Miracle-dz/UniFAR-FTUs huggingface dataset:
Hypercoiling of the Umbilical Cord and Placental Maturation Defect: Associated Pathology?

Our objective was to determine whether there is an association between hypercoiling of the umbilical cord and placental maturation defect. From a database comprising 1147 cases, containing data on all placentas examined at our institution during the study period we selected all cases with a gestational age of at least 37 weeks that exhibited hypercoiling of the umbilical cord (coiling density above the 90th percentile, n = 42); we also examined 2 matched controls for each case, one with hypocoiling and one with normocoiling. The mean number of syncytiocapillary membranes (SCM) per terminal villus was calculated. Presence of a placental maturation defect was defined as the mean number of SCM below the 10th percentile. Correlations were assessed using Spearman's rho. Relations between dichotomous variables were tested using logistic regression. Mean number of SCM per terminal villus (±standard deviation) was 1.25 ± 0.65. Difference in mean between hypo- and hypercoiled cords was 0.37 (95% confidence interval [CI], 0.07 to 0.67). The correlation coefficient between mean number of SCM and umbilical coiling index (UCI, coils/cm) was −0.28 (P = 0.002). The odds ratio (OR) for placental maturation defect in presence of hypercoiling was 2.61 (95% CI, 0.75 to 9.12). The OR for fetal death was 132 (95% CI, 13.2 to 1315) in the presence of a placental maturation defect and 5.49 (95% CI, 1.02 to 29.6) in the presence of hypercoiling. The OR for indication of fetal hypoxia/ischemia was 12.3 (95% CI, 3.0 to 50.3) in the presence of a placental maturation defect and 3.2 (95% CI, 0.95 to 10.9) in the presence of hypercoiling. We found a trend toward placental maturation defect in the presence of hypercoiling and an inverse relationship between the mean number of SCM in the terminal villi and the UCI. We confirmed associations between fetal death and both a maturation defect and hypercoiling and found an association between histological indication of fetal hypoxia/ischemia and a placental maturation defect.
Meta-analysis of serotonin transporter polymorphisms and affective disorders

Polymorphisms in the promoter region (5-HTTLPR) of the serotonin transporter and a variable number of tandem repeats polymorphism in the second intron have been widely studied. However, the results of association studies examining unipolar depression (MDD) or bipolar disorder depression (BPD) have been mixed. To precisely ascertain small associations with both polymorphisms, a meta-analysis was performed involving several thousand subjects, using random-effects modeling. For MDD, the effect of the 5-HTTLPR genotype was significant (χ2=6.1, P<0.05), with 21% of MDD subjects and 17% of controls homozygous for the short (S) allele (odds ratio, 1.16). Similar findings were noted in BPD, with a higher frequency of S/S genotypes in affected patients, although the results did not reach statistical significance. Results of transmission disequilibrium tests trended in a similar direction but also did not reach statistical significance. No consistent effect of the variable number of tandem repeats polymorphism was revealed for either MDD or BPD. The results suggest that the S allele, or a neighboring allele in linkage disequilibrium, is recessive for MDD and possibly BPD. Notably, the association is very small. With these small associations, confounding issues such as population stratification require addressing. Significant heterogeneity between studies was also evident, possibly reflecting differences in diagnosis, different control populations, and different ethnic populations. These factors should Influence the interpretation of the association found in this analysis.
Cytosolic calcium concentration in bovine growth plate chondrocytes

The cytosolic free calcium ion concentration for mammalian cell systems is believed to be maintained within a narrow range compatible with cellular homeostasis. Growth plate chondrocytes have been shown to accumulate large quantities of calcium within their mitochondria, but the cytosolic free calcium concentration has not been determined. This study measures the cytosolic free ionic calcium concentration in growth plate chondrocytes using two variations of the Quin II fluorescence technique. The results indicate that in isolated growth plate chondrocytes, the cytosolic free ionic calcium concentration is similar to other nonmineralizing mammalian cell types (106–137 nM).
Antibody-Dependent Cellular Cytotoxicity-Mediating Antibodies from an HIV-1 Vaccine Efficacy Trial Target Multiple Epitopes and Preferentially Use the VH1 Gene Family

ABSTRACT The ALVAC-HIV/AIDSVAX-B/E RV144 vaccine trial showed an estimated efficacy of 31%. RV144 secondary immune correlate analysis demonstrated that the combination of low plasma anti-HIV-1 Env IgA antibodies and high levels of antibody-dependent cellular cytotoxicity (ADCC) inversely correlate with infection risk. One hypothesis is that the observed protection in RV144 is partially due to ADCC-mediating antibodies. We found that the majority (73 to 90%) of a representative group of vaccinees displayed plasma ADCC activity, usually (96.2%) blocked by competition with the C1 region-specific A32 Fab fragment. Using memory B-cell cultures and antigen-specific B-cell sorting, we isolated 23 ADCC-mediating nonclonally related antibodies from 6 vaccine recipients. These antibodies targeted A32-blockable conformational epitopes (n = 19), a non-A32-blockable conformational epitope (n = 1), and the gp120 Env variable loops (n = 3). Fourteen antibodies mediated cross-clade target cell killing. ADCC-mediating antibodies displayed modest levels of V-heavy (VH) chain somatic mutation (0.5 to 1.5%) and also displayed a disproportionate usage of VH1 family genes (74%), a phenomenon recently described for CD4-binding site broadly neutralizing antibodies (bNAbs). Maximal ADCC activity of VH1 antibodies correlated with mutation frequency. The polyclonality and low mutation frequency of these VH1 antibodies reveal fundamental differences in the regulation and maturation of these ADCC-mediating responses compared to VH1 bNAbs.
Mycobacteria causing human cervical lymphadenitis in pastoral communities in the Karamoja region of Uganda

SUMMARY Mycobacteria from lymph node biopsies of patients with cervical lymphadenitis reporting for tuberculosis treatment in Matany and Moroto Hospitals in the transhumant areas of Karamoja, Uganda were isolated and characterized. The AccuProbe® culture identification kits for Mycobacterium tuberculosis complex (MTC), M. avium complex (MAC) and M. avium were used to identify the isolates. Spoligotyping, IS901 PCR and IS1311 and IS1245 restriction fragment length polymorphism (RFLP) were used to characterize the isolates. Of the 43 biopsies, ten M. avium, seven M. tuberculosis, three M. bovis, and two M. intracellulare were isolated. Two isolates could not be identified with AccuProbe® and from 19 samples no mycobacteria could be isolated. Three isolates with the Beijing spoligotype were identified from the seven M. tuberculosis isolates. The spoligopatterns of the M. bovis isolates had previously been detected in cattle in Uganda. Isolation of members of the MAC group reflects the complex interaction between the transhumant communities, water sources and their cattle. None of the M. avium isolates harboured IS901, and all showed several bands on IS1311 and IS1245 RFLP, in accordance with M. avium subsp. hominissuis. Composite dendrograms of IS1311 and IS1245 RFLP showed that the isolates were similar and identical patterns were found. The isolation of M. bovis confirms the human infection with zoonotic mycobacteria in areas where consumption of raw milk and meat is routine. Isolation of environmental mycobacteria also confirms their increasing role in human disease and the occupational risk of infection in the transhumant ecosystem in the absence of safe drinking water and environmental contamination.
Recombinant human growth hormone post-renal transplantation in children: a randomized controlled study of the NAPRTCS.

BACKGROUND Growth retardation persists in renal allograft recipients despite successful transplantation. The etiology is multi-factorial including the adverse effects of corticosteroids, suboptimal allograft function, and perturbations of the GH/GF axis. Recombinant human growth hormone (rhGH) has been effective in improving growth velocity; however, allograft dysfunction has been reported. Therefore, a randomized controlled study was undertaken. METHODS Sixty-eight growth retarded pediatric renal allograft recipients were enrolled in a one-year randomized controlled study to determine the efficacy and safety of rhGH. A protocol biopsy was performed prior to enrollment. RESULTS After one year, the delta SDS (standardized height) was +0.49 +/- 0.10 in the treatment group (N = 30) compared to -0.10 +/- 0.08 in the control group (N = 22; P < 0.001). During the first year, there were no rejection episodes in the treatment group and three in the control group. After the first year, when all recipients were receiving rhGH, there were three patients in the treatment group and two patients in the control group who experienced an acute rejection episode. Prior to enrollment, more than one acute rejection episode was predictive of a subsequent rejection following enrollment. There was no difference in adverse events between the two groups. CONCLUSION In conclusion, rhGH is effective in improving the growth velocity of pediatric renal allograft recipients and is not associated with an increase in adverse events.
In situ optical microscopic recording of slip line development during plastic deformation of Cu–15at%Al single crystals with high resolution – estimation of dislocation velocities

Observations and measurements of slip line evolution during plastic deformation are performed by optical microscopic video recording. In addition, high resolution in time is achieved by means of photodiodes positioned in the intermediate image plane of the microscope. Examples of measurements at room temperature on short‐range ordered Cu−15at%Al single crystals are given and evaluated to estimate the velocities of edge and screw dislocation groups from the observed rates of growth of slip steps in height and in length, respectively, on one side of the specimen. By means of a second microscope observing the opposite side, the average rates for the dislocations to cross the whole specimen can be obtained. The measured values are discussed in terms of the movement of correlated dislocation groups in the crystals.
Bone Mass Is Compromised by the Chemotherapeutic Trabectedin in Association With Effects on Osteoblasts and Macrophage Efferocytosis

Macrophages have established roles supporting bone formation. Despite their professional phagocytic nature, the role of macrophage phagocytosis in bone homeostasis is not well understood. Interestingly, apoptosis is a pivotal feature of cellular regulation and the primary fate of osteoblasts is apoptosis. Efferocytosis (phagocytosis of apoptotic cells) is a key physiologic process for the homeostasis of many tissues, and is associated with expression of osteoinductive factors. To test effects of macrophage depletion and compromised phagocytosis on bone, 16‐week‐old male C57BL/6J mice were treated with trabectedin—a chemotherapeutic with established anti‐macrophage effects. Trabectedin treatment reduced F4/80+ and CD68+ macrophages in the bone marrow as assessed by flow cytometry, osteal macrophages near the bone surface, and macrophage viability in vitro. Trabectedin treatment significantly reduced marrow gene expression of key phagocytic factors (Mfge8, Mrc1), and macrophages from treated mice had a reduced ability to phagocytose apoptotic mimicry beads. Macrophages cultured in vitro and treated with trabectedin displayed reduced efferocytosis of apoptotic osteoblasts. Moreover, efferocytosis increased macrophage osteoinductive TGF‐β production and this increase was inhibited by trabectedin. Long‐term (6‐week) treatment of 16‐week‐old C57BL/6J mice with trabectedin significantly reduced trabecular BV/TV and cortical BMD. Although trabectedin reduced osteoclast numbers in vitro, osteoclast surface in vivo was not altered. Trabectedin treatment reduced serum P1NP as well as MS/BS and BFR/BS, and inhibited mineralization and Runx2 gene expression of osteoblast cultures. Finally, intermittent PTH 1‐34 (iPTH) treatment was administered in combination with trabectedin, and iPTH increased trabecular bone volume fraction (BV/TV) in trabectedin‐treated mice. Collectively, the data support a model whereby trabectedin significantly reduces bone mass due to compromised macrophages and efferocytosis, but also due to direct effects on osteoblasts. This data has immediate clinical relevance in light of increasing use of trabectedin in oncology. © 2017 American Society for Bone and Mineral Research.
Psychological predictors of peptic ulcer incidence in the Alameda County Study.

It has often been suggested that mood and personality predispose to peptic ulcer, but little prospective evidence exists. We used longitudinal data from the Alameda County Study to seek associations of psychological characteristics with later ulcer development, taking into account the possible confounding or mediating, taking into account the possible confounding or mediating roles of nonpsychological factors. Among 4,595 Alameda County Study subjects ulcer-free in 1965, we studied five baseline psychological measures (depression, hostility, ego resiliency, social alienation or anomy, and personal uncertainty) with respect to reported ulcer in 1973-1974. All five measures had significant age-adjusted associations with incident ulcer [odds ratio (O.R.) 1.8-2.6]. After adjustment for smoking, drinking, skipping breakfast, lack of sleep, painful medical conditions, and liver disease, three measures remained significant: depression, anomy, and hostility. The age-adjusted O.R. of 2.8 [95% confidence interval (C.I.) 1.6, 4.8] for an upper versus a lower tertile index of independently predictive psychological factors fell to 2.1 with adjustment for health-related behaviors and medical conditions, and reached 1.7 (C.I. 1.0, 3.1) after addition of education to the model. We conclude that depression, maladjustment, and hostility are prospectively associated with peptic ulcer. These associations are partially accounted for by confounding or mediation by standard risk factors, and are to some extent related to socioeconomic status.
Health behaviour change theories: contributions to an ICF-based behavioural exercise therapy for individuals with chronic diseases

Abstract Purpose: The purpose of this perspective is (1) to incorporate recent psychological health behaviour change (HBC) theories into exercise therapeutic programmes, and (2) to introduce the International Classification of Functioning (ICF)-based concept of a behavioural exercise therapy (BET). Methods: Relevant personal modifiable factors of physical activity (PA) were identified based on three recent psychological HBC theories. Following the principles of intervention mapping, a matrix of proximal programme objectives specifies desirable parameter values for each personal factor. As a result of analysing reviews on behavioural techniques and intervention programmes of the German rehabilitation setting, we identified exercise-related techniques that impact the personal determinants. Finally, the techniques were integrated into an ICF-based BET concept. Results: Individuals' attitudes, skills, emotions, beliefs and knowledge are important personal factors of PA behaviour. BET systematically addresses these personal factors by a systematic combination of adequate exercise contents with related behavioural techniques. The presented 28 intervention techniques serve as a theory-driven “tool box” for designing complex BET programmes to promote PA. Conclusion: The current paper highlights the usefulness of theory-based integrative research in the field of exercise therapy, offers explicit methods and contents for physical therapists to promote PA behaviour, and introduces the ICF-based conceptual idea of a BET. Implications for Rehabilitation Irrespective of the clients' indication, therapeutic exercise programmes should incorporate effective, theory-based approaches to promote physical activity. Central determinants of physical activity behaviour are a number of personal factors: individuals' attitudes, skills, emotions, beliefs and knowledge. Clinicians implementing exercise therapy should set it within a wider theoretical framework including the personal factors that influence physical activity. To increase exercise-adherence and promote long-term physical activity behaviour change, the concept of a behavioural exercise therapy (BET) offers a theory-based approach to systematically address relevant personal factors with a combination of adequate contents of exercise with exercise-related techniques of behaviour change.
The twin‐arginine translocation (Tat) systems from Bacillus subtilis display a conserved mode of complex organization and similar substrate recognition requirements

The twin arginine translocation (Tat) system transports folded proteins across the bacterial plasma membrane. In Gram‐negative bacteria, membrane‐bound TatABC subunits are all essential for activity, whereas Gram‐positive bacteria usually contain only TatAC subunits. In Bacillus subtilis, two TatAC‐type systems, TatAdCd and TatAyCy, operate in parallel with different substrate specificities. Here, we show that they recognize similar signal peptide determinants. Both systems translocate green fluorescent protein fused to three distinct Escherichia coli Tat signal peptides, namely DmsA, AmiA and MdoD, and mutagenesis of the DmsA signal peptide confirmed that both Tat pathways recognize similar targeting determinants within Tat signals. Although another E. coli Tat substrate, trimethylamine N‐oxide reductase, was translocated by TatAdCd but not by TatAyCy, we conclude that these systems are not predisposed to recognize only specific Tat signal peptides, as suggested by their narrow substrate specificities in B. subtilis. We also analysed complexes involved in the second Tat pathway in B. subtilis, TatAyCy. This revealed a discrete TatAyCy complex together with a separate, homogeneous, ∼ 200 kDa TatAy complex. The latter complex differs significantly from the corresponding E. coli TatA complexes, pointing to major structural differences between Tat complexes from Gram‐negative and Gram‐positive organisms. Like TatAd, TatAy is also detectable in the form of massive cytosolic complexes.
Inheritance of resistance to a new non-steroidal ecdysone agonist, fufenozide, in the diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae).

BACKGROUND The diamondback moth (DBM), Plutella xylostella (L.), is a cosmopolitan pest of cruciferous crops. Fufenozide, a novel non-steroidal ecdysone agonist, exhibits good efficacy and plays an increasingly important role in the control of Lepidopterous pests in China. A laboratory strain of DBM was selected for resistance to fufenozide, and the genetic basis of resistance was studied. RESULTS The resistant strain, selected under laboratory conditions, exhibited a higher level of resistance to fufenozide (302.8-fold based on LC(50)s) than the laboratory susceptible strain. Mortality data from the testing of F(1) progeny of reciprocal crosses of resistant and susceptible DBM indicated that resistance was autosomal and incompletely recessive with a degree of dominance of -0.664. Chi-square analysis from responses of a backcross of crossed F(1) progeny and the resistant strain and F(2) progeny were highly significant, suggesting that the resistance was probably controlled by more than one gene. The estimated realised heritability (h(2)) of fufenozide resistance was 0.08, indicating that diamondback moth may have a lower chance of developing resistance to fufenozide than other kinds of insecticide. CONCLUSION The resistance of DBM to fufenozide might be autosomal and incompletely recessive, and the resistance is probably controlled by more than one gene. These results provide the basic information for pest management programmes.
Photoaffinity Labeling Demonstrates Physical Contact between Vasoactive Intestinal Peptide and the N-terminal Ectodomain of the Human VPAC1 Receptor*

Vasoactive intestinal peptide (VIP) is a prominent neuropeptide whose actions are mediated by VPAC receptors belonging to class II G protein-coupled receptors. To identify contact sites between VIP and its VPAC1 receptor, an analog of VIP substituted with a photoreactive para-benzoyl-l-Phe (Bpa) at position 22 has been synthesized and evaluated in Chinese hamster ovary cells stably expressing the recombinant human receptor. Bpa22-VIP and native VIP are equipotent in stimulating adenylyl cyclase activity in cell membranes. Cyanogen bromide cleavage of the covalent 125I-[Bpa22-VIP]-hVPAC1R complex yielded a single labeled fragment of 30 kDa that shifted to 11 after deglycosylation, most consistent with the 67–137 fragment of the receptor N-terminal ectodomain. Further cleavage of this fragment with V8 endoproteinase and creation of receptor mutants with new CNBr cleavage sites (XàMet), demonstrated that 125I-[Bpa22-VIP] was covalently attached to the short receptor 109–120 fragment (GWTHLEPGPYPI). In a three-dimensional model of the receptor N-terminal ectodomain, this fragment is located on one edge of the putative VIP binding groove and encompasses several amino acids previously shown to be crucial for VIP binding (reviewed in Laburthe, M., Couvineau, A., and Marie, J. C. (2002) Receptors Channels 8, 137–153). Our data provide the first direct evidence for a physical contact between VIP and the N-terminal ectodomain of the hVPAC1 receptor.
Prognostic factors in the palliation of pancreatic cancer.

AIM Few patients with pancreatic cancer are eligible for resection. In the remainder, estimation of prognosis is important to optimise various aspects of care, including palliation of biliary obstruction and trial of chemotherapy. The aim is to evaluate the prognostic significance of clinical and laboratory variables in patients with unresectable pancreatic cancer. METHODS Information was gathered retrospectively for 325 patients with unresectable pancreatic cancer who underwent palliative interventions, including surgical bypass, endoscopic or percutaneous stenting or who received supportive care only. RESULTS Histological proof was obtained in 182 patients (56%). Median survival was 5.7 months. Absence of therapeutic intervention, leukocytosis (WCC> or =11 x 10(9)/l), gamma glutamyl transferase (gamma GT)>165U/L, prothrombin time ratio > or =1.1, and C-reactive protein (CRP) > or = 5mg/dL were associated with shorter survival on univariate analysis. Only absence of therapeutic intervention, leukocytosis, and gamma GT>165 U/L reached significance on multivariate analysis. In the 51 patients in whom serum CRP was available, CRP was the only significant predictor of survival on multivariate analysis. CONCLUSIONS Leukocytosis, elevated gamma GT and raised CRP predict shorter survival and may help to guide the choice of palliative intervention for patients with unresectable pancreatic cancer.