Subunit exchange and the role of dimer flexibility in DNA binding by the Fis protein.
Fis is an abundant bacterial DNA binding protein that functions in many different reactions. We show here that Fis subunits rapidly exchange between dimers in solution by disulfide cross-linking mixtures of Fis mutants with different electrophoretic mobilities and by monitoring energy transfer between fluorescently labeled Fis subunits upon heterodimer formation. The effects of detergents and salt concentrations on subunit exchange imply that the dimer is predominantly stabilized by hydrophobic forces, consistent with the X-ray crystal structures. Specific and nonspecific DNA strongly inhibit Fis subunit exchange. In all crystal forms of Fis, the separation between the DNA recognition helices within the Fis dimer is too short to insert into adjacent major grooves on canonical B-DNA, implying that conformational changes within the Fis dimer and/or the DNA must occur upon binding. We therefore investigated the functional importance of dimer interface flexibility for Fis-DNA binding by studying the DNA binding properties of Fis mutants that were cross-linked at different positions in the dimer. Flexibility within the core dimer interface does not appear to be required for efficient DNA binding, Fis-DNA complex dissociation, or Fis-induced DNA bending. Moreover, FRET-based experiments provided no evidence for a change in the spatial relationship between the two helix-turn-helix motifs in the Fis dimer upon DNA binding. These results support a model in which the unusually short distance between DNA recognition helices on Fis is accommodated primarily through bending of the DNA.


[A surgical case of peritoneal dissemination metastasis of bile duct carcinoma after pancreaticoduodenectomy].
The patient was a 50-year-old woman who had undergone pancreaticoduodenectomy for bile duct carcinoma in April 2010. In August 2011, abdominal computed tomography (CT) revealed a solitary tumor (30×17 mm in diameter) behind the anastomosis of gastrojejunostomy. Gastrointestinal endoscopy revealed gastrojejunal ulceration (biopsy: Group V adenocarcinoma). Positron emission tomography (PET)-CT revealed a solitary tumor without any recurrence. We diagnosed the patient as having solitary recurrence of peritoneal dissemination of bile duct carcinoma. In September 2011, we performed resection of the peritoneal dissemination. The patient was discharged from the hospital 12 days after the operation and had a good postoperative course. Histologically, the tumor was diagnosed as peritoneal dissemination of bile duct carcinoma. Subsequently, the patient received postoperative chemotherapy. The patient remains alive with recurrence of peritoneal dissemination 37 months after pancreaticoduodenectomy and 20 months after resection of the peritoneal dissemination.


[Blood picture in the early diagnosis of neonatal septicemia].
In the search of a fast and simple laboratory test for the diagnosis of neonatal septicemia the blood pictures of 29 cases of septicemia were compared with normal values derived from 390 healthy newborns. In each case the leucocyte count, the neutrophil count, the band count and its percentage, the ratio of band forms to segmented neutrophils and the platelet count were analysed in the blood smear taken on the day of clinical suspicion of septicemia. The leucocyte count, the neutrophil count and the band count are within the pathological range in 70% of the cases. The percentage of band forms and the ratio of bands forms to segmented neutrophils are, with one exception, always abnormally elevated. Thrombocytopenia is present in only 60% of the cases. Among the different criteria the percentage of band forms is evidently the most practical and most significant one. Considering our normal values, the pathological range for this percentage is above 20% on the first day of life, above 15% on the second day and above 8% from the third day on.


[A Case of Rectal Cancer with Multiple Pulmonary and Liver Metastases Could Be Resected through Chemotherapy].
The patient was a 47-year-old man, whose chief complaint was melena. He visited a nearby hospital, and further evaluation showed rectal cancer invading the prostate, with multiple lung and liver metastases. The clinical diagnosis was cT4b(prostate), cN1, cM1b(H2, PUL2), cStage IV . We performed colostomy in the transverse colon prior to chemotherapy. He was administered 1 course of mFOLFOX6 plus bevacizumab and 7 courses of FOLFOXIRI plus bevacizumab. The primary tumor showed PR. The liver metastases were localized and shrunken, while the lung metastases disappeared. Approximately 6 months after the start of chemotherapy, a laparoscopic total pelvic exenteration and ileal conduit were performed following the diagnosis of ycT4b(prostate), ycN1, ycM1a(H2), ycStage IV . About 3 months later, a partial resection of the left liver lobes(S1 and S5/S8)was performed laparoscopically. He has been cancer-free for 8 months.


New aspects of an old drug--diclofenac targets MYC and glucose metabolism in tumor cells.
Non-steroidal anti-inflammatory drugs such as diclofenac exhibit potent anticancer effects. Up to now these effects were mainly attributed to its classical role as COX-inhibitor. Here we show novel COX-independent effects of diclofenac. Diclofenac significantly diminished MYC expression and modulated glucose metabolism resulting in impaired melanoma, leukemia, and carcinoma cell line proliferation in vitro and reduced melanoma growth in vivo. In contrast, the non-selective COX inhibitor aspirin and the COX-2 specific inhibitor NS-398 had no effect on MYC expression and glucose metabolism. Diclofenac significantly decreased glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), and monocarboxylate transporter 1 (MCT1) gene expression in line with a decrease in glucose uptake and lactate secretion. A significant intracellular accumulation of lactate by diclofenac preceded the observed effect on gene expression, suggesting a direct inhibitory effect of diclofenac on lactate efflux. While intracellular lactate accumulation impairs cellular proliferation and gene expression, it does not inhibit MYC expression as evidenced by the lack of MYC regulation by the MCT inhibitor α-cyano-4-hydroxycinnamic acid. Finally, in a cell line with a tetracycline-regulated c-MYC gene, diclofenac decreased proliferation both in the presence and absence of c-MYC. Thus, diclofenac targets tumor cell proliferation via two mechanisms, that is inhibition of MYC and lactate transport. Based on these results, diclofenac holds potential as a clinically applicable MYC and glycolysis inhibitor supporting established tumor therapies.


Comparison of the usefulness of plasma levels of oxidatively modified forms of albumin in estimating kidney dysfunction in diabetic patients.
Advanced oxidation protein products (AOPP) and ischemia-modified albumin (IMA) are forms of oxidatidatively modified albumin and have recently been investigated as indicators of oxidative stress. They are increased in different disorders, including diabetes mellitus, as a result of hyperglycaemia, oxidative stress and hypoxia. The usefulness of the plasma levels of these two parameters in estimating kidney dysfunction in type 2 diabetic patients (T2DM) was compared in this study. Plasma levels of AOPP and IMA were determined spectrophotometrically in 218 individuals, 153 patients with T2DM and 65 healthy people.. The urinary albumin/creatinine ratio (UACR) was used as the reference to define the stage of kidney dysfunction by the assessment of the degree of albuminuria. Receiver Operating Characteristic (ROC) curve analysis, likelihood ratio (LR), and Youden's index (J) revealed that AOPP and IMA had acceptable sensitivities and specificities in individuals with different degrees of albuminuria; however, AOPP had higher values of the area under the curve (AUC: 0.934) than IMA, as well as 100% sensitivity and 77.01% specificity for distinguishing patients with micro- and macroalbuminuria. Both AOPP and IMA may be helpful clinical markers for estimating kidney dysfunction, but AOPP is better able to identify diabetic patients with nephropathy. We suggest that AOPP is almost ideal for discriminating between T2DM patients with micro- and macroalbuminuria.


Signs of Gas Trapping in Normal Lung Density Regions in Smokers.
A substantial proportion of subjects without overt airflow obstruction have significant respiratory morbidity and structural abnormalities as visualized by computed tomography. Whether regions of the lung that appear normal using traditional computed tomography criteria have mild disease is not known. To identify subthreshold structural disease in normal-appearing lung regions in smokers. We analyzed 8,034 subjects with complete inspiratory and expiratory computed tomographic data participating in the COPDGene Study, including 103 lifetime nonsmokers. The ratio of the mean lung density at end expiration (E) to end inspiration (I) was calculated in lung regions with normal density (ND) by traditional thresholds for mild emphysema (-910 Hounsfield units) and gas trapping (-856 Hounsfield units) to derive the ND-E/I ratio. Multivariable regression analysis was used to measure the associations between ND-E/I, lung function, and respiratory morbidity. The ND-E/I ratio was greater in smokers than in nonsmokers, and it progressively increased from mild to severe chronic obstructive pulmonary disease severity. A proportion of 26.3% of smokers without airflow obstruction had ND-E/I greater than the 90th percentile of normal. ND-E/I was independently associated with FEV1 (adjusted β = -0.020; 95% confidence interval [CI], -0.032 to -0.007; P = 0.001), St. George's Respiratory Questionnaire scores (adjusted β = 0.952; 95% CI, 0.529 to 1.374; P < 0.001), 6-minute-walk distance (adjusted β = -10.412; 95% CI, -12.267 to -8.556; P < 0.001), and body mass index, airflow obstruction, dyspnea, and exercise capacity index (adjusted β = 0.169; 95% CI, 0.148 to 0.190; P < 0.001), and also with FEV1 change at follow-up (adjusted β = -3.013; 95% CI, -4.478 to -1.548; P = 0.001). Subthreshold gas trapping representing mild small airway disease is prevalent in normal-appearing lung regions in smokers without airflow obstruction, and it is associated with respiratory morbidity. Clinical trial registered with www.clinicaltrials.gov (NCT00608764).


Depression of adenosylmethionine content of Escherichia coli by thioglycerol.
The mechanism of growth inhibition of Escherichia coli by thioglycerol was probed. The extent of growth inhibition depended on the ratio of thioglycerol to initial cell concentration. Exogenously added methionine and several methionine analogues reversed the inhibition of 2 to 40 mM thioglycerol. Exposure to thioglycerol elevated the intracellular concentration of methionine, but the level of S-adenosylmethionine was depressed. Thioglycerol was methylated in vivo to 3-methylthio-1,2-propanediol.


Timeline of changes in spike conformational dynamics in emergent SARS-CoV-2 variants reveal progressive stabilization of trimer stalk with altered NTD dynamics.
SARS-CoV-2 emergent variants are characterized by increased viral fitness and each shows multiple mutations predominantly localized to the spike (S) protein. Here, amide hydrogen/deuterium exchange mass spectrometry has been applied to track changes in S dynamics from multiple SARS-CoV-2 variants. Our results highlight large differences across variants at two loci with impacts on S dynamics and stability. A significant enhancement in stabilization first occurred with the emergence of D614G S followed by smaller, progressive stabilization in subsequent variants. Stabilization preceded altered dynamics in the N-terminal domain, wherein Omicron BA.1 S showed the largest magnitude increases relative to other preceding variants. Changes in stabilization and dynamics resulting from S mutations detail the evolutionary trajectory of S in emerging variants. These carry major implications for SARS-CoV-2 viral fitness and offer new insights into variant-specific therapeutic development.


ME-ACP: Multi-view neural networks with ensemble model for identification of anticancer peptides.
Cancer remains one of the most threatening diseases, which kills millions of lives every year. As a promising perspective for cancer treatments, anticancer peptides (ACPs) overcome a lot of disadvantages of traditional treatments. However, it is time-consuming and expensive to identify ACPs through conventional experiments. Hence, it is urgent and necessary to develop highly effective approaches to accurately identify ACPs in large amounts of protein sequences. In this work, we proposed a novel and effective method named ME-ACP which employed multi-view neural networks with ensemble model to identify ACPs. Firstly, we employed residue level and peptide level features preliminarily with ensemble models based on lightGBMs. Then, the outputs of lightGBM classifiers were fed into a hybrid deep neural network (HDNN) to identify ACPs. The experiments on independent test datasets demonstrated that ME-ACP achieved competitive performance on common evaluation metrics.


Population pharmacokinetics of efavirenz in HIV and TB/HIV coinfected children: the significance of genotype-guided dosing.
The current WHO weight-based dosing recommendations for efavirenz result in a wide variability of drug exposure in children. Our objectives are to characterize the effects of rifampicin- and isoniazid-containing anti-TB therapy and CYP2B6 activity on efavirenz concentrations in children, using non-linear mixed-effects modelling. This is a pharmacokinetic (PK) substudy of a prospective study that examined the interactions between anti-TB therapy and efavirenz in HIV-infected children with and without TB. PK samples were obtained 4 weeks after starting efavirenz (PK1) and repeated 4 weeks after completing TB therapy (PK2) in TB/HIV coinfected patients. Drug concentrations were measured using LC-MS/MS. Composite CYP2B6 516/983/15582 genotype was determined. Population PK modelling was performed in Monolix. Simulations were performed to obtain the predicted mid-dose concentrations (C12). One hundred and five HIV-infected Ghanaian children (46 with TB/HIV) were included. The median age and weight were 7 years and 19 kg. The efavirenz concentrations over time were adequately described using a one-compartment model. Weight, composite CYP2B6 genotype and PK visit had a significant influence on the PK parameters, while TB therapy had no significant effect. Simulations showed adequate C12 for intermediate composite CYP2B6 metabolizers only. Our model showed that rifampicin- and isoniazid-containing anti-TB therapy does not influence efavirenz PK parameters. On the other hand, it describes the effect of efavirenz autoinduction after completing TB treatment. In addition, dosing efavirenz in children based only on weight results in a large variability in drug exposure. We propose dose adjustments for slow and extensive composite CYP2B6 metabolizers.


Special report: reassessment of the ORL-HNS workforce: perceptions and realities.
This Workforce Study re-examined the current scope and geographic distribution of Otolaryngology practice and assessed the otolaryngologists' role in relation to other specialists in the diagnosis and treatment of disorders of the ear, nose, throat, and related structures of the head and neck. Study design A national survey and review of federal, corporate and administrative databases, coupled wih a focus group of otolaryngologists, were analyzed to compile physician manpower figures, state and regional demographic data, and prediction modeling of Managed Care and FFS environments. The current and predicted workforce supply and demographic data support a geographic and proportionate increase in the number of otolaryngologists practicing and entering the workforce. Additional findings involving the role of the specialty specifically identified an increase in the treatment of allergic disease within the Managed Care sector and a diminution of the gatekeeper concept. Demographic findings represent a stable age distribution of 40 to 49 and 50 to 59 year old otolaryngologists, with a noted increase in the number of women entering the field. Empiric data reflects the continuous, diverse and dominant role otolaryngologists maintain in the treatment and care of patients with otolaryngologic and head and neck disease. This study continues the effort to identify otolaryngology workforce demographic profiles and make recommendations for a future national practice model. Continuous reassessment of the specialty is required.


Therapeutic modulation of cutaneous autoimmunity by regulatory T cells.
Cutaneous autoimmunity is characterized by the presence of autoantibodies and/or autoreactive T cells. Several mechanisms have been developed to avoid loss of immunotolerance to self such as activation-induced cell death, deletion, ignorance and active suppression of autoreactivity. Regulatory ('suppressor') T cells play a pivotal role in inhibiting the activation and function of effector T cells. CD4(+)CD25(+) T cells constitute a subset of regulatory T cells, which have been shown to suppress the development of organ-specific autoimmunity in mice. Recent understanding in the generation and function of human regulatory T cells indicates that these cells are involved in the appearance of inflammatory as well as bullous autoimmune dermatosis. These findings suggest that modulation of regulatory T cell numbers or function might be a promising therapeutic alternative for the treatment of such disorders. In the following, recent strategies aimed at inducing antigen-specific or non-specific regulatory T cells for the immunotherapy of ongoing cutaneous autoimmunity are presented and discussed. Hopefully, pursuing these strategies in the future will result in the initiation of randomized clinical studies analysing the usefulness of regulatory T cells for human skin diseases in great detail.


Patient navigation for lung cancer screening in an urban safety-net system: Protocol for a pragmatic randomized clinical trial.
The National Lung Screening Trial demonstrated improved lung cancer mortality with annual low-dose computed tomography (CT) screening, leading to lung cancer screening endorsement by the United States Preventive Services Task Force and coverage by the Centers for Medicare and Medicaid. Adherence to annual CT screens in that trial was 95%, which may not be representative of real-world, particularly medically underserved populations. This pragmatic trial will determine the effect of patient-focused, telephone-based patient navigation on adherence to CT-based lung cancer screening in an urban safety-net population. 340 adults who meet standard eligibility for lung cancer screening (age 55-77years, smoking history≥30 pack-years, quit within 15years if former smoker) are referred through an electronic medical record-based order by physicians in community- and hospital-based primary care settings within the Parkland Health and Hospital System in Dallas County, Texas. Eligible patients are randomized to usual care or patient navigation, which addresses adherence, patient-reported barriers, smoking cessation, and psycho-social concerns related to screening completion. Patients complete surveys and semi-structured interviews at baseline, 6-month, and 18-month follow-ups to assess attitudes toward screening. The primary endpoint of this pragmatic trial is adherence to three sequential, prospectively defined steps in the screening protocol. Secondary endpoints include self-reported tobacco use and other patient-reported outcomes. Results will provide real-world insight into the impact of patient navigation on adherence to CT-based lung cancer screening in a medically underserved population. This study was registered with the NIH ClinicalTrials.gov database (NCT02758054) on April 26, 2016.


Cetirizine therapy for seasonal allergic rhinitis: alternative dosage schedules.
A double-blind, placebo-controlled clinical trial was undertaken for two weeks to evaluate three dosing schedules for administration of cetirizine in patients with seasonal allergic rhinitis. Average severity scores from the patients' ratings for sneezing and nasal itching were significantly reduced in all three cetirizine groups (10 mg QAM or QHS and 5 mg BID), compared with placebo. The effectiveness of cetirizine in once-daily dosing schedules indicates that significant antihistaminic activity is delivered over a full 24 hours. The possibility for flexibility in dosing combined with its relatively short half-life and low incidence of adverse effects make cetirizine an important second-generation H1-antihistamine for the management of seasonal allergic rhinitis.


Pinacol Coupling Strategy for the Construction of the Bicyclo[6.4.1]tridecane Framework of Schiglautone A.
The synthesis of the tricyclic carbon framework of schiglautone A (1) is reported herein. The generation of the bicyclo[6.4.1]tridecane 19 was accomplished via a SmI2-mediated pinacol coupling of dialdehyde 18. The side chain in 18 was introduced using a selective 1,4-addition. A further key step of the synthesis was the homologation of a Wieland-Miescher ketone derivative to establish the 7-membered ring.


Simultaneous determination of trace cadmium and arsenic in biological samples by hydride generation-double channel atomic fluorescence spectrometry.
Hydride generation atomic fluorescence spectrometry (HG-AFS) has been used for determination of hydride-forming elements because of its high sensitivity, simplicity, and low costs, but most of such work has been concentrated on single element analysis, and reports dealing with multielement determination by HG-nondispersive (ND)AFS are rare. In this work, a sensitive HG-NDAFS method was developed for simultaneous determination of trace cadmium and arsenic in biological materials. The conditions for the generation of volatile cadmium and arsenic species from the reaction with KBH4 in aqueous solution were investigated using a double-channel AFS integrated with an intermittent flow reactor. Like thiourea and Co(II), ascorbic acid was found to significantly enhance the generation efficiency of volatile Cd and As species. The interferences of coexisting ions were evaluated. Under optimal conditions, the detection limits for Cd and As were determined to be 10 and 150 ng L(-1), respectively. The precision for 11 replicate determinations at the 1 microg L(-1) Cd level and the 10 microg L(-1) As level were 3.5 and 2.7% (RSD), respectively. The recoveries of spike analytes in the biological samples studied ranged from 94 to 109%. The proposed method was successfully applied to the simultaneous determination of Cd and As in a variety of biological samples.


Clinicopathological and prognostic value of epithelial cell adhesion molecule in solid tumours: a meta-analysis.
Malignant tumors, mainly solid tumors, are a significant obstacle to the improvement of life expectancy at present. Epithelial cell adhesion molecule (EpCAM), a cancer stem cell biomarker, showed widespread expression in most normal epithelial cells and most cancers. Although the clinical significance of EpCAM in various malignant solid tumors has been studied extensively, the latent relationships between EpCAM and pathological and clinical characteristics in solid tumors and differences in the roles of EpCAM among tumors have not been clearly determined. The destination point of this study was to analyze the value of EpCAM in solid tumors in clinicopathological and prognostic dimension using a meta-analysis approach. A comprehensive and systematic search of the researches published up to March 7th, 2022, in PubMed, EMBASE, Web of Science, Cochrane library and PMC databases was performed. The relationships between EpCAM overexpression, clinicopathological characteristics, and survival outcomes were analyzed. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) and odds ratios (ORs) were estimated as indicators of the degree of correlation. This research was registered on PROSPERO (International prospective register of systematic reviews), ID: CRD42022315070. In total, 57 articles and 14184 cases were included in this study. High EpCAM expression had a significant coherence with a poorer overall survival (OS) (HR: 1.30, 95% CI: 1.08-1.58, P < 0.01) and a worse disease-free survival (DFS) (HR: 1.58, 95% CI: 1.28-1.95, P < 0.01), especially of gastrointestinal tumors' OS (HR: 1.50, 95% CI: 1.15-1.95, P < 0.01), and DFS (HR: 1.84, 95% CI: 1.52-2.33, P < 0.01). The DFS of head and neck tumors (HR: 2.33, 95% CI: 1.51-3.61, P < 0.01) was also associated with the overexpression of EpCAM. There were no positive relationships between the overexpression of EpCAM and sex (RR: 1.03, 95% CI: 0.99-1.07, P = 0.141), T classification (RR: 0.93, 95% CI: 0.82-1.06, P = 0.293), lymph node metastasis (RR: 0.85, 95% CI: 0.54-1.32, P = 0.461), distant metastasis (RR: 0.97, 95% CI: 0.84-1.10, P = 0.606), vascular infiltration (RR: 1.05, 95% CI: 0.85-1.29, P = 0.611), and TNM stage (RR: 0.93, 95% CI: 0.83-1.04, P = 0.187). However, the overexpression of EpCAM exhibited a significant association with the histological grades (RR: 0.88, 95% CI: 0.80-0.97, P < 0.01). Based on pooled HRs, the positive expression of EpCAM was totally correlated to a worse OS and DFS in solid tumors. The expression of EpCAM was related to a worse OS in gastrointestinal tumors and a worse DFS in gastrointestinal tumors and head and neck tumors. Moreover, EpCAM expression was correlated with the histological grade. The results presented pointed out that EpCAM could serve as a prognostic biomarker for gastrointestinal and head and neck tumors. https://www.crd.york.ac.uk/prospero, identifier CRD42022315070.


Safety profile of almotriptan, a new antimigraine agent. Effects on central nervous system, renal function and respiratory dynamics.
Almotriptan (3-[2-(dimethylamino) ethyl]-5-(pyrrolidin-1-ylsulfonylmethyl)-1H-indole, CAS 154323-57-6) is a new 5-HT1B/1D agonist whose clinical efficacy has been demonstrated in Phase III clinical trials. This study aimed to evaluate the safety of almotriptan with respect to the central nervous system, renal function and respiratory dynamics using preclinical animal models. The results indicate that almotriptan does not cross the blood-brain barrier, since no effects on/interaction with spontaneous locomotor activity, hexobarbital-induced sleeping time, caffeine-induced increase of spontaneous locomotor activity, or hypothermia (caused by stimulation of central 5-HT1D receptors) was observed following treatment. Almotriptan had a mild antiemetic effect and a slight, transient diuretic effect in dogs, although the latter effect is probably of no clinical relevance. In addition, no effect on the respiratory system of conscious guinea pigs was observed following almotriptan treatment. These results indicate that almotriptan has a favourable safety profile with respect to the central nervous, renal and respiratory systems.


Effect of cellulose in the diet on the recovery of dietary plant sterols from the feces.
In one normal subject, J.S., fed several formula diets in a sterol balance study, only 25-58% of the ingested plant sterols were recovered from the stool. The dietary plant sterols were completely recovered from the stools of five other men. Plant sterol recovery was complete in all men when a diet of mixed general foods was consumed. Since the chief differences in composition of the formula and the diet of mixed general foods were related to the different contents of cellulose and lactose, these components were added to the formula diet of J.S., and plant sterol balance studies were then carried out. The addition of fresh celery or pulverized cellulose to the formula diet partially corrected the usual fecal loss of plant sterols (80% being recovered). Lactose in the formula was only slightly corrective. However, the addition of both cellulose and lactose led to complete recovery of the ingested plant sterols in the feces. Bacterial cultures of stools were incubated with added cholesterol-4-(14)C, and a linear relationship between losses of sterol during balance studies and in vitro incubations was observed; that is, a considerable loss of the labeled cholesterol from cultures after the formula diet, but not after the diet of mixed general foods. This in vitro loss was also corrected by the addition of cellulose and lactose to the formula diet. The loss of the sterol nucleus in the intestinal tract may occur at times because of the lack of certain dietary constituents. It is hypothesized that the metabolism of intestinal tract bacteria is altered when certain constituents are not present in the diet, and that these bacteria may then degrade the sterol nucleus.


Further studies on the cell surface charge of Trypanosoma cruzi.
Trypanosoma cruzi has a negative surface which varies according to the ionic strength and the pH of the solution in which the cells are suspended. At low pH there is a decrease in the negative surface charge with an isoelectric point at pH 2.6 and 3.0 for epimastigote and trypomastigote forms, respectively. Below these pH values the cells have a positive surface charge. At higher pH there is an increase in the surface charge. Glutaraldehyde fixation did not interfere with the electrophoretic mobility (EPM) of the cells. Epimastigote and trypomastigote forms of T. cruzi have a characteristic EPM independent of the medium in which the cells were grown, the origin of the trypomastigotes or the strain of the parasite. Trypomastigotes have a higher negative surface charge than epimastigotes. Based on the change in the EPM of the cells treated with neuraminidase, is concluded that sialic acid is present on the cell surface of T. cruzi and that it is the main component responsible for the high negative surface charge of the trypomastigote form. Trypsin treatment also reduces the EPM of T. cruzi. Neuraminidase or trypsin-treated parasites recovered their normal EPM when incubated for 4 h in fresh culture medium. This process involves synthesis of protein since it is inhibited by puromycin.


Personalized acute kidney injury treatment.
Acute kidney injury (AKI) is a complex syndrome that might be induced by different causes and is associated with an increased morbidity and mortality. Therefore, it is a very heterogeneous syndrome and establishing a "one size fits all" treatment approach might not work. This review aims to examine the potential of personalized treatment strategies for AKI. The traditional diagnosis of AKI is based on changes of serum creatinine and urine output, but these two functional biomarkers have several limitations. Recent research identified different AKI phenotypes based on clinical features, biomarkers, and pathophysiological pathways. Biomarkers, such as Cystatin C, NGAL, TIMP2∗IGFBP7, CCL14, and DKK-3, have shown promise in predicting AKI development, renal recovery, and prognosis. Biomarker-guided interventions, such as the implementation of the KDIGO bundle, have demonstrated an improvement in renal outcomes in specific patient groups. A personalized approach to AKI treatment as well as research is becoming increasingly important as it allows the identification of distinct AKI phenotypes and the potential for targeted interventions. By utilizing biomarkers and clinical features, physicians might be able to stratify patients into subphenotypes, enabling more individualized treatment strategies. This review highlights the potential of personalized AKI treatment, emphasizing the need for further research and large-scale clinical trials to validate the efficacy of these approaches.


Cyclospora cayetanensis infections among diarrheal outpatients in Shanghai: a retrospective case study.
Cyclospora cayetanensis is a foodborne and waterborne pathogen that causes endemic and epidemic human diarrhea worldwide. A few epidemiological studies regarding C. cayetanensis infections in China have been conducted. During 2013, a total of 291 stool specimens were collected from patients with diarrhea at a hospital in urban Shanghai. C. cayetanensis was not detected in any of the stool specimens by traditional microscopy, whereas five stool specimens (1.72%, 5/291) were positive by PCR. These positive cases confirmed by molecular technology were all in the adult group (mean age 27.8 years; 2.94%, 5/170) with watery diarrhea. Marked infection occurred in the rainy season of May and July. Sequence and phylogenetic analyses of the partial 18S rRNA genes of C. cayetanensis isolated showed intra-species diversity of this parasite. This study showed, for the first time, that C. cayetanensis is a pathogen in outpatients with diarrhea in Shanghai, albeit at a low level. However, the transmission dynamics of this parasite in these patients remain uncertain.


Lignocaine 2% with adrenaline for epidural caesarean section. A comparison with 0.5% bupivacaine.
A randomised double blind controlled trial of freshly prepared 2% lignocaine with 1/200,000 adrenaline and 0.5% plain bupivacaine was conducted on 60 women undergoing elective Caesarean section. The use of the former enabled epidural blockade to above the T6 dermatome to be established in a significantly shorter time than with bupivacaine (p less than 0.005). The quality of sensory blockade and incidence of complications was similar in the two groups. The solutions were of similar potency as measured by the volume required per segment blocked. Motor blockade was more intense with 2% lignocaine with adrenaline (p less than 0.03). More neonates had moderately depressed Apgar scores (5-7) at one minute in the lignocaine group but this difference was not statistically significant, and there was no difference in the distribution of Apgar scores at 3 minutes. Lignocaine with 1/200,000 adrenaline is a useful alternative to 0.5% plain bupivacaine when it is desired to establish rapidly epidural blockade for Caesarean section.


A wearable skin stretch haptic feedback device: Towards improving balance control in lower limb amputees.
Haptic feedback to lower limb amputees is essential to maximize the functionality of a prosthetic device by providing information to the user about the interaction with the environment and the position of the prostheses in space. Severed sensory pathway and the absence of connection between the prosthesis and the Central Nervous System (CNS) after lower limb amputation reduces balance control, increases visual dependency and increases risk of falls among amputees. This work describes the design of a wearable haptic feedback device for lower limb amputees using lateral skin-stretch modality intended to serve as a feedback cue during ambulation. A feedback scheme was proposed based on gait event detection for possible real-time postural adjustment. Preliminary perceptual test with healthy subjects in static condition was carried out and the results indicated over 98% accuracy in determining stimuli location around the upper leg region, suggesting good perceptibility of the delivered stimuli.


Nutritional risk screening 2002 and ASA score predict mortality after elective liver resection for malignancy.
The aim of the study was to evaluate whether Nutritional risk screening 2002 (NRS 2002) at hospital admission may predict postoperative mortality and complications within 90 days after elective liver resection for malignancy. A retrospective cohort study of a prospective database was performed. Two-hundred and three patients with elective liver resection for malignancy between 9 November 2007 and 27 May 2014 were included. Clinical data, NRS 2002, surgical procedures and histology were recorded. The primary endpoint was 90-day mortality. Complications were registered within 90 days postoperatively according to the Clavien-Dindo classification. The 90-day mortality was 5.9% and the overall complication rate was 59.1%. Multivariate analysis identified NRS 2002 score ≥ 4 (odds ratio (OR) = 9.24; p = 0.005) and American Society of Anesthesiologists (ASA) score ≥ 3 (OR = 6.20; p = 0.009) as predictors of 90-day mortality. The 90-day mortality was 27.6% (8/29) for patients with both risk factors (NRS 2002 score ≥ 4 and ASA score ≥ 3) vs. 2.3% (4/174) for patients without or with only one risk factor (p < 0.001). In the present study NRS 2002 score ≥ 4 and ASA score ≥ 3 were predictors of 90-day mortality after elective liver resection for malignancy.


Non-opioid medications for the relief of chronic breathlessness: current evidence.
To evaluate systematically randomised clinical trials investigating non-opioid medications for the management and treatment of chronic breathlessness. Areas covered: The evidence for the role of benzodiazepines, anxiolytics, selective serotonin re-uptake inhibitors (SSRIs), tricyclic antidepressants, antihistamines, cannabinoids, nebulized furosemide and herbal-based treatments were critically reviewed. Search of the Clinical Trials Registry (Clinicaltrial.gov) identified ongoing studies expected to generate new data in the near future in several classes of non-opioid medications for their net effect on chronic breathlessness. Expert commentary: Morphine still has the best level of evidence for the symptomatic treatment of chronic breathlessness. Non-opioid treatments for chronic breathlessness are less studied than morphine and morphine-related medications although evidence is emerging in relation to some options. Currently, there is insufficient evidence to recommend non-opioids in the routine treatment of chronic breathlessness. There is a need to find agents, new as well as re-purposed, that can be used as alternative therapies to opioids for chronic breathlessness for people who are unable to tolerate morphine.


Draft Genome Sequence of the Root-Colonizing Fungus Trichoderma harzianum B97.
Trichoderma harzianum is one of the most beneficial microorganisms applied on diverse crops against biotic and abiotic stresses and acts also as a plant growth-promoting fungus. Here, we report the genome of T. harzianum B97, originating from a French agricultural soil and used as a biofertilizer that can tolerate abiotic stresses.


[Long-term results of revascularization surgery in oblitertive arteriosclerosis of the lower extremities].
The authors evaluated their 15-year experience with revascularization operations for atherosclerosis obliterans (ASO) of the lower extremities. Over the period from 1975 to 1990, 1112 patients with ASO were admitted to their department and in 674 (60.6%) of them revascularization operation was performed. Direct revascularization surgery (bypass, desobliteration, angioplasty) was performed in 318 (47.2%) patients and indirect revascularization, sympathectomy in 326 (52.8%) patients. On evaluating the long-term results of aortobifemoral (AF2), femoropopliteal (FP) and femorocrural (FC) bypasses the following long-term patency was established: AF2 bypass--patency up to 2 years 92%, up to 5 years 90%, up to 10 years 76%, up to 15 years 75%; FP bypass--patency up to 2 years 90%, up to 5 years 84%, up to 10 years 62%, up to 15 years 46%; FC bypass--patency up to 2 years 63%, up to 5 years 50%, up to 10 years 25%. Complications developed in 10%, the mortality rate was 2.5% and 8% in FP and AF2, respectively. The obtained results are comparable with the data published in the literature. The authors achieved the best results in the suprainguinal region with AF2 bypasses on using mostly dacron prostheses and in the infrainguinal region FP bypasses on using the autologous great saphenous vein. (Tab. 3, Fig. 4, Ref. 17.)


In Vitro Cytotoxicity Effects of Zinc Oxide Nanoparticles on Spermatogonia Cells.
Zinc Oxide Nanoparticles (ZnO NPs) are a type of metal oxide nanoparticle with an extensive use in biomedicine. Several studies have focused on the biosafety of ZnO NPs, since their size and surface area favor entrance and accumulation in the body, which can induce toxic effects. In previous studies, ZnO NPs have been identified as a dose- and time-dependent cytotoxic inducer in testis and male germ cells. However, the consequences for the first cell stage of spermatogenesis, spermatogonia, have never been evaluated. Therefore, the aim of the present work is to evaluate in vitro the cytotoxic effects of ZnO NPs in spermatogonia cells, focusing on changes in cytoskeleton and nucleoskeleton. For that purpose, GC-1 cell line derived from mouse testes was selected as a model of spermatogenesis. These cells were treated with different doses of ZnO NPs for 6 h and 12 h. The impact of GC-1 cells exposure to ZnO NPs on cell viability, cell damage, and cytoskeleton and nucleoskeleton dynamics was assessed. Our results clearly indicate that higher concentrations of ZnO NPs have a cytotoxic effect in GC-1 cells, leading to an increase of intracellular Reactive Oxygen Species (ROS) levels, DNA damage, cytoskeleton and nucleoskeleton dynamics alterations, and consequently cell death. In conclusion, it is here reported for the first time that ZnO NPs induce cytotoxic effects, including changes in cytoskeleton and nucleoskeleton in mouse spermatogonia cells, which may compromise the progression of spermatogenesis in a time- and dose-dependent manner.


[Cytological method of diagnosis of breakthrough bleeding].
The studies have been carried out by means of analysis of cytological diagnoses made during the assessment of uterobrush preparations of the endometrium. Cytological material has been sampled in the case of pathological bleeding of low intensity. Glandular hyperplasia occurred in 18% of cases, cancer in about 1%, inflammatory process in 11%. The comparison of received data with the results of histological examinations of scrapings from the uterine cavity does not show any significant differences. The authors think that the cytological method of diagnosing a pathological state of endometrium is credible.


Fecal Impaction and Nonperforated Stercoral Colitis: Red Flags for Poor Outcomes.
Fecal impaction and stercoral colitis are common, yet little research has been performed on the associated mortality risk. We performed a retrospective cohort study of 970 hospital encounters representing 885 unique patients in which fecal impaction or stercoral colitis was identified in CT reports. Among the 535 patients with fecal impaction, 13.3% died or were discharged to hospice, compared to 13.1% among the 428 patients with nonperforated stercoral colitis (p = 0.93). Of the seven patients with perforation, five died or were discharged to hospice. The risk of death or discharge to hospice for patients with fecal impaction or nonperforated stercoral colitis aged 18-49 was 2.9% and rose approximately 4% each decade thereafter to 21.9% for patients 90 and older (p< 0.001). Patients with a body mass index of 25-30 had an 8.1% risk of death or discharge to hospice, compared to 23.4% for those with a BMI < 18.5 (p< 0.001). Patients with at least one ICD-10 code for dementia, paralysis/neuromuscular disease, or malnutrition/failure to thrive had a risk of death or discharge to hospice of 21.6%, compared to 1.9% among patients with none of these risk factors (p< 0.001). ICD-10 codes for sepsis were associated with 90.0% of the deaths and 44.3% of the discharges to hospice. Patients diagnosed in less than three hours had a risk of death or discharge to hospice of 8.0%, compared to a risk of 20.1% for those diagnosed in ≥ 12 hours (p< 0.001).


NK1-receptors mediate the proliferative response of human fibroblasts to tachykinins.
1. The effect of synthetic tachykinin selective receptor agonists was studied on the growth of cultured human skin fibroblasts (HF). 2. Human fibroblasts were grown in serum-free conditions in the presence of natural tachykinins (substance P and neurokinin A) and of three synthetic agonists, [beta-Ala4, Sar9, Met(O2)11]-SP(4-11), [beta-Ala8]-NKA(4-10) and [MePhe7]-NKB selective for NK1-, NK2- and NK3-receptors respectively. Cell proliferation was measured by percentage increase in cell number and by [3H]-thymidine uptake following 48 h exposure to agents compared to baseline condition. 3. Neurokinin A (NKA) and substance P (SP) significantly increased cell proliferation the threshold concentrations being 10(-12) and 10(-11) M, respectively. Addition of thiorphan to culture conditions enhanced the effect of SP but not of NKA. 4. The selective NK1-receptor agonist produced a dose-dependent increase in cell proliferation as judged by total cell number and [3H]-thymidine uptake. No significant effect was observed with NK2- and NK3-receptor agonists. 5. These data indicate that the effect of SP on fibroblast proliferation is mediated by interaction with a NK1-receptor type and local metabolism can interfere with the full expression of this effect of SP on cell proliferation.


The Small Protein SgrT Controls Transport Activity of the Glucose-Specific Phosphotransferase System.
The bacterial small RNA (sRNA) SgrS has been a fruitful model for discovery of novel RNA-based regulatory mechanisms and new facets of bacterial physiology and metabolism. SgrS is one of only a few characterized dual-function sRNAs. SgrS can control gene expression posttranscriptionally via sRNA-mRNA base-pairing interactions. Its second function is coding for the small protein SgrT. Previous work demonstrated that both functions contribute to relief of growth inhibition caused by glucose-phosphate stress, a condition characterized by disrupted glycolytic flux and accumulation of sugar phosphates. The base-pairing activity of SgrS has been the subject of numerous studies, but the activity of SgrT is less well characterized. Here, we provide evidence that SgrT acts to specifically inhibit the transport activity of the major glucose permease PtsG. Superresolution microscopy demonstrated that SgrT localizes to the cell membrane in a PtsG-dependent manner. Mutational analysis determined that residues in the N-terminal domain of PtsG are important for conferring sensitivity to SgrT-mediated inhibition of transport activity. Growth assays support a model in which SgrT-mediated inhibition of PtsG transport activity reduces accumulation of nonmetabolizable sugar phosphates and promotes utilization of alternative carbon sources by modulating carbon catabolite repression. The results of this study expand our understanding of a basic and well-studied biological problem, namely, how cells coordinate carbohydrate transport and metabolism. Further, this work highlights the complex activities that can be carried out by sRNAs and small proteins in bacteria.IMPORTANCE Sequencing, annotation and investigation of hundreds of bacterial genomes have identified vast numbers of small RNAs and small proteins, the majority of which have no known function. In this study, we explore the function of a small protein that acts in tandem with a well-characterized small RNA during metabolic stress to help bacterial cells maintain balanced metabolism and continue growing. Our results indicate that this protein acts on the glucose transport system, inhibiting its activity under stress conditions in order to allow cells to utilize alternative carbon sources. This work sheds new light on a key biological problem: how cells coordinate carbohydrate transport and metabolism. The study also expands our understanding of the functional capacities of small proteins.


Orthostatic hypotension as an unusual clinical manifestation of pheochromocytoma: a case report.
Pheochromocytoma is a rare endocrine tumor which can have a highly variable presentation related to increased catecholamine secretion. We report the case of a 74-year-old man in whom recurrent episodes of syncope due to orthostatic hypotension were the only clinical manifestations of this challenging entity. Diagnosis of pheochromocytoma was achieved by biochemical test samples and computed tomography scans. Surgical excision of the tumor resulted in clinical improvement with normalization of catecholamine concentrations and no more episodes of orthostatic hypotension during a follow-up of 24 months. Although rare, pheochromocytoma may frequently cause disorders of orthostatic tolerance; because of its meaningful implications, screening for this entity should be considered in case of recurrent syncopal episodes due to new-onset orthostatic hypotension.


Acute viral hepatitis C-induced jaundice in pregnancy.
Acute viral hepatitis C-induced jaundice in pregnancy is very rare and may be fatal. Here, we report a complicated case with acute hepatitis C-induced jaundice in pregnancy with successful management. A 27-year-old pregnant woman, gravida 2, para 1, with gestational age of 36 weeks and 5 days, was referred to our hospital due to jaundice and elevated liver enzymes of undetermined cause. She had been suffering from general weakness, diarrhea and vomiting for 1 week, and jaundice with tea-colored urine for 3 days. At our medical center, acute viral hepatitis C-induced jaundice was suspected. Since her general condition deteriorated at 36 weeks and 6 days of gestation, we decided to induce labor. A male baby was born smoothly via the vaginal route, with birth weight 2,857 g, birth length 48.6 cm, and 1- and 5-minute Apgar scores of 7 and 9, respectively. Maternal condition improved dramatically after delivery and her serum liver enzymes and bilirubin levels gradually approached normal ranges. Mothers and fetuses with acute viral hepatitis C-induced jaundice during pregnancy are at great risk of mortality and morbidity. Timely termination may be one of the choices of treatment when fetal maturity has been reached and the maternal condition has deteriorated.


Dosimetric factors used for thoracic X-ray radiotherapy are not predictive of the occurrence of radiation pneumonitis after carbon-ion radiotherapy.
Radiation pneumonitis (RP) is one of the most common dose-limiting toxicities in thoracic X-ray radiotherapy (XRT). Dosimetric factors are used for prediction of the occurrence of RP after XRT. Carbon-ion radiotherapy (CRT) is a promising modality because of its excellent dose localization and high biological effect on tumors. This study aims to analyze the relationship between dosimetric factors developed for XRT and the incidence of RP in patients with stage I non-small cell lung cancer (NSCLC) after CRT. We examined 80 inoperable patients with NSCLC. The ranges of the daily fraction sizes and the total doses were from 3.3 to 8.8 GyE and from 59.4 to 95.4 GyE, respectively. These doses were successfully delivered with acceptable toxicity; >or= grade 2 RP was observed in 8 patients (10%). The severity of RP was graded within 6 months of the initiation of CRT using the Radiation Therapy Oncology Group criteria. These results indicate the excellent dose distribution of CRT. We then compared the dosimetric data of the 8 patients developed >or= grade 2 RP with those of 72 patients developed <or= grade 1 RP. Dosimetric factors useful for predicting RP in XRT, such as the percentage of the computed tomography-defined total lung volume receiving > 5, > 20, and > 30 GyE, and mean lung dose, were not predictive factors for RP after CRT. The dosimetric factors used for XRT are not applicable for CRT in patients with NSCLC. The dosimetric factors for CRT remain to be developed.


Action profile of biosynthetic human proinsulin trials with the BIOSTATOR in metabolically normal subjects.
Studies to examine the pharmacokinetics and pharmacodynamic properties of biosynthetic human proinsulin were conducted with the aid of the "glucose-controlled insulin infusion system BIOSTATOR". Seven metabolically normal healthy volunteers were given subcutaneous injections of 0.1 mg human proinsulin per kg body weight, and the subsequent behaviour of the serum proinsulin concentration was monitored over a period of 21 hours. The drop in the blood-sugar levels was counteracted by corresponding infusions of glucose by the BIOSTATOR via a special clamp technique. The intensity and frequency of the glucose infusions given by the BIOSTATOR equipment enable us to draw conclusions regarding the hypoglycaemic efficacy of human proinsulin. Two to three hours after the subcutaneous injection, the serum proinsulin concentration had reached its plateau-like maximum value. After approximately 5 hours it had dropped to 2/3 of the maximum, and after another 3 to 4 hours it had fallen further to 1/3 of the maximum. It returned virtually to its initial value after a total of 14 to 16 hours. The dextrose infusion rate calculated by the BIOSTATOR reflects these changes in the form of an "action profile". Proinsulin has a mean transit time (MTT) of 322 minutes. This is longer than the MTT of normal insulin (188 minutes) but markedly shorter than that of NPH insulin (625 minutes). If the hypoglycaemic effects of insulin and human proinsulin are compared on the basis of the areas under their respective action profile curves, the hypoglycaemic effect of 1 mg human proinsulin corresponds to 5.2 IU insulin.(ABSTRACT TRUNCATED AT 250 WORDS)


Introduction: Obesity and reproduction.
Women bear the predominant burden of our obesogenic environment, with a higher incidence of obesity than men, more impact on their fertility and success with treatment, and significant maternal and perinatal morbidity and mortality. In this series, the causes, consequences, and solutions regarding the obesity pandemic, the mechanisms of the effect of obesity on the female and male, the epigenetic consequences of male obesity, the marked effects on perinatal outcomes, and the effects of weight loss before conception and during pregnancy are explored. Lifestyle modifications, in particular a healthy diet and exercise during the 3-6 months before conception and during treatment, should result in better outcomes than requiring weight loss before fertility treatments. Such fundamental changes toward a healthier lifestyle will achieve steady and sustainable weight loss and long-term benefits for general health. The role of bariatric surgery before pregnancy requires careful consideration.


The influence of selected gastrointestinal parasites on apoptosis in intestinal epithelial cells.
Studies on the parasite-host interaction may provide valuable information concerning the modulation of molecular mechanisms as well as of the host immune system during infection. To date, it has been demonstrated that intestinal parasites may affect, among others, the processes of digestion in the gastrointestinal system of the host, thus limiting the elimination of the parasite, the immune response as well as inflammation. However, the most recent studies suggest that intestinal parasites may also affect modulation of the apoptosis pathway of the host. The present paper presents the latest scientific information on the influence of intestinal parasite species (Blastocystis sp., Giardia sp., Cryptosporidium sp., Trichuris sp., Entamoeba histolytica, Nippostrongylus brasiliensis, Heligmosomoides polygyrus) on the molecular mechanisms of apoptosis in intestinal epithelial cells. This paper stresses that the interdependency between the intestinal parasite and the host results from the direct effect of the parasite and the host's defense reactions, which lead to modulation of the apoptosis pathways (intrinsic and extrinsic). Moreover, the present paper presents the role of proteins involved in the mechanisms of apoptosis as well as the physiological role of apoptosis in the host's intestinal epithelial cells.


Cross-language measurement equivalence of the Center for Epidemiologic Studies Depression (CES-D) scale in systemic sclerosis: a comparison of Canadian and Dutch patients.
Increasingly, medical research involves patients who complete outcomes in different languages. This occurs in countries with more than one common language, such as Canada (French/English) or the United States (Spanish/English), as well as in international multi-centre collaborations, which are utilized frequently in rare diseases such as systemic sclerosis (SSc). In order to pool or compare outcomes, instruments should be measurement equivalent (invariant) across cultural or linguistic groups. This study provides an example of how to assess cross-language measurement equivalence by comparing the Center for Epidemiologic Studies Depression (CES-D) scale between English-speaking Canadian and Dutch SSc patients. The CES-D was completed by 922 English-speaking Canadian and 213 Dutch SSc patients. Confirmatory factor analysis (CFA) was used to assess the factor structure in both samples. The Multiple-Indicator Multiple-Cause (MIMIC) model was utilized to assess the amount of differential item functioning (DIF). A two-factor model (positive and negative affect) showed excellent fit in both samples. Statistically significant, but small-magnitude, DIF was found for 3 of 20 items on the CES-D. The English-speaking Canadian sample endorsed more feeling-related symptoms, whereas the Dutch sample endorsed more somatic/retarded activity symptoms. The overall estimate in depression scores between English and Dutch was not influenced substantively by DIF. CES-D scores from English-speaking Canadian and Dutch SSc patients can be compared and pooled without concern that measurement differences may substantively influence results. The importance of assessing cross-language measurement equivalence in rheumatology studies prior to pooling outcomes obtained in different languages should be emphasized.


Accuracy of diagnosis and counseling of fetal brain anomalies prior to 24 weeks of gestational age.
To evaluate the accuracy of prenatal neurosonography in diagnosing underlying causes of fetal ventriculomegaly, posterior fossa anomalies and microcephaly before 24 weeks' gestational age (GA) and to study the accuracy of prenatal counseling on postnatal prognosis. A retrospective cohort study based on 146 cases of these fetal brain anomalies before 24 weeks' GA. Counseling on prognosis was compared with postnatal outcome. Data on genetic testing was analyzed. Out of 146 cases, 135 (92%) were diagnosed correctly before 24 weeks' GA. Accuracy was 98% (97/99) in cases with multiple anomalies and 81% (38/47) in cases with an isolated abnormality. Counseling on prognosis was correct in 143 out of 146 cases (98%). Prenatal genetic diagnostics detected an anomaly in 51/113 (45%) of cases. In 14/62 (23%) cases prenatal karyotyping was normal, but postnatal array-CGH detected a pathogenic anomaly. Despite the challenges of early gestation, accuracy in diagnosing and counseling fetal brain anomalies before 24 weeks' GA was high. Prenatal genetic testing is a valuable diagnostic tool and should be offered to all women with fetal brain anomalies. Considering the many different types of anomalies and diverse etiologies, a multidisciplinary approach is essential for counseling on postnatal outcome.


Dispersal, vicariance, and timing of diversification in Nothonotus darters.
The species diversity of North American freshwater fishes is unparalleled among temperate regions of the planet. This diversity is concentrated in the Central Highlands of eastern North America and this distribution pattern has inspired different models involving either dispersal or vicariance to explain the high species diversity of North American fishes. The most popular of these models is the Central Highlands vicariance hypothesis (CHVH), which proposes an ancient and diverse widespread fauna that existed across a previously continuous highland landscape that is much different from today. The mechanisms of isolation in the CHVH involve specific instances of vicariance that affected several diverse lineages of Central Highlands fishes. We tested predictions of the CHVH and alternative models using a cytochrome b-inferred phylogeny of the darter clade Nothonotus. A Bayesian mixed-model method was used for phylogenetic analysis. The phylogenetic data set included all 20 recognized Nothonotus species, and most species were represented with multiple sequences. We were able to convert genetic branch lengths to absolute age using external fossil calibrations in the freshwater perciform fish clade Centrarchidae. Using a well-resolved Nothonotus phylogeny and divergence time estimates, we identify equal numbers of instances of both vicariance and dispersal among disjunct regions of the Central Highlands, biogeographic pseudocongruence, rather recent speciation in Nothonotus, and a surprisingly large amount of speciation within highland areas. With regard to Nothonotus, previous Central Highlands biogeographic models offer little in the way of providing possible mechanisms responsible for diversification in the clade. Patterns of speciation in Nothonotus are similar to those discovered in recent efforts that have included speciation as a parameter into classic models of island biogeography.


[Effect of Modified Huanglian Jiedu Decoction Purgation Combined Electroacupuncture in Intervening Gastrointestinal Dysfunction of Critically Ill Patients Undergoing Abdominal Surgery].
To observe the effect of purgation and detoxification therapy on gastrointestinal dysfunction of critically ill patients undergoing abdominal surgery. Totally 56 inpatients with severe gastrointestinal dysfunction after abdominal surgery at ICU of Guangdong Provincial Hospital of Traditional Chinese Medicine were assigned to the treatment group and the control group, 28 in each group. All patients received routine Western medical treatment. Patients in the treatment group additionally took Modified Huanglian Jiedu Decoction (MHJD) and received electroacupuncture (EA) for 7 days. The first exhaust time, defecation time, scores for gastrointestinal dysfunction, mechanical ventilation time, ICU hospitalization time, and 28-day fatality rate were observed. Furthermore, serum levels of diamine oxidase (DAO) and D-lactic acid were detected at day 1, 3, and 7 after treatment. The first exhaust time and the first defecation time in the treatment group were ahead of schedule, when compared with those of the control group (P <0. 05). Scores for gastrointestinal dysfunction, mechanical ventilation time, serum levels of DAO obviously decreased in the treatment group (P <0. 05). There was no statistical difference in serum levels of D-lactic acid, ICU stay time, the incidence of pulmonary infection, and 28-day mortality between the two groups (P >0. 05). Results of Logistic analysis showed that scores for gastrointestinal dysfunction were related with the incidence of pulmonary infection (P <0. 05). MHJD combined EA could promote the recovery of gastrointestinal function in critically ill patients after abdominal surgery via improving intestinal barrier function, which was benefit for shortening mechanical ventilation time.


The roles of Pol and Env in the assembly pathway of human foamy virus.
Human foamy virus (HFV) is the prototype of the Spumavirus genus of retroviruses. These viruses have a genomic organization close to that of other complex retroviruses but have similarities to hepadnaviruses such as human hepatitis B virus (HBV). Both HFV and HBV express their Pol protein independently of their structural proteins. Retroviruses and hepadnaviruses differ in their requirements for particle assembly and genome packaging. Assembly of retroviral particles containing RNA genomes requires only the Gag structural protein. The Pol protein is not required for capsid assembly, and the Env surface glycoprotein is not required for release of virions from the cell. In contrast, assembly of extracellular HBV particles containing DNA requires core structural protein and polymerase (P protein) for assembly of nucleocapsids and requires surface glycoproteins for release from the cell. We investigated the requirements for synthesis of extracellular HFV particles by constructing mutants with either the pol or env gene deleted. We found that the Pol protein is dispensable for production of extracellular particles containing viral nucleic acid. In the absence of Env, intracellular particles are synthesized but few or no extracellular particles could be detected. Thus, foamy virus assembly is distinct from that of other reverse transcriptase-encoding mammalian viruses.


Reduction of the domino effect in osteoporotic vertebral compression fractures through short-segment fixation with intravertebral expandable pillars compared to percutaneous kyphoplasty: a case control study.
Osteoporotic vertebral compression fracture is the leading cause of disability and morbidity in elderly people. Treatment of this condition remains a challenge. Osteoporotic vertebral compression fractures can be managed with various approaches, but each has limitations. In this study, we compared the clinical outcomes obtained using short-segment fixation with intravertebral expandable pillars (I-VEP) to those obtained with percutaneous kyphoplasty in patients who had suffered vertebral compression fractures. The study included 46 patients with single-level osteoporotic thoracolumbar fractures. Twenty-two patients in Group I underwent short-segment fixation with I-VEP and 24 patients in Group II underwent kyphoplasty. All patients were evaluated pre- and postoperatively using a visual analogue scale, anterior height of the fractured vertebra, and kyphotic angle of the fractured vertebra. The latter 2 radiological parameters were measured at the adjacent segments as well. There was no significant difference between the groups in terms of gender or fracture level, but the mean age was greater in Group II patients (p = 0.008). At the 1-year follow-up, there were no significant differences in the visual analogue scale scores, anterior height of the fractured vertebra, or the value representing anterior height above the fractured vertebra and kyphotic angle below the fractured vertebra, after adjusting for the patients' gender, fracture level, and age. When considered separately, the anterior height below the fractured vertebra was significantly higher and the kyphotic angle above the fractured vertebra was significantly smaller in Group I than in Group II (p = 0.029 and p = 0.008, respectively). The kyphotic angle of the fractured vertebra was significantly smaller in Group II than in Group I (p < 0.001). In older individuals with vertebral compression fractures, kyphoplasty restored and maintained the collapsed vertebral body with less kyphotic deformity than that induced by short-segment fixation with I-VEP. Short-segment fixation with I-VEP was more effective in maintaining the integrity of adjacent segments, which prevented the domino effect often observed in patients with osteoporotic kyphotic spines.


Commentary on 'interventions for promoting re-integration and reducing harmful behaviour and lifestyles in street-connected children and young people' with a response from the review authors.
This is a commentary on a Cochrane review, published in the issue of EBCH, first published as: Coren E, Hossain R, Pardo Pardo J, Veras MMS, Chakraborty K, Harris H, Martin AJ. Interventions for promoting re-integration and reducing harmful behaviour and lifestyles in street-connected children and young people. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD009823. DOI: 10.1002/14651858.CD009823.pub2.


[Chlamydia trachomatis: should it be systematically be screened or treated? Literature review and cost/benefit estimation in France].
Chlamydia trachomatis is a primary cause of acute or silent salpingitis leading to infertility and ectopic pregnancy. The C. trachomatis epidemic, undiscovered in most cases, spreads, mostly in adolescents, during the years following the onset of sexual activity. As opposed to gonococcal infection which has greatly decreased, C. trachomatis cervical and urethral infection is commun in young occidentals. More then 30 different studies covering 200-12000 subjects screened in family planning centers, college women and men, students and military recruits in different parts of the USA, in Scandinavian countries and France, indicate a prevalence of 5-20% (mean 10%) in apparently healthy young females < 25 years and 5-10% in males. Female prevalence is strongly related to age, being highest (5-20%) in women < 20 years old. Several cost-benefit analysis show that the total cost of the general screening in young populations, which can easily be carried out for women in family planning centers, could save twice the cost of treatment for pelvic inflammatory disease caused by C. trachomatis and six times the total cost of C. trachomatis epidemics if late sequelae are taken into account (tubal infertility treatment, ectopic pregnancy). In France, screening should save 12 to 48 millions French francs each year, depending of the cost of detection. The final benefit of detection should be the eradication of the epidemic as obtained to date in Scandinavian countries.


This is your brain on sports. Measuring concussions in high school athletes in the Twin Cities metropolitan area.
Concussions can have a negative impact on students' ability to perform in the classroom as well as on their health and well-being. Therefore, timely treatment is especially important. To better understand the scope of the problem in Minnesota, the Minnesota Department of Health piloted an online sports-related concussion reporting system in 36 public high schools in the Twin Cities metropolitan area. In the 2013-2014 academic year, 730 concussions were reported to our system from certified athletic trainers working with those schools, with one out of every 100 athletes sustaining concussions. From this, we estimated that 2,974 sports-related concussions occurred among high school athletes statewide. This information is useful for evaluating and guiding prevention efforts and for informing clinicians on how to treat concussions.


Time course efficiency of MICE and HIIE on inhibitory control and HRV in adolescents with obesity and different cardiorespiratory fitness.
Adolescent obesity is associated with impaired inhibitory control. Acute exercise can improve executive function. However, due to the influence of exercise intensity, cognitive test timing, and cardiorespiratory fitness (CF) level, the most effective exercise program remains controversial. The current study investigated the time-course effects of moderate-intensity continuous exercise (MICE) and high-intensity interval exercise (HIIE) on inhibitory control (Stroop) and task-related heart rate variability (HRV) in adolescents with different CF. A mixed experimental design of 2 CF levels (high CF, HCF; low CF, LCF) × 3 exercise methods (MICE, HIIE, CON) × 3 test timing (pre, post-0, post-20) was adopted. Heart rate variability (HRV) and Stroop task tests were conducted before exercise (pre), immediately after exercise (post-0), and 20 min after exercise (post-20). Individuals with HCF exhibited a positive decrease in Stroop response time immediately and 20 min after MICE and HIIE, compared to pretest response times (RT). Conversely, individuals with LCF showed a slight increase in Stroop task (RT) only immediately after HIIE. All individuals had a slight increase in ACC after MICE and HIIE compared to before exercise. In addition, compared with the control group, the time-domain index (the square root of the mean squared differences of successive NN intervals, RMSSD) of HRV was significantly decreased, the frequency-domain index (the absolute power of the Low-Frequency band/the absolute power of the High-Frequency band ratio, LF/HF) was significantly increased after MICE and HIIE, and the effect of HIIE on RMSSD and LF/HF was significantly greater than that of MICE. The current study found that the acute effects of MICE and HIIE on inhibitory control in obese adolescents were influenced by the interaction of cognitive test timing and cardiorespiratory fitness. Individuals with high cardiorespiratory fitness performed better on the Stroop task than individuals with low cardiorespiratory fitness. The inhibitory control of HIIE in high-cardiorespiratory obese adolescents produced positive effects similar to those in MICE but more lasting, suggesting that HIIE is more beneficial for high-cardiorespiratory obese adolescents. MICE promoted inhibitory control in obese adolescents with low cardiorespiratory fitness, but HIIE impaired inhibitory control in obese adolescents with low cardiorespiratory fitness immediately after exercise, suggesting that low cardiopulmonary fitness obese adolescents may be suitable for MICE rather than HIIE exercise intervention. The shift from balanced HRV to sympathetic dominance after acute exercise reflects increased arousal levels and may be one of the underlying mechanisms by which acute exercise brings benefits to executive function.


Alkylated isocoumarins from Pituranthos scoparius.
Two isocoumarins have been isolated from the ethyl acetate extract of the root of Pituranthos scoparius: 3-n-propyl-5-methoxy-6-hydroxy-isocoumarin and 3-n-propyl-5,7-dimethoxy-6-hydroxy-isocoumarin. Their structures were assigned by spectral analysis.


Combination of Ascorbic Acid and Menadione Induces Cytotoxic Autophagy in Human Glioblastoma Cells.
We investigated the ability of the ascorbic acid (AA) and menadione (MD) combination, the well-known reactive oxidative species- (ROS-) generating system, to induce autophagy in human U251 glioblastoma cells. A combination of AA and MD (AA+MD), in contrast to single treatments, induced necrosis-like cell death mediated by mitochondrial membrane depolarization and extremely high oxidative stress. AA+MD, and to a lesser extent MD alone, prompted the appearance of autophagy markers such as autophagic vacuoles, autophagosome-associated LC3-II protein, degradation of p62, and increased expression of beclin-1. While both MD and AA+MD increased phosphorylation of AMP-activated protein kinase (AMPK), the well-known autophagy promotor, only the combined treatment affected its downstream targets, mechanistic target of rapamycin complex 1 (mTORC1), Unc 51-like kinase 1 (ULK1), and increased the expression of several autophagy-related genes. Antioxidant N-acetyl cysteine reduced both MD- and AA+MD-induced autophagy, as well as changes in AMPK/mTORC1/ULK1 activity and cell death triggered by the drug combination. Pharmacological and genetic autophagy silencing abolished the toxicity of AA+MD, while autophagy upregulation enhanced the toxicity of both AA+MD and MD. Therefore, by upregulating oxidative stress, inhibiting mTORC1, and activating ULK1, AA converts MD-induced AMPK-dependent autophagy from nontoxic to cytotoxic. These results suggest that AA+MD or MD treatment in combination with autophagy inducers could be further investigated as a novel approach for glioblastoma therapy.


Comparative mitochondrial genome analysis of the Mongolian redfin, Chanodichthys mongolicus (Xenocyprididae) from China reveals heteroplasmy.
This study determined the mitochondrial genome (mitogenome) of Chanodichthys mongolicus from China's Qiantang River and analyzed its phylogenetic history in the Subfamily Cultrinae. Next-generation sequencing was used to obtain the mitogenome of C. mongolicus, GenBank Accession Number MZ032228. The mitochondrial genome length of C. mongolicus from China's Qiantang River is 16,622 bp. The genome contains 13 protein-coding genes, 22 transfer RNAs, two ribosomal RNAs, and two central noncoding regions (the control region and the origin of light strand replication). Based on BLAST comparisons, the sequence identity of C. mongolicus MZ032228 from China's Qiantang River was 99.84% to that of Ancherythroculter wangi MG783573 from China's Nei River, 99.75% to C. mongolicus AP009060 from Russia's Black River. The phylogenetic analysis is consistent with BLAST comparisons in confirming that A. wangi MG783573 and C. mongolicus MZ032228 show a high genetic similarity. This study also confirms mitochondrial DNA heteroplasmy in C. mongolicus for the first time and documents 35 heterogeneous loci that were detected.


[Bacterial translocation in acute pancreatitis. Experimental study in rats].
Ninety Wistar rats were studied to confirm if the intestinal tract is a source of infection in acute pancreatitis. Bacterial translocation to the mesenteric lymph nodes, pancreas, peritoneal cavity, and blood was determined at 6 h, 24 h, 48 h and 96 hours after induction of non lethal acute pancreatitis. Bacterial growing was present in 60% (6 h), 90% (24 h), 70% (48 h) and 40% (96 h) (p < 0.05) of the mesenteric lymph nodes. Live bacteria were recovered from 67% (6 h), 90% (24 h), 50% (48 h) and 40% (96 h) (p < 0.05) of the pancreas. Gram-positive bacteria translocate more frequently than Gram-negative bacteria in the early period (6 h). Lately (24-96 h), Gram-negative bacteria were much more frequently isolated (p < 0.05). The most common organism isolated was Escherichia coli. No overgrowth of cecal Gram-negative bacteria was found. It is concluded that bacterial translocation in acute pancreatitis is an early phenomena, initially caused by Gram-positive bacteria and lately by Gram-negative bacteria, and associated with the severity of pancreatic lesions.


[Acute renal damage secondary to acute tubulointerstitial nephritis drug use. Case report].
Acute tubulointerstitial nephritis (ATIN) is a rare entity in the pediatric age. It is de fined by the infiltration of the renal parenchyma by mononuclear and/or polynuclear cells with se condary involvement of the tubules, without glomerular injury. It can be triggered by infections or immunological diseases, drugs like NSAIDs or be of idiopathic origin. To raise awareness among pediatricians about the prescription of NSAIDs, especially to patients of less than a year old, since they can provoke renal damage. A ten month old child, with no nephrological an tecedents of interest, was transferred to our hospital due to acute renal failure stage 3 KDIGO 2012. The three previous days received treatment with amoxicillin and ibuprofen for acute otitis media. Physical examination revealed mild eyelid edema with normal blood pressure. In the urine analysis, there were non-nephrotic proteinuria with tubular component, microhematuria and leukocyturia. Renal ultrasound showed no abnormalities. ATIN was suspected and so the antibiotic was changed to intravenous cefotaxime and ibuprofen was discontinued, opting for conservative management of acute renal damage. There was an increase in the number of creatinine up to 4.14 mg/dL and eosinophilia, with the immunological study being negative. Treatment with methylprednisolone was initiated, achieving normalization of renal function. NTIA can be produced by any me dication through an idiosyncratic immune reaction. Among the responsible drugs, there are ones commonly used in the pediatric age, such as NSAIDs. Therefore, the pediatricians should pay special attention during prescriptions and have a high diagnostic suspicion of this disease.


IgA nephropathy with mimicking Fabry disease: A case report and literature review.
Fabry disease (FD) is a rare, inherited disease lysosomal storage disorder caused by the lack of an alpha-galactosidase enzyme. This genetic disease can affect both men and women. The understanding of FD is very important as this condition can be effectively treated. For women who may exhibit normal residual enzyme activity, the diagnosis is more challenging. Herein, we reported on a case of IgA nephropathy and renal disease that mimicked FD in a female patient. The presence of zebra bodies in the cytoplasm of glomerular podocytes is widely accepted as a hallmark pathological manifestation of FD. In the present case, renal biopsy analysis revealed the presence of zebra bodies; however, genetic testing indicated that the patient did not have FD. The mechanisms and causes of zebra body formation remained unclear in the present case. However, the patient responded well to treatment with an angiotensin receptor blocker. The reported findings can be useful for the differential diagnosis of FD and renal diseases in the future. Our results also highlight the clinical significance of zebra bodies in renal disease.


Reproductive functions of progesterone receptors.
The steroid hormone progesterone plays a central role in the reproductive events associated with pregnancy establishment and maintenance. Physiological effects of progesterone are mediated by interaction of the hormone with specific intracellular progesterone receptors (PRs) that are expressed as two protein isoforms, PR-A and PR-B. Both proteins arise from the same gene and are members of the nuclear receptor superfamily of transcription factors. Since these two isoforms were identified in the early 1970s, extensive controversy has existed regarding the selective contributions of the individual PR proteins to the physiological functions of progesterone. During the past decade, significant progress has been made in this regard using two complimentary approaches. First, analysis of the structural and functional relationships of each isoform using in vitro systems has generated compelling evidence to support the conclusion that PR-A and PR-B have different transcription activation properties when liganded to progesterone. Second, the advent of gene-targeting approaches to introduce subtle mutations into the mouse genome has facilitated the evaluation of the significance of observations made in vitro in a physiological context. Selective ablation of PR-A and PR-B proteins in mice using these technologies has allowed us to address the spatiotemporal expression and contribution of the individual PR isoforms to the pleiotropic reproductive activities of progesterone. Analysis of the phenotypic consequences of these mutations on female reproductive function has provided proof of concept that the distinct transcriptional responses to PR-A and PR-B observed in cell-based transactivation assays are, indeed, reflected in an ability of the individual isoforms to elicit distinct, physiological responses to progesterone. In PR-A knockout mice, in which the expression of the PR-A isoform is selectively ablated (PRAKO), the PR-B isoform functions in a tissue-specific manner to mediate a subset of the reproductive functions of PRs. Ablation of PR-A does not affect responses of the mammary gland or thymus to progesterone but instead results in severe abnormalities in ovarian and uterine function, leading to female infertility. These tissue-selective activities of PR-B are due to this isoform's ability to regulate a subset of progesterone-responsive target genes in reproductive tissues rather than to differences in its spatiotemporal expression relative to the PR-A isoform. More recent studies using PR-B knockout (PRBKO) mice have shown that ablation of PR-B does not affect ovarian, uterine, or thymic responses to progesterone but rather results in reduced mammary ductal morphogenesis. Thus, PR-A is both necessary and sufficient to elicit the progesterone-dependent reproductive responses necessary for female fertility, while PR-B is required to elicit normal proliferative responses of the mammary gland to progesterone. This chapter will summarize recent progress in our understanding of the selective contribution of the two PR isoforms to progesterone action.


Cocaine affects foraging behaviour and biogenic amine modulated behavioural reflexes in honey bees.
In humans and other mammals, drugs of abuse alter the function of biogenic amine pathways in the brain leading to the subjective experience of reward and euphoria. Biogenic amine pathways are involved in reward processing across diverse animal phyla, however whether cocaine acts on these neurochemical pathways to cause similar rewarding behavioural effects in animal phyla other than mammals is unclear. Previously, it has been shown that bees are more likely to dance (a signal of perceived reward) when returning from a sucrose feeder after cocaine treatment. Here we examined more broadly whether cocaine altered reward-related behaviour, and biogenic amine modulated behavioural responses in bees. Bees developed a preference for locations at which they received cocaine, and when foraging at low quality sucrose feeders increase their foraging rate in response to cocaine treatment. Cocaine also increased reflexive proboscis extension to sucrose, and sting extension to electric shock. Both of these simple reflexes are modulated by biogenic amines. This shows that systemic cocaine treatment alters behavioural responses that are modulated by biogenic amines in insects. Since insect reward responses involve both octopamine and dopamine signalling, we conclude that cocaine treatment altered diverse reward-related aspects of behaviour in bees. We discuss the implications of these results for understanding the ecology of cocaine as a plant defence compound. Our findings further validate the honey bee as a model system for understanding the behavioural impacts of cocaine, and potentially other drugs of abuse.


Cloning of cDNA encoding the common alpha subunit precursor molecule of pituitary glycoprotein hormones in the Australian lungfish, Neoceratodus forsteri.
We have isolated cDNA clones encoding a putative glycoprotein hormone alpha subunit precursor molecule from a pituitary cDNA library of the Australian lungfish (Neoceratodus forsteri) by a two-step plaque hybridization technique initially using cDNA encoding the toad glycoprotein hormone alpha subunit precursor molecule as the hybridization probe. The inserts (799 bp) of two of the isolated cDNA clones contained sequences of 5' and 3' untranslated regions, including a poly(A) stretch, and the entire coding sequence of the alpha subunit precursor molecule. The deduced amino acid sequence showed that its signal peptide consists of 24 residues and its mature protein 97 residues. In the mature protein, there is an insert of one residue (Ala) just after the 9th residue. This insert is unique to the Australian lungfish among vertebrate species studied. The amino acid sequence of the mature protein shares the common, or the same-group, amino acid residues at 9 positions with tetrapod and not actinopterygian vertebrates, while only one residue is common to some teleosts and the lungfish to the exclusion of the tetrapods. The overall sequence of the mature protein of the Australian lungfish also shares more similarity with those of tetrapods (69 to 84%) than it does with teleosts (57 to 74%). These results on the relation of the alpha subunit precursor molecule between the lungfish and other vertebrates are consistent with the recent molecular phylogenetic studies suggesting a closer relationship between lungfish and tetrapods than between lungfish and teleosts. We also found that the primary structure of the lungfish alpha subunit is slightly but significantly more similar to that of homeothermic vertebrates than to that of amphibians. This may be due to specialization of the amphibian alpha subunit molecules.


Travelling in old age.
Expanding the "journey test", the author recommends a simple diagnostic test by which the physician can gain a quick information on the psycho-motoric-somatic status of the old patients--as evidenced by 100 cases examined. To make a journey is recommended by the physician even to old people provided the following conditions are fulfilled: I. intact capacity of reasoning; II. satisfactory somatic condition; III. ability of harmonic (co-ordinated) locomotion; IV. financial (objective) resources available for the journey.


Body Composition Differences in Military Pilots and Aircrew.
BACKGROUND: This research aimed to analyze the body composition (BC) of different military units in the Spanish Armed Forces.METHODS: We studied 179 male aircrew members (86 airplane pilots, 15 helicopter pilots and 78 transport aircrew) using bioimpedance.RESULTS: Airplane pilots (AP) had higher means than transport aircrew (TA) in height (179.56 cm vs. 173.90 cm), total body water (46.72 L vs. 42.96 L), intracellular body water (29.45 L vs. 26.89 L), extracellular body water (17.27 L vs. 16.07 L), proteins (12.72 kg vs.11.63 kg), minerals (4.50 kg vs. 4.15 kg), soft lean mass (60.21 kg vs. 55.29 kg), fat free mass (63.95 kg vs. 58.74 kg), skeletal muscle mass (36.41 kg vs. 33.07 kg), and lower means in body mass index (24.01 kg vs. 25.49 kg), body fat mass (BFM) (13.53 kg vs. 18.81 kg) and percentage of body fat (PBF) (16.83 kg vs. 23.79 kg). Helicopter pilots also had significantly lower means in BFM (13.21 kg vs. 18.81 kg) and PBF (17.11 kg vs. 18.81 kg) than TA.DISCUSSION: The different types of activity between AP (active coping with G forces) and TA (inactive) during operational flights negatively affects the body composition of TA. These results suggest differences in aircrews training and job tasks. Specific training is needed for each unit: it should be individualized, prevent injuries, and be directed by qualified personnel.Bustamante-Sánchez Á, Clemente-Suárez VJ. Body composition differences in military pilots and aircrew. Aerosp Med Hum Perform. 2020; 91(7):565-570.


National Early Rectal Cancer Treatment Revisited.
Treatment of early stage rectal cancer has excellent oncological results. To reduce treatment-related mortality and morbidity and improve functional results, a focus on local resections is increasingly important. The purpose of this study was to compare outcomes after transanal endoscopic microsurgery and total mesorectal excision for early stage rectal cancer (T1 + T2) in Norway. This was an observational study based on prospective data from the Norwegian Colorectal Cancer Registry. The study was conducted as a national, population-based study. All 543 patients with T1 and 1593 patients with T2 rectal cancer without distant metastases that was treated by transanal endoscopic microsurgery or total mesorectal excision without radiochemotherapy during 2000-2009 were included. The primary outcomes were 5-year relative survival and 5-year local recurrence rate. Among 543 patients with T1 cancer, the 5-year overall survival rate was 65.3% after transanal endoscopic microsurgery versus 81.5% after total mesorectal excision (p = 0.012). Adjusted for age and sex there was no excess mortality for transanal endoscopic microsurgery (HR = 1.28 (95% CI, 0.8-1.9); p = 0.22). The 5-year relative survival rate was 96.8% after transanal endoscopic microsurgery versus 98.2% after total mesorectal excision (p = 0.603), and the 5-year local recurrence rate was 14.5% versus 1.4% (p < 0.001). Among 1593 patients with T2 cancer, 5-year overall survival was 42.1% versus 76.1% (p < 0.001), 5-year relative survival was 65.4% versus 93.9% (p < 0.001), and 5 year local recurrence rate was 11.4% versus 4.4% in the 2 groups. The study is limited by its observational design and that the 2 groups were different according to patient and tumor characteristics. Another limitation was the low number of transanal endoscopic microsurgery procedures. Transanal endoscopic microsurgery had comparable 5-year relative survival to total mesorectal excision in T1 rectal cancer but inferior 5-year relative survival in T2 rectal cancer. Transanal endoscopic microsurgery was associated with higher local recurrence rates for both T1 and T2 tumors.


The Expression of IL-6, TNF-α, and MCP-1 in Respiratory Viral Infection in Acute Exacerbations of Chronic Obstructive Pulmonary Disease.
Viral infection is a common trigger for acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The aim of this study is to investigate the expression of cytokines in AECOPD. Patients with AECOPD requiring hospitalization were recruited. Meanwhile healthy volunteers of similar age that accepted routine check-ups and showed no clinical symptoms of inflammatory diseases were also recruited. Induced sputum and serum were collected. Induced sputum of participants was processed and tested for thirteen viruses and bacteria. Forty cytokines were assayed in serum using the Quantibody Human Inflammation Array 3 (Ray Biotech, Inc.). The most common virus detected in virus positive AECOPD (VP) was influenza A (16%). No virus was found in controls. Circulating levels of IL-6, TNF-α, and MCP-1 were elevated in VP and coinfection subjects (p < 0.05), while the levels of 37 other cytokines showed no difference, compared with virus negative groups and controls (p > 0.05). Additionally, VP patients were less likely to have received influenza vaccination. VP patients had a systemic inflammation response involving IL-6, TNF-α, and MCP-1 which may be due to virus-induced activation of macrophages. There are important opportunities for further investigating AECOPD mechanisms and for the development of better strategies in the management and prevention of virus-related AECOPD.


[Research of adaptive notch filter based on QRD-LS algorithm for power line interference in ECG].
In this paper, an adaptive notch filter based on QRD-LS algorithm for power line interference in ECG is researched. It can automatically eliminate the power line interference in order to improve the signal-to-interference ratio. Furthermore, QLD-LS algorithm, which is recursive least-squares minimization using systolic arrays, is employed to adjust the weight vector. Compared with the adaptive notch filter based on LMS (least mean square) algorithm, it has good robustness. Simulation examples confirm the results. QRD-LS adaptive notch filter has better performance in comparison with LMS method.


Polychlorinated naphthalenes in Great lakes air: assessing spatial trends and combustion inputs using PUF disk passive air samplers.
Passive air samplers made from polyurethane foam (PUF) disks housed in stainless steel chambers were deployed over four seasons during 2002-2003, at 15 sites in the Laurentian Great lakes, to assess spatial and temporal trends of polychlorinated naphthalenes (PCNs). Sampling rates, determined using depuration compounds pre-spiked into the PUF disk prior to exposure, were, on average, 2.9 +/- 1.1 m3 d(-1), consistent with previous studies employing these samplers. PCN air concentrations exhibited strong urban-rural differences-typically a few pg m(-3) at rural sites and an order of magnitude higher at urban sites (Toronto, 12-31 pg m(-3) and Chicago,13-52 pg m(-3)). The high concentrations at urban sites were attributed to continued emissions of historically used technical PCN. Contributions from combustion-derived PCNs seemed to be more important at rural locations where congeners 24 and 50, associated with wood and coal burning, were elevated. Congener 66/67, associated with incineration and other industrial thermal processes, was elevated at two sites and explained by nearby and/or upwind sources. Probability density maps were constructed for each site and for every integration period were shown to be a useful complement to seasonally integrated passive sampling data to resolve source-receptor relationship for PCNs and other pollutants.


Applying voting theory in natural resource management: a case of multiple-criteria group decision support.
Voting theory has a lot in common with utility theory, and especially with group decision-making. An expected-utility-maximising strategy exists in voting situations, as well as in decision-making situations. Therefore, it is natural to utilise the achievements of voting theory also in group decision-making. Most voting systems are based on a single criterion or holistic preference information on decision alternatives. However, a voting scheme called multicriteria approval is specially developed for decision-making situations with multiple criteria. This study considers the voting theory from the group decision support point of view and compares it with some other methods applied to similar purposes in natural resource management. A case study is presented, where the approval voting approach is introduced to natural resources planning and tested in a forestry group decision-making process. Applying multicriteria approval method was found to be a potential approach for handling some challenges typical for forestry group decision support. These challenges include (i) utilising ordinal information in the evaluation of decision alternatives, (ii) being readily understandable for and treating equally all the stakeholders in possession of different levels of knowledge on the subject considered, (iii) fast and cheap acquisition of preference information from several stakeholders, and (iv) dealing with multiple criteria.


Using Serology to Anticipate Measles Post-honeymoon Period Outbreaks.
Measles vaccination is a public health 'best buy', with the highest cost of illness averted of any vaccine-preventable disease (Ozawa et al., Bull. WHO 2017;95:629). In recent decades, substantial reductions have been made in the number of measles cases, with an estimated 20 million deaths averted from 2000 to 2017 (Dabbagh et al., MMWR 2018;67:1323). Yet, an important feature of epidemic dynamics is that large outbreaks can occur following years of apparently successful control (Mclean et al., Epidemiol. Infect. 1988;100:419-442). Such 'post-honeymoon period' outbreaks are a result of the nonlinear dynamics of epidemics (Mclean et al., Epidemiol. Infect. 1988;100:419-442). Anticipating post-honeymoon outbreaks could lead to substantial gains in public health, helping to guide the timing, age-range, and location of catch-up vaccination campaigns (Grais et al., J. Roy. Soc. Interface 2008003B6:67-74). Theoretical conditions for such outbreaks are well understood for measles, yet the information required to make these calculations policy-relevant is largely lacking. We propose that a major extension of serological studies to directly characterize measles susceptibility is a high priority.


The Plasma Membrane Calcium ATPases and Their Role as Major New Players in Human Disease.
The Ca2+ extrusion function of the four mammalian isoforms of the plasma membrane calcium ATPases (PMCAs) is well established. There is also ever-increasing detail known of their roles in global and local Ca2+ homeostasis and intracellular Ca2+ signaling in a wide variety of cell types and tissues. It is becoming clear that the spatiotemporal patterns of expression of the PMCAs and the fact that their abundances and relative expression levels vary from cell type to cell type both reflect and impact on their specific functions in these cells. Over recent years it has become increasingly apparent that these genes have potentially significant roles in human health and disease, with PMCAs1-4 being associated with cardiovascular diseases, deafness, autism, ataxia, adenoma, and malarial resistance. This review will bring together evidence of the variety of tissue-specific functions of PMCAs and will highlight the roles these genes play in regulating normal physiological functions and the considerable impact the genes have on human disease.