-dioxins and dibenzofurans from various industrial sources.
This study characterized the emissions of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) from the stack flue gases of 17 industrial sources, which were classified into 10 categories. The results show that the mean PCDD/PCDF concentration of secondary zinc smelter (Zn-S) and secondary copper smelter (Cu-S) is 2.44 ng international toxic equivalent (I-TEQ)/Nm3 (N represents normal conditions at 0 degrees C, 760 mmHg), which was found to be significantly greater than that of industrial waste incinerators (mean concentration = 0.15 ng I-TEQ/Nm3). These results imply that the controlling of secondary metallurgical melting processes is more important than industrial waste incineration for the reduction of PCDD/PCDF emissions. The mean emission factors of cement production, Zn-S and Cu-S, are 0.052, 1.99, and 1.73 microg I-TEQ/t product, respectively. For industrial waste incineration, the mean emission factors of waste rubber, waste liquor, waste sludge, industrial waste solid (IWI)-1, IWI-2, IWI-3, and IWI-4 are 0.752, 0.435, 0.760, 6.64, 1.67, 2.38, and 0.094 microg I-TEQ/t feed, respectively. Most of the PCDD/PCDF emission factors established in this study are less than those reported in previous studies, which could be because of the more stringent regulations for PCDD/PCDF emissions in recent years.


Insulin sensitivity indices calculated from basal and OGTT-induced insulin, glucose, and FFA levels.
Insulin Sensitivity Indices for glycemia [ISI(gly)] and blood FFA [ISI(ffa)] can be calculated with the formulas: ISI(gly) = 2/[(INSp x GLYp) + 1], and ISI(ffa) = 2/[(INSp x FFAp) + 1], where INSp, GLYp and FFAp = insulinemic, glycemic, and FFA areas during OGTT (75 g glucose) of the person under study, simplified by considering only data at 0 and 2 h (0-2 h areas), according to WHO criteria or, better, at 0, 1 and 2 h (0-1-2 h areas). Expressed as unit/ volume.h-1, 0-1-2 h area is equal to 1/2 value at 0 min + value at 1 h + 1/2 value at 2 h, while 0-2 h area is equal to value at 0 + value at 2 h. Instead of areas, basal levels can also be used. Basal levels and areas are expressed taking the mean normal value as unit, so that in normal subjects ISI(gly) and ISI(ffa) are always around 1, with maximal variations between 0 and 2. Each laboratory should have its normal reference values for basal levels and OGTT areas. However, reliable mean normal values were selected from literature. Based on meta-analysis of published data, ISI(gly) and ISI(ffa) were reduced in subjects who were overweight and/or IGT and in NIDDM patients and their relatives. Moreover, correlation of ISI(gly) with the euglycemic clamp data was significant. However, it should be stressed that the clamp procedure is performed under artificially induced steady-state whereas ISI(gly) and ISI(ffa) are obtained under rather physiological conditions, with hormonal and metabolic variables unmodified, thus being suitable to assess whole-body insulin sensitivity in the clinical setting.


Health-Care Access during the Ebola Virus Epidemic in Liberia.
The Ebola virus disease (EVD) epidemic, which began in West Africa in December 2013, claimed more than 11,000 lives, with more than 4,800 of these deaths occurring in Liberia. The epidemic had an additional effect of paralyzing the health-care systems in affected countries, which led to even greater mortality and morbidity. Little is known about the impact that the epidemic had on the provision of basic health care. During the period from March to May 2015, we undertook a nationwide, community-based survey to learn more about health-care access during the EVD epidemic in Liberia. A cluster sampling strategy was used to administer a structured in-person survey to heads of households located within the catchment areas surrounding all 21 government hospitals in Liberia. A total of 543 heads of household from all 15 counties in Liberia participated in the study; more than half (67%) of urban respondents and 46% of rural respondents stated that it was very difficult or impossible to access health care during the epidemic. In urban areas, only 20-30% of patients seeking care during the epidemic received care, and in rural areas, only 70-80% of those seeking care were able to access it. Patients requiring prenatal and obstetric care and emergency services had the most difficulty accessing care. The results of this survey support the observation that basic health care was extremely difficult to access during the EVD epidemic in Liberia. Our results underscore the critical need to support essential health-care services during humanitarian crises to minimize preventable morbidity and mortality.


Prognostic significance of the combination of preoperative fibrinogen and the neutrophil-lymphocyte ratio in patients with non-small cell lung cancer following surgical resection.
The purpose of the present study was to evaluate the prognostic value of preoperative coagulation factor levels (including fibrinogen and D-dimer) and inflammatory indicators in patients with non-small cell lung cancer (NSCLC). The medical records of 456 patients with NSCLC who had undergone curative resection were retrospectively analysed. The recommended cut-off values for preoperative fibrinogen, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio and lymphocyte-monocyte ratio were determined using receiver operating characteristic curve analyses. The associations between preoperative fibrinogen or D-dimer levels and clinicopathological variables were analysed using the χ2 test. Univariate Kaplan-Meier analysis and a multivariate Cox proportional hazards model were applied to identify which prognostic variables were significantly associated with overall survival (OS) rates. Multivariate analyses revealed that lymph node metastasis (P<0.001), preoperative fibrinogen (P=0.024) and NLR (P=0.028) were effective independent prognostic variables associated with OS. Based on this result, a novel, single inflammation-based combination of fibrinogen and NLR (COF-NLR) score was proposed for the determination of prognosis. Patients with elevated fibrinogen and NLR levels were allocated a score of 2 (n=136), and those that demonstrated elevated levels of one or neither were allocated a score of 1 (n=152) or 0 (n=168), respectively. The 5-year OS rates were significantly poorer for patients with COF-NLR=2 compared with those with COF-NLR=1 or 0 (23.5% vs. 34.2% vs. 50.0%, P<0.001). A subgroup analysis demonstrated that the prognostic significance of COF-NLR was independent of histological subtype, lymph node metastasis and pathological stage. Therefore, COF-NLR has potential as a novel and useful blood marker for predicting tumour progression and the postoperative survival of patients with NSCLC. It may assist clinicians in risk stratification, prognosis predictions and facilitating individualised treatment.


Physiologically based GPS speed zones for evaluating running demands in Women's Rugby Sevens.
High-speed running (>5 m · s⁻¹) is commonly reported in men's rugby union and sevens; however, the appropriateness of using the same speed threshold for Women's Rugby Sevens players is unclear, and likely underestimates the degree of high-intensity exercise completed by female players. The aim of this study was to establish, for international Women's Rugby Sevens players, a physiologically defined threshold - speed at the second ventilatory threshold (VT(2peed)) - for the analysis of high-intensity running, using mean and individualised thresholds. Game movement patterns (using 5 Hz GPS) of 12 international Women's Rugby Sevens players (23.5 ± 4.9 ears, 1.68 ± 0.04 m, 68.2 ± 7.7 kg; mean ± s) were collected at an international tournament. Seven of these players also completed a treadmill VO(2max) test to estimate VT(2speed). Compared to the mean VT(2speed) threshold (3.5 m · s⁻¹), the industry-used threshold of 5 m · s⁻¹ underestimated the absolute amount of high-intensity running completed by individual players by up to 30%. Using an individualised threshold, high-intensity running could over- or underestimating high-intensity running by up to 14% compared to the mean VT(2peed) threshold. The use of individualised thresholds provides an accurate individualised assessment of game demands to inform the prescription of training.


Biocompatible Hydroxylated Boron Nitride Nanosheets/Poly(vinyl alcohol) Interpenetrating Hydrogels with Enhanced Mechanical and Thermal Responses.
Poly(vinyl alcohol) (PVA) hydrogels with tissue-like viscoelasticity, excellent biocompatibility, and high hydrophilicity have been considered as promising cartilage replacement materials. However, lack of sufficient mechanical properties is a critical barrier to their use as load-bearing cartilage substitutes. Herein, we report hydroxylated boron nitride nanosheets (OH-BNNS)/PVA interpenetrating hydrogels by cyclically freezing/thawing the aqueous mixture of PVA and highly hydrophilic OH-BNNS (up to 0.6 mg/mL, two times the highest reported so far). Encouragingly, the resulting OH-BNNS/PVA hydrogels exhibit controllable reinforcements in both mechanical and thermal responses by simply varying the OH-BNNS contents. Impressive 45, 43, and 63% increases in compressive, tensile strengths and Young's modulus, respectively, can be obtained even with only 0.12 wt% (OH-BNNS:PVA) OH-BNNS addition. Meanwhile, exciting improvements in the thermal diffusivity (15%) and conductivity (5%) can also be successfully achieved. These enhancements are attributed to the synergistic effect of intrinsic superior properties of the as-prepared OH-BNNS and strong hydrogen bonding interactions between the OH-BNNS and PVA chains. In addition, excellent cytocompatibility of the composite hydrogels was verified by cell proliferation and live/dead viability assays. These biocompatible OH-BNNS/PVA hydrogels are promising in addressing the mechanical failure and locally overheating issues as cartilage substitutes and may also have broad utility for biomedical applications, such as drug delivery, tissue engineering, biosensors, and actuators.


The safety of liposome bupivacaine, a novel local analgesic formulation.
Pooled safety data from 10 randomized, double-blind studies of liposome bupivacaine, a novel local analgesic formulation, were examined. Eight hundred twenty-three patients received liposome bupivacaine (dose, 66 to 532 mg) given locally at the surgical site in 5 different settings (hemorrhoidectomy, bunionectomy, breast augmentation, total knee arthroplasty, and hernia repair); 446 received bupivacaine HCl (dose, 75 to 200 mg) and 190 received placebo. Adverse events (AEs) were monitored for up to 36 days after administration. Overall, 48% of patients were men and 21% were 65 years and older. Incidence of AEs was 62% for patients receiving liposome bupivacaine, versus 75% and 43% for patients receiving bupivacaine HCl and placebo, respectively. The most common AEs (incidence >10%) in the liposome bupivacaine arms were nausea, constipation, and vomiting. One death was reported in the liposome bupivacaine group and 1 in the bupivacaine HCl group; both deemed unrelated to study drug. Serious AEs were reported in 2.7% of patients receiving liposome bupivacaine, versus 5.4% and 1.1% of those receiving bupivacaine HCl and placebo, respectively. In both the liposome bupivacaine and bupivacaine HCl groups, 6% of patients experienced a cardiac AE; these were primarily tachycardia (4% vs. 5%, respectively) and bradycardia (2% vs. 1%, respectively). Overall incidence of treatment-related cardiac AEs was <1%; all were associated with liposome bupivacaine. All of these events were assessed by investigators as possibly related to study drug; all were mild or moderate in severity, and none required therapeutic intervention. Liposome bupivacaine exhibited acceptable tolerability across 823 patient exposures.


Therapeutic effect of cefotetan in an experimental local infection with facultative and obligate anaerobes in granuloma pouches in rats.
The therapeutic activities of cefotetan against experimentally induced infections with Escherichia coli. Serratia marcescens, Bacteroides fragilis or Fusobacterium mortiferum in the granuloma pouches of rats were compared with those of cefmetazole and cefazolin. Of these antibiotics, cefotetan showed the greatest therapeutic effect against the four bacterial infections after a single intramuscular administration. Cefotetan was found to give much higher pouch exudate concentrations than cefmetazole, and to show prolonged antibacterial levels even when compared with cefazolin. In the granuloma pouch, cefotetan produced similar morphological changes in the cells of E. coli NY-17 as have been observed in vitro by microscopy. Elongation and bulge formation were noted.


A reductionist approach to extract robust molecular markers from microarray data series - Isolating markers to track osseointegration.
Complexities in the full genome expression studies hinder the extraction of tracker genes to analyze the course of biological events. In this study, we demonstrate the applications of supervised machine learning methods to reduce the irrelevance in microarray data series and thereby extract robust molecular markers to track biological processes. The methodology has been illustrated by analyzing whole genome expression studies on bone-implant integration (ossointegration). Being a biological process, osseointegration is known to leave a trail of genetic footprint during the course. In spite of existence of enormous amount of raw data in public repositories, researchers still do not have access to a panel of genes that can definitively track osseointegration. The results from our study revealed panels comprising of matrix metalloproteinases and collagen genes were able to track osseointegration on implant surfaces (MMP9 and COL1A2 on micro-textured; MMP12 and COL6A3 on superimposed nano-textured surfaces) with 100% classification accuracy, specificity and sensitivity. Further, our analysis showed the importance of the progression of the duration in establishment of the mechanical connection at bone-implant surface. The findings from this study are expected to be useful to researchers investigating osseointegration of novel implant materials especially at the early stage. The methodology demonstrated can be easily adapted by scientists in different fields to analyze large databases for other biological processes.


Psychological stress in inflammatory bowel disease: Psychoneuroimmunological insights into bidirectional gut-brain communications.
Inflammatory bowel disease (IBD), mainly including ulcerative colitis (UC) and Crohn's disease (CD), is an autoimmune gastrointestinal disease characterized by chronic inflammation and frequent recurrence. Accumulating evidence has confirmed that chronic psychological stress is considered to trigger IBD deterioration and relapse. Moreover, studies have demonstrated that patients with IBD have a higher risk of developing symptoms of anxiety and depression than healthy individuals. However, the underlying mechanism of the link between psychological stress and IBD remains poorly understood. This review used a psychoneuroimmunology perspective to assess possible neuro-visceral integration, immune modulation, and crucial intestinal microbiome changes in IBD. Furthermore, the bidirectionality of the brain-gut axis was emphasized in the context, indicating that IBD pathophysiology increases the inflammatory response in the central nervous system and further contributes to anxiety- and depression-like behavioral comorbidities. This information will help accurately characterize the link between psychological stress and IBD disease activity. Additionally, the clinical application of functional brain imaging, microbiota-targeted treatment, psychotherapy and antidepressants should be considered during the treatment and diagnosis of IBD with behavioral comorbidities. This review elucidates the significance of more high-quality research combined with large clinical sample sizes and multiple diagnostic methods and psychotherapy, which may help to achieve personalized therapeutic strategies for IBD patients based on stress relief.


Molecular vibrational frequencies from analytic Hessian of constrained nuclear-electronic orbital density functional theory.
Nuclear quantum effects are important in a variety of chemical and biological processes. The constrained nuclear-electronic orbital density functional theory (cNEO-DFT) has been developed to include nuclear quantum effects in energy surfaces. Herein, we develop the analytic Hessian for cNEO-DFT energy with respect to the change in nuclear (expectation) positions, which can be used to characterize stationary points on energy surfaces and compute molecular vibrational frequencies. This is achieved by constructing and solving the multicomponent cNEO coupled-perturbed Kohn-Sham (cNEO-CPKS) equations, which describe the response of electronic and nuclear orbitals to the displacement of nuclear (expectation) positions. With the analytic Hessian, the vibrational frequencies of a series of small molecules are calculated and compared to those from conventional DFT Hessian calculations as well as those from the vibrational second-order perturbation theory (VPT2). It is found that even with a harmonic treatment, cNEO-DFT significantly outperforms DFT and is comparable to DFT-VPT2 in the description of vibrational frequencies in regular polyatomic molecules. Furthermore, cNEO-DFT can reasonably describe the proton transfer modes in systems with a shared proton, whereas DFT-VPT2 often faces great challenges. Our results suggest the importance of nuclear quantum effects in molecular vibrations, and cNEO-DFT is an accurate and inexpensive method to describe molecular vibrations.


Utility of CD44/CD24 in the Outcome and Prognosis of Oral Squamous Cell Carcinoma: A Systematic Review.
Cancer stem cells (CSCs) are characterized by their capacity for self-renewal and differentiation. CD44 and CD24 are two commonly used markers to identify these CSCs. Despite the enormous amount of data available in the literature, their specificity and coexistence remain elusive in oral squamous cell carcinoma (OSCC). In the present review, we aimed to assess the diagnostic utility of the CD44/CD24 combination in tumor development and metastasis in OSCC. Two investigators independently performed a systematic search to identify all the relevant studies from various electronic databases. Out of 694 articles, 9 were found eligible for further evaluation. Details including the number of patients, gender, site, tobacco and alcohol consumption, histological stage, CD24 expression, CD44 expression, CD44/CD24 expression, nodal status, disease-free survival, and overall survival were extracted. CD44+CD24- expression was noted in 35/207 (16.9%) cases, CD44+CD24+ in 53/207 (25.6%) cases, CD44-CD24- in 49/207 subjects (23.67%), and CD44-/CD24+ in 70/207 (33.81%) cases. CD44 or CD24 or their co-expression did not correlate with the disease-free survival rate, and double negatives (CD44-/CD24-) demonstrated a higher overall survival than other immunotypes. CD44/CD24 profile may be used on small incisional biopsies to predict the outcome and treatment planning. This finding may help in developing new therapeutic targets to suppress cancer metastasis and provide a better long-term prognosis for patients diagnosed with OSCC.


The ACA and Cancer Screening and Diagnosis.
The Patient Protection and Affordable Care Act (ACA) included multiple provisions expected to increase cancer screening and subsequently early diagnosis of cancer. Key provisions included new coverage options for low-income adults and young adults, as well as elimination of cost sharing for recommended preventive services across most health insurance plans. This article reviews relevant quantitative studies published since the ACA's passage to assess whether the goal of increasing access to preventive services has been met. Because of lags in data availability, most studies examined only a short period post-ACA. Findings on changes in screening in the general population were mixed, although impacts were greatest among those with lower education and income, as well as groups that previously faced the highest cost barriers to screening. Furthermore, multiple studies found evidence of increases in early-stage diagnoses for certain cancers. Thus, certain targeted populations appear to have better access to cancer screening after the ACA.


[Dependence of Escherichia coli K-12 viability and mutability on the balance of DNA and protein syntheses. VI. Molecular mechanisms underlying the phenomena of imbalance death and metabolic mutagenesis].
In this report the results of further studies of the molecular mechanisms of the disbalance death and metabolic (disbalance) mutagenesis are presented. As reported previously, the relationship of viability and mutability of Escherichia coli cells from the extent disturbance of DNA-protein synthesis balance is determined by the processes of stabilization and repair of metabolic disbalance gaps in DNA strands. It is established that polB, recB, SSB gene products are involved in the processes of stabilization and repair of metabolic disbalance gaps.


Effects of Biotin Deficiency on Biotinylated Proteins and Biotin-Related Genes in the Rat Brain.
Biotin is a water-soluble vitamin that functions as a cofactor for biotin-dependent carboxylases. The biochemical and physiological roles of biotin in brain regions have not yet been investigated sufficiently in vivo. Thus, in order to clarify the function of biotin in the brain, we herein examined biotin contents, biotinylated protein expression (e.g. holocarboxylases), and biotin-related gene expression in the brain of biotin-deficient rats. Three-week-old male Wistar rats were divided into a control group, biotin-deficient group, and pair-fed group. Rats were fed experimental diets from 3 wk old for 8 wk, and the cortex, hippocampus, striatum, hypothalamus, and cerebellum were then collected. In the biotin-deficient group, the maintenance of total biotin and holocarboxylases, increases in the bound form of biotin and biotinidase activity, and the expression of an unknown biotinylated protein were observed in the cortex. In other regions, total and free biotin contents decreased, holocarboxylase expression was maintained, and bound biotin and biotinidase activity remained unchanged. Biotin-related gene (pyruvate carboxylase, sodium-dependent multivitamin transporter, holocarboxylase synthetase, and biotinidase) expression in the cortex and hippocampus also remained unchanged among the dietary groups. These results suggest that biotin may be related to cortex functions by binding protein, and the effects of a biotin deficiency and the importance of biotin differ among the different brain regions.


Self-determination, control, and reactions to changes in workload: a work simulation.
The objective of this experimental study is to capture the dynamic temporal processes that occur in changing work settings and to test how work control and individuals' motivational predispositions interact to predict reactions to these changes. To this aim, we examine the moderating effects of global self-determined and non-self-determined motivation, at different levels of work control, on participants' adaptation and stress reactivity to changes in workload during four trials of an inbox activity. Workload was increased or decreased at Trial 3, and adaptation to this change was examined via fluctuations in anxiety, coping, motivation, and performance. In support of the hypotheses, results revealed that, for non-self-determined individuals, low work control was stress-buffering and high work control was stress-exacerbating when predicting anxiety and intrinsic motivation. In contrast, for self-determined individuals, high work control facilitated the adaptive use of planning coping in response to a change in workload. Overall, this pattern of results demonstrates that, while high work control was anxiety-provoking and demotivating for non-self-determined individuals, self-determined individuals used high work control to implement an adaptive antecedent-focused emotion regulation strategy (i.e., planning coping) to meet situational demands. Other interactive effects of global motivation emerged on anxiety, active coping, and task performance. These results and their practical implications are discussed.


[The locked-in syndrome. Clinical study of 10 cases].
Ten cases of locked-in syndrome of syndrome of ischaemic nature are described. Seven of them are conform to the original description. In the other three, the oculomor disturbances are less severe. The clinical spectrum of this syndrome is discussed, special attention being paid to the gaze palsies.


Long-term outcomes of major trauma without head injury in the West of Scotland: pilot case-control study.
The aim of this study was to identify the outcomes of survivors of blunt major trauma (without head injury) 2 years or more following injury. The study uses a case-control design, is set in the West of Scotland and includes trauma patients treated in Greater Glasgow NHS Board hospitals. Participants consisted of patients who had sustained major trauma (injury severity score >15) with little or no head injury at least 2 years before assessment, identified from the Scottish Trauma Audit Group database, and age and sex-matched controls nominated by the index case's general practitioner. Nineteen cases and seven controls completed the study from 223 potential cases and 39 potential controls. Participants and non-participants had comparable injury severity score, probability of survival (Ps) and length of stay. American Medical Association impairment scores show survivors were more impaired than controls (25.9 vs 7.4%, P=0.043). No differences were observed in Functional Independence Measure (FIM) or Community Integration Questionnaire (CIQ) scores, although a type II error is possible. Short-form 36 (SF36) Physical Component Summary (PCS) scores of survivors showed no difference compared with controls although survivors' PCS scores were below UK and US means (P=0.008). SF36 Mental Component Summary (MCS) scores of survivors were below those of controls (45.07 vs 56.65, P=0.004) and normal values of the UK population (P=0.036). No differences in work status were noted, but small sample sizes were used. Non-head-injured survivors of major trauma in the West of Scotland have poorer health status (SF36), physically and mentally, than the UK population. They have greater impairment, but have an employment status comparable to that of the controls. The lack of differences in FIM and CIQ scores between survivors and controls may be due to small sample sizes.


QUANTITATIVE GENETICS OF OVARIOLE NUMBER IN DROSOPHILA MELANOGASTER. I. SEGREGATING VARIATION AND FITNESS.
The number of ovarioles of the Drosophila melanogaster ovary is a trait thought to be associated with female fecundity, and therefore is expected to be under strong natural selection. This hypothesis may be tested by examining patterns of genetic and environmental variation for ovariole number in natural populations, and by determining the association between ovariole number and fitness in isogenic lines derived from a natural population. We measured ovariole number, and competitive fitness and its components, for 48 homozygous chromosome 3 substitution lines in a standard inbred background; and body size in a sample of 15 chromosome 3 substitution lines. We found significant segregating genetic variation for ovariole number, with a broad-sense heritability (H2 ) of 0.403 and correspondingly high coefficients of genetic variation (CVC = 20.8) and residual variation (CVR = 25.3). Estimates of quantitative genetic parameters for body size (H2 = 0.191, CVG = 2.15, and CVR = 3.87) are similar to those previously reported for this trait. Although the isogenic chromosome 3 substitution lines varied significantly for components of fitness, there was no significant linear or quadratic association of ovariole number and body size with fitness. There was, however, highly significant sex × genotype interaction for fitness among these lines. This special case of genotype × environment interaction for fitness may contribute to the maintenance of genetic variation for fitness in natural populations.


Inositol and In Vitro Fertilization with Embryo Transfer.
Recently, studies on inositol supplementation during in vitro fertilization program (IVF) have gained particular importance due to the effect of this molecule on reducing insulin resistance improving ovarian function, oocyte quality, and embryo and pregnancy rates and reducing gonadotropin amount during stimulation. Inositol and its isoforms, especially myoinositol (MYO), are often used as prestimulation therapy in infertile patients undergoing IVF cycle. Inositol supplementation started three months before ovarian stimulation, resulting in significant improvements in hormonal responses, reducing the amount of FSH necessary for optimal follicle development and serum levels of 17beta-estradiol measured the day of hCG injection. As shown by growing number of trials, MYO supplementation improves oocyte quality by reducing the number of degenerated and immature oocytes, in this way increasing the quality of embryos produced. Inositol can also improve the quality of sperm parameters in those patients affected by oligoasthenoteratozoospermia.


Ouabain rescues rat nephrogenesis during intrauterine growth restriction by regulating the complement and coagulation cascades and calcium signaling pathway.
Intrauterine growth restriction (IUGR) is associated with a reduction in the numbers of nephrons in neonates, which increases the risk of hypertension. Our previous study showed that ouabain protects the development of the embryonic kidney during IUGR. To explore this molecular mechanism, IUGR rats were induced by protein and calorie restriction throughout pregnancy, and ouabain was delivered using a mini osmotic pump. RNA sequencing technology was used to identify the differentially expressed genes (DEGs) of the embryonic kidneys. DEGs were submitted to the Database for Annotation and Visualization and Integrated Discovery, and gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted. Maternal malnutrition significantly reduced fetal weight, but ouabain treatment had no significant effect on body weight. A total of 322 (177 upregulated and 145 downregulated) DEGs were detected between control and the IUGR group. Meanwhile, 318 DEGs were found to be differentially expressed (180 increased and 138 decreased) between the IUGR group and the ouabain-treated group. KEGG pathway analysis indicated that maternal undernutrition mainly disrupts the complement and coagulation cascades and the calcium signaling pathway, which could be protected by ouabain treatment. Taken together, these two biological pathways may play an important role in nephrogenesis, indicating potential novel therapeutic targets against the unfavorable effects of IUGR.


[Effect of Tiaoshen Kaiyu Acupuncture (Regulating Vitality and Dredging Stasis) Combined with Psychological Intervention on Patients of Mild Depression After Stroke].
To observe the effect of Tiaoshen Kaiyu acupuncture (regulating vitality and dredging stasis) combined with psychological intervention for treating mild depression after stroke. Ninety-four patients were enrolled and were randomly divided into acupuncture (48 cases) and control (46 cases) groups. Patients in the control group were given standard treatment plus psychological intervention, while patients in the acupuncture group were treated with Tiaoshen Kaiyu acupuncture plus standard treatment and psychological intervention. Acupoints of Sishencong(EX-HN 1), Baihui(GV 20), and Yintang(EX-HN 3) were selected in the acupuncture group. Each group received treatment once daily, five times weekly, for a total of 6 weeks. A self-rating depression scale (SDS), Hamilton depression scale (HAMD), simplified Fugl-Meyer motor function assessment (FMA), and modified Barthel index (MBI) were used before and after treatment to evaluate the efficacy. After the treatment the four indexes were improved significantly compared with those before treatment in the acupuncture and control groups (P<0.01). The FMA and MBI scores in the acupuncture group were higher than those in the control group (P<0.05). The HAMD and SDS scores were significantly lower in the acupuncture group than in the control group (P<0.01). In both the acupuncture and control groups, the differences before and after treatment of the HAMD and FMA scores (rs=0.332, P<0.01) and the HAMD and MBI scores (rs=0.356, P<0.01) were positively correlated. Tiaoshen Kaiyu acupuncture combined with psychological intervention is more effective than psychological intervention therapy alone. The efficacy is correlated with motor function and mild depression scores of patients after stroke.


Epidemiology of depression throughout the female life cycle.
Women are at an increased risk for first onset of major depression from early adolescence until their mid-50s and have a lifetime rate of major depression 1.7 to 2.7 times greater than that for men. There is accumulating evidence that certain reproductive-related hormonal changes place women at increased risk for depression. For example, puberty marks the beginning of increased risk for depression in women. Most women report physical or emotional symptoms premenstrually, with some severe enough to be diagnosed as premenstrual dysphoric disorder. While pregnancy does not increase the risk for depression, women with past histories of depression are at risk for recurrent episodes or relapse if antidepressant medications are discontinued. Hormonal changes during the postpartum period also increase the incidence of depression. Similarly, women transitioning through perimenopause, particularly those with past psychiatric histories, report depressive symptoms. Prophylaxis and treatment to minimize severity in cases of recurrence are discussed in the article, using reproductive transitional events as markers.


Acupotomy ameliorates subchondral bone absorption and mechanical properties in rabbits with knee osteoarthritis by regulating bone morphogenetic protein 2-Smad1 pathway.
To investigate the effects of acupotomy on the subchondral bone absorption and mechanical properties in rabbits with knee osteoarthritis (KOA). The rabbits were divided into blank control, model, acupotomy and electroacupuncture (EA) groups, with 12 rabbits in each. Modified Videman's method was used to prepare KOA model. The acupotomy and EA group were given indicated intervention for 3 weeks. The behavior of rabbits in each group was recorded. Subsequently, cartilage-subchondral bone units were obtained and morphological changes were observed by optical microscope and micro computed tomography. Compression test was used to detect the mechanical properties of subchondral bone, Western blot and real-time polymerase chain reaction (RT-PCR) were applied to detect the expression of bone morphogenetic protein 2-Smad1 (BMP2-Smad1) pathway in subchondral bone. Compared with the control group, rabbits in the KOA group showed lameness, knee pain, and cartilage degradation; the subchondral bone showed active resorption, the mechanical properties decreased significantly and the BMP2-Smad1 pathway downregulated significantly. Both acupotomy and EA intervention could increase the thickness of trabecular bone (Tb. Th), the bone volume fraction (BV/TV) and the thickness of subchondral bone plate, reduce the separation of trabecular bone (Tb. Sp), improve the maximum load and elastic modulus of subchondral bone, and effectively delay cartilage degeneration in KOA rabbits. This process may be achieved through upregulation the related proteins of BMP2-Smad1 pathway. The maximum load and elastic modulus of subchondral bone in the acupotomy group were slightly better than those in the EA group. Acupotomy could effectively protect cartilage by inhibiting abnormal bone resorption and improving mechanical properties of subchondral bone thorough the related proteins of BMP2-Smad1 pathway in KOA rabbits.


Notes on the conservation threats to the western lesser spot-nosed monkey (Cercopithecus petaurista buettikoferi) in the Bijagós Archipelago (Guinea-Bissau, West Africa).
The lesser spot-nosed monkey (Cercopithecus petaurista) is a widely distributed West African guenon, which is generally considered less vulnerable to local extinctions than many sympatric primate species. Guinea-Bissau harbours the westernmost populations of the species, which is thought to be very rare or even extinct on the mainland, but to have putative populations on some islands of the Bijagós Archipelago. However, due to a lack of regional studies, baseline information on these insular populations is missing. We collected baseline data on the anthropogenic activities that possibly threaten the long-term conservation of this primate by using non-systematic ethnographic methodologies. The species was reported to be decreasing in number or rare by locals on two of the islands, and we identified two main conservation threats to it: generalised habitat loss/degradation, and hunting. While subsistence hunting has been recorded before in these areas, we report, to the best of our knowledge for the first time for these islands, the presence of a semi-organised commercial wild meat trade. The carcasses of western lesser spot-nosed monkeys were observed being stored and shipped from seaports to be sold at urban hubs (Bissau and Bubaque Island). The effect of commercial trade on the species could be severe, considering the small, naturally occurring, carrying capacities typical of insular ecosystems. The results of this study highlight the importance of understanding the leading social drivers of wild meat hunting of lesser spot-nosed monkeys on the Bijagós Archipelago, and the need to conduct baseline research on these insular populations, for which qualitative and quantitative methods could be combined.


Products from pyrolysis of gas-phase propionaldehyde.
A hyperthermal nozzle was utilized to study the thermal decomposition of propionaldehyde, CH3CH2CHO, over a temperature range of 1073-1600 K. Products were identified with two detection methods: matrix-isolation Fourier transform infrared spectroscopy and photoionization mass spectrometry. Evidence was observed for four reactions during the breakdown of propionaldehyde: α-C-C bond scission yielding CH3CH2, CO, and H, an elimination reaction forming methylketene and H2, an isomerization pathway leading to propyne via the elimination of H2O, and a β-C-C bond scission channel forming methyl radical and (•)CH2CHO. The products identified during this experiment were CO, HCO, CH3CH2, CH3CH═C═O, H2O, CH3C≡CH, CH3, H2C═C═O, CH2CH2, CH3CH═CH2, HC≡CH, CH2CCH, H2CO, C4H2, C4H4, and CH3CHO. The first eight products result from primary or bimolecular reactions involving propionaldehyde while the remaining products occur from reactions including the initial pyrolysis products. While the pyrolysis of propionaldehyde involves reactions similar to those observed for acetaldehyde and butyraldehyde in recent studies, there are a few unique products observed which highlight the need for further study of the pyrolysis mechanism.


SENP1 promotes triple-negative breast cancer invasion and metastasis via enhancing CSN5 transcription mediated by GATA1 deSUMOylation.
TNBC is characterized by high incidence of visceral metastasis and lacks effective clinical targets. This study aims to delineate the molecular mechanisms of SENP1 in TNBC invasion and metastasis. By using IHC to test the SENP1 expression in TNBC tissues, we analyzed the relationship between SENP1 expression and TNBC prognosis. We showed that SENP1 expression was higher in TNBC tumor tissues and related to TNBC prognosis, supporting SENP1 as an independent risk factor. High expression of SENP1 was significantly associated with histologic grade and tumor lymph node invasion. Intriguingly, the expression levels of SENP1 in TNBC tumors were significantly correlated with that of CSN5, GATA1 and ZEB1. Importantly, SENP1 promoted TNBC cell migration and invasion by regulating ZEB1 deubiquitination and expression through CSN5. Further studies showed that deSUMOylation at lysine residue K137 of GATA1 enhanced the binding of GATA1 to the CSN5 promoter and transactivated CSN5 expression. In addition, we showed that ZEB1 is deubiquitinated at lysine residue K1108. Our in vivo studies also indicated that reduction in SENP1 expression upregulated GATA1 SUMOylation, and thus resulted in decreased expression of CSN5 and ZEB1 in the tumor microenvironment, which decelerated TNBC progression and metastasis. SENP1 promoted CSN5-mediated ZEB1 protein degradation via deSUMOylation of GATA1, and thus influenced TNBC progression. These findings suggest that SENP1 could be utilized as a potential target for blockade of TNBC development and thus provide a totally new approach for TNBC treatment.


Examining the Outcomes of Project ECHO® as an Interprofessional Community of Practice for Pediatric Feeding Clinicians.
Project ECHO® is a virtual, interprofessional, cased-based peer-learning model. To date, no studies have explored ECHO as a model for pediatric feeding education. This study examined the outcomes of establishing a pediatric feeding ECHO network. Using a prospective, mixed-methods design, two cohorts of allied health professionals were recruited. Each cohort participated in eight, 90-min videoconference sessions incorporating a didactic presentation and clinical case presentation. The case was presented by a participant, with questions and recommendations provided by the ECHO network. Participants completed: (1) a learning needs analysis before the ECHO series, (2) a self-reported confidence questionnaire pre, post, and 3-month post, (3) a satisfaction questionnaire after each session, and (4) an overall satisfaction questionnaire post-ECHO series. Time spent by hospital allied health clinicians providing impromptu phone/email feeding support to external clinicians was recorded for 8 weeks prior to and 8 weeks during the ECHO series. Forty-seven participants were included in the study, attending an average of 5.8 sessions. Significant improvements in self-reported confidence were observed across the three time points (p < 0.01) with less experienced participants demonstrating greater improvements. Participants reported high satisfaction with ECHO, with 93% (40/43) wanting continued access to ECHO in future. The multidisciplinary format, interactivity, structure, and case-based nature of ECHO were considered beneficial. A 75% reduction in requests for support from clinicians in the same catchment area was noted during the ECHO series. Results demonstrated that Project ECHO is a viable model for pediatric feeding education for clinicians working in the field. Further research is needed to investigate the long-term effects and impacts on clinical care.


Virtues and pitfalls of EAE for the development of therapies for multiple sclerosis.
Experimental autoimmune encephalomyelitis (EAE) is a useful model for aiding the development of new treatments for MS. All therapies approved for MS ameliorate EAE. Two approved medications, glatiramer acetate and Natalizumab, were developed directly from studies in EAE. Several trials are ongoing in MS after success in EAE, including altered peptide ligands of myelin, DNA vaccines and statins. However, EAE has failed to predict the outcome of certain approaches. The reasons underlying such failures are discussed here.


Clinical aspects of late sequelae of trichinellosis.
Clinical analysis and the set of laboratory studies, performed in 25 patients one, two, three or six years after surviving acute period of trichinellosis, documented complaints in 22 patients (88.0%) in the form of muscle complaints (68.2%), cardiovascular complaints (45.4%), generalized weakness (40.9%) and fatigability (31.8%). No significant alterations were demonstrated in electrocardiographic records. In 71.4% examined patients lactic dehydrogenase activity was augmented. Presence of IgG antibodies against the E/S antigen of Trichinella sp. was disclosed in 24 (96%) patients, including 22 patients (88.0%), in whom high titres of the antibodies were found. Morphological studies on muscle tissue (performed in 5 patients) disclosed alterations typical of trichinellosis in 4 patients and presence of Trichinella larvae, calcified to a significant extent, in 2 patients. The long term persistence of IgG class antibodies against Trichinella antigen in patients who survived acute period of trichinellosis a few years earlier points to a chronic antigenic stimulation, probably reflecting progressive destruction of Trichinella larvae in muscle tissue. This may also be expressed in complaints reported by the patients. The problem requires further observations and clinical studies.


Floating thrombus in the thoracic aorta: what should be done?
Floating thrombus in a non-aneurysmal and non-atherosclerotic thoracic aorta is a rare event with potentially catastrophic complications. Especially younger patients have a higher risk of embolization. Transesophageal echocardiography is the diagnostic method of choice. However, the treatment of this pathology is still controversial and includes both medical and surgical options. We report our experience with a 43-year-old patient and a review of the literature, and make a proposal for therapeutic interventions.


Chronic Effects of Boxing: Diffusion Tensor Imaging and Cognitive Findings.
We used magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to evaluate the effects of boxing on brain structure and cognition in 10 boxers (8 retired, 2 active; mean age = 45.7 years; standard deviation [SD] = 9.71) and 9 participants (mean age = 43.44; SD = 9.11) in noncombative sports. Evans Index (maximum width of the anterior horns of the lateral ventricles/maximal width of the internal diameter of the skull) was significantly larger in the boxers (F = 4.52; p = 0.050; Cohen's f = 0.531). Word list recall was impaired in the boxers (F(1,14) = 10.70; p = 0.006; f = 0.84), whereas implicit memory measured by faster reaction time (RT) to a repeating sequence of numbers than to a random sequence was preserved (t = 2.52; p < 0.04). Fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) measured by tractography did not significantly differ between groups. However, DTI metrics were significantly correlated with declarative memory (e.g., left ventral striatum ADC with delayed recall, r = -0.74; p = 0.02) and with RT to the repeating number sequence (r = 0.70; p = 0.04) in the boxers. Years of boxing had the most consistent, negative correlations with FA, ranging from -0.65 for the right ventral striatum to -0.92 for the right cerebral peduncle. Years of boxing was negatively related to the number of words consistently recalled over trials (r = -0.74; p = 0.02), delayed recall (r = -0.83; p = 0.003), and serial RT (r = 0.66; p = 0.05). We conclude that microstructural integrity of white matter tracts is related to declarative memory and response speed in boxers and to the extent of boxing exposure. Implications for chronic traumatic encephalopathy are discussed.


A case of colon necrosis resulting from a delayed traumatic diaphragmatic hernia.
We present the case of a 71 years old woman who came at the emergency room for abdominal pain and symptoms of occlusion. The scanner demonstrated a colonic occlusion resulting from an incarceration, diagnosed as a hernia of Bochdalek. But two old rib fractures and a past history of a fall directed us to the diagnostic of delayed diaphragmatic rupture. The patient was operated in emergency and post-operative follow-up was simple. Traumatic diaphragmatic hernias are rarely diagnosed directly after trauma. Complications such as pneumonia, occlusion, enteric ischemia, visceral perforation and twisting of splenic hilium can occur many years after the trauma. This is why, for patients with intestinal obstruction or association of pulmonary abdominal symptoms and history of thoraco-abdominal injury, the diagnostic of diaphragmatic hernia should be considered. When patients present complications, there is a higher rate of morbidity and mortality (31%) reason why, emergency surgery is mandatory.


A nucleophilic substitution reaction performed in different types of self-assembly structures.
A nucleophilic substitution reaction between 4-tert-butylbenzyl bromide and potassium iodide has been performed in oil-in-water microemulsions based on various C12Em surfactants, i.e., dodecyl ethoxylate with m number of oxyethylene units. The reaction kinetics was compared with the kinetics of reactions performed in other self-assembly structures based on very similar surfactants and in homogeneous liquids. The reaction was fastest in the micellar system, intermediate in rate in the microemulsions, and most sluggish in the liquid crystalline phase. Reaction in a Winsor I system, i.e., a two-phase system comprising an oil-in-water microemulsion in equilibrium with excess oil, was equally fast as reaction in a one-phase microemulsion. The reactions in microemulsion were surprisingly fast compared to reaction in homogeneous, protic liquids such as methanol and ethanol. The rate was independent of the microstructure of the microemulsion; however, the rate was very dependent on the type of surfactant used. When the C12Em surfactant was replaced by a sugar-based surfactant, octyl glucoside, the reaction was much more sluggish. The high reactivity in microemulsions based on C12Em surfactants is belived to be due to a favorable microenvironment in the reaction zone. The reaction is likely to occur within the surfactant palisade layer, where the water activity is relatively low and where the attacking species, the iodide ion, is poorly hydrated and, hence, more nucleophlic than in a protic solvent such as water or methanol. Sugar surfactants become more hydrated than alcohol ethoxylates and the lower reactivity in the microemulsion based on the sugar surfactant is probably due to a higher water activity in the reaction zone.


Expression, characterization, and mutagenesis of the Yersinia pestis murine toxin, a phospholipase D superfamily member.
A phospholipase D (PLD) superfamily was recently identified that contains proteins of highly diverse functions with the conserved motif HXKX4DX6G(G/S). The superfamily includes a bacterial nuclease, human and plant PLD enzymes, cardiolipin synthases, phosphatidylserine synthases, and the murine toxin from Yersinia pestis (Ymt). Ymt is particularly effective as a prototype for family members containing two conserved motifs, because it is smaller than many other two-domain superfamily enzymes, and it can be overexpressed. Large quantities of pure recombinant Ymt allowed the formation of diffraction-quality crystals for x-ray structure determination. Dimeric Ymt was shown to have PLD-like activity as demonstrated by the hydrolysis of phosphatidylcholine. Ymt also used bis(para-nitrophenol) phosphate as a substrate. Using these substrates, the amino acids essential for Ymt function were determined. Specifically, substitution of histidine or lysine in the conserved motifs reduced the turnover rate of bis(para-nitrophenol) phosphate by a factor of 10(4) and phospholipid turnover to an undetectable level. The role of the conserved residues in catalysis was further defined by the isolation of a radiolabeled phosphoenzyme intermediate, which identified a conserved histidine residue as the nucleophile in the catalytic reaction. Based on these data, a unifying two-step catalytic mechanism is proposed for this diverse family of enzymes.


The Slow Cycling Phenotype: A Growing Problem for Treatment Resistance in Melanoma.
Treatment resistance in metastatic melanoma is a longstanding issue. Current targeted therapy regimes in melanoma largely target the proliferating cancer population, leaving slow-cycling cancer cells undamaged. Consequently, slow-cycling cells are enriched upon drug therapy and can remain in the body for years until acquiring proliferative potential that triggers cancer relapse. Here we overview the molecular mechanisms of slow-cycling cells that underlie treatment resistance in melanoma. Three main areas of molecular reprogramming are discussed that mediate slow cycling and treatment resistance. First, a low microphthalmia-associated transcription factor (MITF) dedifferentiated state activates various signaling pathways. This includes WNT5A, EGFR, as well as other signaling activators, such as AXL and NF-κB. Second, the chromatin-remodeling factor Jumonji/ARID domain-containing protein 1B (JARID1B, KDM5B) orchestrates and maintains slow cycling and treatment resistance in a small subpopulation of melanoma cells. Finally, a shift in metabolic state toward oxidative phosphorylation has been demonstrated to regulate treatment resistance in slow-cycling cells. Elucidation of the underlying processes of slow cycling and its utilization by melanoma cells may reveal new vulnerable characteristics as therapeutic targets. Moreover, combining current therapies with targeting slow-cycling subpopulations of melanoma cells may allow for more durable and greater treatment responses. Mol Cancer Ther; 16(6); 1002-9. ©2017 AACR.


Insights into Bacteriophage Application in Controlling Vibrio Species.
Bacterial infections from various organisms including Vibrio sp. pose a serious hazard to humans in many forms from clinical infection to affecting the yield of agriculture and aquaculture via infection of livestock. Vibrio sp. is one of the main foodborne pathogens causing human infection and is also a common cause of losses in the aquaculture industry. Prophylactic and therapeutic usage of antibiotics has become the mainstay of managing this problem, however, this in turn led to the emergence of multidrug resistant strains of bacteria in the environment; which has raised awareness of the critical need for alternative non-antibiotic based methods of preventing and treating bacterial infections. Bacteriophages - viruses that infect and result in the death of bacteria - are currently of great interest as a highly viable alternative to antibiotics. This article provides an insight into bacteriophage application in controlling Vibrio species as well underlining the advantages and drawbacks of phage therapy.


Multiple administrations of oligodeoxynucleotides containing CpG motifs influence Ig isotype production.
Oligodeoxynucleotides containing CpG motifs (CpG-ODN) activate cells of the innate immune system. Recent studies have shown that sole CpG-ODN administration induces resistance against infection and tumors. Effects of CpG-ODN administration are rapidly induced, and regarding infections only short-term protection was seen. One conceivable strategy to prolong protective effects is multiple administrations of CpG-ODN. However, inappropriate immune activation via CpG motifs has been implicated in septic shock and autoimmunity. To investigate effects of multiple CpG-ODN administrations, we analyzed Th1- and Th-2-associated Ig antibody levels, during and after multiple treatment with CpG-ODN. Our results show that multiple administrations of CpG-ODN lead to an increase in total IgG2c levels in CpG-ODN-treated mice in comparison to controls with distinct time and frequency correlation, in the absence of additional stimuli. This indicates a humoral Th1 bias based on stimulation of Th1-Ig isotype-producing B cells. These effects could account for observed anti-infection and anti-tumor properties of multiple CpG-ODN administrations; on the other hand, they might cause autoimmune disease.


Validity of questionnaire information on frequency of coitus.
A total of 91 women provided reproductive histories, including usual frequency of coitus, at their enrollment into prospective studies conducted by the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina, in 1984-1986. Those data were compared with coital data recorded during study participation. Overall, women reported a significantly higher frequency of coitus on the interviewer-administered questionnaire than they recorded daily, by an average of 0.8 episodes per week. The size of this difference did not vary significantly for subgroups of women defined by demographic and other covariates. Excluding days of menses from the prospective records reduced the difference by 25%. The authors attribute the overestimate on the questionnaire to a tendency to report a coital frequency that might exist in the absence of travel, illness, and other transient factors that are likely to decrease frequency. This nondifferential information bias is unlikely to produce misleading comparisons or erroneous associations in epidemiologic studies of reproduction.


Every gene everywhere all at once: High-precision measurement of 3D chromosome architecture with single-cell Hi-C.
The three-dimensional (3D) structure of chromosomes influences essential biological processes such as gene expression, genome replication, and DNA damage repair and has been implicated in many developmental and degenerative diseases. In the past two centuries, two complementary genres of technology-microscopy, such as fluorescence in situ hybridization (FISH), and biochemistry, such as chromosome conformation capture (3C or Hi-C)-have revealed general principles of chromosome folding in the cell nucleus. However, the extraordinary complexity and cell-to-cell variability of the chromosome structure necessitate new tools with genome-wide coverage and single-cell precision. In the past decade, single-cell Hi-C emerges as a new approach that builds upon yet conceptually differs from bulk Hi-C assays. Instead of measuring population-averaged statistical properties of chromosome folding, single-cell Hi-C works as a proximity-based "biochemical microscope" that measures actual 3D structures of individual genomes, revealing features hidden in bulk Hi-C such as radial organization, multi-way interactions, and chromosome intermingling. Single-cell Hi-C has been used to study highly dynamic processes such as the cell cycle, cell-type-specific chromosome architecture ("structure types"), and structure-expression interplay, deepening our understanding of DNA organization and function.


Tardive dyskinesia in elderly psychiatric patients in Singapore.
The prevalence of tardive dyskinesia (TD) in 514 psychiatric patients who were 60 years and above in Singapore was found to be 27.6%. This is low compared with other studies done on elderly psychiatric patients in the West. Among the different ethnic groups, the Eurasians have the highest prevalence of 53.8% compared to the Chinese, Malays or Indians. Inpatients have a higher prevalence (31.5%) than outpatients (10.5%). Higher prevalence was also found in women, who were 2.2 times more common than men. 50% of the mentally retarded patients were found to have TD.


The Utility of Sonogashira Coupling Reaction for the Derivatization of Aryl Halides with Fluorescent Alkyne.
Aryl halides are a very important category of compounds that include many vital drugs and key industrial additives, such as clofibrate and bromobenzene, respectively. Due to their importance, our research group previously developed a novel fluorescence labeling approach for their analysis using a fluorescent aryl boronic acid as a reagent, based on the Suzuki coupling reaction. This coupling reaction was successfully applied for the determination of aryl halides in biological fluids; however, there was a limitation of low reactivity towards ortho-substituted aryl halides. In the present study, a novel fluorescence derivatization approach for aryl halides was developed using, 2-(4-ethynylphenyl)-4,5-diphenyl-1H-imidazole (DIB-ET) as a fluorescent alkyne reagent, based on the Sonogashira coupling reaction. DIB-ET reacted with aryl bromides in the presence of palladium and copper as catalysts, yielding fluorescent derivatives that could be subsequently determined by an HPLC system with fluorescence detection. The detection limits (S/N = 3) for aryl bromides were in the range of 14 - 23 nM, which is 3.5 - 18-times more sensitive than our previously developed approach, Suzuki coupling derivatization. Moreover, in contrast to the previous technique, the reactivity of DIB-ET to ortho-substituted aryl bromides was almost equivalent to that of the para-substituted aryl bromides. Hence, by using this newly developed approach we could label the aryl halides with more sensitivity and reactivity. Finally, the proposed method was successfully applied for the selective determination of aryl bromides in human serum with good recovery (84.6 - 107%), which proves the ability of the developed method to determine occupational exposure to aryl halides.


Prediction of ALK mutations mediating ALK-TKIs resistance and drug re-purposing to overcome the resistance.
Alectinib has shown a greater efficacy to ALK-rearranged non-small-cell lung cancers in first-line setting; however, most patients relapse due to acquired resistance, such as secondary mutations in ALK including I1171N and G1202R. Although ceritinib or lorlatinib was shown to be effective to these resistant mutants, further resistance often emerges due to ALK-compound mutations in relapse patients following the use of ceritinib or lorlatinib. However, the drug for overcoming resistance has not been established yet. We established lorlatinib-resistant cells harboring ALK-I1171N or -G1202R compound mutations by performing ENU mutagenesis screening or using an in vivo mouse model. We performed drug screening to overcome the lorlatinib-resistant ALK-compound mutations. To evaluate these resistances in silico, we developed a modified computational molecular dynamic simulation (MP-CAFEE). We identified 14 lorlatinib-resistant ALK-compound mutants, including several mutants that were recently discovered in lorlatinib-resistant patients. Some of these compound mutants were found to be sensitive to early generation ALK-TKIs and several BCR-ABL inhibitors. Using our original computational simulation, we succeeded in demonstrating a clear linear correlation between binding free energy and in vitro experimental IC50 value of several ALK-TKIs to single- or compound-mutated EML4-ALK expressing Ba/F3 cells and in recapitulating the tendency of the binding affinity reduction by double mutations found in this study. Computational simulation revealed that ALK-L1256F single mutant conferred resistance to lorlatinib but increased the sensitivity to alectinib. We discovered lorlatinib-resistant multiple ALK-compound mutations and an L1256F single mutation as well as the potential therapeutic strategies for these ALK mutations. Our original computational simulation to calculate the binding affinity may be applicable for predicting resistant mutations and for overcoming drug resistance in silico. FUND: This work was mainly supported by MEXT/JSPS KAKENHI Grants and AMED Grants.


Diagnosis and treatment of communicating bronchopulmonary foregut malformation: Report of two cases and review of the literature.
Communicating bronchopulmonary foregut malformation (CBPFM) is a rare congenital malformation involving both the digestive and respiratory systems. To our best knowledge, most cases of CBPFM reported in the literature were in infancy or adulthood and CBPFM in infantile is even rarer with a high case-fatality rate partly due to misdiagnosis. We presented 2 cases of neonatal CBPFM. A 11-hour male newborn was admitted because of moaning for 7 hours, and a 1-day male newborn was referred to us with profuse foams, choking on breast-milk feeding and facial cyanosis. With the assistance of upper gastrointestinal tract imaging and contrast-enhanced chest computed tomography (CT), the diagnosis was established according to the most recent diagnostic criteria. The case one recieved a lower left pneumonectomy and surgical repair of esophageal fistula. The case two was performed with a surgical repair of esophageal atresia and esophageal tracheal fistula firstly, and then also received a repair of communicating bronchopulmonary foregut malformation two weeks after the first operation. The case one was cured and discharged 2 weeks after admission. Unfortunately the case two died from respiratory failure. Pediatric surgeons should therefore be aware that type I CBPMF is rare and preoperative diagnosis is usually difficult. Maldiagnosis is uncommon because clinicians often focus their attention on esophageal atresia and neglect pulmonary abnormalities. Other than upper gastrointestinal tract radiography and CT scan, bronchoscopy should be considered in pediatric patients with esophageal atresia complicated with pulmonary abnormalities, knowing that bronchoscopy may help confirm the diagnosis and select surgical strategies.


Resectability Status of Pancreatic Cancer Having Tumor Contact with an Aberrant Right Hepatic Artery: Is Upfront Surgery Justified?
The NCCN guidelines define pancreatic cancer that has contact with an aberrant right hepatic artery (A-RHA) as a borderline-resectable tumor. However, the impact of tumor contact with an A-RHA on surgical and survival outcomes has not been well discussed. A total of 541 patients who underwent pancreatoduodenectomy for resectable and borderline-resectable pancreatic cancer between 2002 and 2019 were retrospectively analyzed. The presence of an A-RHA and tumor contact with an A-RHA were evaluated based on the preoperative computed tomography findings. Patients with resectable tumors and tumors with A-RHA-contact (having contact with an A-RHA without involvement of the major arteries) were generally treated by upfront surgery, whereas those with borderline-resectable tumors generally underwent neoadjuvant therapy and subsequent resection. Among the 541 patients, 116 (21.4%) had an A-RHA and 15 (2.8%) had tumor with A-RHA-contact. The A-RHA was resected in 12, and arterial reconstruction was performed in 8. The rates of morbidity and R1 resection in patients with an A-RHA (32.8 and 10.3%, respectively) were comparable to those without an A-RHA (27.3 and 11.3%, respectively). The overall survival in patients with A-RHA-contact was significantly worse than that in patients with borderline-resectable tumors (median survival time, 14.6 vs. 35.3 months, p = 0.048). Although upfront resection was safely performed and led to a high R0 resection rate in patients with A-RHA-contact, the survival outcome was dismal. A tumor with A-RHA-contact should be regarded as technically resectable but oncologically borderline-resectable. Upfront surgery may not be appropriate for patients with A-RHA-contact.


CYP2D6*11 and challenges in clinical genotyping of the highly polymorphic CYP2D6 gene.
CYP2D6 is genotyped clinically for prediction of response to tamoxifen, psychotropic drugs and other medications. Phenotype prediction is dependent upon accurate genotyping. The CYP Allele Nomenclature Committee maintains the allelic nomenclature for CYP2D6; however, in some cases, the list of polymorphisms associated with a given allele is incomplete. Clinical laboratories and in vitro diagnostic manufacturers rely upon this nomenclature, in addition to the literature, to infer allelic function and haplotypes and when they design CYP2D6-testing platforms. This article provides more complete sequencing data for the CYP2D6*11 allele and describes the difficulties encountered in genotyping CYP2D6 when incomplete data are available. The CYP Allele Nomenclature Committee should provide clear information about the completeness of the original data used to define each allele.


Stacking self-association of pyrimidine nucleosides and of cytosines: effects of methylation and thiolation.
Stacking self-association equilibria in aqueous solutions of m3uridine, m34,2',3',5'uridine, 2'-deoxyuridine, m13,4,4cytosine, m14,4,4,5cytosine, s2cytidine and s4thymidine were studied at various temperatures by vapour-pressure osmometry. Equilibrium constants Kst's were computed on the assumption of the isodesmic model of self-association. Enthalpies of association were also obtained from the temperature dependence of Kst according to the van't Hoff equation. Analysis of the equilibrium and thermodynamic parameters demonstrated involvement of hydrophobic interactions in the stabilization of complexes of tetramethyluridine. Dipole-induced dipole interactions seem to predominate in the formation of s2C, s4T and of both dimethylaminocytosine complexes.


Lithocholic Acid Stimulates IL-8 Expression in Human Colorectal Cancer Cells Via Activation of Erk1/2 MAPK and Suppression of STAT3 Activity.
The secondary bile acid lithocholic acid (LCA), an established tumor promoter, has been implicated in colorectal cancer (CRC) metastasis. Overexpression of interleukin-8 (IL-8) has been detected in CRC, and it contributes to poor prognosis. However, the effect of LCA on IL-8 expression is still undefined. In this study, we observed that LCA treatment induced IL-8 expression in CRC HCT116 cells. Pharmacological inhibition and mutagenesis studies indicated that Erk1/2 is critical for LCA-induced IL-8 expression. Furthermore, LCA reduced the phosphorylation of STAT3, and the STAT3 inhibitor Stattic, accelerated LCA-induced IL-8 expression, suggesting that STAT3 is involved in LCA-induced IL-8 expression. Activation of Erk1/2 functioned as an upstream signal of the STAT3 suppression induced by LCA. In conclusion, LCA activated Erk1/2 and in turn, suppressed STAT3 phosphorylation to induce IL-8 expression in HCT116 cells, thus stimulating endothelial cell proliferation and tube like formation. J. Cell. Biochem. 118: 2958-2967, 2017. © 2017 Wiley Periodicals, Inc.


IgA Deficiency and Nephrotic Syndrome in Children.
Background: Imunoglobulin A (IgA) deficiency (IgAD) is the most common form of primary immunodeficiency in Western countries. There have been several reports on IgAD complicated by glomerulonephritis in adults, but only very few cases of IgAD with nephropathy have been reported in children. We present two cases of IgAD with relapsing nephrotic syndrome in pediatric age. Case presentation: A 4-year-old boy and a 2-year-old boy presented with bilateral periorbital oedema and weight gain. The results of laboratory tests revealed IgAD (IgA < 7 mg/dL), normal creatinine, hypoprotidaemia, hypoalbuminaemia, and nephrotic proteinuria. A diagnosis of IgAD and idiopathic nephrotic syndrome was made, and steroid treatment (prednisone 60 mg/mq/day) was started. During steroid tapering, the children experienced several relapses and to obtain a positive outcome they required therapy with human monoclonal anti-CD20 antibodies (rituximab in the first child, ofatumumab in the second one). Conclusions: Our cases highlight that IgAD can be observed in nephrotic syndrome and nephropathy in children with IgAD appears to be complicated and difficult to treat with corticosteroids alone. Further research is needed to better describe the clinical manifestations and pathological pictures among subjects with IgAD and nephrotic syndrome to understand whether IgAD has a prognostic value in children with nephrotic syndrome and to let clinical physicians define a more personalized and appropriate approach for the management of these patients.


A procedure for decreasing uncertainty in the identification of chemical compounds based on their literature citation and cocitation. Two case studies.
An identification procedure connected with selection of candidates for identification according to high values of their literature citation and cocitation is suggested. The citation rate of the compound is the number of different literature units, such as papers, patents, etc., recording its name. The cocitation rate is the number of such units mutually recording the names of two corresponding compounds or the compound and the sample/matrix. General citation of a chemical compound is assumed to be related to the prior probability of its being contained in a sample to be analyzed. This citation measures abundance and popularity of the compound. Cocitation of a compound with a known/identified constituent of a sample is related to their mutual similarity in structure or properties, origin, use, etc. This data processing method is validated by counting citations and cocitations for detected impurities in pure n-hexane and naphthalene, polycyclic aromatic hydrocarbons in waste gas, as compared with counts for similar or dissimilar compounds that are absent in the samples. The analytes are preidentified by combined gas chromatography and mass spectrometry techniques. A median and a mean value of citation and cocitation are always higher for the group of unambiguously identified compounds. A difference between identified and similar compounds in citations or cocitations may be rather insignificant, with combined evaluation of both indicators distinguishing these groups. Chemical dissimilarity results in a large difference in cocitation values.


[The laparoscopic approach to renal tumors outcome of 121 laparoscopic radical and partial nephrectomy procedures].
We present and review a single center experience with laparoscopic renal surgery for renal cancer including laparoscopic radical and partial nephrectomy. During the period September 2002 - January 2005, 180 patients underwent laparoscopic renal surgery at our center for several indications. A total of 121 patients underwent radical nephrectomy (76) or partial nephrectomy (45) for solid renal tumors. Their data was recorded and analyzed including age, indication for surgery, operative time, blood loss, intra- and postoperative complications, conversion rates, histological results and outpatient follow-up. The mean age at surgery was 65 years (range: 21-89 years). The indications for surgery were solid, enhancing renal masses. For tumors larger than 4 cm, a radical nephrectomy was performed. Tumors that were smaller than 4 cm were removed by partial nephrectomy. The mean operative time was minutes (range: 70-280 minutes) and the mean blood loss was 220 cc (range: 30-700 cc). The mean blood loss was significantly lower in the radical nephrectomy group (120 cc) than in the partial nephrectomy group (320 cc). In eight patients major intraoperative complications were noted including injury of the hilar vessels (5 cases), inferior vena cava (1 case), large bowel and spleen (one patient) and duodenum (1 case). Conversion to open surgery was needed in nine patients (7.4%), four in the radical nephrectomy and five in the partial nephrectomy group. Major postoperative complications were recorded in two patients who underwent radical nephrectomy (pneumothorax and incarcerated inguinal hernia) and in two patients who underwent partial nephrectomy (urine leakage). The pathological examination demonstrated renal cell carcinoma in 109 cases, oncocytoma in 6 cases, angiomyolipoma in 2 cases, sarcoma of the kidney and metastasis from lung cancer in one case each and a hemorrhagic cyst in one case. In all patients who underwent radical nephrectomy negative surgical margins were obtained, in three patients after partial nephrectomy the surgical margins were focally involved by tumor. The mean tumor size was 5.1 cm and 3.1 cm after radical or partial nephrectomy respectively. During follow-up, none of the patients developed local or distant recurrence. The laparoscopic approach to kidney cancer seems to be safe and oncologically sound. The low morbidity rate together with the inherent advantages of laparoscopic surgery make this approach attractive and we believe it should be considered the new standard of care for renal cancer.