Linear signal combination T2 spectroscopy.
A technique is presented for performing T2 spectroscopy in magnetic resonance imaging (MRI). It is based on a weighted linear combination of T2 decay data. The data is combined in a manner that acts like a filter on the T2 spectrum. The choice of weighting coefficients determines the filter specifications (e.g. passband/stopband locations, stopband suppression factors). To perform spectroscopy, a series of filters are designed with narrow passbands centered about consecutive regions of the T2 spectrum. This provides an estimate of every region of the spectrum. Taken together, an initial estimate of the full T2 spectrum is thus obtained. However, the filtering process causes a distortion of the estimate relative to the true spectrum. To reduce this distortion, deconvolution is performed. The characteristics of the technique are first evaluated through simulation. The technique is then applied to experimental MRI data to demonstrate practical feasibility. T2 spectroscopy falls into a class of problems requiring inverse transformation with a set of exponential basis functions (i.e. the Laplace Transform). It is demonstrated how the present technique may be applied to problems involving non-exponential basis functions as well.


Fenofibrate prevents the disruption of the outer blood retinal barrier through downregulation of NF-κB activity.
There is clinical evidence that fenofibrate, a PPARα agonist, arrests the progression of diabetic macular edema (DME). However, the underlying mechanisms of this beneficial effect remain to be elucidated. We previously reported that fenofibric acid (FA), the active metabolite of fenofibrate, prevents the disorganization of tight junction proteins and the hyperpermeability provoked by the diabetic milieu in the retinal pigment epithelium (RPE). The aim of the present study was to evaluate whether this effect is mediated by inhibiting the proinflammatory transcription factor NF-κB, as well as the expression of several proinflammatory cytokines involved in the pathogenesis of DME. Human RPE cells were cultured under standard conditions and under conditions leading to the disruption of the monolayer [IL-1β (10 ng/ml)]. The effect of FA, QNZ (a NF-κB inhibitor), WY14643 (a PPARα agonist), and MK-866 (a PPARα antagonist) in the disruption of the monolayer was determined by dextran permeability and immunohistochemistry analyses. The effect of FA on NF-κB activity was assessed by EMSA and by NF-κB/p65 nuclear translocation analyses. The expression of cytokines (IL-6, IL-8, MCP-1) was measured by RT-PCR. FA prevented RPE monolayer disruption, and the consequent hyperpermeability induced by IL-1β, through inhibition of NF-κB activity. This effect was due to PPARα activation and was associated with a significant downregulation of the expression of proinflammatory cytokines. Our findings suggest that the anti-inflammatory effects of FA through inhibition of NF-κB activity play a key role in the beneficial effect of fenofibrate for treating DME.


Engineering bacterial translation initiation - Do we have all the tools we need?
Reliable tools that allow precise and predictable control over gene expression are critical for the success of nearly all bioengineering applications. Translation initiation is the most regulated phase during protein biosynthesis, and is therefore a promising target for exerting control over gene expression. At the translational level, the copy number of a protein can be fine-tuned by altering the interaction between the translation initiation region of an mRNA and the ribosome. These interactions can be controlled by modulating the mRNA structure using numerous approaches, including small molecule ligands, RNAs, or RNA-binding proteins. A variety of naturally occurring regulatory elements have been repurposed, facilitating advances in synthetic gene regulation strategies. The pursuit of a comprehensive understanding of mechanisms governing translation initiation provides the framework for future engineering efforts. Here we outline state-of-the-art strategies used to predictably control translation initiation in bacteria. We also discuss current limitations in the field and future goals. Due to its function as the rate-determining step, initiation is the ideal point to exert effective translation regulation. Several engineering tools are currently available to rationally design the initiation characteristics of synthetic mRNAs. However, improvements are required to increase the predictability, effectiveness, and portability of these tools. Predictable and reliable control over translation initiation will allow greater predictability when designing, constructing, and testing genetic circuits. The ability to build more complex circuits predictably will advance synthetic biology and contribute to our fundamental understanding of the underlying principles of these processes. "This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue.


"I do those things to pass the time.": Active ageing during fourth age.
Active ageing is a dominant but disputed discourse in the field of ageing. Since it is usually associated with the third age, this article will focus on the active ageing of older adults who need care and services, who are known as the fourth agers. Our data consists of interviews collected from 16 older adults. We analysed the data through content analysis that was guided by the Active Ageing Index (AAI) that is a measuring tool concerning active ageing. According to our results, active ageing during the fourth age can be understood through the lens of small actions and precarity. Although some actions had to be given up or modified, participants were active in various ways, and help from other people and from services was essential. Based on our results, there is a need for further discussion about theorisation and defining active ageing for fourth agers.


Investigating phase separation properties of chromatin-associated proteins using gradient elution of 1,6-hexanediol.
Chromatin-associated phase separation proteins establish various biomolecular condensates via liquid-liquid phase separation (LLPS), which regulates vital biological processes spatially and temporally. However, the widely used methods to characterize phase separation proteins are still based on low-throughput experiments, which consume time and could not be used to explore protein LLPS properties in bulk. By combining gradient 1,6-hexanediol (1,6-HD) elution and quantitative proteomics, we developed chromatin enriching hexanediol separation coupled with liquid chromatography-mass spectrometry (CHS-MS) to explore the LLPS properties of different chromatin-associated proteins (CAPs). First, we found that CAPs were enriched more effectively in the 1,6-HD treatment group than in the isotonic solution treatment group. Further analysis showed that the 1,6-HD treatment group could effectively enrich CAPs prone to LLPS. Finally, we compared the representative proteins eluted by different gradients of 1,6-HD and found that the representative proteins of the 2% 1,6-HD treatment group had the highest percentage of IDRs and LCDs, whereas the 10% 1,6-HD treatment group had the opposite trend. This study provides a convenient high-throughput experimental method called CHS-MS. This method can efficiently enrich proteins prone to LLPS and can be extended to explore LLPS properties of CAPs in different biological systems.


Elevated AST/ALT ratio is associated with all-cause mortality in patients with stable coronary artery disease: a secondary analysis based on a retrospective cohort study.
The aim of this study is to explore the association between the aspartate amino transferase (AST)/alanine aminotransferase (ALT) ratio and all-cause mortality (ACM) in stable coronary artery disease (CAD) patients treated by percutaneous coronary intervention (PCI). The study is a secondary analysis of a retrospective cohort study involving 203 stable CAD patients. Patients were divided into two groups, based on the optimal AST/ALT ratio threshold calculated by the ROC curve (low group: AST/ALT ratio < 1.40; high group: AST/ALT ratio ≥ 1.40). Results were compared using hazard ratio (HR) and a 95% confidence interval (CI). ACM occurred in 18 patients after an average follow-up time of 749 (435-1122) days. Among them, ACM occurred in 6 patients in the low group and 12 patients in the high group, with significant differences between the groups (4.65% versus 16.22%, P value = 0.005). In the Kaplan-Meier analysis, an elevated AST/ALT ratio was associated with increased ACM in stable ACD patients (HR 3.78, 95% CI 1.44-9.93, P value < 0.001). An elevated AST/ALT ratio was still found to be an independent prognostic factor for ACM (HR 2.93, 95% CI 1.08-7.91, P value = 0.034) after adjusting for potential confounders. Therefore, an elevated AST/ALT ratio is an independent prognostic factor for ACM in stable ACD patients.


Latent herpes simplex virus type 1 in human geniculate ganglia.
Viral infection, especially by reactivation of herpes simplex virus (HSV) has been considered to be a possible explanation for the pathogenesis of idiopathic peripheral facial nerve palsy (Bell's palsy). We investigated whether the geniculate ganglia of man contain latent HSV type 1 (HSV-1), and compared the frequency of HSV-infected ganglia and that of latently infected neurons in human geniculate ganglia and in trigeminal ganglia. From autopsy specimens of eight adults 15 geniculate ganglia and 16 trigeminal ganglia were examined by means of in situ hybridization and immunohistochemical staining. The HSV-1 genome was detected in 11 of the 15 (71%) geniculate ganglia and in 13 of the 16 (81%) trigeminal ganglia. No HSV antigen was noted in any of the ganglia. The incidence of latently infected neurons was 0.9% in the trigeminal ganglia and 5.3% in the geniculate ganglia. The difference in percentages between the two types of ganglia was significant. Our results suggest that reactivation of latent HSV in the geniculate ganglia is a probable cause of some cases of herpetic stomatitis and of idiopathic peripheral facial nerve palsy.


Expression of pRb, Ki67 and HER 2/neu in gastric carcinomas: Relation to different histopathological grades and stages.
Gastric carcinoma is one of the aggressive malignancies with poor prognosis. The expression of pRb, Ki67, Her-2 in relation to tumor grade and stage in gastric carcinoma still needs more exploration. This study was performed aiming to study the immunohistochemical expression of altered retinoblastoma encoding protein (pRb), Ki67 and Her-2 in gastric carcinoma and to investigate their clinical and pathological significance. We studied tumor tissue specimens from 48 patients with gastric carcinoma. Paraffin sections were submitted for immunohistochemistry using pRb, Ki67 and Her-2. Statistical analysis was performed for clinical and pathological data of all studied cases. Altered pRb was expressed in 79% of the studied tumors, inversely correlated with tumor invasion and stage with no significant relation with tumor grade, age, and gender and tumor size. Ki67 LI was significantly associated with tumor grade and stage but not related to sex, age, tumor size, site, depth of invasion and lymph node metastasis. Her2 was expressed in 75% of studies tumors with significant association with tumor grade, the depth of invasion, lymph node metastasis and higher tumor stage. However, there was no significant association between Her-2 expression and gender, tumor site and size. In conclusion, altered pRb is frequently expressed in gastric carcinoma, inversely correlates with tumor invasion and tumor stage suggesting an early event in gastric carcinogenesis. Ki67 expression in gastric carcinoma is directly correlated with the tumor grade and depth of invasion. Her2 expression is significantly correlated with tumor grade, depth of invasion and stage.


[Efficacy-safety relationship of AT1 angiotensin II receptor antagonists: current data].
In evolution of hypertension's treatment it may no be sufficient to lower blood pressure to achieve beneficial effects in long term outcomes. Several goals of antihypertensive treatment remain unrealized. There is so great interest for new drugs that may protect target organs and improve outcomes. The angiotensin II, the major effector of the renin-angiotensin-aldosterone system, causes a variety of potentially noxious cardiovascular effects which are specially mediated by AT1 subtype receptors. AT1 receptor blockers (losartan, candesartan, irbesartan, valsartan) are available drugs in the angiotensin-II-antagonist class. This paper examine the peculiar features of this new class of drugs.


Clinical validation of an elastin-derived trifunctional peptide for skin regeneration.
Aging is associated with progressive skin fragility, characterized in part by extracellular matrix (ECM) fragmentation. This degradation produces matrikines which have an impact on ECM rremodeling. Our group previously designed and characterized a trifunctional peptide (TFP), constituted of i) an elastokine motif (VGVAPG)3, able to increase the expression of matrix constituent through the stimulation of the elastin-binding protein receptor, ii) a tripeptide inhibiting matrix metalloproteinase-1 activity (GIL), and iii) a linker domain acting as a competitive substrate for urokinase (RVRL). TFP was shown to activate the production of matrix constituents while inhibiting Matrix MetalloProtease MMP-1 in vitro on fibroblasts and ex vivo on skin explants. In the present study, TFP properties were evaluated in a clinical assay. Twenty-two volunteers applied a TFP-based cream on one hemi-face and a placebo-based cream on the other hemi-face, twice a day during 28 days, before undergoing a surgical lifting. Cutometry and skin relief measurements were performed at days 0 and 28, and skin explants from lifting surgery were used for histological analyses. Cutometry and skin relief measurements reveal TFP firming properties and wrinkle depth decrease in 28 days on TFP- as compared to placebo-treated hemi-faces. These results are confirmed by histological analyses showing an increase of the ratio between basal lamina and stratum corneum. Furthermore, immunostaining of collagen reveals a modification of the ratio between type I and III collagens. The combined analysis of phenotypic and histologic parameters demonstrates a reorganization of the ECM towards a regenerative profile upon TFP treatment.


Optical and electrochemical-based nano-aptasensing approaches for the detection of circulating tumor cells (CTCs).
More recently, detection of circulating tumor cells (CTCs) has been considered as an appealing prognostic and diagnostic approach for cancer patients. CTCs as a type of tumor-derived cells are secreted by the tumor and released into the blood circulation. Since the migration of CTCs is an early event in cancer progression, patients who still have tumor-free lymph nodes have to be well examined for the CTCs presence in their blood circulation. Nowadays, there is a broad range of detection methods available to identify CTCs. As artificial RNA oligonucleotides or single-stranded DNA with receptor and catalytic characteristics, aptamers have been standing out, owing to their target-induced conformational modifications, elevated stability, and target specificity to be implemented in biosensing techniques. To date, several sensitivity-enhancement methods alongside smart nanomaterials have been used for the creation of new aptasensors to address the limit of detection (LOD), and improve the sensitivity of numerous analyte identification methods. The present review article supports a focused overview of the recent studies in the identification and quantitative determination of CTCs by aptamer-based biosensors and nanobiosensors.


IgA nephropathy in a patient with ulcerative colitis, Graves' disease and positive myeloperoxidase ANCA.
We report a case of a 38-year old woman with a history of ulcerative colitis and Graves' disease who presented with pyoderma gangrenosum, microscopic hematuria, proteinuria, and positive myeloperoxidase ANCA. A renal biopsy revealed a focal proliferative glomerulonephritis with IgA deposits. All these manifestations are likely secondary to ulcerative colitis or to a common pathogenetic mechanism.


Cluster analysis of human autoantibody reactivities in health and in type 1 diabetes mellitus: a bio-informatic approach to immune complexity.
Informatic methodologies are being applied successfully to analyze the complexity of the genome. But beyond the genome, the immune system reflects the state of the body in health and disease. Traditionally, immunologists have reduced the immune system, where possible, to one-to-one relationships between particular antigens and particular antibodies or T-cell clones. Autoimmune diseases, caused by an immune attack against a body component, are usually investigated by following the response to single self-antigens. In this study, we apply informatics to analyze patterns of autoantibodies rather than single species of autoantibodies. This study was designed not to replace traditional approaches to immune diagnosis, but to test whether meaningful patterns of autoantibodies might exist. Using an unbiased solid-phase ELISA antibody test, we detected serum IgG and IgM antibodies in the sera of 20 healthy persons and 20 persons with type 1 diabetes mellitus binding to an array of 87 different antigens, mostly self-antigens. The healthy subjects manifested autoantibodies to a variety of self-antigens, many known to be associated with autoimmune diseases. We investigated the patterns of these autoantibodies using a coupled two-way clustering algorithm developed for analyzing data from gene arrays. We now report that the reactivity patterns of autoantibodies to particular subsets of self-antigens exhibited non-trivial structure, which significantly discriminated between healthy persons and persons with type 1 diabetes. The results show that despite the wide prevalence of autoantibodies, the patterns of reactivity to defined subsets of self-antigens can provide information about the state of the body.


Chemotactic disorders.
Clinical disorders of phagocyte chemotaxis have heterogeneous etiologies. The physiologic defect can involve adherence, the cytoskeleton, deformability, granule dysfunction, regulation of receptors, or a variety of soluble mediators. At present, successful clinical management depends on early and compulsive attention to infectious complications. A host of new immunomodulators (GM-CSF, gamma interferon, tumor necrosis factor, etc.), made available through recombinant gene technology, are now under study and may provide new and more effective means of treatment for these life-threatening disorders.


Revisiting the oral glucose tolerance test criterion for the diagnosis of diabetes.
The Expert Committee on the Diagnosis and Classification of Diabetes retained the 2-hour glucose concentration on an oral glucose tolerance test of >/=11.1 mmol/L (200 mg/dL) as a criterion to diagnose diabetes. Since glycated hemoglobin levels have emerged as the best measure of long-term glycemia and an important predictor of microvascular and neuropathic complications, we evaluated the distribution of hemoglobin A1C (Hb A1C) levels in individuals who had undergone an oral glucose tolerance test to determine how well 2-hour values could identify those with normal versus increased Hb A1C levels. A cross-sectional analysis of 2 large data sets was performed. We cross-tabulated 2-hour glucose concentrations on an oral glucose tolerance test separated into 4 intervals (<7.8 mmol/L [140 mg/dL], 7.8-11.0 mmol/L [140-199 mg/dL], 11.1-13.3 mmol/L [200-239 mg/dL], and >/=13.3 mmol/L [240 mg/dL]) with Hb A1C levels separated into 3 intervals (normal; <1% above the upper limit of normal; and greater than or equal to the upper limit of normal + 1%). Approximately two thirds of patients in both data sets with 2-hour glucose concentrations of 11.1 to 13.3 mmol/L (200-239 mg/dL) had normal Hb A1C levels. In contrast, 60% to 80% of patients in both data sets with 2-hour glucose concentrations >/=13.3 mmol/L (240 mg/dL) had elevated Hb A1C levels. Since Hb A1C levels are the best measures presently available that reflect long-term glycemia, we conclude that the 2-hour glucose concentration criterion on an oral glucose tolerance test for the diagnosis of diabetes should be raised from >/= 11.1 mmol/L (200 mg/dL) to >/= 13.3 mmol/L (240 mg/dL) to remain faithful to the concept that diagnostic concentrations of glucose should predict the subsequent development of specific diabetic complications (e.g., retinopathy).


Revealing the Organ-Specific Expression of SPTBN1 using Single-Cell RNA Sequencing Analysis.
Despite the recent technological advances in single-cell RNA sequencing, it is still unknown how three marker genes (SPTBN1, EPDR1, and PKDCC), which are associated with bone fractures and highly expressed in the muscle tissue, are contributing to the development of other tissues and organs at the cellular level. This study aims to analyze three marker genes at the single-cell level using 15 organ tissue types of adult human cell atlas (AHCA). The single-cell RNA sequencing analysis used three marker genes and a publicly available AHCA data set. AHCA data set contains more than 84,000 cells from 15 organ tissue types. Quality control filtering, dimensionality reduction, clustering for cells, and data visualization were performed using the Seurat package. A total of 15 organ types are included in the downloaded data sets: Bladder, Blood, Common Bile Duct, Esophagus, Heart, Liver, Lymph Node, Marrow, Muscle, Rectum, Skin, Small Intestine, Spleen, Stomach, and Trachea. In total, 84,363 cells and 228,508 genes were included in the integrated analysis. A marker gene of SPTBN1 is highly expressed across all 15 organ types, particularly in the Fibroblasts, Smooth muscle cells, and Tissue stem cells of the Bladder, Esophagus, Heart, Muscle, Rectum, Skin, and Trachea. In contrast, EPDR1 is highly expressed in the Muscle, Heart, and Trachea, and PKDCC is only expressed in Heart. In conclusion, SPTBN1 is an essential protein gene in physiological development and plays a critical role in the high expression of fibroblasts in multiple organ types. Targeting SPTBN1 may prove beneficial for fracture healing and drug discovery.


Changes in rat hind limb vascular resistance following intracerebroventricular drug administration.
The right hind limbs of rats (which had previously implanted intraventricular guide cannulae) were isolated from the systemic circulation, but with the nerves to the limb remaining intact, and perfused using a constant output blood pump. Using this preparation, changes in vascular resistance, blood pressure and heart rate were monitored following injection of noradrenaline, phentolamine and propranolol into the lateral cerebral ventricles (i.c.v.) of rats anaesthetised with alpha-chloralose. All three drugs lowered blood pressure. Noradrenaline administered i.c.v. induced a nervously mediated vasocilatation and an insignificant fall in heart rate whereas i.c.v. phentolamine administration was followed by a nervously mediated vasoconstriction in the isolated hind limb and a gradual rise in heart rate. After i.c.v. administration of propranolol there was no evidence of an immediate nervously mediated vasodilatation but heart rate fell significantly. Following i.c.v. phentolamine or propranolol vasodilatation did not occur in the hind limb until after the time taken for circulating blood ro reach the isolated vascular bed. The vasodilatatory and hypotensive responses to i.c.v. noradrenaline were not evident following prior i.c.v. injection of phentolamine. These results indicate the suitability of this preparation for investigations of central actions of other drugs.


Module to facilitate self-directed learning among medical undergraduates: Development and implementation.
Currently, self-directed learning (SDL) is emphasized in medical institutions all over the world. The skills of SDL enable one to be a lifelong learner, a necessity to cope up with fast-expanding medical knowledge. This study aims to develop and implement an "SDL" module for medical undergraduates and find out their perception about the same. A cross-sectional study using a mixed-method design (having both qualitative and quantitative components) was conducted in the Department of Community Medicine, UCMS, Delhi, India. A module was developed following an extensive literature review and focus group discussions with the teaching staff of the institute. First-semester undergraduate students were invited to participate in the study and asked for feedback using a semi-structured questionnaire. Quantitative data were expressed in mean, range, and frequency. For qualitative data, thematic analysis was performed. The module was implemented with 160 students, in November for 10 hour distributed over 5 weeks. Feedback could be obtained from 130 students. Sixty-seven percent of students were satisfied and 66% reported as motivated to study the allotted topic further. Qualitative analysis showed that though the students liked the learning process based on this module, they also felt facilitators could have been more active in imparting knowledge and skills. To make learners equipped with the ability to learn throughout a professional learning course, SDL as a learning tool should be introduced in the medical undergraduate curriculum.


The succinate/fumarate transporter Acr1p of Saccharomyces cerevisiae is part of the gluconeogenic pathway and its expression is regulated by Cat8p.
The product of the ACR1 gene is essential for growth of Saccharomyces cerevisiae on ethanol or acetate as sole carbon source, and its expression is subject to glucose repression. It was previously shown that Acr1p is a membrane protein which specifically transports succinate and fumarate. Its suggested function is to shuttle cytosolic succinate from the glyoxylate cycle into the mitochondria in exchange for fumarate, an activity that is essential during gluconeogenic growth on C2 compounds. In this study we show that ACR1 is coregulated with the genes coding for the key enzymes of the glyoxylate cycle and gluconeogenesis: ICL1, MLS1 and PCK1, FBP1 respectively. We demonstrate that derepression of ACR1 is strictly dependent on the Zn2Cys6-type transcriptional activator Cat8p. A detailed deletion analysis of the ACR1 promoter revealed that 69% of the derepression of ACR1 is mediated by three cis-acting elements, located between positions -679 and -569 relative to the translational start, which show a high degree of similarity to the UAS/CSRE elements of PCK1, FBP1, ICL1 and MLS1. Our results, in conjunction with previous biochemical data, clearly identify Acr1p as an element which is directly involved in gluconeogenesis, functioning as the mitochondrial carrier which links the anaplerotic reactions of the glyoxylate cycle to the TCA cycle.


Relationship among settling, demography and habitat selection: an approach and a case study.
We explore the demographic consequences of site selection by animals on their abundance among habitats. We found that pre and post settling survivorship are important links between the behavioral decisions where to settle and the distribution of a population among habitats. This was demonstrated for 10 generations of the desert isopod, Hemilepistus reaumuri, in three habitats in the Negev Desert, Israel. The populations exhibit low survivorship before settling (≈12%) and high survivorship (≈55%) after settling. According to our model this implies high site selection. Theoretical considerations and the case study led us to suggest the following relationship among settling, demography and habitat selection: 1) Individuals search for suitable settling sites to inhabit and reproduce. 2) Their decision where and when to settle is a cost benefit decision. They weigh the benefit of searching for a high quality site against mortality due to increased searching time. 3) The individual's decision to settle determines the pre and post settling survivorship pattern. 4) Survivorship pattern dictates density pattern in time and space. 5) Density pattern in a given habitat determines its quality for the individual. 6) Settling selection among habitats and the number of safe sites controls the distribution of densities among habitats.


Therapeutic Potential of BMP7 in the Treatment of Osteoporosis Caused by the Interaction between Inflammation and Corticosteroids in Inflammatory Bowel Disease.
Individuals with inflammatory bowel disease (IBD) have an increased risk of bone impairment, which is a process controlled by the RANKL/RANK/OPG system, mostly due to chronic inflammation and corticosteroid treatment. Bone morphogenic protein 7 (BMP7) has a complex role in maintaining inflammation and bone remodeling but little is known about its anti-inflammatory potential in chronic colitis. We investigated the effect of systemically administered BMP7 and corticosteroids on the severity of inflammation, macrophage differentiation, and bone regeneration in a chronic IBD model. Chronic colitis was induced in male Sprague Dawley rats via weekly administration of 2,4,6-trinitrobenzenesulfonic acid over 21 days following BMP7 or corticosteroid treatment for five days. The levels of serum and colon tissue inflammatory cytokines, RANKL/OPG system, as well as markers of macrophage polarization, were detected using RT-PCR, ELISA, or immunohistochemistry. Long bone and spine analyses were performed using microcomputed tomography (micro-CT). The administration of BMP7 reduced the adverse effects of colitis and led to elevated OPG and RANK in the colon with a simultaneous decrease in TNF-α and an increase in IL-10 and TGF-β. Decreased expression of the M2 macrophage marker CD163 was found in the BMP7-treated rats compared with the colitis group, whereas the number of M1 marker iNOS-positive cells did not differ between the groups. As a result of the BMP7 treatment, morphometric parameters of trabecular bone increased, and increased trabecular separation noted in the colitis group did not appear. We showed that BMP7 suppressed the inflammatory response in chronic colitis, mainly by shifting the cytokine balance and by triggering alterations in the RANKL/OPG system rather than through a macrophage polarization imbalance. In addition, considering the demonstrated effect of BMP7 on bone morphology and structure, it can be suggested that BMP7 plays a role in the managing of osteoporosis in chronic colitis, and thus, its therapeutic potential in the treatment of IBD should be further evaluated.


The impact of next-generation sequencing technology on preimplantation genetic diagnosis and screening.
Largely because of efforts required to complete the Human Genome Project, DNA sequencing has undergone a steady transformation with still-ongoing developments of high-throughput sequencing machines for which the cost per reaction is falling drastically. Similarly, the fast-changing landscape of reproductive technologies has been improved by genetic approaches. Preimplantation genetic diagnosis and screening were established more than two decades ago for selecting genetically normal embryos to avoid inherited diseases and to give the highest potential to achieve stable pregnancies. Most recent additions to the IVF practices (blastocyst/trophectoderm biopsy, embryo vitrification) and adoption of new genetics tools such as array comparative genome hybridization have allowed setting up more precise and efficient programs for clinical embryo diagnosis. Nevertheless, there is always room for improvements. Remarkably, a recent explosion in the release of advanced sequencing benchtop platforms, together with a certain maturity of bioinformatics tools, has set the target goal of sequencing individual cells for embryo diagnosis to be a realistically feasible scenario for the near future. Next-generation sequencing technology should provide the opportunity to simultaneously analyze single-gene disorders and perform an extensive comprehensive chromosome screening/diagnosis by concurrently sequencing, counting, and accurately assembling millions of DNA reads.


Simultaneous antibiotic removal and mitigation of resistance induction by manganese bio-oxidation process.
Microbial degradation to remove residual antibiotics in wastewater is of growing interest. However, biological treatment of antibiotics may cause resistance dissemination by mutations and horizontal gene transfer (HGT) of antibiotic resistance genes (ARGs). In this study, a Mn(Ⅱ)-oxidizing bacterium (MnOB), Pseudomonas aeruginosa MQ2, simultaneously degraded antibiotics, decreased HGT, and mitigated antibiotic resistance mutation. Intracellular Mn(II) levels increased during manganese oxidation, and biogenic manganese oxides (BioMnOx, including Mn(II), Mn(III) and Mn(IV)) tightly coated the cell surface. Mn(II) bio-oxidation mitigated antibiotic resistance acquisition from an E. coli ARG donor and mitigated antibiotic resistance inducement by decreasing conjugative transfer and mutation, respectively. BioMnOx also oxidized ciprofloxacin (1 mg/L) and tetracycline (5 mg/L), respectively removing 93% and 96% within 24 h. Transcriptomic analysis revealed that two new multicopper oxidase and one peroxidase genes are involved in Mn(II) oxidation. Downregulation of SOS response, multidrug resistance and type Ⅳ secretion system related genes explained that Mn(II) and BioMnOx decreased HGT and mitigated resistance mutation by alleviating oxidative stress, which makes recipient cells more vulnerable to ARG acquisition and mutation. A manganese bio-oxidation based reactor was constructed and completely removed tetracycline with environmental concentration within 4-hour hydraulic retention time. Overall, this study suggests that Mn (II) bio-oxidation process could be exploited to control antibiotic contamination and mitigate resistance propagation during water treatment.


Standardized Perioperative Patient Education Decreases Opioid Use after Hand Surgery: A Randomized Controlled Trial.
Despite the growing hand surgery literature on postoperative opioid use, there is little research focused on patient-centered interventions. The purpose of this randomized controlled trial was to create a standardized patient education program regarding postoperative pain management after hand surgery and to determine whether that education program would decrease postoperative opioid use. Patients scheduled to undergo ambulatory hand surgery were recruited and randomized to standardized pain management education or standard of care. All patients received a webinar with instructions for study participation, whereas the education group received an additional 10 minutes of education on postoperative pain management. All patients completed a postoperative daily log documenting opioid consumption. The total number of opioid pills consumed was compared between groups. The authors constructed a linear regression model to determine risk factors for postoperative opioid use after surgery. A total of 267 patients were enrolled in the study. One hundred ninety-one patients completed the study (standardized education, n = 93; control group, n = 97). Patients in the standardized education group were more likely to take no opioid medication (42 percent versus 25 percent; p = 0.01) and took significantly fewer opioid pills (median, two) than those in the control group (median, five) (p < 0.001). Standardized education predicted decreased postoperative opioid pill consumption, whereas higher number of pills prescribed and a history of psychiatric illness were risk factors for increasing opioid use. Perioperative patient education and limitation of postoperative opioid prescription sizes reduced postoperative opioid use following ambulatory hand surgery. Therapeutic, II.


Assessment of genetic polymorphism at 20 autosomal STR loci in scheduled caste population of Himachal Pradesh.
In this study, we evaluated the genetic diversity indices and forensic parameters of scheduled caste population of Himachal Pradesh, India, at 20 autosomal STR loci. Altogether, 233 alleles were observed with an average of 11.65 ± 0.88 alleles per locus. In exception of locus D13S317, no loci deviated from Hardy Weinberg equilibrium. Locus Penta E was found to be the most polymorphic and discriminative loci. The combined power of discrimination and the combined power of exclusion were 1 and 0.999. Further, we established the phylogenetic relationship between the scheduled caste population of Himachal Pradesh and 14 other populations of India. We found 20 autosomal STR loci used in the present study were polymorphic and can be used in population genetic studies and forensic related case works.


Abdominal Aortic Aneurysms (Etiology, Epidemiology, and Natural History).
Abdominal aortic aneurysm is a potentially lethal condition that is decreasing in frequency as tobacco use declines. The exact etiology remains unknown, but smoking and other perturbations seem to trigger an inflammatory state in the tunica media. Male sex and advanced age are clear demographic risk factors for the development of abdominal aortic aneurysms. The natural history of this disease varies, but screening remains vital as it is rarely diagnosed on physical examination, and elective repair (most commonly done endovascularly) offers significant morbidity and mortality advantages over emergent intervention for aortic rupture.


Sacred psychiatry in ancient Greece.
From the ancient times, there are three basic approaches for the interpretation of the different psychic phenomena: the organic, the psychological, and the sacred approach. The sacred approach forms the primordial foundation for any psychopathological development, innate to the prelogical human mind. Until the second millennium B.C., the Great Mother ruled the Universe and shamans cured the different mental disorders. But, around 1500 B.C., the predominance of the Hellenic civilization over the Pelasgic brought great changes in the theological and psychopathological fields. The Hellenes eliminated the cult of the Great Mother and worshiped Dias, a male deity, the father of gods and humans. With the Father's help and divinatory powers, the warrior-hero made diagnoses and found the right therapies for mental illness; in this way, sacerdotal psychiatry was born.


Diagnosis and treatment of depression comorbid with neurologic disorders.
Depression is common in patients with neurologic disorders such as Alzheimer disease, stroke, Parkinson disease, and multiple sclerosis. Diagnosing depression in the context of neurologic disease is challenging, given the overlap between many signs and symptoms of depression with those of the neurologic disorders. Cognitive impairment further complicates diagnostic evaluation. The etiology of depression in these patients is not well understood and variously has been attributed to emotional reaction to the diagnosis or disability associated with the neurologic condition, the anatomical and/or neurochemical outcomes of neurodegeneration, and the influence of other disease factors. Beyond the inherent burden depression places on patients and caregivers, it increases cognitive and functional disability and, depending on the neurologic disorder, poorer treatment adherence and recovery, earlier institutionalization, and increased suicide risk. Few controlled antidepressant trials are available to guide treatment. In the absence of validated diagnostic guidelines for depression in each neurologic condition, clinicians are urged to remain vigilant for this treatable comorbidity. Although more controlled trials clearly are needed, existing studies suggest that depression in patients with neurologic disorders responds to antidepressant medication and, in some disorders, to psychotherapeutic approaches. Investigating the neuroanatomical and neurochemical correlates of depression comorbid with neurologic conditions also may clarify depression etiology and treatment in the general population.


Gender differences in personal values of national and local Italian politicians, activists and voters.
Theorists of politics of presence postulate that women elected to political office would still hold values similar to ordinary women and therefore represent them better than male politicians. Gender differences in personal values, which underline and give coherence to core political values, have been found among voters: males score higher on self-enhancement values (power and achievement) and females higher on self-transcendence values (universalism and benevolence). Our study aims to explore if gender differences in personal values are still present among activists, local and national politicians. We administer a shortened version of the Portrait Values Questionnaire to 233 Italian national politicians (46% females), 425 local politicians (56% females), 626 political activists (44% females), and 3249 ordinary citizens (49% females). Our results confirm only partially politics of presence theory: females at all levels of political involvement score higher in self-transcendent values that emphasise concern for the welfare of others, but no significant gender differences emerge for self-enhancement, which favour the pursuit of self-interest. Our findings support ethical struggles for more balanced gender representation: a higher proportion of women in politics could strengthen the political representation of self-transcendence values.


A randomized study of 12-mm and 15.9 mm cannulas in midtrimester abortion by laminaria and vacuum curettage.
We evaluated the adequacy of a new large-bore vacuum cannula system for midtrimester abortion by randomly allocating patients to be treated with a standard 12-mm vacuum system or the new 15.9-mm system. Cervical dilataion was accomplished by overnight placement of laminaria tents. Blood loss was similar for the two treatment groups and was significantly greater at gestational ages 17 to 18 weeks than for abortions at 16 weeks or less. Operating time was slightly less in the large-cannula group. When the 12-mm cannula was used beyond 13 weeks' gestation, forceps were usually needed to empty the uterus completely. The large-cannula system was able to empty the uterus through 16 weeks, but at 17 and 18 weeks it offered no advantage over the smaller system and forceps were always needed. Complications were minimal. We caution against forcible cervical dilatation to 16 mm and urge the use of laminaria instead. Our findings, together with published reports of the safety of late dilatations and evacuation, would appear to justify wider clinical trials by experienced investigators.


Tuberculosis Diagnosis by Metagenomic Next-generation Sequencing on Bronchoalveolar Lavage Fluid: a cross-sectional analysis.
Metagenomic next-generation sequencing (mNGS) is an effective diagnostic method for infectious diseases, however, its clinical utility for tuberculosis (TB) diagnosis remains to be demonstrated. A total of 322 bronchoalveolar lavage fluid (BALF) samples were collected from 311 suspected and confirmed pulmonary TB patients and tested by mNGS, acid-fast bacillus (AFB) smear by microscopy, Xpert® MTB/RIF (Xpert), mycobacterium culture and bacterial/fungal culture. Diagnostic performance of mNGS was compared with conventional methods for detection of Mycobacterium tuberculosis complex (MTBC) and other pathogens in BALF. Underlying factors associated with positive detection in pulmonary TB patients were investigated. mNGS, Xpert and culture presented a high proportion of complete matching for MTBC detection (244/322, 75.8%). In pulmonary TB patients pre-treatment the sensitivity of MTBC detection by mNGS, Xpert, culture and smear was 59.9% (85/142), 69.0% (98/142), 59.9% (85/142) and 24.6% (35/142), respectively, and 79.6% overall; MTBC was detected by mNGS in 33.2% (5/34) Xpert and culture negative samples. Positive MTBC detection by mNGS was affected by Vitamin D, erythrocyte sedimentation rate, TB initial treatment/retreatment, and cavity in chest imaging (χ2 = 37.42, P < 0.001), but not by prior anti-TB therapy within 3 months. mNGS was able to detect new potential pathogens in 8.7% (28/322) of samples. Combining mNGS with conventional detection methods could increase the detection rate for MTBC. Additionally, mNGS could identify pathogens in a non-targeted approach for better diagnosis of coinfection.


Adjuvant methods to improve results of local bladder irrigations by chemotherapy for NMIBC.
Non-muscle-invasive bladder cancer is characterized by frequent recurrences requiring repeated transurethral resections and carries a risk of progression to muscle-invasive disease. The routinely used, passive diffusion irrigation of the bladder with mitomycin C has achieved limited success in avoiding these events. We review two methods that may improve penetration of mitomycin C into the bladder wall, thus leading to better results in terms of recurrence rate and bladder preservation.


An electrocardiography score predicts heart failure hospitalization or death beyond that of cardiovascular magnetic resonance imaging.
The electrocardiogram (ECG) and cardiovascular magnetic resonance imaging (CMR) provide powerful prognostic information. The aim was to determine their relative prognostic value. Patients (n = 783) undergoing CMR and 12-lead ECG with a QRS duration < 120 ms were included. Prognosis scores for one-year event-free survival from hospitalization for heart failure or death were derived using continuous ECG or CMR measures, and multivariable logistic regression, and compared. Patients (median [interquartile range] age 55 [43-64] years, 44% female) had 155 events during 5.7 [4.4-6.6] years. The ECG prognosis score included (1) frontal plane QRS-T angle, and (2) heart rate corrected QT duration (QTc) (log-rank 55). The CMR prognosis score included (1) global longitudinal strain, and (2) extracellular volume fraction (log-rank 85). The combination of positive scores for both ECG and CMR yielded the highest prognostic value (log-rank 105). Multivariable analysis showed an association with outcomes for both the ECG prognosis score (log-rank 8.4, hazard ratio [95% confidence interval] 1.29 [1.09-1.54]) and the CMR prognosis score (log-rank 47, hazard ratio 1.90 [1.58-2.28]). An ECG prognosis score predicted outcomes independently of CMR. Combining the results of ECG and CMR using both prognosis scores improved the overall prognostic performance.


Activity of locus coeruleus neurons in amygdala kindled rats: role in the suppression of afterdischarge.
Kindling is a model of epilepsy. The mechanisms of kindling development are unknown but may involve attenuation of noradrenergic neurotransmission. Single unit recordings, pharmacologic and lesion techniques were used to test the hypothesis that the increased seizure duration of kindled rats is the consequence of an inactivation of noradrenergic neurons in the locus coeruleus (LC). No difference was found between unkindled (naive) and kindled rats in the firing rates of recorded LC neurons either between or during seizures in the paralyzed, ventilated condition. Moreover, in naive rats, frank destruction of the LC did not lengthen seizure duration. We conclude that the lengthened seizure duration of kindled rats, in the paralyzed, ventilated conditions, is not the consequence of inactivation of the LC since the firing rate of recorded LC neurons in kindled rats was not decreased and since destruction of the LC in naive rats did not lengthen seizure duration. If attenuation of noradrenergic neurotransmission does contribute to the kindling phenomenon, then the LC is not likely to be the site at which this attenuation occurs.


Discovery of a new class of potent prolylcarboxypeptidase inhibitors derived from alanine.
Efforts to modify the central proline portion of lead compound 4 lead to the discovery of novel prolylcarboxypeptidase (PrCP) inhibitors. Especially, replacement with alanine afforded compound 19 displaying more potent human and mouse PrCP inhibitory activity than 4 and an overall comparable profile.


Association between first trimester vaginal bleeding and uterine artery Doppler measured at second and third trimesters of pregnancy.
To evaluate the prevalence of first trimester vaginal bleeding among patients with abnormal second and third trimester uterine artery Doppler. A prospective study of patients with a uterine artery Doppler measurement between 27 and 42 weeks' gestation was undertaken. A comparison was made between two groups: patients with and without first trimester vaginal bleeding. Abnormal uterine artery Doppler was defined as PI >95th% or the presence of a diastolic notch. Of the 277 patients that were included in the study, 65 (23%) had first trimester vaginal bleeding. No differences were noted in uterine artery Doppler waveforms among patients with and without first trimester vaginal bleeding. Among patients with first trimester vaginal bleeding, 9 (14%) had a bilateral uterine artery notch and 56 (86%) did not, compared with 51 (24%) and 161 (76%), in the control group, respectively. Patients with first trimester vaginal bleeding, and a bilateral uterine artery notch had significantly higher rates of small for gestational age neonates, low-Apgar scores (<7) at one minute and cesarean deliveries compared to patients with first trimester vaginal bleeding who did not have bilateral uterine artery notch. First trimester vaginal bleeding was not associated with a higher incidence of abnormal uterine artery waveforms or with placental related conditions. However, adverse perinatal outcomes were found when first trimester vaginal bleeding was associated with second and third trimester bilateral uterine artery notchs.


Effects of [6]-shogaol on cholinergic signaling in HT22 cells following neuronal damage induced by hydrogen peroxide.
Cholinergic neurons play a major role in memory and attention. The dysfunction and death of these neurons, especially in the hippocampus, are thought to contribute to the pathophysiology of memory deficits associated with Alzheimer's disease (AD). Therefore, studying the cholinergic properties and cell survival may help in treating this disease. We investigated the possible effects of [6]-shogaol on cholinergic signaling in HT22 hippocampal neuronal cells. HT22 cells express essential cholinergic markers, including choline acetyltransferase (ChAT) and choline transporter (ChTp). HT22 cells treated with H(2)O(2) for 3h showed an increase in ROS production (35%). These features were partly recovered by [6]-shogaol. Treating H(2)O(2)-treated HT22 cells with [6]-shogaol markedly increased the expression of ChAT and ChTp, an effect similar to that of brain-derived neurotrophic factor (BDNF). Furthermore, K-252a, an inhibitor of the BDNF receptor Trk B, attenuated the effects of both [6]-shogaol and BDNF. These data suggest that [6]-shogaol protects neurons by increasing ChAT and ChTp expression through a BDNF increase and thus may be useful for treating neurodegenerative diseases.


Perforation with the GyneFix intrauterine implant: is there a common factor?
This report describes an asymptomatic perforation with the GyneFix intrauterine contraceptive implant. A review of all other reports of this complication has been performed. Analysis of these reports suggests prolonged amenorrhoea secondary to continuous progestogen use as a possible common predisposing factor.


Nano drug delivery systems for antisense oligonucleotides (ASO) therapeutics.
Cancer, infectious diseases, and metabolic and hereditary genetic disorders are a global health burden affecting millions of people, with contemporary treatments offering limited relief. Antisense technology treats diseases by targeting their causal agents using its ability to alter or inhibit endogenous or malfunctioning genes. Nine antisense oligonucleotide (ASO) drugs that represent four different chemical classes have been approved for the treatment of rare diseases, including nusinersen, the first new oligonucleotide-based drug. Advances in medicinal chemistry, understanding the molecular pathways, and the availability of vast genetic data have resulted in enormous improvements in the therapeutic performance of ASO drugs; however, their susceptibility to degradation in the circulation, rapid renal clearance, and immunostimulatory adverse effects greatly limit their clinical applications. An increasing number of ASO-based therapeutics is being tested in clinical trials. Improvements to the delivery of ASO drugs could potentially change the therapeutic landscape for many conditions in the near future. This review describes the technological advances and developments in drug delivery systems pertaining to ASO therapeutics.


Anti-melanoma differentiation-associated gene 5 and anti-Ro52 antibody-dual positive dermatomyositis accompanied by rapidly lung disease: Three case reports.
Clinically amyopathic deramatomyositis was manifested as the various cutaneous dermatomyositis (DM) manifestations without muscle weakness. Anti-melanoma differentiation-associated gene 5 (anti-MDA5) and anti-Ro52 antibody-dual positive clinically amyopathic DM patients are at a high risk of developing rapidly progressive interstitial lung disease, and they exhibit an immensely high half-year mortality. We presented three patients with anti-MDA5 and anti-Ro52 antibody-dual positive DM patients and we reviewed the previous studies on the link between anti-MDA5 and anti-Ro52 antibody-dual positive DM. Although we aggressively treated these patients similarly, but they all exhibited different prognoses. We reviewed the importance of clinical cutaneous rashes as well as the pathogenesis and treatment in the dual positive anti-MDA5 and anti-Ro52 associated DM. Patients with anti-MDA5 anti-Ro52 antibody-dual positive DM should be accurately diagnosed at an early stage and should be treated aggressively, thus, the patient's prognosis can be significantly modified.


Immunopathophysiology of babesial infections.
Humans infected with Plasmodium falciparum and bovines infected with Babesia bovis display severe haemolysis, alterations in red cell deformability and rigidity, and endothelial cell damage leading to pulmonary oedema and cerebral dysfunction. Much of the pathology associated with these infections is not easily attributable to the relatively small numbers of parasites present. This paper considers the possible roles of soluble mediators released from macrophages, and chemical and physical changes in the infected red cell membrane, in the pathogenesis of babesial infections, and also discusses the effects of prior immunization with various immunogens.


Epithelial crescent in diabetic glomeruli. A case report.
The kidney as a target organ for secondary microvascular complications of diabetes mellitus represents a major problem. The pathology of diabetic glomerulopathy is well known. The coexistence of immunocomplex-mediated glomerulonephritis and diabetes mellitus has rarely been reported. The presence of crescents in glomerular disease of diabetes mellitus has been usually ignored in the literature. The present study describes one patient with epithelial crescentic diabetic glomerulopathy with rapidly progressive renal failure.


Effect of in vitro aging on prostaglandin synthesis in cultured rat vascular smooth muscle cells.
Cultured rat vascular smooth muscle cells from mesenteric artery produced prostaglandin (PG)E2, PGF2 alpha, PGI2 and thromboxane (TX)A2 in response to arachidonic acid, calcium ionophore A23187, vasopressin and angiotensin II. PGI2 was the major product among these PGs. PG synthesis in these cells decreased with in vitro aging, but the distribution pattern of PG synthesis did not change up to the passage level 56. Therefore, it is suggested that imbalance among PGs may not be directly implicated in vascular diseases in aging.


The human symbiont Bacteroides thetaiotaomicron promotes diet-induced obesity by regulating host lipid metabolism.
The gut microbiome plays an important role in lipid metabolism. Consumption of a high-fat diet (HFD) alters the bacterial communities in the gut, leading to metabolic disorders. Several bacterial species have been associated with diet-induced obesity, nonalcoholic fatty liver disease, and metabolic syndrome. However, the mechanisms underlying the control of lipid metabolism by symbiotic bacteria remain elusive. Here, we show that the human symbiont Bacteroides thetaiotaomicron aggravates metabolic disorders by promoting lipid digestion and absorption. Administration of B. thetaiotaomicron to HFD-fed mice promoted weight gain, elevated fasting glucose levels, and impaired glucose tolerance. Furthermore, B. thetaiotaomicron treatment upregulated the gene expression of the fatty acid transporter and increased fatty acid accumulation in the liver. B. thetaiotaomicron inhibits expression of the gene encoding a lipoprotein lipase inhibitor, angiopoietin-like protein 4 (ANGPTL4), thereby increasing lipase activity in the small intestine. In particular, we found that B. thetaiotaomicron induced the expression of hepcidin, the master regulator of iron metabolism and an antimicrobial peptide, in the liver. Hepcidin treatment resulted in a decrease in ANGPTL4 expression in Caco-2 cells, whereas treatment with an iron chelator restored ANGPTL4 expression in hepcidin-treated cells. These results indicate that B. thetaiotaomicron-mediated regulation of iron storage in intestinal epithelial cells may contribute to increased fat deposition and impaired glucose tolerance in HFD-fed mice.


Attachment of people to companion animals.
Cat and dog owners appear to be equally attached to their pets, engage in similar behaviors, and hold similar opinions regarding their pets. The universality and strength of this attachment may be because household pets fit into the biological attachment system that exists to bond parents and children. Additionally, pets may convey a feeling of security or a sense of well-being that is rooted in our evolutionary past.


Basic vascular anatomy and the reimplantation of the amputated hand through the palm.
Thirty adult upper extremities were used to study the blood vessels of the hand by angiography, cross-sectional measurement and operative microscopic dissection. The arteries in the middle segment of the palm are arranged in three planes, while in the upper or lower segment there are two planes only. The division of the territories of the radial and ulnar arteries are not same in the three different layers. There are three main anastomotic pathways between the radial and ulnar arteries in the radial-ulnar direction, while in the palmar-dorsal direction there are three anastomotic zones between the palmar and dorsal planes. According to the rate of appearance, sources, cross-sectional area, irrigation territories and anastomoses of the arteries in the three segments, the clinical significance in the reimplantation of the amputated hand through the palm has been discussed.


Definition of the human immunoglobulin variable lambda (IGLV) gene subgroups.
Comparison of 60 human immunoglobulin variable lambda (IGLV) sequences allowed us to define seven subgroups designated V lambda I to V lambda VII. We demonstrate that all lambda proteins sequenced so far fall into the subgroups I, II, III and VI, and that the lambda regions previously assigned to subgroups IV and V belong, in fact, to subgroups III and II, respectively. Four sequences not belonging to any of the subgroups I, II, III and VI define the new subgroups IV, V and VII. Interestingly, these subgroups show a higher homology to rabbit or mouse V lambda genes than to the other human V lambda subgroups. By comparison of the proteins either with the sequences deduced from the germ-line genes or with the consensus sequences, the rate of amino acid changes due to somatic mutations or allelic variations was evaluated in several lambda proteins. Framework and complementarity-determining regions of the human IGLV genes and proteins were delineated. Alignment of the lambda sequences shows that functional V-J rearrangement occurs, with or without deletion of nucleotides encoding one or two amino acids at the 3' end of the V gene. Diversity of the third complementarity-determining region is due to somatic mutations and to flexible V-J junction, but there is no evidence of N-diversity in the human lambda locus.


Absence of intervening sequences and point mutations in the V domain within 23S rRNA in Campylobacter lari isolates.
Although the absence of intervening sequences (IVSs) within the 23S rRNA genes in Campylobacter lari isolates has been described, there are apparently no reports regarding correlations between the nucleotide sequences of 23S rRNA genes and erythromycin (Ery) susceptibility in C. lari isolates. Here, we determined the minimum inhibitory concentrations of 35 C. lari isolates [n = 19 for urease-positive thermophilic Campylobacter (UPTC); n = 16 urease-negative (UN) C. lari] obtained from Asia, Europe, and North America. We found that the 18 isolates were resistant to the Ery (defined as ≧8 μg/mL), and three isolates, UPTC A1, UPTC 92251, and UPTC 504, showed increased resistance (16 μg/mL). No correlations between the IVSs in the helix 45 region within the 23S rRNA gene sequences and Ery resistance were identified in the C. lari isolates examined. In addition, no point mutations occurred at any expected or putative position within the V domain in the isolates. In conclusion, antibiotic resistance against the macrolide erythromycin is mediated through an alternative pathway to that described above.


The effect of vinyl chloride monomer, chloroethylene oxide and chloracetaldehyde on DNA synthesis in regenerating rat liver.
Vinyl chloride monomer used in the manufacture of polyvinyl chloride is a chemical of increasing industrial importance but has recently been incriminated as a carcinogen, producing a mutagenic effect after being metabolized to active metabolites. The initial effect of vinyl chloride monomer and two of its presumed metabolites, chloracetaldehyde and chloroethylene oxide, on DNA synthesis was investigated in vivo in regenerating rat liver. The established control curve for the DNA synthesis rate after partial hepatectomy demonstrated two waves of synthetic activity at 21 and 30 h. Vinyl chloride, injected intravenously immediately on completion of the operation, depressed the first wave of DNA synthesis by 49.6%. The second peak of DNA synthetic activity was similar to that of the control. Chloracetaldehyde and chloroethylene oxide both produced similar effects on the first wave of DNA synthesis after partial hepatectomy, inhibiting the DNA synthesis rate by approx. 50%. After a regenerating period of 27 h, however, they produced very different effects, chloroethylene oxide raising the control DNA synthesis rate at 30 h by 49% while chloracetaldehyde tended to desynchronize the well-defined second peak of the control. The test compounds have been compared to literature reports of the inhibitory effects of various carcinogens on DNA synthesis.


Structure of LARP7 Protein p65-telomerase RNA Complex in Telomerase Revealed by Cryo-EM and NMR.
La-related protein 7 (LARP7) are a family of RNA chaperones that protect the 3'-end of RNA and are components of specific ribonucleoprotein complexes (RNP). In Tetrahymena thermophila telomerase, LARP7 protein p65 together with telomerase reverse transcriptase (TERT) and telomerase RNA (TER) form the core RNP. p65 has four known domains-N-terminal domain (NTD), La motif (LaM), RNA recognition motif 1 (RRM1), and C-terminal xRRM2. To date, only the xRRM2 and LaM and their interactions with TER have been structurally characterized. Conformational dynamics leading to low resolution in cryo-EM density maps have limited our understanding of how full-length p65 specifically recognizes and remodels TER for telomerase assembly. Here, we combined focused classification of Tetrahymena telomerase cryo-EM maps with NMR spectroscopy to determine the structure of p65-TER. Three previously unknown helices are identified, one in the otherwise intrinsically disordered NTD that binds the La module, one that extends RRM1, and another preceding xRRM2, that stabilize p65-TER interactions. The extended La module (αN, LaM and RRM1) interacts with the four 3' terminal U nucleotides, while LaM and αN additionally interact with TER pseudoknot, and LaM with stem 1 and 5' end. Our results reveal the extensive p65-TER interactions that promote TER 3'-end protection, TER folding, and core RNP assembly and stabilization. The structure of full-length p65 with TER also sheds light on the biological roles of genuine La and LARP7 proteins as RNA chaperones and core RNP components.


Immunohistochemical distribution of the histone H1(0)/H5 variant in various tissues of adult Xenopus laevis.
The cellular distribution of the histone H1(0)/H5 variant has been examined immunohistochemically in various tissues of adult Xenopus laevis, using monoclonal antibodies against this variant that was isolated from erythrocyte nuclei. The H1(0)/H5 variant appears not to be erythrocyte-specific and appears to be present in all cell types of liver, stomach, and skin. In contrast, in oocyte nuclei the H1(0)/H5 variant cannot be detected, whereas they do contain H1; the nuclei of spermatogenic cells contain the H1(0)/H5 variant, but probably less than the somatic cells. In Xenopus no H1(0) variant distinct from H5 seems to occur and the H1(0)/H5 variant apparently may perform a functional role related to mammalian H1(0).


Molecular integrity and usefulness of episomal expression vectors derived from BK and Epstein-Barr virus.
High-level and stable production of a protein of interest is one of the most important parameters when considering the development of an efficient vector system for heterologous gene expression. In order to achieve this goal, we have used episomal vector elements derived from Epstein-Barr virus (EBV) or BK virus (BKV) in combination with the strictly regulated interferon-inducible Mx promoter. Here we demonstrate that EBV-derived vectors replicate efficiently in all cell lines tested (i.e. HEK293, HeLaH21 and Vero), yielding stable transfectants with a high, inducible expression level and almost no background. In contrast, BKV-derived vectors are much more restricted to particular cell types and hampered by DNA rearrangements, which is a serious drawback for use over a longer timespan.


The Unstable Carotid Plaque.
Carotid revascularization is performed to prevent cerebrovascular events in patients with symptomatic (>50%) and asymptomatic high degree (>70%) carotid stenosis. As this operation carries significant risks for perioperative stroke, careful selection of patients who will benefit from the procedure is essential. Certain plaque characteristics, including texture, are associated with increased tendency for rupture and can be used to identify high-risk patients. Medical therapy, carotid endarterectomy, and carotid stenting are the mainstays for patient management. With careful selection of patients, all anesthesia techniques (general anesthesia, monitored anesthesia care, and regional anesthesia) can be used safely for these revascularization procedures.


Association between serum copper/zinc ratio and lung cancer: A systematic review with meta-analysis.
Numerous studies have investigated the relationship between serum copper/zinc ratio and lung cancer. However, the results are inconsistent. Therefore, we evaluated the association between copper/zinc ratio and lung cancer. Observational studies reporting serum copper/zinc ratio in lung cancer patients and controls were identified from PubMed, Web of Science, EMBASE, CNKI and Wanfang databases online before December 2021. Summary standard mean difference (SMD) and the corresponding 95 % confidence interval (95 % CI) were applied to compare the serum serum copper/zinc ratio between lung cancer patients and controls using a random-effects model. Thirty-nine articles including 3598 lung cancer patients, 1402 benign lung diseases, and 3314 healthy controls were included in this study. The pooled results showed that the lung cancer patients had significantly higher serum copper/zinc ratio than healthy controls [SMD (95 % CI): 1.62 (1.31, 1.93)] and patients with benign lung diseases [SMD (95 % CI): 0.60 (0.36, 0.84)]. The results were robust according to sensitivity analysis. Meanwhile, consistent results were obtained both in European populations and Asian populations. Moreover, serum copper/zinc ratio was significant higher in patients with advanced stage of lung cancer than that in patients with early stage of lung cancer. The results showed that elevated serum copper/zinc ratio might be associated with increased risk of lung cancer.


Giving birth in exile: motherhood as reterritorialization.
This paper explores the effects of exile on the subjectivity of pregnant migrant women through the lens of the processes of deterritorialization and reterritorialization. Having escaped the gaze of the parental superego, the subject's encounter with sexuality becomes possible. However, in addition to the emancipatory aspects of migration, we observe particular somatic-psychical effects on reproductive ability. These "exile" pregnancies are generally experienced as difficult and painful, laying bare a symptomatology that is as much psychical as somatic, and which highlights the cost of a desire for independence. In this context, where perinatal risks must be evaluated and treated through an interdisciplinary approach, a clinical accompaniment proves to be indispensable for the maternity to progress smoothly on foreign soil.


Chest radiography in acute aortic syndrome: pearls and pitfalls.
Acute aortic syndrome is a group of life-threatening diseases of the thoracic aorta that usually present to the emergency department. It includes aortic dissection, aortic intramural hematoma, and penetrating aortic ulcer. Rare aortic pathologies of aorto-esophageal fistula and mycotic aneurysm may also be included in this list. All these conditions require urgent treatment with complex clinical care and management. Most patients who present with chest pain are evaluated with a chest radiograph in the emergency department. It is important that maximum diagnostic information is extracted from the chest radiograph as certain signs on the chest radiograph are extremely useful in pointing towards the diagnosis of acute aortic syndrome.


Relatives' experiences of brief admission in borderline personality disorder and self-harming behaviour.
The aim of this study is to describe experiences of brief admission (BA) of people with borderline personality disorder and self-harming behaviour, from the perspective of their relatives. A descriptive qualitative design was chosen. Twelve relatives of people with borderline personality disorder and self-harming behaviour who had access to BA were interviewed. Data were analysed with qualitative conventional content analysis. One overarching category: Hope for the future and three categories occurred: Breathing space, Personal responsibility and Structure. BA created hope for the future and the relatives appreciated that BA is a freer and easily accessible form of care that enables help at an early stage, compared with usual care. When BA functions, the structure and pre-determined days of care give relatives a breathing space, and the uncertainty diminishes for the children, as the parent can still be present during inpatient care. The lack of places was described as a disadvantage of BA.


Integration of multiple-ion-sensing on a capillary-assembled microchip.
Multiple-ion-sensing functions are integrated on a capillary-assembled microchip (CAs-CHIP). Since the CAs-CHIPs are fabricated by embedding various chemically functionalized square capillaries onto a lattice PDMS channel plate having same channel dimensions as outer dimensions of square capillaries, integration of parallel multiple-ion-sensing is easily realized. Here, three ion-sensing capillaries are prepared and used for integrating these functions onto a single microchip. Ion-sensing square capillaries (sodium, potassium, calcium) are prepared by attaching ion-selective optode membranes to inner wall of capillaries, and are characterized in terms of response time, response range, and ion selectivity. Finally, fully characterized ion-sensing capillaries are embedded into PDMS channel plate in parallel to fabricate a multiple-ion-sensing chip. The CAs-CHIP-based strategy is promising for integrating multiple chemical sensing functions onto a single microchip.


Cleavage of a RNA analog containing uridine by a bifunctional dinuclear Zn(II) catalyst.
The macrocyclic ligand, 1,4-bis((1-oxa-4,7,10-triazacyclododecan-7-yl)methyl)benzene (L1) is prepared. L1 binds two Zn(II) ions at neutral pH to form Zn(2)(L1) as studied by using pH-potentiometric titrations. Zn(2)(L1) binds two uridines at pH 7.0, I=0.100M (NaCl) and the mononuclear analog Zn(L2) (L2=1-oxa-4,7,10-triazacyclododecane) binds a single uridine; dissociation constants for both complexes are in the millimolar range. Both complexes promote the cleavage of a simple RNA analog lacking a nucleobase (HpPNP=2-hydroxypropyl-4-nitrophenylphosphate), and a uridine containing RNA analog UpPNP (uridine-3'-4-nitrophenylphosphate). Plots of the first-order rate constant for cleavage of HpPNP as a function of Zn(L2) concentration from 0.5mM to 20.0mM are linear, consistent with weak complexation to substrate K(d)>20mM. In contrast, first-order rate constants for cleavage of UpPNP by Zn(L2) or Zn(2)(L1) over similar concentration ranges exhibit a downward curvature, consistent with the formation of a complex between catalyst and UpPNP. Comparison of second-order rate constants (k(2)=k(cat)/K(d)) shows that the dinuclear complex Zn(2)(L1) is a better catalyst than Zn(L2) for both HpPNP and UpPNP cleavage.


Cloning of three ZIP/Nramp transporter genes from a Ni hyperaccumulator plant Thlaspi japonicum and their Ni2+-transport abilities.
Ni homeostasis is essential for plant cell activity, but the mechanisms of Ni-transport and delivery are unknown. To elucidate the role of ZIP and NRAMP metal-transporters for Ni2+-transport and homeostasis, we cloned their homologous genes from the Ni hyperaccumulator Thlaspi japonicum, and investigated their Ni-transporting abilities by expression in yeast. The deduced amino acid sequences of the two Zip transporter genes (TjZnt1, TjZnt2) and one Nramp transporter gene cloned had high homologies with TcZNT1 and TcZNT2 of Thlaspi caerulescens and AtNRAMP4 of Arabidopsis thaliana, respectively, and were predicted as integral membrane proteins with 6 or 12 transmembrane domains. TjZNT1 and TjZNT2 had two long histidine-rich domains in the putative cytoplasmic domain between transmembrane domains III and IV. TjNRAMP4 conserved a consensus transporter motif between transmembrane domains VIII and IX. The yeast transformed with TjZNT1 or TjZNT2 showed a marked increase in Ni2+ tolerance with the gene expression. In contrast, the expression of TjNramp4 caused elevation of Ni2+ sensitivity and Ni2+ concentration. These data suggest that ZIP/NRAMP transporters participate in Ni2+ homeostasis of Ni hyperaccumulator plants. TjZNT1 had Zn2+-, Cd2+- and Mn2+-transporting abilities and TjZNT2 also had Zn2+- and Mn2+-transporting abilities, but TjNRAMP4 could transport Ni2+ but not Zn2+, Cd2+ or Mn2+.


Network 'small-world-ness': a quantitative method for determining canonical network equivalence.
Many technological, biological, social, and information networks fall into the broad class of 'small-world' networks: they have tightly interconnected clusters of nodes, and a shortest mean path length that is similar to a matched random graph (same number of nodes and edges). This semi-quantitative definition leads to a categorical distinction ('small/not-small') rather than a quantitative, continuous grading of networks, and can lead to uncertainty about a network's small-world status. Moreover, systems described by small-world networks are often studied using an equivalent canonical network model--the Watts-Strogatz (WS) model. However, the process of establishing an equivalent WS model is imprecise and there is a pressing need to discover ways in which this equivalence may be quantified. We defined a precise measure of 'small-world-ness' S based on the trade off between high local clustering and short path length. A network is now deemed a 'small-world' if S>1--an assertion which may be tested statistically. We then examined the behavior of S on a large data-set of real-world systems. We found that all these systems were linked by a linear relationship between their S values and the network size n. Moreover, we show a method for assigning a unique Watts-Strogatz (WS) model to any real-world network, and show analytically that the WS models associated with our sample of networks also show linearity between S and n. Linearity between S and n is not, however, inevitable, and neither is S maximal for an arbitrary network of given size. Linearity may, however, be explained by a common limiting growth process. We have shown how the notion of a small-world network may be quantified. Several key properties of the metric are described and the use of WS canonical models is placed on a more secure footing.


[Expression and antigenicity analysis of p46000 antigen from newborn larvae of Trichinella spiralis].
To express and analyze p46000 antigen from newborn larvae of Trichinella spiralis. p46000 antigen gene was subcloned to the pET28a expression system by PCR. The recombinant transformant was induced by IPTG and the antigenicity was analyzed with ELISA and Western blotting. The molecular weight of the expressed protein was about Mr 48000. ELISA and Western blotting showed that this recombinant protein could be recognized by T. spiralis infected swine serum and rabbit anti-recombinant protein serum, and the rabbit anti-recombinant protein serum could recognize a Mr 46000 protein from newborn larvae of T. spiralis. p46000 recombinant antigen from newborn larvae of T. spiralis was expressed which shows a specific antigenicity.


Experimental ovine salmonellosis (Salmonella abortusovis): pathogenesis and vaccination.
Salmonella enterica subsp. enterica ser. Abortusovis, a sheep-adapted serotype, causes a contagious disease. Abortion is the major symptom and the main source of contamination. Research on this ovine disease may aid farmers, but may also contribute to comparative biological knowledge. Innate resistance partly controlled by the Ity locus, increased resistance to reinfection and humoral and T-cell-mediated immunity were observations gained with a murine model. In ewes, abortion regularly occurs following subcutaneous challenge carried out from the third month of gestation onwards. This ovine model was used to evaluate prevention methods for Salmonella Abortusovis infection. One subcutaneous injection of a live attenuated lyophilized vaccine containing a selected streptomycin-independent reverse mutant was shown to protect ewes against abortion and excretion of Salmonella Abortusovis. This vaccine could be administered simultaneously with other commercial live vaccines such as Brucella melitensis Rev. 1 vaccine. In sheep, application of the vaccine to the conjunctiva (an easy, individual and hygienic route of mucosal vaccination) was followed by lymph node bacterial colonization and a serological response without local or general clinical reactions. The early events of natural infection remain to be explored, as do the mechanisms underlying the host specificity of Salmonella Abortusovis.


Documented nutritional therapy in relation to nutritional guidelines post burn injury - a retrospective observational study.
Intensive nutritional therapy is an essential component of burn care. Regarding post-minor burn injuries, the literature is lacking. The aim of this study was to evaluate documented nutritional therapy in relation to international guidelines after both minor and major burn injuries. The secondary aim of this study was to evaluate the adequacy of energy and protein intake compared to individual nutritional goals post-burn injury. A retrospective observational single-centre study including patients admitted between 2017 and 2019 at a burn centre in Sweden was performed. The patients included in the study were ≥18 years old and in need of hospital care for ≥72 h post-burn injury. Information about patients' demographics, nutritional therapy, and clinical characteristics of burn injury was collected. The patients were divided according to total body surface area burnt (TBSA %) into minor burn injuries (TBSA <20%) and major burn injuries (TBSA ≥20%). Descriptive statistics were used to analyse data. Adherence to guidelines was established by comparing 24 nutritional therapy recommendations to documented treatment. If documented nutritional treatment were in accordance with guidelines, adherence was considered high (≥80%), moderate (60-79.9%) or low (<59.9%). One hundred thirty-four patients were included, 90 patients with minor burn injuries and 44 patients with major burn injuries. Documented adherence to the nutritional guideline was overall low. After minor burn injury, 8% (2/24) of nutritional therapy recommendations had a high adherence (fat intake <35% of total energy intake and enteral nutrition as prioritized feeding route), 17% (4/24) a moderate adherence, and 75% (18/24) a low adherence. In patients treated after a major burn injury, there were two recommendations with documented high adherence (Vitamin C and Zinc); 25% (6/24) had moderate adherence, and 67% (16/24) had low adherence. In addition, quite a large amount of missing data was found. Adequacy of documented nutritional intake, compared to the individual documented goal, was 78% (±23%) for energy and 66% (±22%) for protein after minor burn injury. After major burn injury, the adequacy was 89% (±21%) for energy and 78% (±19%) for protein, respectively. This study revealed low adherence to nutritional guidelines in patients treated for minor and major burn injuries. Compared to major burn injuries, lower documented adequacy for both energy and proteins was found in minor burn injuries. Given the disparity between guidelines and documented nutritional therapy, and the lack of specific guidelines for minor burn injuries, there could be a considerable risk of inadequate nutritional therapy post-burn injury.


Modeling the C. elegans nematode and its environment using a particle system.
A particle system, as understood in computer science, is a novel technique for modeling living organisms in their environment. Such particle systems have traditionally been used for modeling the complex dynamics of fluids and gases. In the present study, a particle system was devised to model the movement and feeding behavior of the nematode Caenorhabditis elegans in three different virtual environments: gel, liquid, and soil. The results demonstrate that distinct movements of the nematode can be attributed to its mechanical interactions with the virtual environment. These results also revealed emergent properties associated with modeling organisms within environment-based systems.


Narrowing of band gap and effective charge carrier separation in oxygen deficient TiO2 nanotubes with improved visible light photocatalytic activity.
Oxygen vacancies are introduced into hydrothermally processed TiO2 nanotube by vacuum calcination. Formation of oxygen vacancies modifies the local coordination in TiO2 as evident from Raman spectroscopy and secondary ion mass spectrometry (SIMS) results. The surface area is increased from 172.5m(2)/g in pure to 405.1m(2)/g in defective TiO2 nanotube. The mid-band gap electronic states created by oxygen vacancies are mostly responsible for the effective narrowing of band gap. Charge carrier separation is sufficiently prolonged as the charged oxygen defect states inhibit facile carrier recombination. With high surface area, narrowed band gap and separated charge carriers defective TiO2 nanotube is a suitable candidate in the photodegradation of methylene blue (MB) and phenol under visible light illumination. Photosensitized electron transfer from MB to the conduction band of TiO2 and the photodegradation of MB is facilitated in presence of high density of oxygen vacancies. Unlike MB, phenol absorbs in the UV region and does not easily excited under visible light. Phenol shows activity under visible light by forming charge transfer complex with TiO2. Defect trapped carriers become available at the phenol-TiO2 interface and finally interact with phenol molecule and degrade it.


Altered regulation of breathing after bilateral lung transplantation.
In our previous animal studies on dogs, regulation of breathing was found to be altered after en bloc transplantation of the heart and both lungs. During carbon dioxide (CO2) inhalation the minute volume was increased due to an increase of tidal volume after transplantation whereas before transplantation both respiratory frequency and tidal volume increased. The success of the heart-lung transplantation was based on experiments on baboons as no long-term survivors were obtained in dogs. It was thought that the regulation of breathing is different in dogs and primates. We therefore decided to study the regulation of breathing in humans after bilateral lung transplantation during CO2 stimulation. The regulation of breathing was tested 2 to 4 months after bilateral lung transplantation in six patients. Six healthy subjects with intact lungs were tested as controls. The test persons were allowed to breathe first room air, then 5% CO2 in air for 4 min and then room air again. The frequency of respiration, tidal volume and minute ventilation were recorded using a phneumotachograph. Simultaneously samples of arterial blood were drawn from a cannulated brachial artery for analysis of pressure of arterial oxygen (PaO2), pressure of arterial carbon dioxide (PaCO2), base excess (BE) and pH. During inhalation of CO2 for 4 min the minute volume doubled in both transplant patients and in controls. The tidal volume of the transplant patients increased significantly more than that of the controls (P < 0.005) whereas respiratory frequency increased significantly only in the controls with intact lungs (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Perinatal testicular torsion in siblings.
The management of perinatal torsion remains a controversial topic in pediatric urology. We present two cases of brothers diagnosed with perinatal torsion during the postnatal period. The first brother experienced bilateral torsion, with both testes found to be unsalvageable during emergent surgery on day 4 of life. Two years later the second brother was found on his newborn exam to have findings consistent with unilateral left testicular torsion. Emergent exploration was undertaken that confirmed the left testis to be necrotic. The contralateral testis was found to be normal and a fixation procedure was undertaken.


Building a better insect trap; An experimental investigation of prey capture in a variety of spider webs.
Web-building spiders (Araneae; Theridiidae, Linyphiidae, Araneidae) are catagorized as searchers because they devote a large amount of energy to the construction of the web which constitutes the search phase in the foraging sequence. In this study search energy is equated with the density of threads in a web and the effectiveness of a variety of webs in three broad catagories (tangle webs, sheet webs & orb webs) is tested in the light of current foraging theory. Within each web type there is a distinct thread density at which the number of approaching Drosophila (Diptera; Drosophilidae) that are captured is maximized (Figs. 1, 2, 3). That maximum results from a combination of factors that are a function of the density of threads in the web. The visibility of the web to an approaching Drosophila increases which acts to decrease the number of flies that enter the web (Tables 2, 3, 4). The ability of the web to detain a Drosophila that contacts it (capture efficiency) increases to an asymptote as a function of thread density (Fig. 4). These data support an assumption of many optimal foraging models that with increasing investment in search the predator receives a diminishing return.More Drosophila intercept orb webs than intercept sheet or tangle webs. In addition orb webs detain a greater proportion of the flies that contact them (Fig. 4). Sheet webs are intermediate between orb and tangle webs in their relative abilities to contact and detain Drosophila.


Effects of interferon and glatiramer acetate on cytokine patterns in multiple sclerosis patients.
Multiple sclerosis (MS) is an unpredictable autoimmune disease, which causes neurodegeneration in the central nervous system. Since the main cause of MS remains obscure, in this study, we aimed to evaluate the serum levels of some cytokines, including interleukin-5 (IL-5), IL-8, IL-9, IL-17A, transforming growth factor-beta (TGF-β), and interferon-gamma (IFN-γ) in relapsing-remitting (RR)-MS patients, treated with IFN-β and glatiramer acetate (GA). Serum samples of RR-MS patients, treated with high-dose IFN-β1a, low-dose IFN-β1a, IFN-β1b, and GA, were assessed by ELISA assay and then compared with the results of treatment-naive patients and healthy controls. The findings showed that the serum levels of IL-8, IL-9, and IFN-γ in treatment-naive patients were significantly higher than the healthy controls, while there was no significant difference in terms of other cytokines between the groups. A significant reduction was observed in the levels of IL-9 and IFN-γ, while there was a significant increase in TGF-β level among patients treated with GA. IFN-β1b resulted in a significant decline in the levels of IL-9 and TGF-β. In addition to these findings, some cytokines were positively correlated in different groups. Overall, the present results support the inflammatory and aggravating effects of IL-8, IL-9, and IFN-γ on MS. Furthermore, based on the results reported in the GA treatment group, we suggest GA as an effective treatment for RR-MS patients.


Primary cystic midline lesions of the brain in childhood.
It is known that primary cystic lesions of the midline of the brain in infants and children are not rare. In some cases these cystic lesions are considered to be the main cause in the production of hydrocephalus. The use of CT-scan tomography and CT scan metrizamide cisternography helped us to reveal some unsuspected cases of them. Our operative approach of these cystic lesions of the midline of the brain is described.


[Definition of the nomenclature for quality indices for medical equipment products].
The qualimetric approach to the definition of qualitative indices for the medical engineering products allows to propose five initial levels of the "index-tree" with the use of the indices nomenclature comprised in GOST--22.851-77. Due to the proposed method of the expert opinions' formal processing, classification structure of qualitative properties for these products has been revealed.


The legal liability of the medical consultant in pregnancy.
The potential for professional liability that accompanies complications associated with obstetric care can be minimized by an understanding of the roles and responsibilities of both the consultant and the obstetrician. Critical to this is a fundamental knowledge of the medical malpractice action from a legal perspective. This article discusses several issues involved in professional liability as it relates to the obstetrician/gynecologist.


Experimental sleep loss, racial bias, and the decision criterion to shoot in the Police Officer's Dilemma task.
Violent behavior, police brutality, and racial discrimination are currently at the forefront of society's attention, and they should be. We investigated whether mild sleep loss-as typical for many adults throughout the work week-could aggravate the socio-emotional-cognitive processes contributing to violence and discrimination. In a sample of 40 healthy young adults, we either experimentally restricted participants' sleep for four nights (6.2 h/night) or let participants obtain normal sleep (7.7 h/night)-and then had them complete the Police Officer's Dilemma Task. In this computerized task, the participant must rapidly decide to shoot or not shoot at White and Black men who either are or are not holding a gun. Results showed significant racial biases, including more and quicker shooting of Black targets compared to White targets. Furthermore, signal detection analyses demonstrated that mild sleep restriction changed participants' decision criterion, increasing the tendency to shoot, even when controlling for psychomotor vigilance, fluid intelligence, and self-reported desirability to behave in a socially acceptable manner. The increased tendency to shoot was also observed in participants who reported believing that they had adapted to the sleep loss. Future experimental research using trained police officers will help establish the generalizability of these laboratory effects. Importantly, sleep loss is modifiable via organization-level changes (e.g., shift scheduling, light entrainment) and individual-level interventions (e.g., sleep hygiene education, incentives for behavioral change), suggesting that if sleep loss is corrected, it could save lives-including Black lives.


Embryonic loss due to exposure to polycyclic aromatic hydrocarbons is mediated by Bax.
The high miscarriage rates observed in women smokers raises the possibility that chemicals in cigarette smoke could be detrimental to embryo development. Previous studies have established that polycyclic aromatic hydrocarbons (PAHs), transactivate the arylhydrocarbon receptor (AhR), leading to cell death. Herein we show that PAH exposure results in murine embryo cell death, acting as a potential mechanism underlying cigarette-smoking-induced pregnancy loss. Cell death was preceded by increases in Bax levels, activation of caspase-3 and decreased litter size. Chronic exposure of females to PAHs prior to conception impaired development, resulting in a higher number of resorptions. This embryonic loss could not be prevented by the disruption of Hrk, but was diminished in embryos lacking Bax. We conclude that exposure of early embryos to PAHs reduces the allocation of cells to the embryonic and placental lineages by inducing apoptosis in a Bax-dependent manner, thus compromising the developmental potential of exposed embryos.


Mission Tara Microplastics: a holistic set of protocols and data resources for the field investigation of plastic pollution along the land-sea continuum in Europe.
The Tara Microplastics mission was conducted for 7 months to investigate plastic pollution along nine major rivers in Europe-Thames, Elbe, Rhine, Seine, Loire, Garonne, Ebro, Rhone, and Tiber. An extensive suite of sampling protocols was applied at four to five sites on each river along a salinity gradient from the sea and the outer estuary to downstream and upstream of the first heavily populated city. Biophysicochemical parameters including salinity, temperature, irradiance, particulate matter, large and small microplastics (MPs) concentration and composition, prokaryote and microeukaryote richness, and diversity on MPs and in the surrounding waters were routinely measured onboard the French research vessel Tara or from a semi-rigid boat in shallow waters. In addition, macroplastic and microplastic concentrations and composition were determined on river banks and beaches. Finally, cages containing either pristine pieces of plastics in the form of films or granules, and others containing mussels were immersed at each sampling site, 1 month prior to sampling in order to study the metabolic activity of the plastisphere by meta-OMICS and to run toxicity tests and pollutants analyses. Here, we fully described the holistic set of protocols designed for the Mission Tara Microplastics and promoted standard procedures to achieve its ambitious goals: (1) compare traits of plastic pollution among European rivers, (2) provide a baseline of the state of plastic pollution in the Anthropocene, (3) predict their evolution in the frame of the current European initiatives, (4) shed light on the toxicological effects of plastic on aquatic life, (5) model the transport of microplastics from land towards the sea, and (6) investigate the potential impact of pathogen or invasive species rafting on drifting plastics from the land to the sea through riverine systems.


A Paradigm Shift in the Combination Changes of SARS-CoV-2 Variants and Increased Spread of Delta Variant (B.1.617.2) across the World.
Since September 2020, the SARS-CoV-2 variants have gained their dominance worldwide, especially in Kenya, Italy, France, the UK, Turkey, Indonesia, India, Finland, Ireland, Singapore, Denmark, Germany, and Portugal. In this study, we developed a model on the frequency of delta variants across 28 countries (R2= 0.1497), displaying the inheritance of mutations during the generation of the delta variants with 123,526 haplotypes. The country-wise haplotype network showed the distribution of haplotypes in USA (10,174), Denmark (5,637), India (4,089), Germany (2,350), Netherlands (1,899), Sweden (1,791), Italy (1,720), France (1,293), Ireland (1,257), Belgium (1,207), Singapore (1,193), Portugal (1,184) and Spain (1,133). Our analysis shows the highest haplotype in Europe with 84% and the lowest in Australia with 0.00001%. A model of scatter plot was generated with a regression line which provided the estimated rate of mutation, including 24.048 substitutions yearly. Our study concluded that the high global prevalence of the delta variants is due to a high frequency of infectivity, supporting the paradigm shift of the viral variants.