Use of MRSD medium and the hydrophobic grid membrane filter technique to differentiate between pediococci and lactobacilli in fermented meat and starter cultures.
Modifications of MRS medium were made by incorporation of 0.1 M L-arginine-HCl, 0.0025% phenol red, 100 IU polymyxin B sulfate, by deletion of meat extract, use of only 1.2% (w/v) glucose and increase of Mn2+ to 1000 ppm. In addition, adoption of the hydrophobic grid membrane filter (HGMF) system with 0.025% Fast Green FCF dye and adjustment of the agar medium to pH 5.5 gave MRSD (differential) medium. Incubation at 25 degrees C anaerobically under N2 or CO2 followed by a post-growth staining procedure involving use of 0.4% (w/v) bromocresol purple yielded conditions under which pediococci colonies were blue whereas homo- and heterofermentative lactobacilli were green in color. Under these conditions, 7 pediococci, 16 lactobacilli, and 18 commercial meat starter cultures were successfully analyzed by plate count to yield a differential assessment of the lactobacilli and pediococci present without interference from the 9 other genera tested. Streptococcus lactis and Leuconostoc spp. produced blue and green colonies, respectively, at 25 degrees C which might interference but these organisms are not present in significant numbers in fermented meats. Pediococcus parvulus and Streptococcus faecalis produced green and blue colonies, respectively, but their very poor growth at 25 degrees C prevented their interference. Use of the developed MRSD medium was described for enumeration of both pediococci and lactobacilli in starter cultures and in fermenting dry sausages to enable documentation of starter culture performance.


Palladate salts from chiral pyridinium ionic liquids: synthesis and crystal structures.
This paper reports the preparation, characterization and the crystal X-ray structures of metal-containing ionic liquid complexes based on chiral pyridinium cations and tetrachloropalladate (II) [PdCl4]2-.


Structural responsiveness of filamentous bacteriophage Pf1: comparison of virion structure in fibers and solution. The effect of temperature and ionic strength.
X-ray diffraction from fibers and magnetically oriented solutions has been used to study the effect of changes in environment on the helical symmetry and radial structure of the Pf1 virus particle. Detailed analysis of equatorial scattering to a spacing of 8-10 A was used to identify small radial motions of structural elements in the virus particle. R-factor ratios were used to determine the statistical significance of observed changes. Comparison of the structure of virus particles in fibers with those in solution indicated that the helical symmetry of the virions remains unchanged during fiber formation. In most fibers the virions appear to be slightly distorted by the tight packing of virus particles. This distortion results in an apparent increase in the radius of the virus particle of approximately 0.6 A. A change in the radius of the DNA is also observed. Increase in the concentration of solvent molecules during fiber formation results in penetration of the virus interior by some solvent components. NaCl is also able to enter the virus interior. The change in the helical symmetry of the virions at approximately 8 degrees C appears to be the same whether observed by diffraction from fibers or from solutions. Only subtle changes in radial structure are associated with the temperature transition.


The circular RNA circ-ERBIN promotes growth and metastasis of colorectal cancer by miR-125a-5p and miR-138-5p/4EBP-1 mediated cap-independent HIF-1α translation.
Circular RNA (circRNAs) and hypoxia have been found to play the key roles in the pathogenesis and progression of cancer including colorectal cancer (CRC). However, the expressions and functions of the specific circRNAs in regulating hypoxia-involved CRC metastasis, and the circRNAs that are relevant to regulate HIF-1α levels in CRC remain elusive. qRT-PCR was used to detect the expression of circRNAs and mRNA in CRC cells and tissues. Fluorescence in situ hybridization (FISH) was used to analyze the location of circ-ERBIN. Function-based experiments were performed using circ-ERBIN overexpression and knockdown cell lines in vitro and in vivo, including CCK8, colony formation, EdU assay, transwell, tumor growth and metastasis models. Mechanistically, luciferase reporter assay, western blots and immunohistochemical stainings were performed. Circ-Erbin was highly expressed in the CRC cells and Circ-Erbin overexpression facilitated the proliferation, migration and metastasis of CRC in vitro and in vivo. Notably, circ-Erbin overexpression significantly promoted angiogenesis by increasing the expression of hypoxia induced factor (HIF-1α) in CRC. Mechanistically, circ-Erbin accelerated a cap-independent protein translation of HIF-1α in CRC cells as the sponges of miR-125a-5p and miR-138-5p, which synergistically targeted eukaryotic translation initiation factor 4E binding protein 1(4EBP-1). Our findings uncover a key mechanism for circ-Erbin mediated HIF-1α activation by miR-125a-5p-5p/miR-138-5p/4EBP-1 axis and circ-ERBIN is a potential target for CRC treatment.


Use of a physiologically-based pharmacokinetic model to explore the potential disparity in nicotine disposition between adult and adolescent nonhuman primates.
The widespread use and high abuse liability of tobacco products has received considerable public health attention, in particular for youth, who are vulnerable to nicotine addiction. In this study, adult and adolescent squirrel monkeys were used to evaluate age-related metabolism and pharmacokinetics of nicotine after intravenous administration. A physiologically-based pharmacokinetic (PBPK) model was created to characterize the pharmacokinetic behaviors of nicotine and its metabolites, cotinine, trans-3'-hydroxycotinine (3'-OH cotinine), and trans-3'-hydroxycotinine glucuronide (3'-OH cotinine glucuronide) for both adult and adolescent squirrel monkeys. The PBPK nicotine model was first calibrated for adult squirrel monkeys utilizing in vitro nicotine metabolic data, plasma concentration-time profiles and cumulative urinary excretion data for nicotine and metabolites. Further model refinement was conducted when the calibrated adult model was scaled to the adolescents, because adolescents appeared to clear nicotine and cotinine more rapidly relative to adults. More specifically, the resultant model parameters representing systemic clearance of nicotine and cotinine for adolescent monkeys were approximately two- to three-fold of the adult values on a per body weight basis. The nonhuman primate PBPK model in general captured experimental observations that were used for both model calibration and evaluation, with acceptable performance metrics for precision and bias. The model also identified differences in nicotine pharmacokinetics between adolescent and adult nonhuman primates which might also be present in humans.


Immunology of multiple sclerosis.
Evidence points to the conclusion that abnormal regulation of the immune response in MS contributes to ongoing immune activity.


Perceived social supports and associated factors among diabetes mellitus patients.
The aim of this study was to assess the Perceived Social Supports and Associated Factors Among Diabetes Mellitus Patients. A facility-based cross-sectional study on 399 randomly selected adult diabetes patients was conducted at JUMC with data collection between August and September 2021.The data was collected using diabetic social support tool through face-to-face interviews and document review checklist. Logistic regression was used to determine factors associated with perceived social support in diabetes patients. Two hundred nineteen (54.9%) out of 399 diabetes patients reported a good level of perceived social support. Informational support was the most reported (55.4%), followed by emotional support (52.9%), companionship support (52.9%), and instrumental or tangible support (48.8%). Having a family history of diabetes (AOR = 1.90, CI: 1.09, 3.51) and presence of chronic comorbidities (AOR = 2.01; CI: 1.08, 3.75) were positively associated with social support. Whereas unemployment (AOR = 0.09, CI: 0.02, 0.38) was negatively associated with social support. One of every two diabetes patients got adequate level of social support. Health care system, along with other stakeholders could strengthen social support in line with diabetes patients' lifestyle.


Isolated Laryngeal Leishmaniasis: A Diagnostic Dilemma.
Isolated laryngeal Leishmaniasis is a rare entity in the Indian subcontinent. We describe a case of a 45 year old male with hoarseness and noisy breathing. Patient's initial histological and serological workup was inconclusive. Final biopsy findings (suggestive of Leishmania donovani), positive rK-39 serology and his native place being Bihar (endemic for Leishmaniasis) led us to the diagnosis. He was treated with high dose liposomal Amphotericin B to which he responded well. This case report highlights the importance of remaining aware of rare infectious causes of laryngitis. Timely diagnosis and intervention are crucial.


Comparison of imaging methods for localization of parathyroid tumors.
Preoperative localization of parathyroid tumors by computed tomography (CT), thallium-201/technetium-99m pertechnetate subtraction scintigraphy (Tl-201/Tc-99m), ultrasonography (US), and magnetic resonance imaging (MRI) was compared in patients with hyperparathyroidism (HPT) to examine the characteristics of each method. A total of 87 patients with HPT were divided into two groups according to the time when they were examined. Patients in group I were examined before MRI had been introduced in our hospital, and a 2.5-MHz transducer probe was used for US. Those in group II were examined by MRI and US using a 7.5-MHz transducer probe. Group I included 45 patients (36 with primary hyperparathyroidism [PHPT] and 9 with secondary hyperparathyroidism [SHPT]), and group II included 42 patients (15 with PHPT and 27 with SHPT). In both PHPT and SHPT and SHPT of group I and PHPT of group II, there was no significant difference in detection rates between all diagnostic methods. In patients with SHPT in group II, the detection rate was significantly higher for CT than for Tl-201/Tc-99m and MRI (both p less than 0.01), and for US than for Tl-201/Tc-99m (p less than 0.01). In both groups I and II, the detection rate of each study method was significantly higher in patients with PHPT than in those with SHPT (all p less than 0.01). Compared with group I, the rate was significantly improved in group II, in both types of patients. Regarding the location of the parathyroid tumor, the detection rate of CT was significantly higher for upper parathyroid glands than for lower glands, whereas that of US and Tl-201/Tc-99m was significantly higher for lower glands. The detection rate sharply increased when the tumor weight reached 250 mg (CT, US) or 1,000 mg (Tl-201/Tc-99m, MRI).


Alpha lipoic acid (ALA) effects on developmental competence of equine preantral follicles in short-term culture.
The effect of different concentrations of alpha lipoic acid (ALA) on the development and morphology of preantral follicles, as well as the proliferative activity of granulosa cells, was assessed after short-term culture. Ovaries (n = 5) of five seasonal anestrous mares were harvested in a local abattoir. At the laboratory, nine ovarian fragments (5 × 5 × 1 mm) from each animal were used. One fragment was immediately fixed in Bouin and subjected to histological and immunohistochemistry (proliferating cell nuclear antigen, PCNA) analyses (noncultured group; D0 = day 0). The other eight fragments were cultured in situ for two (D2) or six (D6) days in MEM+ or MEM+ plus ALA (50, 100, or 250 μM). After culture, fragments were subjected to histology and PCNA analyses. After two days of culture, ALA 50 and ALA 100 had the greatest (P < 0.05) percentage of normal primordial follicles (97.2 and 95.1%, respectively), when compared to other groups, and did not differ (P > 0.05) from the fresh noncultured control group. Furthermore, the total percentage of normal follicles was greater (P < 0.05) in the ALA 50 and ALA 100 than in the MEM-D2 group. After six days of culture, the highest (P < 0.05) proliferative activity of granulosa cells in developing follicles was observed for the groups MEM+ (92.9%), ALA 50 (100%), and ALA 100 (96.4%). In conclusion, the results of this study demonstrated that (1) ALA 50 and ALA 100 preserved the morphological integrity of equine primordial follicles for up two days of culture, and (2) granulosa cells of developing follicles enclosed in ovarian tissue and cultured for up to six days in MEM+ with or without ALA were highly stained by PCNA.


Detecting interaural time differences and remodeling their representation.
Interaural time differences (ITDs) represent an important cue in sound localization and auditory scene analysis. To assess this cue the auditory system internally delays binaural inputs to compensate for the outer delay, before neurons in the brainstem detect the coincident arrival of the inputs from the two ears. Different origins of internal delays have been controversially discussed and have given rise to conflicting interpretations of the ITD representation ensuing from coincidence detection. Yet, recent findings indicate that ITD representations undergo substantial transformations or remodeling after the detection step. Here we treat the detection step separately from remodeling, and explain why a similar representation of ITD across species may exist in the forebrain despite differences in detection and representation in the midbrain.


Endoscopic-assisted fusion for lumbar pars fracture repair in an adolescent patient.
Minimally invasive repair of pars defects can be achieved via means of cannulation followed by tubular decortication. Given these injuries typically occur in pediatric and adolescent patients, minimal disruption to surrounding tissue during the repair is ideal. The use of an endoscopic approach to assist with repair and fusion across the pars defect is a novel consideration in the pediatric demographic, and in this case report we highlight our experience and rationale for this in treating a 14-year-old male athlete with lumbar 5 pars fracture. Radiographic evidence of bony fusion was seen by the third postoperative month. In this case report we demonstrate the invasive nature of this repair can be minimized further than current convention with successful radiographic and clinical outcomes.


Prognostic significance of combined BAALC and MN1 gene expression level in acute myeloid leukemia with normal karyotype.
Acute myeloid leukemia with normal karyotype (AML-NK) is the largest group of AML patients with very heterogeneous disease outcome. In order to ensure more precise risk stratification new molecular markers have been introduced, like expression level for BAALC (Brain and Acute Leukemia, Cytoplasmic) and MN1 (Meningioma 1) genes. In this study, we investigated expression level of both genes in 111 adult AML-NK at diagnosis and examined their prognostic potential. BAALC and MN1 expression were detected in about one third of the patients, and positive correlation between these two genes was found. The BAALC+ /or MN1+ status was not associated with the presence of FLT3-ITD mutations, but exhibited strong correlation with NPM1wt status (P < .001). Therefore, among BAALC+ /or MN1+ patients the most frequent ones were FLT3-ITD- /NPM1- double negative patients with intermediate prognosis. When BAALC+ /or MN1+ patients were divided into BAALChigh /BAALClow (21/21) and MN1high /MN1low (21/22) groups, we detected that BAALChigh /or MN1high patients had a tendency toward lower complete remission rate. Also, survival analysis showed that BAALChigh /or MN1high patients had shorter disease-free survival and overall survival (OS). The most pronounced influence on prognosis was detected in FLT3-ITD- /NPM1- group of patients that are lacking reliable prognostic markers, where OS in BAALChigh /or MN1high was only 5 months vs 25 months in BAALClow /or MN1low . These findings indicate that BAALC and MN1 expression level could be used for more precise risk stratification of AML-NK patients and especially FLT3-ITD- /NPM1- patients, transforming this intermediate-risk group, into a group with an adverse prognosis.


Liraglutide reduces hyperglycaemia and body weight in overweight, dysregulated insulin-pump-treated patients with type 1 diabetes: The Lira Pump trial-a randomized, double-blinded, placebo-controlled trial.
To investigate the efficacy of adding the glucagon-like peptide-1 receptor agonist liraglutide to continuous subcutaneous insulin infusion (CSII) in overweight or obese persons with type 1 diabetes and non-optimal glycaemic control. A 26-week, randomized, double-blind, placebo-controlled trial including 44 overweight or obese adults with type 1 diabetes randomized 1:1 to liraglutide 1.8 mg once daily (QD) or placebo added to CSII treatment. The primary endpoint was change in haemoglobin A1c (HbA1c). Secondary endpoints included change in insulin dose, CSII settings, glycaemic variability, body weight and patient-reported outcome measures. Finally, adverse effects including hypoglycaemic events were registered. HbA1c was reduced by 5 mmol/mol (0.5%) from a baseline of 66 mmol/mol (8.2%) in patients treated with liraglutide compared with a non-significant change of +2.3 mmol/mol (0.2%) from a baseline of 66 mmol/mol (8.1%) in patients treated with placebo (between-group difference 7 mmol/mol [0.7%], P < 0.001). Liraglutide reduced total insulin dose by 8 units/day or 16% of total insulin dose (P = 0.008). Mean body weight was reduced by 6.3 kg (P < 0.001) compared with placebo. Concomitantly, time spent in glycaemic target range 4-10 mmol/L (71-180 mg/dL) increased while the risk of hypoglycaemia did not differ between groups at the end of treatment. Liraglutide treatment reduced HbA1c, total daily insulin dose and body weight without increasing the risk of hypoglycaemia in CSII-treated patients with type 1 diabetes and insufficient glycaemic control. Liraglutide may be considered a potential add-on therapy to insulin in this subgroup of patients.


A study of the cumulative effects of repeated exposures to radial accelerations.
After exposure to transverse accelerations of 4-10 g changes in the vascular system of the eye and immunobiological resistance of the body persisted from 5 to 15 days. The data give evidence that the state of retinal vessels is the most informative index of the cumulative effect on the body and its recovery.


Regional variations of low-density lipoprotein oxidizability in hemodialysis patients may explain discrepancies in interventional therapy on oxidative profile.
This study aimed at evaluating oxidative stress (OS) markers (i) in a cross-sectional study of hemodialysis (HD) patients to investigate potential regional effects of these markers and (ii) in a prospective crossover study to evaluate vitamin E-coated membrane (VE) effects. At baseline, OS parameters including low-density lipoprotein (LDL) oxidizability were measured in HD patients from five dialysis facilities. Patients were then randomly assigned to two treatment groups: group I patients (n = 33) switching to VE, and group II patients (n = 29) still using reference polysulfone (PS) membrane. After 3 months, patients were switched from VE to PS and vice versa for 6 months. The same OS parameters were measured after each period. At baseline, the cross-sectional analysis of LDL oxidizability showed a regional effect. By contrast, the crossover study did not show beneficial effects of VE on this parameter. Regional variations of LDL oxidizability in HD patients exist and may explain discrepancies in interventional therapy on OS.


Surgical need in an aging population: A cluster-based household survey in Nepal.
With an aging global population comes an obligate and substantial burden of noncommunicable disease, especially in low- and middle-income countries. An unknown proportion of this burden is treatable with surgical expertise. For health system planning, this study aimed to estimate the operative needs of individuals older than 50 of age years in Nepal. A 2-stage, cluster randomized, community-based survey was performed in Nepal using the validated Surgeons OverSeas Surgical Assessment Survey (SOSAS). SOSAS collects household demographics and selects household members randomly for verbal, head-to-toe examinations for surgical conditions; moreover, SOSAS also completes a verbal autopsy for deaths in the preceding year. Only respondents older than 50 years were included in the analysis. The survey sampled 1,350 households, totaling 2,695 individuals (97% response rate). Of these, 273 surgical conditions were reported by 507 persons ages ≥ 50 years. Extrapolating, there are potentially 2.1 million people older than 50 years of age with surgically treatable conditions who need care in Nepal (95% confidence interval 1.8-2.4 million; 46,000-62,600 per 100,000 persons). One in 5 deaths was potentially treatable or palliated by surgical care. Although growths or masses (including hernias and goiters) were the surgical condition reported most commonly (25%), injuries and fractures also were common and associated with the greatest disability. Literacy and distance to secondary and tertiary health facilities were associated with lack of care for operative conditions (P < .05). There is a large, unmet surgical need among the elderly in Nepal. Low literacy and distance from a capable health facility are the greatest barriers to care. As the global population ages, there is an increasing need to improve surgical services and strengthen health systems to care for this group.


Proteomic analysis of differential protein expression by brain metastases of gynecological malignancies.
Brain metastases of gynecological malignancies are rare, but the incidence is increasing. Patients with brain metastases have a poor prognosis, therefore early detection and optimal management is necessary. In order to determine a new biomarker, we aimed to identify proteins that associated with brain metastases. We investigated proteins associated with brain metastases of gynecological malignancies in three patients who underwent surgical resection (stage IIb cervical cancer, stage Ib endometrial cancer, and stage IIIb ovarian cancer). Proteomic analysis was performed on formalin-fixed paraffin-embedded (FFPE) samples of the primary tumors and brain metastases, which were analyzed by liquid chromatography with tandem mass spectrometry. Thereafter, candidate proteins were identified by the Scaffold system and Mascot search program, and were analyzed using western blotting and immunohistochemistry. As a result, a total of 129 proteins were identified. In endometrial and ovarian cancers, western blotting revealed that the expression of alpha-enolase (ENO1) and triosephosphate isomerase (TPI-1) was higher and the expression of Transgelin-2 (TAGLN2) was lower in metastatic tumors than in primary tumors. On the other hand, the expression of TPI-1 and TAGLN2 was lower in metastatic tumors than in primary tumors in cervical cancer. Immunohistochemistry confirmed that ENO1 expression was elevated in the metastatic tumors compared with the primary tumors. In conclusion, the present study showed that FFPE tissue-based proteomics analysis can be powerful tool, and these findings suggested that ENO1, TPI-1, and TAGLN2 may have a role in the development and progression of brain metastasis from gynecological malignancies.


Antibacterial activities, proposed mode of action and cytotoxicity of leaf extracts from Triumfetta welwitschii against Pseudomonas aeruginosa.
Pseudomonas aeruginosa has become a main cause of Gram-negative infection, particularly in patients with compromised immunity. High rates of resistance to antibiotics are associated with nosocomial infections caused by P. aeruginosa strains. The search for novel antimicrobials has been necessitated by the emergence of antimicrobial resistance in some bacteria Plant-based antimicrobials has great potential to combat microbial infections using a variety of mechanisms. Triumfetta welwitschii plant roots are traditionally used to treat symptoms of diarrhoea and fever, suggesting that it possess antimicrobial and immunomodulatory effects. Since research investigating antimicrobial properties of the roots of Triumfetta welwitschii has been explored, there is need to investigate the antimicrobial activity of its leaf extracts in order to probe their prospective use as new antimicrobial agents that can be used to combat nosocomial infections. The objective of this study was to evaluate the antibacterial activities, the mode of action and cytotoxicity of T. welwitschii leaf extracts. Extracts of T. welwitschii leaves were obtained using eight different solvents, the serial exhaustive extraction method and the cold maceration technique. In vitro antibacterial activity evaluation of the extracts was done on eight bacterial isolates using the broth microdilution method. The mode of action for the most potent extracts was investigated using the rhodamine 6G efflux assay and the propidium iodide-based membrane damage assay. Toxicity of the extracts was evaluated using the haemolytic and MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assays. The results showed that acetone, ethanol and dichlorometane: methanol extracts had the most potent antibacterial activities against Pseudomonas aeruginosa (ATCC 27853). All three extracts caused membrane disruption of P. aeruginosa as shown by nucleic acid leakage. All three extracts were unable to inhibit efflux pumps. The presence of antibacterial activities and low toxicity shown by the extracts indicates that the plant may be a source of effective antibacterial against some bacterial infections caused by P. aeruginosa. The disruption of membrane integrity is one possible mode of action of antibacterial activity of the potent extracts.


A method for the determination of glutamate oxaloacetate transaminase in sperm plasma from boars and bulls.
A method is described for the determination of glutamate oxaloacetate transaminase (GOT) activity in sperm plasma from boars and bulls as a test for fertilizing ability.


Soil microplastic pollution in an e-waste dismantling zone of China.
Microplastic pollution is ubiquitous and has emerged as a severe global environmental issue. Recent research on microplastic pollution has mainly focused on aquatic ecosystems, while knowledge gaps still exist regarding microplastic in terrestrial environments. In this study, we established a new method for characterizing microplastic in complex soil substrate using FTIR spectroscopy. Microplastic was separated by density without removing soil organic matter to protect microplastic from damage. The Wizards feature was adopted to automatic, direct and continuous characterize micron-size plastic. Furthermore, 33 soil samples were taken from Guiyu, a notorious e-waste dismantling area in Guangdong Province, China, under different land-use. The results showed that microplastic was involved in 30 samples, and the abundance of microplastic varied considerably among different soils, ranged from 0 to 34,100n kg-1, implying that the e-waste dismantling sites have become the microplastic hotspots. There were 60 kinds of microplastic detected with 6 different shapes and 10 colors, most of which were secondary microplastic. They mainly consisted of engineering-plastic and modified plastic, 88.61% had a size range <1 mm, indicating that the majority of microplastics at Guiyu were derived from e-wastes. The surface morphology of microplastic showed signs of aging and degradation, possibly due to primitive dismantling methods and long-term exposure to the soil. The mean Pb, Cd, Cr, Ba, Cu, Co, As concentrations of microplastic were 20.94, 0.67, 11.82, 308.78, 4.11, 1.26, 3.06 μg·g-1, respectively. Our findings providescientific basis for monitoring and controlling microplastic pollution in terrestrial environments.


The cytoskeleton in myelinated axons: a freeze-etch replica study.
The organization of the cytoskeleton in myelinated axons of the rat has been analyzed without chemical fixation in replicas of deep-etched materials after rapid freezing. Freeze-etch replicas of trigeminal nerves provided three-dimensional views of the well-developed cytoskeleton inside axons. In these preparations, the axonal cytoskeleton was seen to be composed of longitudinally-oriented microtubules and neurofilaments which were interconnected by slender strands. Such strands also connected membranous organelles with microtubules and neurofilaments. After Triton X-100 extraction, the neurofilament-associated interconnecting strands (cross-linking filaments) persisted, indicating that they are not artifactual products of soluble protein condensation during freeze-etching. In non-extracted axons many granular structures were closely associated with cytoskeletal components. These granular elements were not seen after Triton treatment. These findings, together with fluorographic analyses, suggest that the granular structures may represent. These findings, together with fluorographic analyses, suggest that the granular structures may represent slowly transported "soluble proteins' in axoplasm. This freeze-etch replica study, without any chemical fixation, substantiates the reality of the axonal cytoskeleton which is directly involved in the axonal transport. Furthermore, using this approach ultrastructural evidence was obtained of the close association of membranous structures with the cytoskeleton.


Apoptosis of peripheral blood neutrophils in COPD exacerbation does not correlate with serum cytokines.
The study investigated the relationship between apoptosis of peripheral blood neutrophils during exacerbation of chronic obstructive pulmonary disease (COPD) and the inflammatory response that characterises this condition. Twenty-six hospitalised patients with COPD exacerbation and 13 controls were included. Three sequential blood and sputum samples were obtained from patients at admission, after 3 days and at discharge. Blood apoptotic neutrophils were measured by flow-cytometry and light microscopy. Serum and sputum levels of IL-6, IL-8 and TNF-alpha were determined by an immunoassay technique. We found a significantly reduced percentage of apoptotic neutrophils at the onset of COPD exacerbation which increased over time (1.1+/-0.4% at admission vs. 2.4+/-0.4% at discharge, P<0.0001). Patients presented no changes in serum cytokines neither during exacerbation nor in comparison to controls. In contrast, sputum levels of cytokines were significantly increased compared to serum levels. There was no significant correlation between the apoptotic neutrophils and the cytokine concentrations in serum or sputum. None of the clinical parameters, such as smoking, microbial infection, corticosteroids or hypoxemia showed a correlation with neutrophil apoptosis. No relationship could be found between the reduced percentage of apoptotic neutrophils in blood and serum concentration of IL-6, IL-8 and TNF-alpha or other clinical parameters in patients with COPD exacerbation.


Is Care for the Dying Improving in the United States?
Striking changes occurred in health care in the United States between 2000 and 2013, including growth of hospice and hospital-based palliative care teams, and changes in Medicare payment policies. The aim of this study was to compare informants' reports and ratings of the quality of end-of-life care for decedents between 2000 and 2011-2013. The study design comprised retrospective national surveys. Subjects were decedents age 65 years and older residing in the community from two time periods. Similar survey questions were asked at the two time periods. Bivariate and multivariate analyses were conducted, using appropriate survey weights to examine response differences between time periods, after adjusting for the decedent's age, race, pattern of functional decline, and the presence of a cancer diagnosis, as well as the respondent's relationship to the decedent. A total of 1208 informants were interviewed; 622 in 2000 and 586 in 2011-2013. Respondents from deaths in 2011-2013 were more likely to state that their loved ones experienced an unmet need for pain management (25.2% versus 15.5% in 2000, adjusted odds ratio [AOR] 1.9, 95% confidence interval [CI] 1.1-3.3). More respondents reported that religion and spirituality were addressed in the later time period (72.4% not addressed compared with 58.3%, AOR 1.4, 95% CI 1.1-1.9). High rates of unmet need for palliation of dyspnea and anxiety/depression remained. The overall rating of quality did not improve but decreased (with 56.7% stating care was excellent in 2000 and 47.0% in the later survey, AOR 0.70, 95% CI 0.52-0.95). Substantial unmet needs in end-of-life care remain. Continued efforts are needed to improve the quality of end-of-life care.


Association of evening smartphone use with cardiac autonomic nervous activity after awakening in adolescents living in high school dormitories.
Smartphones are prevalently used among adolescents; however, nighttime exposure to blue-enriched light, through electric devices, is known to induce delays of the circadian rhythm phases and poor morning somatic conditions. We therefore investigated whether evening smartphone use may affect sleep-wake cycle and cardiac autonomic nervous system (ANS) activity after awaking in dormitory students. The participants were high school students, living under dormitory rules regarding the curfew, study, meals, lights-out, and wake-up times. The students were forbidden from the use of both television and personal computer in their private rooms, and only the use of a smartphone was permitted. According to prior assessment of smartphone use, we chose age-, sex-, exercise time-matched long (n = 22, >120 min) and short (n = 14, ≤60 min) groups and compared sleep-wake cycle and physiological parameters, such as cardiac ANS activity, blood pressure, and intra-aural temperature. All measurements were performed during 6:30 to 7:00 a.m. in the dormitories. Compared with the short group, the long group showed a significantly lower cardiac ANS activity (2727 ± 308 vs. 4455 ± 667 ms2, p = 0.030) with a tendency toward a high heart rate, in addition to later bedtimes during weekdays and more delayed wake-up times over the weekend. Blood pressure and intra-aural temperature did not differ between the groups. In this population, evening smartphone use may be associated with altered sleep-wake cycle and a diminished cardiac ANS activity after awakening could be affecting daytime activities.


[An analysis of the mechanisms of interpopulation interaction of Yersinia with Tetrahymena pyriformis infusorians at the cellular and subcellular levels].
The mechanisms of interaction between the populations of Yersinia and T. pyriformis have been analyzed on the cellular and subcellular levels. As shown in this investigation, Yersinia, when phagocytized by T. pyriformis, may undergo morphological changes, remain unchanged and also multiply, destroying the host cell in the process.


POEMS syndrome presenting as systemic sclerosis. Clinical and pathologic study of a case with microangiopathic glomerular lesions.
A rare form of plasma cell dyscrasia characterized by the various association of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes has been termed POEMS syndrome. The pathogenesis of the multisystemic features of this syndrome remains unclear. Herein is reported a case of POEMS syndrome with striking clinical similarities with scleroderma, and microangiopathic glomerular lesions, as well as diffuse perivascular non-amyloid deposits, which could explain certain features of the syndrome, including peripheral nerve demyelination. It is proposed that a pathogenic role might be played by a non-immunoglobulin vasculotoxic component.


Premature termination codons in modern human genomes.
The considerable range of genetic variation in human populations may partly reflect distinctive processes of adaptation to variable environmental conditions. However, the adaptive genomic signatures remain to be completely elucidated. This research explores candidate loci under selection at the population level by characterizing recently arisen premature termination codons (PTCs), some of which indicate a human knockout. From a total of 7595 participants from two population exome projects, 246 PTCs were found where natural selection has resulted in new alleles with a high frequency (from 1% to 96%) of derived alleles and various levels of population differentiation (FST = 0.00139-0.626). The PTC genes formed protein and regulatory networks limited to 15 biological processes or gene families, of which seven categories were previously unreported. PTC mutations have a strong tendency to be introduced into members of the same gene family, even during modern human evolution, although the exact nature of the selection is not fully known. The findings here suggest the ongoing evolutionary plasticity of modern humans at the genetic level and also partly provide insights into common human knockouts.


Sarcoidosis in coexistence with chronic granulomatous disease.
Granulomas formations are present in many lung diseases. Coexistence of one or more of these diseases is very rare. Diagnostics of such cases always poses a challenge. We present a case of coexistence of chronic granulomatous disease (CGD) and sarcoidosis.


Genomic characterization of Trichoderma atrobrunneum (T. harzianum species complex) ITEM 908: insight into the genetic endowment of a multi-target biocontrol strain.
So far, biocontrol agent selection has been performed mainly by time consuming in vitro confrontation tests followed by extensive trials in greenhouse and field. An alternative approach is offered by application of high-throughput techniques, which allow extensive screening and comparison among strains for desired genetic traits. In the genus Trichoderma, the past assignments of particular features or strains to one species need to be reconsidered according to the recent taxonomic revisions. Here we present the genome of a biocontrol strain formerly known as Trichoderma harzianum ITEM 908, which exhibits both growth promoting capabilities and antagonism against different fungal pathogens, including Fusarium graminearum, Rhizoctonia solani, and the root-knot nematode Meloidogyne incognita. By genomic analysis of ITEM 908 we investigated the occurrence and the relevance of genes associated to biocontrol and stress tolerance, providing a basis for future investigation aiming to unravel the complex relationships between genomic endowment and exhibited activities of this strain. The MLST analysis of ITS-TEF1 concatenated datasets reclassified ITEM 908 as T. atrobrunneum, a species recently described within the T. harzianum species complex and phylogenetically close to T. afroharzianum and T. guizhouense. Genomic analysis revealed the presence of a broad range of genes encoding for carbohydrate active enzymes (CAZYmes), proteins involved in secondary metabolites production, peptaboils, epidithiodioxopiperazines and siderophores potentially involved in parasitism, saprophytic degradation as well as in biocontrol and antagonistic activities. This abundance is comparable to other Trichoderma spp. in the T. harzianum species complex, but broader than in other biocontrol species and in the species T. reesei, known for its industrial application in cellulase production. Comparative analysis also demonstrated similar genomic organization of major secondary metabolites clusters, as in other Trichoderma species. Reported data provide a contribution to a deeper understanding of the mode of action and identification of activity-specific genetic markers useful for selection and improvement of biocontrol strains. This work will also enlarge the availability of genomic data to perform comparative studies with the aim to correlate phenotypic differences with genetic diversity of Trichoderma species.


A monograph of the African and Madagascan species of Cyperus sect. Incurvi (Cyperaceae).
Cyperus sect. Incurvi (Cyperaceae) contains 31 species worldwide, with important continental radiations in Australasia, Tropical Africa and Madagascar, and the Neotropics. Here, a monograph of the African and Madagascan species of Cyperus sect. Incurvi is presented, including descriptions, illustrations, synonymy, notes on habitat and ecology, geographic distribution ranges and conservation assessments. Our results identify eight species of Cyperus sect. Incurvi endemic to Madagascar, and a further three species native to Tropical Africa. Seven species of Cyperus sect. Incurvi have been typified herein. Six rare Madagascan endemics are assessed as threatened with extinction.


Tribocorrosion behavior of veneering biomedical PEEK to Ti6Al4V structures.
In dentistry, prosthetic structures must be able to support masticatory loads combined with a high biocompatibility and wear resistance in the presence of a corrosive environment. In order to improve the simultaneous wear and corrosion response of highly biocompatible prosthetic structures, a veneering poly-ether-ether-ketone (PEEK) to Ti6Al4V substrate was assessed by tribocorrosion analyses under conditions mimicking the oral environment. Samples were synthesized by hot pressing the PEEK veneer onto Ti6Al4V cylinders. The tribocorrosion tests on Ti6Al4V or PEEK/Ti6Al4V samples were performed on a reciprocating ball-on-plate tribometer at 30N normal load, 1Hz and stroke length of 3mm. The tests were carried out in artificial saliva at 37°C. Open circuit potential (OCP) was measured before, during and after reciprocating sliding tests. The worn surfaces were characterized by scanning electron microscopy. The results revealed a lower wear rate on PEEK combined with a lower coefficient of friction (COF), when compared to Ti6Al4V. In fact, PEEK protected Ti6Al4V substrate against the corrosive environment and wear avoiding the release of metallic ions to the surrounding environment.


[Radiographic study of the development of the permanent dentition of Brazilian children with a chronological age of 84 and 131 months].
With the help of orthopantomograms we analyse the tooth development beside body weight and height from Brazilian healthy boys and girls. So, their dental age were compared to their chronological age. The results of this investigation, according to the methodology employed, indicated that: 1. girls showed accelerated formation of permanent teeth and mean values of dental age higher than boys; 2. the mean values of dental age in girls were higher than their chronological age in all groups; 3. the teeth development stages were appropriate in assessment of the degree of physiological maturity of a growing child.


Targeted disruption of the gene encoding DNA ligase IV leads to lethality in embryonic mice.
DNA ligase IV is the most recently identified member of a family of enzymes joining DNA strand breaks in mammalian cell nuclei [1] [2]. The enzyme occurs in a complex with the XRCC4 gene product [3], an interaction mediated via its unique carboxyl terminus [4] [5]. Cells lacking XRCC4 are hypersensitive to ionising radiation and defective in V(D)J recombination [3] [6], implicating DNA ligase IV in the pathway of nonhomologous end-joining (NHEJ) of DNA double-strand breaks mediated by XRCC4, the Ku70/80 heterodimer and the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) in mammalian cells (reviewed in [7]). The phenotype of a null mutant of the Saccharomyces cerevisiae DNA ligase IV homologue indicates that the enzyme is non-essential and functions in yeast NHEJ [8] [9] [10]. Unlike other mammalian DNA ligases for which cDNAs have been characterised, DNA ligase IV is encoded by an intronless gene (LIG4). Here, we show that targeted disruption of LIG4 in the mouse leads to lethality associated with extensive apoptotic cell death in the embryonic central nervous system. Thus, unlike Ku70/80 and DNA-PKcs [11] [12] [13] [14], DNA ligase IV has an essential function in early mammalian development.


Expression of chitinase gene in BL21 pET system and investigating the biocatalystic performance of chitinase-loaded AlgSep nanocomposite beads.
Chitin, a polysaccharide, is abundant in nature and this substrate can be easily hydrolyzed by chitinase. Pharmaceutical and industrial applications of chitinase are considerably noteworthy, therefore in this study, high scale production of Chit36 enzyme was targeted using the E. coli pET expression system. The purified Chit36 enzyme was immobilized in Ca2+-cross linked alginate/sepiolite (AlgSep) nanocomposite beads for improving the catalytic activity and stability of Chit36 enzyme during the biocatalytic process. Immobilized enzymes require optimal conditions different from soluble enzymes. The AlgSep nanocomposite can save spatial structure and activity of the enzyme which is critical for enzyme immobilization. The catalytic activity and specific activity of the Chit36 entrapped in alginate nanocomposite beads were evaluated. Results showed that the activity of immobilized Chit36 in Ca-Alginate sepiolite composites beads (3.10±0.63U/g gel) was higher than that of immobilized Chit36 in Ca-alginate beads (3.95±0.40U/g gel). Also, the specific activity of Chit36 in AlgSep nanocomposite beads (22.9±1.521U/mg protein) was higher than the immobilized Chit36 in sepiolite-free alginate beads (8.52±0.758U/mg protein). The promising results obtained from this study would have beneficial pharmaceutical and industrial applications.


Glutamatergic stimulation of the medial amygdala induces steroid dependent c-fos expression within forebrain nuclei responsive to mating stimulation.
Neurons within the posterodorsal medial amygdala of female rats are known to process vaginocervical stimulation received during mating through N-methyl-D-aspartate channel activation, conveying information to downstream hypothalamic cell groups that modulate neuroendocrine function. Stimulation of these neurons with an excitatory amino acid cocktail of glutamate, aspartate and glycine initiates 10-12 days of prolactin surge secretion that normally are observed only after the receipt of vaginocervical stimulation. Posterodorsal medial amygdala neurons responsive to vaginocervical stimulation also contain estrogen and progesterone receptors. The present experiment examined which downstream sites involved in prolactin secretion show c-fos expression following glutamate receptor activation within the posterodorsal medial amygdala and whether ovarian steroids influence cellular activation in these areas. Ovariectomized female rats implanted with unilateral cannulas directed at the posterodorsal medial amygdala received injections of estradiol benzoate and progesterone or oil before infusion treatment with either excitatory amino acid or control PBS. An additional group of estradiol benzoate+progesterone-treated females was infused with 1.0 microM glycine alone in PBS. Infusions were administered three times at 30 min intervals. FOS induction 90 min after infusion was determined immunohistochemically on the sides ipsilateral and contralateral to the infusion. Of the examined regions, excitatory amino acid treatment and hormone treatment induced three patterns of c-fos expression: 1) responses to both excitatory amino acid and hormone treatment [posterodorsal medial amygdala, medial preoptic area, ventrolateral ventromedial hypothalamic nucleus, bed nucleus of the stria terminalis]; 2) responses to estradiol benzoate+progesterone treatment only [anteroventral periventricular nucleus and dorsomedial nucleus]; and 3) responses to excitatory amino acid only [arcuate nucleus, suprachiasmatic nucleus, and paraventricular nucleus]. These data identify possible circuits by which vaginocervical stimulation, via activation of posterodorsal medial amygdala glutamate-type receptors, initiates and coordinates a series of events within a larger neuroendocrine circuit important for pregnancy.


Approach to a patient with elevated serum alkaline phosphatase.
Cholestasis develops either from a defect in bile synthesis, impairment in bile secretion, or obstruction to bile flow, and is characterized by an elevated serum alkaline phosphatase and gamma-glutamyltransferase disproportionate to elevation of aminotransferase enzymes. Key elements to the diagnostic workup include visualization of the biliary tree by cholangiography and evaluation of liver histology. The hope is that recent advances in understanding the genetic factors and immune mechanisms involved in the pathogenesis of cholestasis will lead to newer therapeutic interventions in the treatment of these diseases.


Application of the split-ubiquitin membrane yeast two-hybrid system to investigate membrane protein interactions.
The characterization of protein-protein interactions provides the foundation for further studies concerning protein complex function and regulation. Since the advent of the yeast two-hybrid assay, many additional genetic systems based upon the principle of protein fragment complementation have been designed. One such system, the split-ubiquitin membrane yeast two-hybrid system (MbYTH), is able to analyze the interaction status between two integral membrane proteins. This ability of the MbYTH system augments genetic analysis of protein interactions by covering for the inherent limitation of the yeast two-hybrid system when studying membrane protein interactions. Herein, we provide a description of the MbYTH method and detailed protocols in order to monitor protein interactions and discover novel interacting partners using the MbYTH system.


Ultrasonographic echo intensity in the medial femoral cartilage is enhanced prior to cartilage thinning in women with early mild knee osteoarthritis.
We aimed to determine whether altered cartilage echo intensity is associated with knee osteoarthritis (OA) severity and whether the alteration occurs before thinning of the femoral cartilage in knee OA. The medial femoral cartilage thickness and echo intensity of 118 women aged ≥ 50 years were assessed using an ultrasound imaging device. Based on the Kellgren-Lawrence (KL) grade and knee symptoms, participants were classified into five groups: control (asymptomatic grades 0-1), early OA (symptomatic grade 1), grade 2, grade 3, and grade 4. Analysis of covariance, with adjusted age and height, and the Sidak post hoc test were used to assess the differences in cartilage thickness and echo intensity in knees with varying OA severity. The echo intensity on longitudinal images, equivalent to the tibiofemoral weight-bearing surface, was significantly higher in the grade 2 group than that in the control group (p = 0.049). However, no significant difference was noted in cartilage thickness (n.s.). In the grades 3 and 4 groups, cartilage thickness became thinner as OA progressed (p < 0.001 and p < 0.001, respectively). However, the cartilage echo intensity was not significantly enhanced compared with that of the grade 2 group (n.s.). There were no significant differences in the cartilage thickness and echo intensity between the early OA and control groups on the longitudinal images (n.s.). The echo intensity of the medial femoral cartilage was high in patients with KL grade 2, without decreased thickness. Our findings suggested that higher echo intensity is a feature of early cartilage degeneration in mild knee OA. Further studies are needed to establish this feature as a useful screening parameter of early cartilage degeneration in knee OA. Level III.


Selective stabilization by the bacteriophage 434 repressor of the plasmid expressing bovine growth hormone in Escherichia coli.
The maintenance of a plasmid vector-host system that selects for bacteria carrying the plasmid without the need for antibiotics is described. In this system, the bacteriophage 434 repressor gene cloned on the plasmid protects the host from lysis by a lambda imm434 cI- prophage. Cells that occasionally lose the plasmid are killed by prophage induction and therefore do not accumulate in the growing culture. The presence of the phage 434 repressor in the cells does not interfere with the process of lambda repressor inactivation and the high-level production of bovine growth hormone.


Parotid gland leiomyosarcoma in a child: an extremely unusual neoplasm.
We report the case of an 8-year-old boy with a parotid mass diagnosed to be a leiomyosarcoma. Considering the unresectable extent of the mass, the patient was subjected to radiotherapy. The patient developed distant metastasis following the course of radiotherapy and was put on chemotherapy. The child was lost to further follow up. To our knowledge, this is the first reported case in the English-language literature of such an entity in the pediatric age group.


Gated thallium tomography--potential for improved accuracy in the detection of coronary artery disease.
Gated thallium-201 myocardial tomography incorporating perfusion profile analysis was used alone, to assess left ventricular wall perfusion and left ventricular wall movement together in 29 consecutive patients, without prior infarction, who presented with chest pain. All patients had had coronary and left ventricular angiography. The proportion of false positive perfusion defects was reduced when an analysis of corresponding wall movement was made. This combined technique resulted in an improved specificity compared with standard 201Tl myocardial tomography. This approach shows the functional effect of reversible ischaemia on regional myocardial contractility and would appear to be particularly useful in the assessment of patients who present with atypical chest pain.


Surface-enhanced Raman scattering of monolayer transition metal dichalcogenides on Ag nanorod arrays.
In this work, we studied surface-enhanced Raman scattering (SERS) of MS2 (M=Mo, W) monolayers that were transferred onto Ag nanorod arrays. Compared to the suspended monolayers, the Raman intensity of monolayers on an Ag nanorod substrate was strongly enhanced for both in-plane and out-of-plane vibration modes: up to 8 (5) for E2g and 20 (23) for A1g in MoS2 (WS2). This finding reveals a promising SERS substrate for achieving uniform and strong enhancement for two-dimensional materials in the applications of optical detecting and sensing.


Antiepileptic drug therapy in pregnancy II: fetal and neonatal exposure.
The issue of how much an antiepileptic drug (AED) crosses the placenta and relative safety of lactation in mothers receiving AEDs are common clinical questions. Educating potential mothers with epilepsy regarding available information is warranted so that informed decisions and any needed neonatal monitoring is performed. Unfortunately, there is still limited data regarding the degree in which anticonvulsants cross the placenta and penetrate into breast milk. There is a greater appreciation of the factors that influence AED passive transfer across the placenta and into breast milk, as well as factors that ultimately influence neonatal AED distribution. In general, women with epilepsy can have healthy babies even with significant placental exposure and can breast-feed their babies safely with some cautions. Phenobarbital and primidone should be avoided in parents wishing to breast-feed. For the AEDs ethosuximide, levetiracetam, lamotrigine, topiramate, and zonisamide, there is a potential for significant breast milk concentrations; however, there are no firm guidelines on whether lactation is safe. In all cases, parents should be counseled to monitor their child for side effects and the need for routine monitoring.


Speciation of tin ions in oxide glass containing iron oxide through solvent extraction and inductively coupled plasma atomic emission spectrometry after the decomposition utilizing ascorbic acid.
Determining the concentrations of different Sn ions in glass containing iron oxide by wet chemical analysis is a challenge because a redox reaction occurs between Sn2+ and Fe3+. A chemical analysis method for determining the concentrations of Sn2+ and Sn4+ in soda lime glass containing iron oxide was proposed. A mixture of ascorbic acid, hydrochloric acid, and hydrofluoric acid was used to decompose the sample in a vessel with nitrogen flow. Ascorbic acid functioned as a reductant for Fe3+. Subsequently, the Sn2+ were separated as a diethyldithiocarbamate complex. Furthermore, inductively coupled plasma atomic emission spectroscopy was used to determine the concentrations of Sn4+ and total Sn, from which the concentration of Sn2+ can be calculated. The results were validated by comparing ratios of Sn2+ to total Sn to results obtained using Mössbauer spectroscopy. The results were in agreement, thereby validating the use of the proposed approach.


Wharton's jelly mesenchymal stem cells embedded in PF-127 hydrogel plus sodium ascorbyl phosphate combination promote diabetic wound healing in type 2 diabetic rat.
Diabetic cutaneous ulcers (DCU) are a complication of diabetes with diabetic foot ulcers being the most common, and the wounds are difficult to heal, increasing the risk of bacterial infection. Cell-based therapy utilizing mesenchymal stem cells (MSCs) is currently being investigated as a therapeutic avenue for both chronic diabetic ulcers and severe burns. Wharton's jelly mesenchymal stem cell (WJMSC) with PF-127 hydrogel and sodium ascorbyl phosphate (SAP) improved skin wound healing in mice. Whether this combination strategy is helpful to diabetic ulcers wound healing remains to be explored. Firstly, the WJMSCs embedded in PF-127 and SAP combination were transplanted onto excisional cutaneous wound bed in type 2 diabetic Sprague Dawley (SD) rats. Two weeks after transplantation, the skin tissue was collected for histological and immunohistochemical analysis. Further, overexpressing-EGFP WJMSCs were performed to investigate cell engraftment in the diabetic cutaneous ulcer. The apoptosis of WJMSCs which encapsulated with combination of PF-127 and SAP was detected by TUNEL fluorescence assay and RT-PCR in vitro. And the mitochondrial damage induced by oxidative stress assessed by MitoTracker and CMH2DCFDA fluorescence assay. In diabetic cutaneous wound rat model, PF-127 plus SAP-encapsulated WJMSCs transplantation promoted diabetic wound healing, indicating improving dermis regeneration and collagen deposition. In diabetic wound healing, less pro-inflammatory M1 macrophages, more anti-inflammatory M2 tissue-healing macrophages, and neovascularization were observed in PF-127 + SAP + WJMSCs group compared with other groups. SAP supplementation alleviated the apoptosis ratio of WJMSCs embedded in the PF-127 in vitro and promoted cell survival in vivo. PF-127 plus SAP combination facilitates WJMSCs-mediated diabetic wound healing in rat through promoting cell survival, the macrophage transformation, and angiogenesis. Our findings may potentially provide a helpful therapeutic strategy for patients with diabetic cutaneous ulcer.


The effect of the family presence on anxiety and agitation of patients under mechanical ventilation after open heart surgery: a randomized clinical trial.
Family-centered care has been considered as a philosophy of care. Family presence in intensive care units (ICUs), especially in the acute phase of the disease is controversial. This study has been carried out in order to determine the effect of the family presence on anxiety and agitation in patients undergoing coronary artery bypass grafting (CABG). In a clinical trial, 70 patients were randomly allocated into groups of experimental and control. In the experimental group, during the weaning process from the mechanical ventilation, a family member was present at the bedside. The degree of anxiety and Richmond's Agitation and Sedation Scale (RASS) were compared in seven consecutive time stages, including the time of entry into the ICU, the first respiratory drive, the family entrance, 20 min and 1 h after the presence of the family member, the time of extubation, and 1 h after extubation. There was a significant difference between the two groups in the mean scores of the anxiety scale in the first (P =0.008), second (P=0.002), and third stages (P =0.005). This difference was not significant in the fourth to seventh stages (P>0.05). As the baseline anxiety levels were different, a covariate adjustment was used for comparisons between treatments, adjusting the main analyses for baseline anxiety levels. Analysis showed that groups were not different. Also, there was no significant difference in the mean scores of RASS between the two experimental and control groups at any of the seven stages (P> 0.05). According to the findings of the present study, the presence of a family member does not reduce the level of anxiety and agitation of patients undergoing cardiac surgery. However, it can be concluded that this intervention is feasible in acute and complex situations after open heart surgeries. This study has been registered in the Iranian Registry of Clinical Trials with the code IRCT201609014299N4 .


Ephrins are not only unattractive.
The ephrins and their Eph receptors have emerged as repulsive cues for growing axons during the past decade. Since then, great effort has been made to understand the significance and mechanisms of Eph-mediated repulsion. More recently, it has become clear that ephrins perform in many more developmental processes than the repulsion-dependent establishment of topography in the nervous system. As numerous studies suggest functions more akin to adhesion or attraction than to repulsion, increasing attention is now being paid to the intracellular mechanisms that might explain this duality.


IL-6 -572C>G and CARD8 304T>A Genetic Polymorphisms are Associated with the Absolute Neutrophil Count in Patients with Hematological Malignancies Under Chemotherapy: An Application of Multilevel Models to a Preliminary Pharmacogenetic Study.
Neutropenia is a common event in patients undergoing cytotoxic chemotherapy for the treatment of a hematological malignancy. Some polymorphisms, as IL-6 -572C>G (rs1800796), IL-1β -31 G>A (rs1143627), and CARD8 304T>A (rs2043211), in genes related to the inflammatory process, could affect the level of absolute neutrophil count (ANC) after chemotherapy. Since an efficient inflammatory process enhances neutrophil survival, we hypothesize that these polymorphisms are associated with ANC. We carried out a prospective cohort study in two hospitals in Santiago, Chile. The patients included were adults diagnosed with acute myeloblastic leukemia, acute lymphoblastic leukemia, or non-Hodgkin's lymphoma, undergoing cytotoxic chemotherapy. We use a multilevel linear regression model to test our hypothesis. The best model was selected using the Akaike's information criterion (AIC). We analyzed 1726 hemograms and ANCs from 172 hospitalizations from 32 patients. The results show that CC and CG genotypes of IL-6 -572 C>G polymorphism are associated with higher ANCs compared with the GG genotype (Ln (ANC) ~ 0.81 IC95% 0.02-1.55). Similarly, TT and AT genotypes of CARD8 304T>A polymorphism were related to higher ANCs compared with AA (Ln (ANC) ~ 0.95 IC95% 0.02-1.82). IL-1β genetic polymorphism had no statistically significant association with ANC. IL-6 rs1800796 -572C>G and CARD8 rs2043211 304T>A polymorphisms are associated with the absolute neutrophil count in patients undergoing cytotoxic chemotherapy for treatment of hematological malignancies. Our findings might be useful to improve the safety of chemotherapy through predictive ANC models.


Developmental trajectories of late preterm infants and predictors of academic performance.
The trajectories of late preterm development from infancy to kindergarten reading and math, and predictors of academic resilience and risk are unknown. Sample included 1200 late preterm infants (LPIs) from the Early Childhood Longitudinal Study, Birth Cohort. Objective measurements of development at 9 and 24 months (Bayley-SFR) and reading and math academic achievement at preschool and kindergarten were standardized; trajectories of late preterm development from 9 months to kindergarten reading and math were identified using latent class growth analysis. Multinomial logistic regression [aOR, 95% CI] identified predictors of academic resilience and risk. Four trajectory groups were observed for reading and three for math. More optimal trajectories (in reading and math) and academic resilience were associated with experiencing sensitive parenting and preschool attendance. Suboptimal (at-risk) trajectories (in reading or math) and an increased odds of academic risk were associated with <high school education, twin/multiple gestation, prenatal smoking and male sex. LPI trajectories varied from infancy to kindergarten. More sensitive parenting and preschool attendance predicted academic resilience, and should be encouraged. Select risk factors (prenatal smoking, twin/multiple gestation, male sex, <high school education) predicted academic risk, and can help identify LPIs who might benefit from closer monitoring prior to school entry. Late preterm infants (LPIs) have developmental risks compared to full terms. LPI trajectories of early reading and math varied from infancy to kindergarten. We identified predictors of academic resilience and risk, which can help inform anticipatory guidance provided to LPIs prior to kindergarten. Promotive factors (sensitive parenting and preschool enrollment) predicted academic resilience. Select maternal and neonatal characteristics (<high school education, male sex, prenatal smoking, and multiple gestation) predicted academic risk at kindergarten. LPIs account for the majority of preterm infants. Encouraging preschool enrollment and fostering sensitive parenting may promote early academic achievement in LPIs, which has population-level impacts.


Knowledge-building in surgery: An evolving craft.
In surgery, the construction of knowledge is shaped in two scenarios: evidence-based medicine, and experiential learning. The former has become an essential pillar in this process. Based on this fact, clinical practice guidelines have been developed. However, their transient nature, constant renewal, and lack of individualization distance them from daily clinical activity. On the other hand, there is the construction of knowledge through vicarious and experiential learning. Its existence is linked to the beginning of medicine, and its importance is irrefutable. However, it is laden with the "truth effect", surgical dogma and singularism. When integrating the construction of knowledge in these scenarios, critical thinking skills are paramount and necessary to guide the surgeon in the decision-making process within the context of surgical dynamism. This article explores this situation and its impact.


A systematic review and meta-analysis of randomized controlled trials of the effect of barley β-glucan on LDL-C, non-HDL-C and apoB for cardiovascular disease risk reductioni-iv.
There has been recent interest in barley as a therapeutic food owing to its high content of beta-glucan (β-glucan), a viscous soluble fiber recognized for its cholesterol-lowering properties. The objective of this study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating the cholesterol-lowering potential of barley β-glucan on low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (apoB) for cardiovascular disease (CVD) risk reduction. MEDLINE, Embase, CINAHL and the Cochrane CENTRAL were searched. We included RCTs of ⩾3-week duration assessing the effect of diets enriched with barley β-glucan compared with controlled diets on LDL-C, non-HDL-C or apoB. Two independent reviewers extracted relevant data and assessed study quality and risk of bias. Data were pooled using the generic inverse-variance method with random effects models and expressed as mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed by the Cochran Q-statistic and quantified by the I2 statistic. Fourteen trials (N=615) were included in the final analysis. A median dose of 6.5 and 6.9 g/day of barley β-glucan for a median duration of 4 weeks significantly reduced LDL-C (MD=-0.25 mmol/l (95% CI: -0.30, -0.20)) and non-HDL-C (MD=-0.31 mmol/l (95% CI: -0.39, -0.23)), respectively, with no significant changes to apoB levels, compared with control diets. There was evidence of considerable unexplained heterogeneity in the analysis of non-HDL-C (I2=98%). Pooled analyses show that barley β-glucan has a lowering effect on LDL-C and non-HDL-C. Inclusion of barley-containing foods may be a strategy for achieving targets in CVD risk reduction.


Gasless laparoscopy-assisted subtotal gastrectomy for early gastric cancer: a novel minimally invasive surgery.
Due to the highly invasive nature of traditional surgery and the limitation of gas-filling laparoscopic surgery in gastric cancers, we developed a new method of gasless laparoscope-assisted subtotal gastrectomy (GLASG). This study investigated the technique and clinical results of this procedure and compared it with traditional radical subtotal gastrectomy (TRSG) for early gastric cancers. From December 2004 to January 2006, 41 patients diagnosed with early gastric cancer were included in the study. All cases underwent subtotal gastrectomy with standard radical lymph node dissection. Twenty patients underwent GLASG, whereas the other 21 patients underwent TRSG. In the GLASG group, we performed our newly developed method using three working ports created at the bilateral subcostal and umbilicus, which provided a 3-dimensional sensation by direct vision through a minilaparotomy and laparoscopic view simultaneously. B-II gastrojejunostomy reconstruction was performed by intracorporeal anastomosis using an endostapler. The TRSG group underwent the standard open method used for gastric cancer. Preoperative characteristics and postoperative recovery between the two groups were compared. The operative time was comparable between the two groups, but the bleeding was significantly less severe in the GLASG group. Postoperative pain was significantly less in the GLASG group, as well as body temperature from postoperative day 2 to 7. The number of days to first flatus, first oral intake, and discharge were all significantly less in the GLASG group. No major complications were noted in either group. GLASG may be a feasible and safe procedure for early gastric cancer. Gasless laparoscopic gastrectomy has the advantages of less pain, better cosmetic outcome, and earlier recovery. The newly developed gasless environment may hybridize the advantages of open method and pure laparoscopic method.


Lower Extremity Function Is Independently Associated With Hospitalization Burden in Heart Failure With Preserved Ejection Fraction.
Frailty reflects decreased resilience to physiological stressors; its prevalence and prognosis are not fully defined in heart failure with preserved ejection fraction (HFpEF). The Short Physical Performance Battery (SPPB) was prospectively obtained in 114 outpatients with HFpEF. The SPPB tests gait speed, tandem balance, and timed chair rises, each scored from 0 to 4 points. Severe and mild frailty were respectively defined as an SPPB score ≤6 and 7-9 points. We used risk-adjusted logistic, Poisson, and negative binominal regression, respectively, to assess the relationship between SPPB score and risk of death or all-cause hospitalization, number of hospitalizations, and days hospitalized or dead longer than 6 months. Patients were similar to other HFpEF cohorts (age 68 ± 13 years, 58% female, body mass index 36 ± 8 kg/m2, multiple comorbidities). Mean SPPB score was 6.9 ± 3.2, and 80% of patients were at least mildly frail. Over a 6-month period, the SPPB score independently predicted death or all-cause hospitalization (odds ratio 0.81 per point, 95% confidence interval [CI] 0.69-0.94, P = .006), number of hospitalizations (incidence rate ratio 0.92 per point, 95% CI 0.86-0.97, P = .006), and days hospitalized or dead (incidence rate ratio 0.85 per point, 95% CI 0.73-0.99, P = .04). Lower extremity function, as measured by the SPPB, independently predicts hospitalization burden in outpatients with HFpEF. Additional studies are warranted to explore shared mechanisms and treatment implications of frailty in HFpEF.


Changes in Provider Perceptions Regarding Early Mobility in the PICU.
Early mobility in the PICU is safe and feasible. However, PICUs continue to meet barriers to implementing early mobility. PICU providers were surveyed before and after initiating an early mobility protocol to determine perceived barriers and continued challenges in performing early mobility. This single-center prospective study surveyed PICU providers regarding 26 potential barriers to early mobility using a five-point Likert scale. A survey was distributed 1 month prior to and 6 months after beginning an early mobility protocol. Free-standing academic tertiary care children's hospital. PICU providers of various professions. Implementation of PICU-wide early mobility protocol. Paired pre- and post-early mobility protocol implementation surveys from 97 providers were compared. System-based barriers decreased after implementation of the early mobility protocol, such as lack of guidelines (75-20%; p < 0.01), inadequate training (74-33%; p < 0.01), lack of early mobility orders (72-30%; p < 0.01), and delayed recognition of early mobility candidates (68-35%; p < 0.01). Difficulty coordinating early mobility sessions, although significantly decreased, still remained a concern for 66% of providers in the postsurvey. Lack of resources, specifically staff (85-82%; p = 0.68) and equipment (67-60%; p = 0.36), also remained significant barriers. Presence of an endotracheal tube was a barrier for only 29% of providers' post-early mobility protocol, compared with 69% prior (p < 0.01). Clinical instability remained a top concern (82-79%; p = 0.63) as well as agitation (74-67%; p = 0.23). Day shift providers, with more early mobility exposure, perceived fewer barriers compared with night shift providers. Ninety percentage of post-early mobility survey participants felt that early mobility positively impacted their patients. Implementation of an early mobility protocol significantly changed provider perceptions regarding barriers to early mobility. Certain factors, such as staff availability, coordination difficulty, equipment shortage, and patient clinical factors, continue to be significant challenges to early mobility in the PICU population.


[Plasmatic glutathione levels and their relationships with clinical and therapeutic features in patients with schizophrenia].
Altered glutathione systems (GSH) are suggested to participate in the pathophysiology of schizophrenia. The purpose of this study was to determine the plasmatic glutathione levels of patients with schizophrenia compared to healthy controls and to examine their relationships with clinical and therapeutic features. It was a case-control study carried out on 100 patients with schizophrenia according to DSM-IV-TR criteria and 95 healthy controls. All patients were assessed by Clinical Global Impressions-severity (CGI-severity) and Global Assessment of Functioning (EGF). Most of the patients (55%) were under first-generation antipsychotics. Plasmatic glutathione levels (total glutathione GSHt, reduced glutathione GSHr, oxidized glutathione GSSG) were determined by spectrophotometry. The levels of GSHt and GSHr were significantly decreased in schizophrenic patients in comparison with the healthy controls. These reductions were noted to be more pronounced in the untreated patients. No correlation was observed between the GSH levels and the clinical subtypes of schizophrenia and EGF scores. Depending on the therapeutic status, there were no significant differences in the GSH levels. In addition, there was no correlation between the GSH levels and the daily dosage of the antipsychotic treatment. Our results suggest that the observed changes are related to the physiopathology of schizophrenia rather than to the presence of neuroleptic treatment. These results provide support for further studies of the possible role of antioxidants as neuroprotective therapeutic strategies.


Design and Synthesis of a Ferrocene-Based Diol Library and Application in the Hetero-Diels-Alder Reaction.
Diol scaffolds have been utilized as highly effective catalysts and ligands in a wide range of catalytic asymmetric transformations. For scaffolds to be successful as broadly used motifs, they should be prepared cheaply through facile routes and be easily handled. Herein, the synthesis of a family of planar chiral diols based on a modular and robust three-step route is described, which yields catalytically active diols in >99 % de and >99 % ee, with up to seven different chiral elements. These diols have been characterized by X-ray crystallographic analysis, which provides clear evidence for the likely transition state when applied in the asymmetric hetero-Diels-Alder reaction. Without altering the stereochemistry of the catalyst backbone, it is possible to access both enantiomers of the product by varying the substitution of the catalyst at the α-position.


CRAF R391W is a melanoma driver oncogene.
Approximately 75% of melanomas have known driver oncogenic mutations in BRAF, NRAS, GNA11 or GNAQ, while the mutations providing constitutive oncogenic signaling in the remaining melanomas are not known. We established a melanoma cell line from a tumor with none of the common driver mutations. This cell line demonstrated a signaling profile similar to BRAF-mutants, but lacked sensitivity to the BRAF inhibitor vemurafenib. RNA-seq mutation data implicated CRAF R391W as the alternative driver mutation of this melanoma. CRAF R391W was homozygous and over expressed. These melanoma cells were highly sensitive to CRAF, but not BRAF knockdown. In reconstitution experiments, CRAF R391W, but not CRAF WT, transformed NIH3T3 cells in soft-agar colony formation assays, increased kinase activity in vitro, induced MAP kinase signaling and conferred vemurafenib resistance. MAP kinase inducing activity was dependent on CRAF dimerization. Thus, CRAF is a bona fide alternative oncogene for BRAF/NRAS/GNAQ/GNA11 wild type melanomas.


The use of artificial neural networks for the selection of the most appropriate thermal parameters and for the classification of a set of phenylcarbamic acid derivates.
The objective of this work was to apply artificial neural networks (ANNs) to the classification group of 43 derivatives of phenylcarbamic acid. To find the appropriate clusters Kohonen topological maps were employed. As input data, thermal parameters obtained during DSC and TG analysis were used. Input feature selection (IFS) algorithms were used in order to give an estimate of the relative importance of various input variables. Additionally, sensitivity analysis was carried out to eliminate less important thermal variables. As a result, one classification model was obtained, which can assign our compounds to an appropriate class. Because the classes contain groups of molecules structurally related, it is possible to predict the structure of the compounds (for example the position of the substitution alkoxy group in the phenyl ring) on the basis of obtained parameters.


Correction: Age trends in asymptomatic and symptomatic Leishmania donovani infection in the Indian subcontinent: A review and analysis of data from diagnostic and epidemiological studies.
[This corrects the article DOI: 10.1371/journal.pntd.0006803.].


DNA hydrogel-empowered biosensing.
DNA hydrogels as special members in the DNA nanotechnology have provided crucial prerequisites to create innovative gels owing to their sufficient stability, biocompatibility, biodegradability, and tunable multifunctionality. These properties have tailored DNA hydrogels for various applications in drug delivery, tissue engineering, sensors, and cancer therapy. Recently, DNA-based materials have attracted substantial consideration for the exploration of smart hydrogels, in which their properties can change in response to chemical or physical stimuli. In other words, these gels can undergo switchable gel-to-sol or sol-to-gel transitions upon application of different triggers. Moreover, various functional motifs like i-motif structures, antisense DNAs, DNAzymes, and aptamers can be inserted into the polymer network to offer a molecular recognition capability to the complex. In this manuscript, a comprehensive discussion will be endowed with the recognition capability of different kinds of DNA hydrogels and the alternation in physicochemical behaviors upon target introducing. Finally, we offer a vision into the future landscape of DNA based hydrogels in sensing applications.


Binding of S-layer homology modules from Clostridium thermocellum SdbA to peptidoglycans.
S-layer homology (SLH) module polypeptides were derived from Clostridium josui xylanase Xyn10A, Clostridium stercorarium xylanase Xyn10B, and Clostridium thermocellum scafoldin dockerin binding protein SdbA as rXyn10A-SLH, rXyn10B-SLH, and rSdbA-SLH, respectively. Their binding specificities were investigated using various cell wall preparations. rXyn10A-SLH and rXyn10B-SLH bound to native peptidoglycan-containing sacculi consisting of peptidoglycan and secondary cell wall polymers (SCWP) prepared from these bacteria but not to hydrofluoric acid-extracted peptidoglycan-containing sacculi (HF-EPCS) lacking SCWP, suggesting that SCWP are responsible for binding with SLH modules. In contrast, rSdbA-SLH interacted with HF-EPCS, suggesting that this polypeptide had an affinity for peptidoglycans but not for SCWP. The affinity of rSdbA-SLH for peptidoglycans was confirmed by a binding assay using a peptidoglycan fraction prepared from Escherichia coli cells. The SLH modules of SdbA must be useful for cell surface engineering in bacteria that do not contain SCWP.


Deep learning-based automated segmentation of resection cavities on postsurgical epilepsy MRI.
Accurate segmentation of surgical resection sites is critical for clinical assessments and neuroimaging research applications, including resection extent determination, predictive modeling of surgery outcome, and masking image processing near resection sites. In this study, an automated resection cavity segmentation algorithm is developed for analyzing postoperative MRI of epilepsy patients and deployed in an easy-to-use graphical user interface (GUI) that estimates remnant brain volumes, including postsurgical hippocampal remnant tissue. This retrospective study included postoperative T1-weighted MRI from 62 temporal lobe epilepsy (TLE) patients who underwent resective surgery. The resection site was manually segmented and reviewed by a neuroradiologist (JMS). A majority vote ensemble algorithm was used to segment surgical resections, using 3 U-Net convolutional neural networks trained on axial, coronal, and sagittal slices, respectively. The algorithm was trained using 5-fold cross validation, with data partitioned into training (N = 27) testing (N = 9), and validation (N = 9) sets, and evaluated on a separate held-out test set (N = 17). Algorithm performance was assessed using Dice-Sørensen coefficient (DSC), Hausdorff distance, and volume estimates. Additionally, we deploy a fully-automated, GUI-based pipeline that compares resection segmentations with preoperative imaging and reports estimates of resected brain structures. The cross-validation and held-out test median DSCs were 0.84 ± 0.08 and 0.74 ± 0.22 (median ± interquartile range) respectively, which approach inter-rater reliability between radiologists (0.84-0.86) as reported in the literature. Median 95 % Hausdorff distances were 3.6 mm and 4.0 mm respectively, indicating high segmentation boundary confidence. Automated and manual resection volume estimates were highly correlated for both cross-validation (r = 0.94, p < 0.0001) and held-out test subjects (r = 0.87, p < 0.0001). Automated and manual segmentations overlapped in all 62 subjects, indicating a low false negative rate. In control subjects (N = 40), the classifier segmented no voxels (N = 33), <50 voxels (N = 5), or a small volumes<0.5 cm3 (N = 2), indicating a low false positive rate that can be controlled via thresholding. There was strong agreement between postoperative hippocampal remnant volumes determined using automated and manual resection segmentations (r = 0.90, p < 0.0001, mean absolute error = 6.3 %), indicating that automated resection segmentations can permit quantification of postoperative brain volumes after epilepsy surgery. Applications include quantification of postoperative remnant brain volumes, correction of deformable registration, and localization of removed brain regions for network modeling.


ThermoTRP channels and cold sensing: what are they really up to?
Cooling is sensed by peripheral thermoreceptors, the main transduction mechanism of which is probably a cold- and menthol-activated ion channel, transient receptor potential (melastatin)-8 (TRPM8). Stronger cooling also activates another TRP channel, TRP (ankyrin-like)-1, (TRPA1), which has been suggested to underlie cold nociception. This review examines the roles of these two channels and other mechanisms in thermal transduction. TRPM8 is activated directly by gentle cooling and depolarises sensory neurones; its threshold temperature (normally approximately 26-31 degrees C in native neurones) is very flexible and it can adapt to long-term variations in baseline temperature to sensitively detect small temperature changes. This modulation is enabled by TRPM8's low intrinsic thermal sensitivity: it is sensitised to varying degrees by its cellular context. TRPM8 is not the only thermosensitive element in cold receptors and interacts with other ionic currents to shape cold receptor activity. Cold can also cause pain: the transduction mechanism is uncertain, possibly involving TRPM8 in some neurones, but another candidate is TRPA1 which is activated in expression systems by strong cooling. However, native neurones that appear to express TRPA1 respond very slowly to cold, and TRPA1 alone cannot account readily for cold nociceptor activity or cold pain in humans. Other, as yet unknown, mechanisms of cold nociception are likely.


Days-out-of-role associated with insomnia and comorbid conditions in the America Insomnia Survey.
Insomnia is highly prevalent and impairing but also highly comorbid with other chronic physical/mental disorders. Population-based research has yet to differentiate the role impairments uniquely associated with insomnia per se from those due to comorbidity. A representative sample of 6791 adult subscribers to a large national US commercial health plan was surveyed by telephone about sleep and health. Twenty-one conditions previously found to be comorbid with insomnia were assessed with medical/pharmacy claims data and validated self-report scales. The Brief Insomnia Questionnaire, a fully structured, clinically validated scale, generated insomnia diagnoses according to inclusion criteria of DSM-IV-TR, ICD-10, and Research Diagnostic Criteria/International Classification of Sleep Disorders: Diagnostic and Coding Manual, Second Edition. The World Health Organization Disability Assessment Schedule-II assessed number of days in the past 30 when health problems prevented respondents from conducting their usual daily activities. Regression analyses estimated associations of insomnia with days-out-of-role controlling comorbidity. Insomnia was significantly associated with days-out-of-role (.90 days/month) in a gross model. The association was reduced when controls were introduced for comorbidity (.42 days/month). This net association did not vary with number or type of comorbid conditions but was confined to respondents 35+ years of age. Insomnia was one of the most important conditions studied not only at the individual level, where it was associated with among the largest mean days-out-of-role, but also at the aggregate level, where it was associated with 13.6% of all days-out-of-role. Insomnia has a strong net association with days-out-of-role that does not vary as a function of comorbidity.


Integrated microbiomic and metabolomic analyses reveal the mechanisms by which bee pollen and royal jelly lipid extracts ameliorate colitis in mice.
Bee pollen (BP) and royal jelly (RJ) have shown therapeutic effects against colitis, but the functional components contained therein remain elusive. Here, we used an integrated microbiomic-metabolomic strategy to clarify the mechanism by which bee pollen lipid extracts (BPL) and royal jelly lipid extracts (RJL) ameliorated dextran sulfate sodium (DSS)-induced colitis in mice. Lipidomic results showed that levels of ceramide (Cer), lysophosphatidylcholine (LPC), phosphatidylcholine (PC), and phosphatidylethanolamine (PE) were significantly higher in BPL than in RJL. The anti-inflammatory efficacy of BPL surpassed that of RJL, although both BPL and RJL could attenuate DSS-induced colitis through several mechanisms: reducing the disease activity index (DAI); decreasing histopathological damage; inhibiting the expression of genes encoding proinflammatory cytokines; improving intestinal microbial community structure, and modulating host metabolism. These findings demonstrated that BPL and RJL have great potential as functional ingredients for the production of dietary supplements to prevent early colitis.


Outcome following phrenic nerve transfer to musculocutaneous nerve in patients with traumatic brachial palsy: a qualitative systematic review.
The phrenic nerve can be transferred to the musculocutaneous nerve in patients with traumatic brachial plexus palsy in order to recover biceps strength, but the results are controversial. There is also a concern about pulmonary function after phrenic nerve transection. In this paper, we performed a qualitative systematic review, evaluating outcomes after this procedure. A systematic review of published studies was undertaken in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. Data were extracted from the selected papers and related to: publication, study design, outcome (biceps strength in accordance with BMRC and pulmonary function) and population. Study quality was assessed using the "strengthening the reporting of observational studies in epidemiology" (STROBE) standard or the CONSORT checklist, depending on the study design. Seven studies were selected for this systematic review after applying inclusion and exclusion criteria. One hundred twenty-four patients completed follow-up, and most of them were graded M3 or M4 (70.1 %) for biceps strength at the final evaluation. Pulmonary function was analyzed in five studies. It was not possible to perform a statistical comparison between studies because the authors used different parameters for evaluation. Most of the patients exhibited a decrease in pulmonary function tests immediately after surgery, with recovery in the following months. Study quality was determined using STROBE in six articles, and the global score varied from 8 to 21. Phrenic nerve transfer to the musculocutaneous nerve can recover biceps strength ≥M3 (BMRC) in most patients with traumatic brachial plexus injury. Early postoperative findings revealed that the development of pulmonary symptoms is rare, but it cannot be concluded that the procedure is safe because there is no study evaluating pulmonary function in old age.


The association of dietary inflammatory potential with sarcopenia in Chinese community-dwelling older adults.
Dietary-induced inflammation is potentially associated with sarcopenia. Nevertheless, few studies have investigated the structure of the inflammatory diet and its correlation with muscle function and performance in both the upper and lower limbs. This study was performed to explore the association of the dietary inflammatory index (DII) with sarcopenia and its diagnostic parameters. We conducted a cross-sectional survey on a sample of 515 Chinese community-dwelling older adults selected through multistage cluster sampling from three districts in Shanghai. DII scores were calculated using a validated food frequency questionnaire. Sarcopenia and its diagnostic parameters were determined based on the definition set by the Asian Working Group on Sarcopenia (AWGS). The mean age of study participants was 71.31 ± 4.71 years. The prevalence of sarcopenia in the cohort was 12.4%. Older adults in the highest DII quartile had a 3.339 times increased risk of sarcopenia compared to those in the lowest quartile (OR Quartile4vs1:3.339, 95%CI: 1.232, 9.052, p-trend: 0.004) after adjusting for confounding factors. Additionally, a more pro-inflammatory diet was associated with lower appendicular skeletal muscle index (ASMI) (OR Quartile4vs1: 3.005, 95%CI: 1.275, 7.318, p-trend: 0.005), a higher 5-times sit-stand test time score (OR Quartile4vs1: 4.942, 95%CI: 1.745, 13.993, p-trend: 0.005), and lower gait speed (OR Quartile4vs1: 2.392, 95%CI: 1.104, 5.185, p-trend: 0.041) after adjusting for confounding factors. However, there was no significant association between DII, handgrip strength, and Short Physical Performance Battery (SPPB) score in either the unadjusted or adjusted model. This study found that the association between consuming a more pro-inflammatory diet and sarcopenia in Chinese community-dwelling older adults was mainly due to underlying low intakes of dietary energy, protein, and anti-inflammatory foods, and not due to the high intake of pro-inflammatory foods. Meanwhile, DII was more highly correlated with lower limb muscle strength and performance compared to upper limb muscle strength.


From badge of pride to cause of stigma: combatting mal del pinto in Mexico.
Mal del pinto is a dermatological disease characterized by discoloured patches of skin on the face and body. It has been present in what is now the territory of Mexico from before the Spanish conquest up to recent times. Though early concerns for mal del pinto as a public health problem can be traced back to the late 19th century, no campaign to combat the disease was undertaken until the second half of the 20th. Thanks to the effectiveness of treatment with penicillin, the fight against this illness--which was once assumed as a symbol of pride--enjoyed a broader acceptance among the population that other health campaigns.


Transforming growth factor is a potent stimulator of testicular ornithine decarboxylase in immature mouse.
Administration of transforming growth factor, type alpha (TGF-alpha), to eight-day old mice resulted in 22 fold increase of testicular ornithine decarboxylase activity. Two to seven fold increases of enzyme activities by TGF-alpha were also observed in intestine, kidney, spleen, liver, and heart. The maximal enzymatic responses were reached 2-4 h after TGF-alpha administration in vivo. The induction of tissue ornithine decarboxylase activity was accompanied by an increase in new protein synthesis. These effects were found to be comparable to those in littermates administered with mouse epidermal growth factor but were significantly more pronounced than with bovine growth hormone. Daily administration of TGF-alpha to newborn mice also produced a 1.8 fold increase of testicular weight after 14 days. The present studies therefore show that TGF-alpha is an epidermal growth factor-like mitogen and is likely to be important for the testicular development of immature animal.


Bubble Bubble, Senescent Cells Are a Cauldron of Tumor Trouble.
Senescent cells release a mélange of factors that drive multiple forms of pathology, including cancer aggressiveness. In this issue of Cancer Research, Han and colleagues show that small extracellular vesicles (sEV), membrane-enclosed bubbles that carry signaling molecules, from senescent stromal cells can promote tumorigenesis and multidrug resistance in prostate or breast cancer cells. They find that loss of SIRT1 activity drives senescence-associated sEV release, and treatment with a SIRT1 agonist prevented this effect. This adds another mechanism by which senescent cells can promote tumorigenesis and offers another activity of senescent cells that might be targeted to limit the spread of cancer.See related article by Han et al., p. 3383.


A randomized trial of peak-flow and symptom-based action plans in adults with moderate-to-severe asthma.
Peak flow meters (PFM) continue to be recommended as an important part of asthma self-management plans. It remains unclear if there is an advantage in using PFM in people with moderate-to severe asthma who are not poor perceivers of bronchoconstriction. Prospective, randomized controlled trial of 134 adults with moderate-to-severe asthma who did not have evidence of poor perception of bronchoconstriction on histamine challenge testing, who were recruited from inpatients and outpatients of a university teaching hospital. Comparison was made over 12 months of the effectiveness of written action plans using either peak flow monitoring or symptoms to guide management. Subjects were contacted at monthly intervals by telephone for reinforcement and evaluation of use of the action plans, and to provide ongoing education. Spirometry and PD20 histamine were measured at 3-monthly intervals. Measures of health care utilization and morbidity (asthma exacerbations; hospitalizations; emergency department (ED) visits; days absent from work or school due to asthma; medication use and a self-rating of asthma severity) were made monthly. A psychosocial questionnaire (attitudes and beliefs, state-trait anxiety, denial) was given at entry and at 12-months or at withdrawal from the study. There were significant improvements for both groups for hospitalizations, ED visits, days off from school or work, and PD20 histamine, but no between-group differences. Appropriate use of action plans was 85% in the symptoms group and 86% in the PFM group. For all subjects, those who subsequently had an ED visit had significantly higher levels of denial (P=0.04) and lower scores for self-confidence (P=0.04), compared to those who did not have an ED visit. Use of written action plans, combined with regular contact to reinforce self-management, improved airway reactivity and reduced health care utilization. However, use of PFM was not superior to symptom-based plans.