The bad seed: PDGF receptors link adult neural progenitors to glioma stem cells.
In this issue of Neuron, Jackson et al. show that adult neural stem cells (B cells) express PDGF receptors. Functional analysis of PDGF signaling in these neural progenitors resonates in provocative ways with an older body of literature on PDGF autocrine loops in malignant glioma and with more recent observations on the bHLH transcription factor Olig2.


Diurnal variation in excretion of N-acetyl-beta-glucosaminidase during pregnancy: implications for the prediction of pre-eclampsia.
Significant differences in urinary excretion of N-acetyl-beta-glycosaminidase (NAG) were observed between nulliparous and multiparous patients and between fasted and nonfasted individuals. No significant difference was observed between patients with normal and those with abnormal glucose tolerance. Multiple regression analysis confirmed that the significant independent determinants of NAG/creatinine ratio were age, parity, gestation and fasting state. Significant diurnal variation in urinary NAG/Cr ratio was observed, the highest levels being recorded in early morning fasting specimens, falling in each postprandial specimen and beginning to rise again by midnight. The urinary NAG/Cr ratio is influenced by fasting, parity, gestation and age. More consistent results for prediction of pre-eclampsia are therefore likely to be obtained using fasting (early morning) urine specimens and adjusting cut-off criteria for the other factors.


Surgery for tardive dyskinesia.
Tardive dyskinesia (TD) is an often bothersome side effect of antipsychotic treatment. Medical treatment options are usually disappointing. A few single case reports have suggested some efficacy of lesionning surgery (i.e. pallidotomy or thalamotomy). A much greater number of series (including one controlled-study) have assessed the effects of deep brain stimulation applied to the internal globus pallidus. All of them have shown a marked improvement of motor symptoms without any major psychiatric side effects.


Differential dependence of reovirus-associated enzyme activities on genome RNA as determined by psoralen photosensitivity.
Irradiation with long wavelength UV light in the presence of 4'-substituted psoralens abolished the in fectivity of reovirus and reovirus subviral particles Photoreaction of intact virions, cores, or genome RNA resulted in the formation of psoralen monoadducts and cross-links, demonstrating that the viral genome RNA in situ is double-stranded. Virus-associated RNA polymerase activity was lost following psoralen photoreaction, consistent with dependence on the genome RNA as template for viral mRNA synthesis. By contrast, reovirus guanylyl transferase and methyl transferase activities that catalyze the formation of mRNA 5'-terminal cap, m GpppG, were relatively unaffected by photoreaction. Cations that inhibit psoralen binding to nucleic acids also protected against loss of RNA polymerase activity. Partially photoinactivated viral cores produced decreased amounts of full length viral mRNAs. The absence of prematurely terminated transcripts indicates that template RNA modification by psoralen adducts has an all-or-none effect on initiation of mRNA synthesis by the core-associated RNA polymerase.


High performance solutions and data for nZEBs offices located in warm climates.
This data article contains eleven tables supporting the research article entitled: Cost-Optimal Design For Nearly Zero Energy Office Buildings Located In Warm Climates [1]. The data explain the procedure of minimum energy performance requirements presented by the European Directive (EPBD) [2] to establish several variants of energy efficiency measures with the integration of renewable energy sources in order to reach nZEBs (nearly zero energy buildings) by 2020. This files include the application of comparative methodological framework and give the cost-optimal solutions for non-residential building located in Southern Italy. The data describe office sector in which direct the current European policies and investments [3], [4]. In particular, the localization of the building, geometrical features, thermal properties of the envelope and technical systems for HVAC are reported in the first sections. Energy efficiency measures related to orientation, walls, windows, heating, cooling, dhw and RES are given in the second part of the group; this data article provides 256 combinations for a financial and macroeconomic analysis.


The physical interactome between Peregrinus maidis proteins and the maize mosaic virus glycoprotein provides insights into the cellular biology of a rhabdovirus in the insect vector.
Rhabdovirus glycoproteins (G) serve multifunctional roles in virus entry, assembly, and exit from animal cells. We hypothesize that maize mosaic virus (MMV) G is required for invasion, infection, and spread in Peregrinus maidis, the planthopper vector. Using a membrane-based yeast two-hybrid assay, we identified 107 P. maidis proteins that physically interacted with MMV G, of which approximately 53% matched proteins with known functions including endocytosis, vesicle-mediated transport, protein synthesis and turnover, nuclear export, metabolism and host defense. Physical interaction networks among conserved proteins indicated a possible cellular coordination of processes associated with MMV G translation, protein folding and trafficking. Non-annotated proteins contained predicted functional sites, including a diverse array of ligand binding sites. Cyclophilin A and apolipophorin III co-immunoprecipitated with MMV G, and each showed different patterns of localization with G in insect cells. This study describes the first protein interactome for a rhabdovirus spike protein and insect vector.


Protein composition of cerebrospinal fluid in the developing chick embryo.
Proteins from cerebrospinal fluid of chick embryos at 4-19 days of development were qualitative and quantitatively analyzed. The total protein concentration and the relative concentration of each protein fraction were calculated for each day. The main proteins found along development were immunoglobulin G, transferrin, alpha-fetoprotein, serum albumin, ovalbumin, prealbumin, and an unidentified component. alpha-Fetoprotein was found to be the major protein at 4-16 days, and serum albumin at 17-19 days of development. The unidentified fraction was present from 4 to 11 days; at day 5 it represented 28% of the total cerebrospinal fluid protein concentration.


Sequential tibial and peroneal intraneural ganglia arising from the superior tibiofibular joint.
We present a patient who developed a peroneal intraneural ganglion and an adventitial cyst following the incomplete treatment of a tibial intraneural ganglion. These separate cysts all originated from the superior tibiofibular joint and dissected along their respective articular branches. A logical mechanistic explanation for these coexisting cysts is provided, which highlights the shared pathogenesis--its joint-related nature--rather than a multifocal de novo process. These observations would not only be consistent with, but would extend previous evidence in support of, the unifying articular (synovial) theory.


Hematological Changes after Caprine Demineralized Bone Matrix Implantation in Ulnar Critical Defect of Rabbit Model.
Objective Several animal models have been used in fracture healing and bone graft studies, but hematological responses are seldom reported. Therefore, the present study reported the hematological changes observed in rabbits that underwent xenografting of caprine demineralized bone matrix (CDBM). Method Twenty-four (24) male rabbits (2.5 ± 0.5kg) were acquired for the purpose of this study and were randomly assigned to three groups: autologous bone graft (ABG), unfilled (NC), and caprine demineralized bone matrix (CDBM). Blood samples were collected through cardiac puncture under xylazine-ketamine anesthesia on day 0 (baseline), and on days 28 and 56 postsurgery and were analyzed manually within 2 hours of collection. Statistical analysis was performed using a two-way analysis of variance (ANOVA) with repeated measures, and a p -value < 0.05 was considered significant. Result There was an overall significant difference in the values of total white blood cell count ( p = 0.0043), neutrophil count ( p < 0.0001), monocyte count ( p = 0.0184), red blood cell count ( p = 0.003), hemoglobin concentration ( p < 0.0001) and packed cell volume ( p < 0.0001) across the days and the treatment groups. There was, however, no overall significant difference in lymphocyte count ( p = 0.4923), basophil count ( p = 0.4183), and eosinophil count (0.4806) within days. Conclusion Response to CDBM grafting in rabbits could, therefore, be said to be characterized by marked leukocytosis with neutrophilia, lymphocytosis, and monocytosis by day 28 of postgrafting. This could form the basis with which hematology can be used to monitor body response of bone graft animal models.


Antibiotic Therapy for Culture-Proven Bacterial Overgrowth in Children With Intestinal Failure Results in Improved Symptoms and Growth.
To evaluate symptoms, enteral tolerance, growth, and antibiotic regimens in pediatric intestinal failure (IF) patients after treated with antibiotic therapy for small bowel bacterial overgrowth (SBBO). Single-center retrospective review of children 0-18 years with IF with endoscopic cultures demonstrating >10 5 CFU/mL from 2010 to 2017. Symptoms, enteral tolerance, growth, and antibiotic regimens were evaluated at the time of endoscopy and 6 months later. Of 505 patients followed in our intestinal rehabilitation program, 104 underwent upper gastrointestinal endoscopy and 78 had positive duodenal cultures. Clinical data pre- and post-endoscopy were available for 56 patients. Compared to baseline, in the 6 months following targeted antibiotic treatment, children showed significant improvement in emesis or feeding intolerance (58.9% vs 23.2%, P < 0.001), abdominal pain (16.1% vs 7.1%, P = 0.02), high stool output (42.9% vs 19.6%, P = 0.002), and gross GI bleeding (19.6% vs 3.6%, P = 0.003). Mean BMI-for-age z scores increased significantly (-0.03 ± 0.94 vs 0.27 ± 0.82, P = 0.03); however, height-for-age z scores, weight-for-age z scores, and percent of calories from enteral intake were not significantly different after therapy. Antibiotic regimens remained highly variable. Children with IF and culture-positive SBBO showed significant improvement in symptoms and BMI-for-age z scores after duodenal culture with subsequent targeted antibiotic therapy. Longer follow-up may be needed to detect improvements in linear growth and percent of calories from enteral feeds. Antibiotic regimens remain highly variable. Long-term consequences of chronic antimicrobial therapy, including antimicrobial resistance, remain unknown. Prospective studies focused on standardizing duodenal sampling technique, correlating culture and pathology data, and evaluating antibiotic resistance patterns are needed.


Peripheral plasma immunoreactive 6-oxo-prostaglandin F1 alpha and gynaecological tumours.
Peripheral plasma levels of immunoreactive 6-oxo-PGF1 alpha, the stable hydrolysis product of prostacyclin, were significantly higher in female patients with tumours of the genital tract than in normal controls. In the groups with malignant tumours, these high levels declined after operation and/or radiotherapy if the tumour responded to treatment. In patients who did not respond to treatment or with tumour recurrence, levels of plasma 6-oxo-PGF1 alpha remained high or even rose further. Benign gynaecological tumours were also associated with significantly raised plasma 6-oxo-PGF1 alpha levels, and these fell to normal levels immediately on surgical removal of the tumour. Possible reasons for these alterations are described. Further investigations are warranted to see whether serial measurements of plasma 6-oxo-PGF1 alpha could be used as a prognostic index for the clinical status of patients with gynaecological tumours.


The effects of pollination distance on seed production in three populations of Amianthium muscaetoxicum (Liliaceae).
We examined the effects of varying pollination distances on seed production and its components in three populations of the perennial lily Amianthium muscaetoxicum. We performed hand pollinations using pollen from near neighbors and from plants separated by 5, 15, and 60 meters. Pollination by near neighbors reduced fruit set and the numbers of seeds per fruit in comparison to other treatments in two of the three populations; variation in pollination distance beyond near-neighbor pollination produced no effect. In the third population, in which nearneighbor pollination did not affect seed production, nearneighbor pollination reduced seed weight by 11%, compared to other pollination distances. Seed weights from the 5-, 15-, and 60-m pollination treatments did not differ, and pollination distance did not affect seed weight in the other two populations. The effects of pollination-distance treatments explained a very small proportion of the variance in seed production and seed weight. Heterogeneity among individual plants, despite full hand pollination of every plant, accounted for much more variance (by one to two orders of magnitude) than variation in pollination distance.


Rehospitalization of extremely-low-birth-weight infants in first 2 years of life.
To determine whether (1) chronic lung disease (CLD) is the prime reason for extremely-low-birth-weight (ELBW) infant readmission during the first 2 years of life, (2) surfactant and other advanced therapies have reduced ELBW infant readmissions, (3) home oxygen therapy (HOT) is efficacious for this group. The hospital records of these ELBW infants were reviewed retrospectively. Data on age, diagnosis, treatment, and duration of each hospitalization were compiled and analyzed for their association to CLD and to readmission for CLD and other reasons. All 60 surviving infants with a birth body weight of less than 1001 g (ELBW) born from January 1993 to February 1998 were followed up to 2 years (mean 20.4 +/- 7.4 months) to evaluate their respiratory outcome. Forty-two percent of these infants developed CLD. Upon discharge from the hospital, 28% (7/25) of the patients were given HOT for a median period of 60 days. Of the 47 ELBW infants who were studied the entire 2-year period, 72% were readmitted. Infants with CLD were readmitted more frequently (p=0.045) and had longer hospital stays during the first 2 years of life (p=0.034) than those without CLD. Respiratory illness was the main reason for readmission (55%) of these ELBW infants. The incidence of readmission due to respiratory tract infection was not significantly different in infants with CLD (61%) and infants without respiratory complications (44%) (p=0.159). Infants with CLD (whether receiving HOT or not) showed no higher readmission rate due to respiratory infection, but the HOT group did have higher morbidity. The premature lung itself rather than the presence of CLD, as we would expect, makes ELBW infants more prone to readmission for respiratory illness.


The Hordaland Homocysteine Studies.
The Hordaland Homocysteine Study is a population-based screening of total plasma homocysteine (tHcy) in approximately 18,000 men and women aged 40-67 yr that took place in 1992-1993 in the county of Hordaland in Western Norway. In this cohort, tHcy was associated with several physiologic and life-style factors, including age and gender, blood pressure, serum cholesterol, smoking, alcohol and coffee consumption, physical activity, diet, and vitamin status. All associations with established cardiovascular risk factors were in the direction expected to confer increased risk. In a subset of 5,883 women aged 40-42 yr, tHcy was associated with previous pregnancy outcomes, including preeclampsia, placental abruption, and neural tube defects. This article reviews the published results from the Hordaland Homocysteine Study in the light of relevant literature. The Hordaland Homocysteine cohort will be used for future investigations of the stability of tHcy and vitamin status over time, and to investigate associations with mortality and morbidity including cancer incidence.


[Blood levels of vitamins in neonatal infants before and after correction of vitamin deficiency in their mothers].
The paper presents the data of a study of the vitamin status in the neonatal infants before and after correction of vitamin deficiency in their apparently healthy mothers.


Combined toxicity of organophosphate flame retardants and cadmium to Corbicula fluminea in aquatic sediments.
Organophosphate flame retardants (OPFRs), as alternatives to polybrominated biphenyl ethers (PBDEs), are frequently detected in various environmental matrices. Owing to urbanization and industrial pollution, co-contamination of OPFRs and heavy metals is ubiquitous in the environment. The toxicity of OPFRs in aqueous phase is a significant concern, but uncertainty still exists regarding the co-toxicity to benthic organisms of OPFRs and metals in sediments. Hence, we explored the physiological response of Corbicula fluminea to OPFRs and Cd in sediments. The results indicated that the antioxidant system in the clams was stimulated in the presence of OPFRs and Cd, and the oxidative stress increased with increasing concentrations of OPFRs. In contrast, the cytochrome P450 (CYP450) content and acetylcholinesterase (AChE) activity were reduced by exposure to both OPFRs and Cd. The cytochrome P450 4 family (CYP4) mRNA expression and OPFR toxicity were lower than those in previously reported experiments conducted in the water phase. Moreover, the expression levels of metallothionein (MT) and AChE mRNA decreased when OPFRs and Cd were present together. The highest integrated biomarker response (IBR) index (IBR = 15.41) was observed in the presence of 45 mg kg-1 Cd + 200 mg kg-1 OPFRs, rather than the 45 mg kg-1 Cd + 400 mg kg-1 OPFRs treatment (IBR = 9.48). In addition, CYP450 and AChE in the digestive glands of C. fluminea exhibited significant correlations with the concentration of the OPFR/Cd mixture (p < 0.01) and could be effective biomarkers for OPFR and Cd co-contamination. The results potentially contribute to more realistic predictions and evaluations of the environmental risks posed by OPFRs in aquatic sediments contaminated with heavy metals, particularly with respect to the risk to benthic organisms.


Plasma cerebrosterol and magnetic resonance imaging measures in multiple sclerosis.
The concentration in plasma of the brain-specific cholesterol metabolite cerebrosterol has been proposed as a biomarker of neurodegeneration in multiple sclerosis (MS) and other neurological diseases. It is unknown, however, which pathophysiological process in MS best accounts for variations in plasma cerebrosterol. In this study, we related plasma cerebrosterol concentrations in 46 MS patients - 27 with a relapsing-remitting (RR) disease course and 19 with a primary progressive (PP) course - to three conventional magnetic resonance imaging measures: on T(1)-weighted brain scans, volume of gadolinium-enhanced lesions (a marker of active inflammation) and hypointense lesions (a marker of edema or axonal loss) and on T(2)-weighted scans, volume of hyperintense lesions (a marker of disease extent). By multiple-regression analysis, we uncovered negative correlations between the cerebrosterol-cholesterol ratio in plasma and both age at sampling (beta=-0.35 and p=0.079 in RRMS; beta=-0.76 and p=0.006 in PPMS) and volume of T(2)-weighted lesions (beta=-0.52 and p=0.078 in RRMS; beta=-0.50 and p=0.247 in PPMS). We hypothesize that decreases in plasma cerebrosterol may reflect the total spatiotemporal burden of MS-the cumulative effects of its dissemination in space and its duration in time.


Cells transformed by adenovirus type 12 but not by type 5 are dependent on insulin or insulin-like growth factor I for their proliferation.
We have investigated the responsiveness to growth factors (GFs) of primary baby rat kidney (BRK) cells transformed by the E1 region of adenovirus 5 or 12. The in vitro growth of non-oncogenic adenovirus 5-transformed BRK cells is largely independent of serum GFs, whereas growth of highly oncogenic adenovirus 12-transformed cells is strictly dependent on GFs present in serum. For the growth of adenovirus 12 E1-transformed BRK cells serum can be replaced by insulin or insulin-like growth factor-I but not by epidermal growth factor. To maintain the in vitro growth of adenovirus 12-transformed cells physiological levels of insulin-like growth factor-I, but not of insulin, are sufficient. Similar results have been found with adenovirus-transformed primary murine cells and with transformants of an established rat cell line, NRK 49F. This indicates that the observed GF responsiveness is not dependent of the cell type used but is determined by the serotype of the adenovirus-transforming region. Using hybrid E1 regions consisting of E1A of one serotype and E1B of the other, we show that the pattern of GF-responsiveness correlates with the origin of the E1A region. The differences in the GF-responsiveness of the adenovirus 5-transformed and adenovirus 12-transformed cells will be discussed in terms of the oncogenicity of these cells.


Functional analysis of the enteropathogenic Escherichia coli type III secretion system chaperone CesT identifies domains that mediate substrate interactions.
In many Gram-negative bacteria, a key indicator of pathogenic potential is the possession of a specialized type III secretion system, which is utilized to deliver virulence effector proteins directly into the host cell cytosol. Many of the proteins secreted from such systems require small cytosolic chaperones to maintain the secreted substrates in a secretion-competent state. One such protein, CesT, serves a chaperone function for the enteropathogenic Escherichia coli (EPEC) translocated intimin receptor (Tir) protein, which confers upon EPEC the ability to alter host cell morphology following intimate bacterial attachment. Using a combination of complementary biochemical approaches, functional domains of CesT that mediate intermolecular interactions, involved in both chaperone-chaperone and chaperone-substrate associations, were determined. The CesT N-terminal is implicated in chaperone dimerization, whereas the amphipathic alpha-helical region of the C-terminal, is intimately involved in substrate binding. By functional complementation of chaperone domains using the Salmonella SicA chaperone to generate chaperone chimeras, we show that CesT-Tir interaction proceeds by a mechanism potentially common to other type III secretion system chaperones.


The impact of hypertension on chronic kidney disease and end-stage renal disease is greater in men than women: a systematic review and meta-analysis.
Hypertension (HTN) is an established risk factor for chronic kidney disease (CKD) and end-stage renal disease (ESRD). Whether sex differences in the effect of HTN on CKD and ESRD incidence exist remains unclear. This systematic review and meta-analysis was conducted to evaluate the relative impact of HTN on CKD and ESRD risk in women compared with men. We systematically searched Embase and PubMed for cohort studies until 24 July 2020. Studies were selected if they reported a sex-specific association between systolic blood pressure (SBP) and CKD or ESRD. Random effects meta-analyses with inverse variance weighting were used to pool sex-specific relative risks (RRs) and the women-to-men ratio of RRs (the RRR) for incident CKD and ESRD. Data from six cohorts, including 2,382,712 individuals and 6856 incident CKD events, and 833 ESRD events, were included in the meta-analysis. The RR for incident CKD or ESRD associated with HTN (SBP ≥140 mmHg) versus ideal BP (SBP < 120 mmHg) was 1.56 (95% CI, 1.39-1.75) in women and 2.06 (95% CI, 1.64-2.60) in men. The RR for incident CKD or ESRD was 23% lower in women than in men RRR 0.77 [95% CI, 0.63-0.95] with no significant heterogeneity between studies (p-value for Q test = 0.507, I2 = 17.7%). HTN confers about a fifth lower excess risk of incident CKD or ESRD in women than men. Sex differences in onset, duration, and severity of some risk factors, such as albuminuria, diabetes, cardiovascular disease, obesity, and socioeconomic status, may explain part of the excess risk in men. Another explanation could be that women might be under-diagnosed and less likely to initiate dialysis. Future studies are needed to demonstrate the mechanisms responsible for the observed sex difference.


Carbomycin resistance in mouse L cells.
A mutant has been isolated from the mouse cell line LM(TK-) which is stably resistant to the macrolide antibiotic, carbomycin. Mitochondrial protein synthesis in this mutant was carbomycin resistant and chloramphenicol sensitive. Fusions between carbomycin-resistant and -sensitive cells produced hybrids, most of which were sensitive to 10 microgram/ml carbomycin. At 7.5 microgram carbomycin/ml, the average population resistance is low initially but increases with time. Carbomycin-resistant cells were enucleated and fused with carbomycin-sensitive cells under a variety of selective regimes designed to allow growth of carbomycin-resistant cytoplasmic hybrids (cybrids). No transfer of carbomycin resistance via the cytoplasm was detected. Karyoplasts from carbomycin-resistant cells showed a low transfer of resistance to 7.5 microgram carbomycin/ml in karyoplast-cell fusions. Carbomycin resistance in this mutant is therefore most likely encoded in a nuclear gene.


Natural biocide disrupts nestmate recognition in honeybees.
Honeybee colonies are under the threat of many stressors, biotic and abiotic factors that strongly affect their survival. Recently, great attention has been directed at chemical pesticides, including their effects at sub-lethal doses on bee behaviour and colony success; whereas the potential side effects of natural biocides largely used in agriculture, such as entomopathogenic fungi, have received only marginal attention. Here, we report the impact of the fungus Beauveria bassiana on honeybee nestmate recognition ability, a crucial feature at the basis of colony integrity. We performed both behavioural assays by recording bee guards' response towards foragers (nestmate or non-nestmate) either exposed to B. bassiana or unexposed presented at the hive entrance, and GC-MS analyses of the cuticular hydrocarbons (CHCs) of fungus-exposed versus unexposed bees. Our results demonstrated that exposed bees have altered cuticular hydrocarbons and are more easily accepted into foreign colonies than controls. Since CHCs are the main recognition cues in social insects, changes in their composition appear to affect nestmate recognition ability at the colony level. The acceptance of chemically unrecognizable fungus-exposed foragers could therefore favour forager drift and disease spread across colonies.


Branched-chain amino acids, history of gestational diabetes, and breastfeeding: The Bogalusa Heart Study.
To examine the associations between history of gestational diabetes mellitus (GDM) and breastfeeding with branched-chain amino acids (BCAA) and their metabolites in later life. 638 women (mean age 48.0 y) who had participated in the Bogalusa Heart Study and substudies of pregnancy history had untargeted, ultrahigh performance liquid chromatography-tandem mass spectroscopy conducted by Metabolon© on serum samples. Metabolites were identified that were BCAA or associated with BCAA metabolic pathways. History of GDM at any pregnancy (self-reported, confirmed with medical records when possible) as well as breastfeeding were examined as predictors of BCAA using linear models, controlling for age, race, BMI, waist circumference, and menopausal status. None of the BCAA differed statistically by history of either GDM or breastfeeding, although absolute levels of each of the BCAA were higher with GDM and lower with breastfeeding. Of the 27 metabolites on the leucine, isoleucine and valine metabolism subpathway, 1-carboxyethylleucine, 1-carboxyethyvaline, and 3-hydroxy-2-ethylpropionate were higher in women with a history of GDM, but lower in women in women with a history of breastfeeding. Similar results were found for alpha-hydroxyisocaproate, 1-carboxyethylisoleucine, and N-acetylleucine. GDM and breastfeeding are associated in opposite directions with several metabolites on the BCAA metabolic pathway.


Childhood secondhand smoke exposure and respiratory disease mortality among never-smokers: the Japan collaborative cohort study for evaluation of cancer risk.
The main source of secondhand smoke (SHS) exposure during childhood occurs at home due to close family members who smoke. This study examined the association between childhood SHS exposure and the risk of respiratory disease mortality among non-smoking adults. Data from 44 233 never-smoking Japanese men and women aged 40-79 years who participated in the JACC study between 1988 and 1990 were analyzed. The Cox proportional hazards model was used to calculate hazard ratios and 95% confidence intervals of respiratory disease mortality according to the number of smoking family members during childhood. Subdistribution HRs (SHRs) were calculated as a competing risk analysis. A total of 735 deaths from respiratory diseases were documented in a median follow-up of 19.2 years. Living with three or more smoking family members during childhood was associated with a higher risk of respiratory disease mortality in adulthood among women; multivariable SHR compared with participants with no family member smokers during childhood was 1.60 (1.01-2.54) for participants with three or more family members who smoked during their childhood. SHS exposure from three or more family members during childhood was associated with an increased risk of respiratory disease-related mortality in adulthood.


Effect of enzymes on rotavirus infectivity.
The infectivity of a bovine rotavirus was enhanced 140-, 8-, and 3-fold, respectively, by trypsin, protease, and lactase. Ficin, carboxypeptidases A and B, lysozyme, and beta-galactosidase had little effect on the infectivity. Chymotrypsin caused a threefold decrease in the infectivity. Trypsin acts directly on the rotavirus and not on the host cell.


Global Myocardial Work Combined with Treadmill Exercise Stress to Detect Significant Coronary Artery Disease.
Myocardial work (MW) derived from the left ventricular pressure-strain loop is a novel and noninvasive method for assessing left ventricular function that accounts for loading conditions. We aimed to explore whether global MW combined with treadmill exercise stress could detect significant coronary artery disease (CAD) in patients with angina pectoris. Eighty-five patients with angina pectoris and no prior CAD history were included. All patients underwent treadmill exercise stress echocardiography and coronary angiography. Global MW was constructed from speckle-tracking echocardiography indexed to the brachial systolic blood pressure. The association between MW parameters and the presence of significant CAD was assessed with logistic regression. The discriminative power of MW parameters to detect CAD was assessed with receiver operative characteristic curve, net reclassification improvement, and integrated discrimination improvement analysis. Twenty-five patients had a positive exercise echocardiogram, while significant coronary artery stenosis (≥70% in one or more major epicardial vessels or ≥50% in the left main coronary artery) was observed in 41 patients. The global wasted work (GWW) and global work efficiency (GWE) were significantly higher or lower, respectively, in patients with significant CAD compared with those of nonsignificant CAD at the peak exercise and during recovery periods (P < .05 for all). Multivariate logistic regression analysis demonstrated that peak GWE and recovery GWW could predict significant CAD. Peak GWE had the highest area under the receiver operating characteristic curve (AUC) among all global MW parameters (AUC = 0.836). Furthermore, a model comprising peak GWE and recovery GWW performed better for the identification of significant CAD than peak GWE alone (AUC = 0.856). Peak GWE could detect significant CAD. The new model, incorporating peak GWE and recovery GWW, not only identified but also provided additional value for estimating the probability of significant CAD. Global MW parameters combined with exercise stress perform as an accurate noninvasive screening before the invasive diagnostic technique.


Influence of Resistance Training Proximity-to-Failure on Skeletal Muscle Hypertrophy: A Systematic Review with Meta-analysis.
This systematic review with meta-analysis investigated the influence of resistance training proximity-to-failure on muscle hypertrophy. Literature searches in the PubMed, SCOPUS and SPORTDiscus databases identified a total of 15 studies that measured muscle hypertrophy (in healthy adults of any age and resistance training experience) and compared resistance training performed to: (A) momentary muscular failure versus non-failure; (B) set failure (defined as anything other than momentary muscular failure) versus non-failure; or (C) different velocity loss thresholds. There was a trivial advantage for resistance training performed to set failure versus non-failure for muscle hypertrophy in studies applying any definition of set failure [effect size=0.19 (95% confidence interval 0.00, 0.37), p=0.045], with no moderating effect of volume load (p=0.884) or relative load (p=0.525). Given the variability in set failure definitions applied across studies, sub-group analyses were conducted and found no advantage for either resistance training performed to momentary muscular failure versus non-failure for muscle hypertrophy [effect size=0.12 (95% confidence interval -0.13, 0.37), p=0.343], or for resistance training performed to high (>25%) versus moderate (20-25%) velocity loss thresholds [effect size=0.08 (95% confidence interval -0.16, 0.32), p=0.529]. Overall, our main findings suggest that (i) there is no evidence to support that resistance training performed to momentary muscular failure is superior to non-failure resistance training for muscle hypertrophy and (ii) higher velocity loss thresholds, and theoretically closer proximities-to-failure do not always elicit greater muscle hypertrophy. As such, these results provide evidence for a potential non-linear relationship between proximity-to-failure and muscle hypertrophy.


Quantification of neurons in the hippocampal formation of chimpanzees: comparison to rhesus monkeys and humans.
The hippocampal formation is important for higher brain functions such as spatial navigation and the consolidation of memory, and it contributes to abilities thought to be uniquely human, yet little is known about how the human hippocampal formation compares to that of our closest living relatives, the chimpanzees. To gain insight into the comparative organization of the hippocampal formation in catarrhine primates, we quantified neurons stereologically in its major subdivisions-the granular layer of the dentate gyrus, CA4, CA2-3, CA1, and the subiculum-in archival brain tissue from six chimpanzees ranging from 29 to 43 years of age. We also sought evidence of Aβ deposition and hyperphosphorylated tau in the hippocampus and adjacent neocortex. A 42-year-old animal had moderate cerebral Aβ-amyloid angiopathy and tauopathy, but Aβ was absent and tauopathy was minimal in the others. Quantitatively, granule cells of the dentate gyrus were most numerous, followed by CA1, subiculum, CA4, and CA2-3. In the context of prior investigations of rhesus monkeys and humans, our findings indicate that, in the hippocampal formation as a whole, the proportions of neurons in CA1 and the subiculum progressively increase, and the proportion of dentate granule cells decreases, from rhesus monkeys to chimpanzees to humans. Because CA1 and the subiculum engender key hippocampal projection pathways to the neocortex, and because the neocortex varies in volume and anatomical organization among these species, these findings suggest that differences in the proportions of neurons in hippocampal subregions of catarrhine primates may be linked to neocortical evolution.


Transport of silver in virgin and lactating rats and relation to copper.
Virgin and lactating Sprague Dawley rats were used to determine whether the pathways of silver transport to tissues and milk resemble those for copper. Rats were injected i.p.with small amounts of 110AgNO3. Blood and tissues were examined at various times thereafter for total radioactivity and for incorporation into copper binding proteins in plasma and milk. As with 67Cu, much of the 110Ag was rapidly incorporated into the liver. Skeletal muscle, spleen, mammary gland, ovaries, uterus and adrenals also were significant initial accumulation sites, with or without lactation. Lactation enhanced uptake by the mammary gland, and radioactivity rapidly entered the milk and milk ceruloplasmin. In the plasma, most of the 110Ag bound to a single component of apparent molecular weight 800 k throughout the 52 h period examined. A small proportion was also incorporated into plasma ceruloplasmin, as determined by immunoprecipitation and native gel electrophoresis. There was little or no association of 110Ag with albumin or transcuprein. The binding of 110Ag to the 800 kDa protein was tight. Off rates during pH 7 dialysis were <2.5%/day even in the presence of 100 microM histidine or Cu(II), but were accelarated by mercaptoethanol. Subunits of 145 and 45 kDa in virtually pure peak fractions were those of alpha1-macroglobulin. We conclude that silver resembles copper in aspects of its tissue distribution, response to lactation, and incorporation into ceruloplasmin. However its main plasma carrier appears to be alpha1-macroglobulin, a different macroglobulin than that involved in copper transport.


Antiarrhythmic drug efficacy for ventricular tachyarrhythmias associated with coronary artery disease as assessed by electrophysiologic studies.
The efficacy and proarrhythmic potential of antiarrhythmic agents were evaluated. Programmed ventricular stimulation was performed in 160 consecutive patients with coronary artery disease during a baseline study and 432 subsequent drug studies. The tachyarrhythmias induced during baseline studies were sustained ventricular tachycardia (121 patients), ventricular fibrillation (16 patients), and symptomatic nonsustained ventricular tachycardia (23 patients). Regimens were completely successful if fewer than 6 repetitive ventricular responses were inducible during therapy and partially successful if no more than 15 repetitive ventricular responses were inducible. Procainamide and quinidine were the most successful single agents, with overall success rates of 24% and 35%, respectively. Either procainamide or quinidine combined with mexiletine was the most successful combination (overall success of 23%). Each anti-arrhythmic regimen showed a proarrhythmic potential. The incidence of proarrhythmic effects ranged from 4 to 13%, with no significant difference between regimens. In 13% of patients at least 1 regimen produced a proarrhythmic effect. Patients treated with an antiarrhythmic regimen that prevented induction of arrhythmia had significantly fewer arrhythmia recurrences than patients treated with a regimen that failed to prevent it. In conclusion, identification of an effective drug regimen is possible in 38% of patients with lethal ventricular arrhythmias, proarrhythmic effects occur in a significant number of patients during electrophysiologic testing of antiarrhythmic regimens, and the clinical outcome in patients in whom ventricular arrhythmias are not inducible with ventricular stimulation have a better prognosis than those in whom arrhythmias continue to be inducible on therapy.


Easy detection of karlodinium veneficum using PCR-based dot chromatography strip.
In this study, a novel detection method by PCR-based dot chromatography strip (PDCS) is proposed. To investigate the application of PDCS in the detection of harmful microalgae, the internal transcribed spacer sequence of Karlodinium veneficum, one of the most common bloom-forming species, was cloned and sequenced to design and screen specific primers with tag sequences and probes, including gold nanoparticle probe, test probe, and control probe. The PDCS was prepared manually, and PCR amplicons prepared from the genomic DNA of K. veneficum using tagged specific primers were analyzed by PDCS for visual detection of the target species. The resulting test strip showed red spots at the predicted test and control points visible to the naked eyes, showing the successful development of PDCS. This detection technique is independent of expensive experimental equipment (except a DNA thermal cycler for PCR) but requires an aliquot of PCR amplicons mixed with development buffer to apply to the sample pad of PDCS for approximately 10 min to visualize the analytical results. Cross-reactivity test with 21 microalgae, including K. veneficum, showed that the established PDCS technique has excellent specificity. The detection limit of PDCS was 9.13 × 10-2 ng μL-1 for genomic DNA and 5.3 × 105 cells L - 1 for crude DNA extracts of the target alga. In summary, the PDCS with high sensitivity and specificity can be prepared by hand, which is less expensive than traditional strip, thus providing a promising alternative to the detection of K. veneficum in natural samples.


Squamous cell carcinoma arising in a chronic osteomyelitic sinus tract in the peri-anal region involving pelvis: a rare occurrence.
Squamous cell carcinoma is a rare, but well documented complication of chronic osteomyelitis. Squamous cell carcinoma arising in a sinus tract following chronic osteomyelitis of the pelvic bone is a very rare occurrence. The patient presented with multiple draining sinuses and an ulcerative growth at the mouth of one of the sinuses in the peri-anal region. X-ray findings and sinogram showed de- struction of part of pubic bone. Biopsy from the growth confirmed a well differentiated squamous cell carcinoma. Therefore it is imperative that these lesions be biopsied for accurate diagnosis, adequate therapy and follow-up.


[Rescue from sudden death syndrome and allergy to milk proteins (apropos of a case)].
Allergy to milk proteins may be responsible for the syndrome of unexplained, sudden death of infants, but well-documented cases are rare. The authors report an observation where clinical history and complementary investigations support the incrimination of this factor.


CA-125, but not galectin-3, complements CA 19-9 for discriminating ductal adenocarcinoma versus non-malignant pancreatic diseases.
CA 19-9 is the gold standard biomarker of pancreatic adenocarcinoma despite several weaknesses in particular a high rate of false positives or negatives. CA-125 corresponding to MUC16 and galectin-3, a lectin able to interact with mucin-associated carbohydrates, are tumor-associated proteins. We investigated whether combined measurement of CA 19-9, galectin-3 and CA-125 may help to better discriminate pancreatic adenocarcinoma versus non-malignant pancreatic diseases. We evaluated by immunohistochemistry the expression of MUC4, MUC16 (CA-125) and galectin-3 in 31 pancreatic adenocarcinomas. We measured CA 19-9, CA-125 and Gal-3 in the serum from patients with pancreatic benign diseases (n = 58) or adenocarcinoma (n = 44). Clinical performance of the 3 biomarkers for cancer diagnosis and prognosis was analyzed. By immunohistochemistry, MUC16 and Gal-3 were expressed in 74% and 84% of adenocarcinomas versus 0% and 3.2% in peri-tumoral regions, respectively. At the serum level, CA 19-9 and CA125 were significantly higher in patients with pancreatic adenocarcinoma whereas Gal-3 levels did not differ. The performance of CA 19-9 for cancer detection was higher than those of CA-125 or Gal-3 by ROC analysis. However, CA-125 offers the highest specificity for malignancy (81%) because of an absence of false positives among type 2 diabetic patients. Cancer deaths assessed 6 or 12 months after diagnosis varied according to the initial CA-125 level (p < 0.006). Gal-3 is not an interesting biomarker for pancreatic adenocarcinoma detection. CA 19-9 alone exhibits the best performance but measuring CA-125 provides complementary information in terms of diagnosis and prognosis.


Covered Stents and Coil Embolization for Treatment of Postpancreatectomy Arterial Hemorrhage.
To evaluate the efficacy and clinical outcomes associated with stent-graft placement and coil embolization for postpancreatectomy arterial hemorrhage (PPAH). Retrospective review of 38 stent-graft and/or embolization procedures in 28 patients (23 men; mean age, 65.1 y) for PPAH between 2007 and 2014 was performed. Time of bleeding, source of hemorrhage, intervention and devices used, repeat intervention rate, time to recurrent bleeding, complications, and 30-day mortality were assessed. Independent risk factors for recurrent bleeding and 30-day mortality were identified. Median onset of hemorrhage was at 39 days (mean, 27.9 d; range, 5-182 d). Covered stents were used in 65.7% of interventions, coil embolization in 23.6%, stent-assisted embolization in 5.2%, and stent-graft angioplasty in 2.6%. A total of 28 stent-grafts were placed, of which 19 were self-expandable and nine were balloon-mounted. Mean stent-graft diameter was 6.6 mm (range, 5-10 mm). Recurrent bleeding occurred following 26.3% of interventions in seven patients at a mean interval of 22 days. The site of recurrent bleeding was new in 80% of cases. There was no significant difference in recurrent bleeding rate in early-onset (< 30 d; n = 22) versus late-onset PPAH (> 30 d; n = 6; P > .05). No ischemic hepatic or bowel complications were identified. The 30-day mortality rate was 7.1% (n = 2) and was significantly higher in patients with initial PPAH at ≥ 39 days (n = 5; P = .007). Covered stents and coil embolization are effective for managing PPAH and maintaining distal organ perfusion to minimize morbidity and mortality. Recurrent bleeding is common and most often occurs from new sites of vascular injury rather than previously treated ones.


Role of CD44 in lymphokine-activated killer cell-mediated killing of melanoma.
In the current study, we examined the potential significance of CD44 expression on lymphokine-activated killer (LAK) cells in their interaction and killing of melanoma cells. Stimulation of splenocytes with IL-2 led to a significant increase in the expression of CD44 on T cells, NK cells, and NKT cells. Treatment of melanoma-bearing CD44 WT mice with IL-2 led to a significant reduction in the local tumor growth while treatment of melanoma-bearing CD44 KO mice with IL-2 was ineffective at controlling tumor growth. Furthermore, the ability of splenocytes from IL-2-treated CD44 KO mice to kill melanoma tumor targets was significantly reduced when compared to the anti-tumor activity of splenocytes from IL-2-treated CD44 WT mice. The importance of CD44 expression on the LAK cells was further confirmed by the observation that adoptively transferred CD44 WT LAK cells were significantly more effective than CD44 KO LAK cells at controlling tumor growth in vivo. Next, the significance of the increased expression of CD44 in tumor killing was examined and showed that following stimulation with IL-2, distinct populations of cells with low (CD44(lo)) or elevated (CD44(hi)) expression of CD44 are generated and that the CD44(hi) cells are responsible for killing of the melanoma cells. The reduced killing activity of the CD44 KO LAK cells did not result from reduced activation or expression of effector molecules but was due, at least in part, to a reduced ability to adhere to B16F10 tumor cells.


Factors Affecting Inpatient Mortality and Length of Stay in Nonmetastatic Colorectal Cancer: Insights from the National Inpatient Sample.
The objective of this study was to assess the effect of opioid use and other factors on inpatient length of stay (LOS) and mortality among patients hospitalized with nonmetastatic colorectal cancer (NMCRC). We analyzed discharge encounters collected from the 2016 to 2017 National Inpatient Sample (NIS) to evaluate the effect of long-term opioid use (90 d or longer) and cancer-related complications on LOS and mortality among hospitalized patients with NMCRC. A total of 94,535 patients with NMCRC were included in the analysis. Long-term opioid users had a shorter average LOS and reduced inpatient mortality as compared with nonopioid users (5.97±5.75 vs. 6.66±6.92 d, P<0.01; and adjusted odds ratio=0.72, 95% confidence interval: 0.56-0.93, respectively). Factors that significantly increased both LOS and mortality included infection, venous thromboembolism, and chemotherapy-induced neutropenia; the average LOS was 2.7, 2.6, and 0.7 days longer, and the adjusted odds ratio for risk of inpatient mortality was 3.7, 1.2, and 1.2, respectively (P<0.05), for patients admitted with these cancer-related complications. Long-term opioid use is associated with decreased LOS and inpatient mortality among patients with NMCRC. Individuals admitted for cancer-related complications face a longer LOS and increased mortality as compared with those admitted without these morbidities.


Experimental Raman and IR spectral and theoretical studies of vibrational spectrum and molecular structure of Pantothenic acid (vitamin B5).
Vibrational spectrum of Pantothenic acid has been investigated using experimental IR and Raman spectroscopies and density functional theory methods available with the Gaussian 09 software. Vibrational assignments of the observed IR and Raman bands have been proposed in light of the results obtained from computations. In order to assign the observed IR and Raman frequencies the potential energy distributions (PEDs) have also been computed using GAR2PED software. Optimized geometrical parameters suggest that the overall symmetry of the molecule is C1. The molecule is found to possess eight conformations. Conformational analysis was carried out to obtain the most stable configuration of the molecule. In the present paper the vibrational features of the lowest energy conformer C-I have been studied. The two methyl groups have slightly distorted symmetries from C3V. The acidic OH bond is found to be the smallest one. To investigate molecular stability and bond strength we have used natural bond orbital analysis (NBO). Charge transfer occurs in the molecule have been shown by the calculated highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) energies. The mapping of electron density iso-surface with electrostatic potential (ESP), has been carried out to get the information about the size, shape, charge density distribution and site of chemical reactivity of the molecule.


[Laser microsurgery after ineffective anti-glaucoma surgery].
Authors suggest possibilities to use the laser microsurgery for improvement of the intraocular pressure in the eyes previously operated by means of different antiglaucomatic operations. Argon and YAG lasers were used for indicated microsurgical operations affecting the anterior chamber angle or the iris when the previous operation was not followed by adequate decrease of the intraocular pressure.


Ecological efficiency evaluation and driving factor analysis of the coupling coordination of the logistics industry and manufacturing industry.
The coupling coordination of the logistics industry and manufacturing industry is conducive to the sustainable development of logistics and manufacturing and the stability of sustainable supply chain. The logistics and manufacturing industries are not only the basic industries that support social development, but also the industries with high carbon emissions. This paper constructs the measurement system of coupling coordinating ecological efficiency of two industries based on carbon emission constraints and finds out the driving factors affecting ecological efficiency, which is of great significance to the low-carbon coordinated development of the two industries in the future. Firstly, this paper classifies the carbon emissions from the logistics industry and manufacturing industry as undesirable outputs and evaluates the ecological efficiency of the logistics industry (LEE) and manufacturing industry (MEE) in the three urban agglomerations from 2006 to 2019 by using the unexpected slacks-based measure (SBM) model. Secondly, the coupling coordination method is used to analyze the coupling coordination scheduling of industrial ecological efficiency (MLCC). Finally, the spatial econometric model is used to analyze the driving factors of the MLCC. The results show that during the study period, the coupling coordination of the three urban agglomerations continued to grow, the Pearl River Delta coupling coordination is the highest, the Yangtze River Delta coupling coordination grew the fastest, and the Beijing-Tianjin-Hebei coupling coordination grew slightly slower. The development during the 13th Five-Year Plan period is obviously faster than that during the 11th and 12th Five-Year Plan. The empirical analysis results of spatial econometrics show that the driving factors have an impact on the coupling coordination degree of the three urban agglomerations, but the significance of each factor is different. The driving factors have significant spatial heterogeneity. The three urban agglomerations should formulate low-carbon industry development policies in line with local development according to the actual situation of each region and local conditions.


Transcriptional inhibition of the estrogen response element by antiestrogenic piperidinediones correlates with intercalation into DNA measured by energy calculations.
The energy of interaction of antiestrogenic ligands bound to DNA derived from molecular modeling was compared to the capacity of the ligands to directly inhibit the transcriptional activity of an estrogen responsive gene. 3-Phenylacetylamino-2,6-piperidinedione (A10) and related compounds were intercalated into a partially unwound DNA site in a canonical estrogen response element (ERE). The piperidinedione/ERE complexes were subjected to energy minimization and the strength of interaction of the ligands with the DNA was measured. The ability of the ligands to inhibit transactivation was assessed using a reporter gene constructed with the ERE of the vitellogenin gene promoter (ERE(v)-tk-Luc) transiently transfected into the human estrogen receptor-positive MCF-7 breast cancer cell line. The results demonstrate a direct correlation between the calculated energetic fit of the compounds in the ERE and inhibition of ERE(v) transactivation. The order of potency of the compounds to suppress estrogen-dependent reporter gene activity was identical to that previously shown for inhibiting the growth of MCF-7 cells. To our knowledge, these results provide the first direct experimental evidence that the predicted fit of a class of compounds into a defined DNA binding site correlates with the ability of the compounds to modulate specific gene functions regulated at that site.


First-trimester screening for congenital heart disease.
Advances over the last decade in technology, training, and availability of prenatal care have led to a focus on the detection of congenital heart defects (CHD) and its prenatal management for improved pregnancy outcomes. First-trimester transvaginal heart screening is feasible and well tolerated. Due to advances in the diagnosis of trisomy by nonultrasound methods, a significant effort will now be focused on CHD detection in the first trimester of otherwise uncomplicated pregnancies. Detection of CHD is not being accomplished by heart screening training or postnatal protocols. First-trimester evaluation of fetuses is becoming more common, and a method of evaluation of the heart would improve selection of those who need later fetal echocardiography. Equipment advances are resulting in excellent visualization of the fetal circulatory system even at 12–13 weeks, gestation. Improved first-trimester fetal heart screening will result in a jump in CHD detection and in improved care of these patients during gestation and prior to their cardiac surgery.


Concurrent influenza A and group A beta-hemolytic streptococcal pharyngotonsillitis.
A concurrent group A beta-hemolytic Streptococcus (GABHS)-influenza virus pharyngotonsillitis (PT) is generally not considered in diagnoses, even though mixed bacterial-viral infections are common in other respiratory tract infections. This report describes our experience in diagnosing a potential mixed GABHS-influenza virus PT in children. Acute and convalescent antistreptolysin O (ASO) and anti-DNase B titers were obtained from 12 children with acute PT and clinical presentation that suggested viral infection, and in whom both rapid influenza A virus and rapid GABHS tests were positive. The children did not receive any antimicrobial therapy, and all recovered from their acute PT within 2 to 5 days and were all asymptomatic upon their return visit 3 to 4 weeks later. GABHS was recovered from 2 of the children on their return visit. However, ASO and anti-DNase B titers were not elevated in these individuals. The ASO and anti-DNase B titers determined in the first serum samples were less than the age-adjusted normal values for all of the children. However, these titers rose by at least two-dilution (0.2 logarithm) in the convalescent sera as compared with the acute ones in 4 of the 12 children (33%). One of the 8 children who had no increase in ASO and anti-DNase B titers had an acute GABHS PT 5 months later. One-year follow-up of all of the children showed no anomalies. This report is the first to describe a concomitant GABHS and influenza A virus PT, as evident by increased ASO and anti-DNase B titers in a third of the patients who had both of these organisms detected in their upper airways.


High-responsivity vertical-illumination Si/Ge uni-traveling-carrier photodiodes based on silicon-on-insulator substrate.
Si/Ge uni-traveling carrier photodiodes exhibit higher output current when space-charge effect is overcome and the thermal effects is suppressed. High current is beneficial for increasing the dynamic range of various microwave photonic systems and simplifying high-bit-rate digital receivers in many applications. From the point of view of packaging, detectors with vertical-illumination configuration can be easily handled by pick-and-place tools and are a popular choice for making photo-receiver modules. However, vertical-illumination Si/Ge uni-traveling carrier (UTC) devices suffer from inter-constraint between high speed and high responsivity. Here, we report a high responsivity vertical-illumination Si/Ge UTC photodiode based on a silicon-on-insulator substrate. When the transmission of the monolayer anti-reflection coating was maximum, the maximum absorption efficiency of the devices was 1.45 times greater than the silicon substrate owing to constructive interference. The Si/Ge UTC photodiode had a dominant responsivity at 1550 nm of 0.18 A/W, a 50% improvement even with a 25% thinner Ge absorption layer.


Transcriptional profiling and network pharmacology analysis identify the potential biomarkers from Chinese herbal formula Huosu Yangwei Formula treated gastric cancer in vivo.
Huosu Yangwei (HSYW) Formula is a traditioanl Chinese herbal medicine that has been extensively used to treat chronic atrophic gastritis, precancerous lesions of gastric cancer and advanced gastric cancer. However, the effective compounds of HSYW and its related anti-tumor mechanisms are not completely understood. In the current study, 160 ingredients of HSYW were identified and 64 effective compounds were screened by the ADMET evaluation. Furthermore, 64 effective compounds and 2579 potential targets were mapped based on public databases. Animal experiments demonstrated that HSYW significantly inhibited tumor growth in vivo. Transcriptional profiles revealed that 81 mRNAs were differentially expressed in HSYW-treated N87-bearing Balb/c mice. Network pharmacology and PPI network showed that 12 core genes acted as potential markers to evaluate the curative effects of HSYW. Bioinformatics and qRT-PCR results suggested that HSYW might regulate the mRNA expression of DNAJB4, CALD, AKR1C1, CST1, CASP1, PREX1, SOCS3 and PRDM1 against tumor growth in N87-bearing Balb/c mice.


Polyhydramnios is associated with postnatal dysphagia determining short-term prognosis of the newborn with 22q11.2 deletion syndrome - A case series analysis.
We experienced a case of 22q11.2 deletion syndrome (22qDS), with severe polyhydramnios, and dysphagia, which prompted us to review prognosis in neonates with 22qDS, with a focus on dysphagia. A patient was referred to our hospital at 35 gestational weeks because of polyhydramnios. After amniotic fluid reduction, labor was induced at 38 weeks. The neonate had serious dysphagia, and 22qDS was diagnosed postnatally by fluorescent in situ hybridization analysis. This prompted a retrospective analysis of 9 cases with 22qDS experienced in our facility. Three out of these nine cases showed polyhydramnios, and had severe dysphagia postnatally. In total, 4 cases had dysphagia, while mortality was observed in 2 of these 4 cases. Additionally, 5 cases without dysphagia had normal development and no major complications. Polyhydramnios associated with postnatal dysphagia might be a risk factor related to short-term prognostic outcomes in newborns with 22qDS.


Predictive performance of HAS-BLED risk score for long-term survival in patients with non-ST elevated myocardial infarction without atrial fibrillation.
Predictive value of the Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly, Drugs or alcohol use (HAS-BLED) score for clinical outcomes has been investigated in patients with and without atrial fibrillation. Many factors in the HAS-BLED model have been reported to be prognostic predictors in patients with post-myocardial infarction (MI). However, few studies have investigated the predictive value of HAS-BLED score on long-term survival in patients with post-MI. A total of 617 patients with non-ST elevation MI (NSTEMI) without atrial fibrillation were enrolled. The Thrombolysis In Myocardial Infarction (TIMI), Global Registry of Acute Coronary Events (GRACE), Can Rapid Risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines (CRUSADE), and HAS-BLED risk scores were calculated for each patient. The C-statistics of TIMI, GRACE, CRUSADE, and HAS-BLED scores for 3-year survival were 0.658, 0.749, 0.756, and 0.765, respectively. For 3-year survival prediction, GRACE, CRUSADE, and HAS-BLED scores, respectively demonstrated superior performance than TIMI score and there was no significant difference between these three scores (GRACE vs. TIMI: z=1.615, p=0.027; CRUSADE vs. TIMI: z=1.371, p=0.043; HAS-BLED vs. TIMI: z=1.899, p=0.014; CRUSADE vs. GRACE: z=0.078, p=0.234; HAS-BLED vs. GRACE: z=0.435, p=0.166; HAS-BLED vs. CRUSADE: z=0.353, p=0.181). Multivariate analysis showed left ventricular ejection fraction <40%, old age, stroke history, bleeding history, and abnormal renal and liver function were independent predictors for 3-year mortality. HAS-BLED scoring system is similar to the GRACE and CRUSADE systems but better than TIMI system to predict long-term survival outcomes in patients with NSTEMI without atrial fibrillation. However, HAS-BLED score is easier to calculate than GRACE and CRUSADE scores.


D-ribose-L-cysteine supplementation enhances wound healing in a rodent model.
Wound healing and chronic wounds are serious public health issues. While wounds heal, cellular stores of antioxidants are depleted. d-ribose-l-cysteine (DRLC) is a precursor to the antioxidant glutathione. The effect of oral supplementation with DRLC on wound healing was studied in rats. A rodent model of calibrated wounding was used. Group A rats were given DLRC for 1 week before wounding and for 3, 7, or 14 days after wounding. Group B rats were given DRLC only after wounding. Control animals were given no supplement. Photographic comparisons were made to study wound edema and inflammation. Wound strength was determined by using a laser-vacuum device. During healing, both Group A and B animals showed less edema and inflammation than Control. Group A animals had the weakest wounds at 3 days after surgery, but the strongest wounds after 14 days. Group B animals had similar wound strength to Control animals at 7 days, but stronger wounds after 14 days. DRLC supplementation appears to reduce wound inflammation early after wounding and enhance wound strength by 14 days. This suggests that increased intracellular glutathione levels may improve and enhance wound healing.


Survey of susceptibility to selected antibiotics of Pseudomonas aeruginosa strains isolated from patients with tumor disease and their relationship to serotype.
A total of 51 Pseudomonas aeruginosa strains had been isolated over a year from patients with tumor diseases in the National Institute of Oncology in Bratislava. All strains were subjected to serotyping; in 45 strains quantitative susceptibility to selected antibiotics was determined by the microdilution method. When comparing susceptibility of individual serotypes, resistance of strains belonging to serotype O12 to a number of beta-lactam, aminoglycoside and quinolone antibiotics was found. In addition, resistant strains occurred even among serotype O4 and polyagglutinating strains. The resistant strains as causative agents of nosocomial infections may represent a serious risk particularly for patients of oncological wards.


Mismatch repair proteins in recurrent prostate cancer.
Normal cell function requires strict control over the repair of DNA damage, which prevents excessive mutagenesis. An enhanced accumulation of mutations results in the multistep process generally known as carcinogenesis. Defects in repair pathways fuel such mutagenesis by allowing reiterative cycles of mutation, selection, and clonal expansion that drive cancer progression. The repair of mismatches is an important mechanism in the prevention of such genetic instability. In addition, proteins of this pathway have the unique ability to function in DNA damage response by inducing apoptosis when irreparable damage is encountered. Though originally identified primarily in association with a predisposition to hereditary colon cancer, mismatch repair defects have been identified in many other cancer types, including prostate cancer. From the first discovery of microsatellite instability in prostate cancer cell lines and tumor samples, variations in protein levels and a possible association with recurrence and aggression of disease have been described. Current results suggest that the involvement of mismatch repair proteins in prostate cancer may differ from that found in colorectal cancer, in the type of proteins and protein defects involved and the type of causative mutations. Additional work is clearly needed to investigate this involvement and the possibility that such defects may affect treatment response and androgen independence.


Testing for the "Blues": Using the Modified Emotional Stroop Task to Assess the Emotional Response of Gorillas.
We adapted the emotional Stroop task developed for primates to test whether gorillas would show response slowing for images of 'negative' compared to images of 'positive' items placed within previously reinforced borders. Three zoo-housed male gorillas participated in six phases of an emotional Stroop paradigm. In Phase One, they learned to select blue borders over yellow borders in a forced choice task presented on the touchscreen. In Phase Two, neutral yellow or blue two-dimensional shapes were placed within the borders. On congruent trials, blue images were presented within both blue and yellow borders. On incongruent trials, yellow images were placed within both blue and yellow borders. We continued to use these trials as control trials in subsequent phases. We predicted that response latencies would be slower and accuracy would be lower on incongruent trials. Although the gorillas responded more quickly to incongruent trials, in contrast to predictions, they were more accurate on congruent trials, consistent with predictions. Therefore, we proceeded with Phase Three in which photographs of images assumed to have positive and negative valences for the gorillas were placed within the borders. On test trials, the same positive or negative image was placed within both borders. In Phase Four, a positive image was paired with a negative image on each trial and the positive image appeared in either the blue (congruent trials) or yellow border (incongruent trials). Phases Five and Six replicated Phases Three and Four with images of novel positive and negative items. The gorillas responded more quickly on congruent trials compared to incongruent trials on test trials but not on control trials throughout Phases 3-6. These findings provide some validation for the emotional Stroop task to test attentional shift with emotionally valenced items.


Cryptotanshinone ameliorates MPP+-induced oxidative stress and apoptosis of SH-SY5Y neuroblastoma cells: the role of STAT3 in Parkinson's disease.
Cryptotanshinone (CTN) has shown its neuroprotective and anti-inflammatory qualities in non-genetic mouse model of Alzheimer's disease. According to bioinformatics analysis, CTN and Signal Transducer and Activator of Transcription 3 (STAT3) may interact to form a drug-target network. This study was conducted to identify the role of CTN-STAT3 interaction in Parkinson's disease (PD). PD model was established with MMP+-stimulated SH-SY5Y cells. After pre-treatment with CTN or co-treatment with CTN and STAT3 agonist, MTT assay was performed to observe cell viability; ELISA kit was used to measure the expression level of pro-inflammatory cytokines; DCFH-DA and corresponding assay kits were employed to determine the production of ROS, SOD, CAT and GSH-px; TUNEL assay and western blot were performed to detect cell apoptosis. STAT3 activity was also detected by western blot. Treatment with CTN alone had no impact on SH-SY5Y cell viability, but CTN pre-treatment effectively improved MPP+-induced loss of viability in SH-SY5Y cells. Moreover, pre-treatment with CTN inhibited MPP+-induced oxidative stress, apoptosis and STAT3 activity in SH-SY5Y cells, whereas this inhibitory effect was diminished after additional treatment with STAT3 agonist. CTN ameliorates MPP+-induced oxidative stress and apoptosis of SH-SY5Y neuroblastoma cells by inhibiting the expression of STAT3. Therefore, CTN could be a promising therapeutic agent, and STAT3 could be a potential target for PD treatment.


Variability in the structure and care processes for critically injured children: A multicenter survey of trauma bay and intensive care units.
Evaluate national variation in structure and care processes for critically injured children. Institutions with pediatric intensive care units (PICUs) that treat trauma patients were identified through the Virtual Pediatric Systems (n=72). Prospective survey data were obtained from PICU and Trauma Directors (n=69, 96% response). Inquiries related to structure and care processes in the PICU and emergency department included infrastructure, physician staffing, team composition, decision making, and protocol/checklist use. About one-third of the 69 institutions were ACS-verified Level-1 Pediatric Trauma Centers (32%); 36 (52%) were state-designated Level 1. The surgeon was the primary decision maker in the trauma bay at 88% of sites, and in the PICU at 44%. The intensivist was primary in the PICU at 30% of sites and intensivist consultation was elective at 11%. Free-standing pediatric centers used checklists more often than adult/pediatric centers for DVT prophylaxis (75% vs. 50%, p=0.039), cervical spine clearance (75% vs. 44%, p=0.011), and pain control (63% vs. 34%, p=0.024). Otherwise, protocols/checklists were infrequently utilized by either center type. Variability exists in structure and care processes for critically injured children. Further investigation of variation and its causal relationship to outcomes is warranted to provide optimal care.


NMR studies of the antibody-bound conformation of a carbohydrate-mimetic peptide.
Transferred nuclear Overhauser enhancement (TRNOE) experiments have been performed at 800 MHz to investigate the bound conformation of the hexapeptide DRPVPY, a functional molecular mimic of the group A Streptococcus cell-wall polysaccharide. The hexapeptide binds to the monoclonal antibody SA-3, mimicking the branched trisaccharide repeating unit, L-Rha-alpha-(1 --> 2)-(D-GlcNAc-beta-(1 --> 3))-alpha-L-Rha (Rha, rhamnose; GlcNAc, N-acetylglucosamine). The peptide adopts a tight turn conformation with close contacts between the side chains of valine and tyrosine. Relaxation network editing experiments (QUIET-NOESY) were used to confirm the validity of the observed contacts and to evaluate the presence of spin diffusion pathways. Saturation transfer difference (STD-NMR) experiments with selective saturation of protein resonances revealed enhancements of many of the peptide resonances due to close contacts between the peptide and the protein within the antibody combining site.


Target muscles for retrograde gene delivery to specific spinal cord segments.
Targeted retrograde gene delivery into the injured spinal cord is less invasive for the damaged tissue. One of the advantages of this approach is the possible selection of target organs according to the level of spinal cord injury. We evaluated nine candidate target organs for retrograde delivery of an adenovirus vector carrying beta-galactosidase (AdV-LacZ) gene to cervical, thoracic and lumbar spinal cord segments. One week after vector injection into each muscle, we assessed the LacZ gene expression in the spinal cord by X-gal staining. The most appropriate target organs with high transduction efficacy were the sternomastoid and clavotrapezius muscles for cervical spinal cord, tibialis anterior and the gastrocnemius muscles for the lumbar spinal cord. Retrograde gene delivery to the thoracic spinal cord was inefficient probably due to the small number of anterior horn neurons in the region. Gene expression was mainly identified over the anatomical area of innervation and not into other body organs. Our results suggested that retrograde delivery of adenovirus genome to the cervical and lumbar spinal cord segments seems feasible by injection of an adenoviral vector into the appropriate target organ. Adenovirus vector is an efficient retrograde tracer since it can deliver the carried gene to a wide area of the spinal cord and not to other body organs.


Oligodendroglial-specific transcriptional factor SOX10 is ubiquitously expressed in human gliomas.
The two most common types of gliomas: astrocytoma and oligodendroglioma are distinguished based on their morphologic similarities to mature astrocytes and oligodendroglia. Whereas prototypical examples of the tumors have distinct pathogenetic and prognostic differences, the majority of the gliomas falls in the intermediate category and their distinction is problematic. The transcriptional factor SOX10 is one of the key determinants of oligodendroglial differentiation. We applied immunohistochemistry to analyze whether the expression of SOX10 can differentiate astrocytoma and oligodendroglioma. The majority of oligodendrogliomas, but also a large fraction of astrocytomas, including the least differentiated glioblastomas, expressed SOX10, albeit at lower levels. Comparison with 1p and 19q deletion status by FISH analysis also revealed no obvious associations. High levels of expression were also found in pilocytic astrocytoma, consistent with recent studies suggesting that pilocytic astrocytomas have greater overlap with oligodendroglial than astrocytic tumors. Our data raise a possibility that histogenesis of gliomas have more common features than previously anticipated.


[Role of cerebral nitrogen metabolism in the mechanisms of the therapeutic action of oxygen under elevated pressure in hemorrhagic shock].
The hyperbaric oxygen therapy (3 ata O2, 60 min exposure) of hemorrhagic shock in cats (arterial pressure--60/50 mm Hg) prevents a sharp increase of ammonia, urea, alanin, gamma-aminobutyric acid content in the brain, typical of oxygen deficiency, and activates glutamine formation. The processes of ammonia detoxication connected with glutamate and glutamine synthesis intensification course more intensively in the sensory-motor cortex than in the limbic brain structures.


The diagnostic value of contrast-enhanced ultrasound (CEUS) for assessing hepatocellular carcinoma compared to histopathology; a retrospective single-center analysis of 119 patients1.
HCC as the 6th most common tumor entity with the fourth highest mortality and an increasing prevalence especially due to today's lifestyle acquires a high attention in the clinical setting. Beside CECT and CEMRI, CEUS depicts a dynamic, low-risk and radiation free imaging method that finds its use mainly in screening and active surveillance programs. The aim of the retrospective study was to evaluate the diagnostic value of CEUS in correlation to pathologic findings. Between 2004 and 2018 a total number of 119 patients were included in this retrospective single-center study. Every patient underwent CEUS in addition to a native B-mode and Color-Doppler scan. After given informed consent SonoVue® (Bracco, Milan, Italy), a second-generation blood-pool agent, was used as contrast medium. Every examination was performed and interpreted by a single experienced radiologist (EFSUMB level 3). A low mechanical index (MI) of <0,2 was chosen to obtain a good imaging quality. All 119 included patients received CEUS followed by a liver biopsy for inter-modality comparison. In correlation to the pathology results, CEUS showed a diagnostic sensitivity of 96,6%, a specificity of 63,9%, a PPV of 86,7% and a NPV of 88,5% by detecting liver lesions suspicious for HCC. According to the Cohen's Kappa coefficient (k = 0,659) CEUS shows a strong inter-modality agreement in comparison to the histopathological finding. With a high sensitivity and a strong cross-modality comparability to histopathology, the CEUS is highly effective in the detection of suspicious HCC lesions.


Chorion laeve accreta - Another manifestation of morbid adherence.
Smooth muscle in the decidua of fetal membranes (membrane myofibers, MMF) is not mentioned in standard textbooks. The current report presents collected observations on 52 patients with MMF at 2 institutions between 2004 and 2017 - including placentas, postpartum curettages, and hysterectomies. Clinical presentations include observation of adherent membranes during delivery, disrupted and incomplete membranes in placentas submitted for examination, postpartum bleeding associated with retained fetal membranes, association with membrane hematomas and membrane hemosiderin, morbidly adherent fetal membranes in hysterectomies; and association with grossly adherent pieces of tissue or nodules in fetal membranes. Although MMF can be an incidental microscopic observation in a routine placenta, the suggested diagnostic terminology when there are clinical and/or gross presentations is Chorion Laeve Accreta (ChLA). Further study is needed but MMF appears to be the fetal membrane counterpart of BPMF(basal plate myofibers), possibly due to damage of subjacent myometrium by trophoblastic proteases, so that shear stress during delivery causes myofibers to come out attached to the decidua of fetal membranes. Neither the prevalence of MMF, nor its reliability as a marker for placenta accreta is addressed in this collection. Association of MMF with BPMF, and recurrence of MMF, are documented; but the true frequency of these phenomena remains to be established.


Molecular cloning of human macrophage capping protein cDNA. A unique member of the gelsolin/villin family expressed primarily in macrophages.
Macrophage capping protein (MCP) is a Ca(2+)-sensitive protein which reversibly blocks the barbed ends of actin filaments but does not sever preformed actin filaments. The human cDNA for MCP has been cloned and sequenced. The derived amino acid sequence predicts a polypeptide of 38.4 kDa. Human MCP expressed in Escherichia coli using a pET12a vector was functionally identical to the native protein purified from rabbit alveolar macrophages with respect to Ca2+ sensitivity and ability to block monomer exchange at the barbed end of actin filaments. Sequence comparison with other actin-binding protein sequences indicates that MCP is a member of the gelsolin/villin family of barbed end blocking proteins. Unlike gelsolin, this protein has a limited tissue distribution being detected primarily in macrophages where it was abundant, representing 0.9-1% of the total cytoplasmic protein. Northern blot analysis of U937 and HL60 cells differentiated to macrophage-like cells demonstrated that MCP message increases to 2.6 and greater than 7 times initial levels, respectively. Human MCP displays a 93% amino acid sequence identity with two recently described mouse proteins, gCap39 and Mbh1. Its abundance in macrophages and the corresponding increases in mRNA levels upon promyelocyte and monocyte development into macrophages indicate that MCP may play an important role in macrophage function.


[Annotation of complete genomic sequence of 3p24-p25 478 kb of human DNA].
To annotate the human genome 3p24-p25 478 kb complete sequence. The protein-coding genes in the genomic sequence were identified by using ab initio gene finding, homology-based similarity database searching and all or partial mRNA aligning with genomic sequence, and the content feature of the genomic sequence were analyzed by using EMBOSS package. Two known genes SLC6A1 and SLC6A11 were identified; as well as the GC content of this genomic sequence was 47% and 3 putative CpG islands were predicted in the genomic sequence, located in 130,685-131,516 bp, 307,090-307,870 bp and 415,585-416,308 bp, respectively. The methods, as mentioned above, might be used for annotating the biological information in the genomic sequence, such as gene structure, GC content, CpG island.


Unraveling the intrinsic mechanism behind the selective oxidation of sulfonamide antibiotics in the Mn(II)/periodate process: The overlooked surface-mediated electron transfer process.
Mn(II) exhibits a superb ability in activating periodate (PI) for the efficient degradation of aqueous organic contaminants. Nevertheless, ambiguous conclusions regarding the involved reactive species contributing to the removal of organic contaminants remain unresolved. In this work, we found that the Mn(II)/PI process showed outstanding and selective reactivity for oxidizing sulfonamides with the removal ranging from 57.1% to 100% at pH 6.5. Many lines of evidence suggest that the in-situ formed colloidal MnO2 (cMnO2) served as a catalyst to mediate electron transfer from sulfonamides to PI on its surface via forming cMnO2-PI complex (cMnO2-PI*) for the efficient oxidation of sulfonamides in the Mn(II)/PI process. Experimental results and density functional theory (DFT) calculations verify that the inclusive aniline moiety was the key site determining the electron transfer-dominated oxidation of sulfonamides. Furthermore, DFT calculation results reveal that the discrepancies in the removal of sulfonamides in the Mn(II)/PI process were attributed to different kinetic stability and chemical reactivity of sulfonamides caused by their heterocyclic substituents. In addition, a high utilization efficiency of PI was achieved in the Mn(II)/PI process owing to the surface-mediated electron transfer mechanism. This work provides deep insights into the surface-promoted mechanism in the cMnO2-involved oxidation processes.


Development of residual strains in human vertebral trabecular bone after prolonged static and cyclic loading at low load levels.
Development of irreversible residual strains in trabecular bone may be a mechanism by which age-related non-traumatic vertebral fractures occur. To investigate this concept, static and cyclic loading tests were conducted at low loading levels for cylindrical cores of cadaveric vertebral trabecular bone. Stresses were applied equivalent to elastic strains of either 750 or 1,500 microstrain. Creep strains were measured during the tests, which lasted for 125,000 seconds (about 35 h), and for an additional 125,000 seconds after complete unloading. Emphasis was placed on the residual strains that developed, defined as the strain remaining at the end of the unloading phase. The results indicated that appreciable residual strains did develop, and were similar for static and cyclic loading. Irrespective of the applied load levels and loading modes, the residual strains that remained after the unloading phase were similar in magnitude to the originally applied elastic strain. Extrapolation of the observed residual strains to full recovery indicated that the time that would be required for full recovery was over 20 times longer than the duration of the applied loads. These results indicate that human vertebral trabecular bone does not creep in a linear viscoelastic fashion at low stress levels, and that creep mechanisms dominate the residual strains regardless of the loading mode. Taken together, these findings support the concept that non-traumatic vertebral fractures may be related to long-term creep effects because the trabecular bone does not have sufficient time to recover mechanically from creep deformations accumulated by prolonged static or cyclic loading.


Hepatic graft-versus-host disease: what we know, when to biopsy, and how to diagnose.
Graft-versus-host disease (GVHD) is one of the serious complications that may develop after hematopoietic cell transplantation (HCT), for hematologic malignancies, solid organ transplantation, and other hematologic disorders. GVHD develops due to T lymphocytes present in the graft attacking the host antigens, which results in tissue damage. A significant number of HCT patients develop acute or chronic GVHD, which may affect multiple organs including the liver. The diagnosis of hepatic GVHD (hGVHD) is challenging as many other conditions in HCT patients may lead to liver dysfunction. Particularly challenging among the various conditions that give rise to liver dysfunction is differentiating sinusoidal obstruction syndrome and drug-induced liver injury (DILI) from hGVHD on clinical grounds and laboratory tests. Despite the minimal risks involved in performing a liver biopsy, the information gleaned from the histopathologic changes may help in the management of these very complex patients. There is a spectrum of histologic features found in hGVHD, and most involve histopathologic changes affecting the interlobular bile ducts. These include nuclear and cytoplasmic abnormalities including dysmorphic bile ducts, apoptosis, and cholangiocyte necrosis, among others. The hepatitic form of hGVHD typically shows severe acute hepatitis. With chronic hGVHD, there is progressive bile duct loss and eventually fibrosis. Accurate diagnosis of hGVHD is paramount so that timely treatment and management can be initiated. Techniques to prevent and lower the risk of GVHD from developing have recently evolved. If a diagnosis of acute GVHD is made, the first-line of treatment is steroids. Recurrence is common and steroid resistance or dependency is not unusual in this setting. Second-line therapies differ among institutions and have not been uniformly established. The development of GVHD, particularly hGVHD, is associated with increased morbidity and mortality.


Molecular therapy of the intervertebral disc.
Disc degeneration is the loss of the normal nucleus pulposus disc matrix to a more fibrotic and less cartilaginous structure. This change in disc micro-anatomy can be associated with pain and deformity, however, prevention and treatment options of disc degeneration are currently limited. Much research is going on to understand intervertebral discs at a molecular/ cellular level in hopes of creating clinically applicable options for treating disc degeneration. This review article will give insight into the current and developing status of treating intervertebral disc degeneration from a molecular standpoint.


Advances in RNA Labeling with Trifluoromethyl Groups.
Fluorine labeling of ribonucleic acids (RNA) in conjunction with 19 F NMR spectroscopy has emerged as a powerful strategy for spectroscopic analysis of RNA structure and dynamics, and RNA-ligand interactions. This study presents the first syntheses of 2'-OCF3 guanosine and uridine phosphoramidites, their incorporation into oligoribonucleotides by solid-phase synthesis and a comprehensive study of their properties. NMR spectroscopic analysis showed that the 2'-OCF3 modification is associated with preferential C2'-endo conformation of the U and G ribose in single-stranded RNA. When paired to the complementary strand, slight destabilization of the duplex caused by the modification was revealed by UV melting curve analysis. Moreover, the power of the 2'-OCF3 label for NMR spectroscopy is demonstrated by dissecting RNA pseudoknot folding and its binding to a small molecule. Furthermore, the 2'-OCF3 modification has potential for applications in therapeutic oligonucleotides. To this end, three 2'-OCF3 modified siRNAs were tested in silencing of the BASP1 gene which indicated enhanced performance for one of them. Importantly, together with earlier work, the present study completes the set of 2'-OCF3 nucleoside phosphoramidites to all four standard nucleobases (A, U, C, G) and hence enables applications that utilize the favorable properties of the 2'-OCF3 group without any restrictions in placing the modification into the RNA target sequence.


Early genital stimulation of rats lowers limbic seizure latencies for females but increases latencies for males.
The genitals of male and female rats were tactilely stimulated (glass rod) for 10 successive days beginning on postnatal Days 5, 15, 35; handled but nonstimulated litter mates served as the reference groups. Limbic seizures were induced by a single systemic injection of lithium and pilocarpine when the rats were adults. The genitally stimulated female rats displayed a lower seizure threshold (as inferred from shorter seizure-onset times) relative to their cage mates. The single largest effect occurred for those females which had been stimulated after the vagina had opened (postnatal 35-45 days).


Can pain be improved with retention of the posterior cruciate ligament during total knee arthroplasty?
The purpose of the current study was to determine if differences exist between cruciate-retaining (CR) and posterior-stabilized (PS) implant articulations for total knee arthroplasty (TKA) with regards to early post-operative pain. We retrospectively reviewed patients who underwent primary TKA, with the same TKA implant design, at our institution between January 2018 and July 2021. Patients were stratified based on whether they received a CR or non-constrained PS (PSnC) articulation and propensity score matched in a 1:1 ratio. A sub-analysis matching patient who received a constrained PS implant (PSC) to those undergoing CR TKA and PSnC TKA was also carried out. Opioid dosages were converted to morphine milligram equivalents (MME). 616 patients after CR TKA were matched 1:1 to 616 patients with a PSnC implant. There were no significant differences between demographic variables. There were no statistically significant differences in opioid usage measured by MME on post-operative day (POD) 0 (p = 0.171), POD1 (p = 0.839), POD2 (p = 0.307), or POD3 (p = 0.138); VAS pain scores (p = 0.175); or 90-day readmission rate for pain (p = 0.654). A sub-analysis of CR versus PSC TKA demonstrated no significant differences in opioid usage on POD0 (p = 0.765), POD1 (p = 0.747), POD2 (p = 0.564), POD3 (p = 0.309); VAS pain scores (p = 0.293); and 90-day readmission rate for pain (p > 0.9). Our analysis demonstrated no significant difference in post-operative VAS pain scores and MME usage based on implant. The results suggest that neither the type of articulation or constraint used for primary TKA has a significant impact on immediate post-operative pain and opioid consumption. Retrospective Cohort Study.


Key role of voltage-dependent properties of synaptic currents in robust network synchronization.
Robust synchronized activity is ubiquitous in real neural networks. Diverse synaptic properties contribute to such robust synchronization. Synaptic current induced by an input spike is dependent on the voltage of post-synaptic neuron in real neural systems. Current-based synapse models, which neglect the voltage-dependent properties of synaptic currents, are widely used for analysis of robust synchronization in neural networks due to their simplicity. However, it was found in this paper that the voltage-dependent properties of synaptic currents play a key role in robust network synchronization in most cases, implying that current-based synapses are oversimplified for analysis of robust network synchronization.


Excessive daytime sleepiness and associations with sleep-related motor vehicle accidents: results from a nationwide survey.
Insufficient sleep can have fatal consequences, and up to 30% of motor vehicle accidents (MVAs) are related to driving when drowsy. The objective of this study was to investigate how sleep quality and excessive daytime sleepiness (EDS) affect falling asleep while driving and sleep-related MVAs/near-misses. A population-wide sample of Saudi adults was surveyed. The questionnaire gathered data on sleep quality, EDS (Epworth Sleepiness Scale), and episodes of falling asleep while driving and sleep-related MVAs/near-misses in the previous year. Univariable and multivariable analyses were used to assess associations. A total of 19% (902/3802) and 10% (474/4229) of respondents had fallen asleep while driving or had a sleep-related MVA/near-miss in the preceding year, respectively. Being male, married, having a shorter sleep duration, being an office worker, having poor subjective sleep quality, and having moderate or severe EDS were associated with an increased risk of having fallen asleep while driving in the previous year. Younger age, male gender, having worse subjective sleep quality [OR 2.11 (95% CI 1.36-3.29); p < 0.0001 for "very bad" sleep quality], and having moderate or severe EDS [ESS ≥ 13; OR 1.90 (95% CI 1.38-2.60); p < 0.0001 and OR 2.39 (95% CI 1.56-3.67); p < 0.0001, respectively] were associated with having had/nearly had an accident due to being tired or falling asleep while driving in the previous year. Sleepy driving and sleep-related accidents/near-misses are common in Saudi Arabia, and sleep quality and EDS contribute to the burden of MVAs. Further efforts are required to quantify the contribution of sleepiness to MVAs to develop and prioritize interventions to prevent MVA-related injuries and death.


Long-term results of mesh pelvic floor reconstruction to address the empty pelvis syndrome.
As the "empty pelvis syndrome" continues to pose challenges in patients undergoing radical pelvic exenteration, there remains an ongoing need to consider solutions to mitigate or avoid its associated morbidity. As such, this study aims to review the long-term outcomes of a proposed strategy of pelvic reconstruction with BioA mesh. We conducted a retrospective observational cohort study, reviewing cases of pelvic exenteration and/or pelvic bone resection involving BioA mesh pelvic reconstruction between 2017 and 2021 at our quaternary institution, identified from a prospectively collected database. The primary outcome was pelvic complications including perineal fistula, wound breakdown and pelvic collections. Over a 4-year period, there were a total of 36 patients who had pelvic exenteration and/or pelvic bone resection with BioA mesh pelvic reconstruction. The overall pelvic complication rate was 36% (n = 13), including 11 symptomatic pelvic collections, two enteroperineal fistulas, and no cases of perineal hernia. Reoperation was required in two patients. There was no perioperative mortality. Given that pelvic complications post BioA mesh reconstruction are of an acceptable rate and can be considered minor, using this technique is a safe and practical strategy in patients undergoing major pelvic surgery with or without pelvic bone resection.


Predominant structural features of the cell wall arabinogalactan of Mycobacterium tuberculosis as revealed through characterization of oligoglycosyl alditol fragments by gas chromatography/mass spectrometry and by 1H and 13C NMR analyses.
The peptidoglycan-bound arabinogalactan of a virulent strain of Mycobacterium tuberculosis was per-O-methylated, partially hydrolyzed with acid, and the resulting oligosaccharides reduced and O-pentadeute-rioethylated. The per-O-alkylated oligoglycosyl alditol fragments were separated by high pressure liquid chromatography and the structures of 43 of these constituents determined by 1H NMR and gas chromatography/mass spectrometry. The arabinogalactan was shown to consist of a galactan containing alternating 5-linked beta-D-galactofuranosyl (Galf) and 6-linked beta-D-Galf residues. The arabinan chains are attached to C-5 of some of the 6-linked Galf residues. The arabinan is comprised of at least three major structural domains. One is composed of linear 5-linked alpha-D-arabinofuranosyl (Araf) residues; a second consists of branched 3,5-linked alpha-D-Araf units substituted with 5-linked alpha-D-Araf residues at both branched positions. The non-reducing terminal region of the arabinan was characterized by a 3,5-linked alpha-D-Araf residue substituted at both branched positions with the disaccharide beta-D-Araf-(1----2)-alpha-D-Araf. 13C NMR of intact soluble arabinogalactan established the presence of both alpha- and beta-Araf residues in this domain. This non-reducing terminal motif apparently provides the structural basis of the dominant immunogenicity of arabinogalactan within mycobacteria. A rhamnosyl residue occupies the reducing terminus of the galactan core and may link the arabinogalactan to the peptidoglycan. Evidence is also presented for the presence of minor structural features involving terminal mannopyranosyl units. Models for most of the heteropolysaccharide are proposed which should increase our understanding of a molecule responsible for much of the immunogenicity, pathogenicity, and peculiar physical properties of the mycobacterial cell.