[Endobronchial brachytherapy: state of the art in 2013].
Endobronchial brachytherapy is an invasive technique, which allows localizing radioactive sources at the tumour contact. Therefore, high doses are administered to tumour while healthy tissues can be spared. Initially dedicated to a palliative setting, improvements helped reaching 60 to 88% symptoms alleviation and 30 to 100% of endoscopic macroscopic response. New diagnostic techniques and early diagnosis extended the indications to a curative intent: endoluminal primitive tumour, post radiation endobronchial recurrence, inoperable patients. CT-based dosimetry is a keypoint to optimize treatment quality and to minimize potential side effects, making this treatment a safe and efficient technique for specific indications.


Analysis of consultant decision-making in the management of prostate cancer.
The purpose of this study was to assess the consistency of decision-making among consultant urologists in the management of early prostate cancer. Thirty-two UK urology consultants completed a questionnaire containing 70 paper scenarios representing patients with early prostate cancer. Within these were 13 repeat cases to allow assessment of reliability of decision-making. Consultants demonstrated low reliability (on average 56-79%) when formulating decisions. None of the consultants used all of the available patient information when formulating treatment plans. The cue 'patient choice' was not used significantly by any of the consultants and the cue 'patient co-morbidity' was rarely used despite being crucial components of decision-making. These results are surprising and in general represent poor clinical practice. They also justify the increasing use of the multidisciplinary team and protocol-driven pathways to standardize and thus improve patient care.


An audit of physiotherapists' documentation on physical activity assessment, promotion and prescription to older adults attending out-patient rehabilitation.
Identify if physiotherapists document the assessment, promotion and prescription of physical activity to older adults attending out-patient rehabilitation and assist them in the transition to an active lifestyle. An audit of physiotherapists' documentation in medical records of older adults who attended an out-patient rehabilitation program at a tertiary hospital. Fifty-six medical records were reviewed. Mean age (SD) of participants was 79 (7) years. No documentation was found on the use of validated tools to assess physical activity levels of older adults. Prescription of physical activity was documented in 55/56 (98%) medical records. Seven (12.5%) medical records included documentation on goal setting regarding physical activity participation. Advice on regular physical activity post-discharge from the rehabilitation program was documented in 28/56 (50%) medical records. Formal referral to community-based physical activity programs was documented in 4/56 (7%) medical records. Evidence-practice gaps were found in physiotherapists' documentation of the promotion of physical activity to older adults attending out-patient rehabilitation, indicating a lack of assistance in the transition to an active lifestyle. These gaps were evident in the lack of; physical activity assessment, implementation of behaviour change strategies and formal referral to physical activity in the community post-discharge from out-patient rehabilitation.Implications for rehabilitationOur findings suggest that physiotherapists are not widely applying evidence-based practice to promote physical activity to older adults attending out-patient rehabilitation nor supporting them in the transition to engage in physical activity in the community post-discharge from rehabilitation program.Incorporating physical activity assessment and behaviour change strategies into usual care may enable physiotherapists to successfully promote physical activity to older adults attending out-patient rehabilitation.Collaboration between the health care system and community-based physical activity programs is imperative to facilitate the sustainability of an active lifestyle after discharge from rehabilitation program.


Laparoscopic splenectomy in children with sickle cell disease.
Sickle cell disease is a group of genetic disorders that are characterized by the production of hemoglobin S, anemia, and acute and chronic tissue damage secondary to blockages caused by abnormally shaped (i.e., sickle-shaped) red blood cells. In children, complications of sickle cell disease (e.g., splenic sequestration and splenomegaly) increase the risks for postoperative complications due to the physical stress of the large incisions previously require for splenectomy. An intracorporeal splenic fragmentation technique is now being used to avoid these complications and will be discussed in this article.


Chronic use of a GnRH agonist (deslorelin) or immunization against GnRH: effects on testicular function and sperm quality of bucks.
Chronic use of GnRH agonists and immunization against GnRH have been used as reversible contraceptive methods. The aim of this study was to compare the effectiveness of both treatments to inhibit reproductive function of adult bucks, in terms of strength and duration of the effects. We used 9 control untreated bucks (CON), 7 bucks treated chronically with a GnRH agonist (subcutaneous implants with 7.4 mg of deslorelin, Suprelorin, Virbac) (AGO), and another 7 bucks were immunized against GnRH (dose of 2 mL of Improvac-Zoetis with 300 μg of a synthetic incomplete analog of natural GnRH; 300 mg of diethylaminoethyl-dextran; and 2.0 mg of chlorocresol) (IMM). Testicular and sperm evaluations, testosterone concentrations, and male odor were determined from 4 wk before applying the treatments until 17 mo of their application. Scrotal circumference of CON (21.0 ± 0.1 cm) and IMM (21.2 ± 0.2 cm) was greater than that of AGO bucks (19.9 ± 0.2 cm) (P < 0.05 for each), without difference between CON and IMM bucks. Pixels' color intensity of testicular ultrasound images was not affected by treatment (general mean ± SEM: 116.0 ± 1.8). Testosterone concentration was greater in CON than AGO and IMM in months 3 and 4, greater in CON and IMM than AGO bucks in months 15 and 16, and greater in IMM than CON and AGO bucks in month 17 (P < 0.05 for all comparisons). Male odor was greater in CON (1.5 ± 0.0) than IMM bucks (1.3 ± 0.0) and greater in IMM than AGO (1.1 ± 0.0) bucks (P < 0.05 for each). Treatment negatively affected all the sperm variables: the total number of sperm in the ejaculate, sperm motility, sperm with normal morphology and sperm with integral membrane function. It was concluded that both treatments were effective in inhibiting the reproductive axis; however, neither of them produced azoospermia or decreased testosterone concentrations to undetectable levels. With both treatments, there were individual males exhibiting characteristics of fertility in all periods of the study. However, chronic use of a GnRH agonist seemed to be the most effective treatment in terms of duration and strength.


Subculture of rabbit articular chondrocytes within a collagen gel: growth and analysis of differentiation.
Primary cultures of rabbit articular chondrocytes have been subcultured within three-dimensional (3D) collagen gels. Under these conditions, the cells remained viable and divided, but with a lower proliferation rate than that observed in control monolayer cultures. Flow cytometric analysis of progression of the cells into the cell cycle has confirmed and extended these findings. Also the cellular volume was decreased in 3D-culture, being in the same range as thein vivo size of cartilage cells. Specific staining for proteoglycans and type II collagen immunolocalization on sections of gels showed the expression of differentiated phenotypes and revealed the accumulation of these matrix components in the immediate surroundings of the cells. The use of Ultroser G (a serum substitute) improved the conditions for 3D- culture of rabbit articular chondrocytes.


Three-dimensional assessment of the temporal bone and mandible deformations in patients with congenital aural atresia.
To investigate the deformations of temporal bone and mandible combined with congenital aural atresia. A total of 158 patients with congenital aural atresia were included in the study. The raw CT data of the temporal bone was imported into MIMICS v 12 and threshold dissection, region growing and three-dimensional (3D) calculation were used to calculate 3D models. The 3D characteristics of the temporal bone and upper part of mandible were assessed. The tympanic part of the temporal bone was all undeveloped. Of all the patients included, 14 patients were found to have severe maxillofacial malformations. Among them, 2 cases have floating arch, 4 cases have interrupted arch, 5 cases have mandibular processes hypoplasia and 3 cases have interrupted arch combined with severe maxillary malformation. Ten of the 14 patients were suffered from dysplasia of the mastoid part of the temporal bone as well. Maxillofacial malformations may sometimes coexist with congenital aural atresia. Otolaryngologists should not neglect the coexisted maxillofacial malformations and give timely referral to maxillofacial surgeons.


Salt stress limitation of seedling recruitment in a salt marsh plant community.
Seedling recruitment in salt marsh plant communities is generally precluded in dense vegetation by competition from adults, but is also relatively rare in disturbance-generated bare space. We examined the constraints on seedling recruitment in New England salt marsh bare patches. Under typical bare patch conditions seed germination is severely limited by high substrate salinities. We examined the germination requirements of common high marsh plants and found that except for one notably patch-dependent fugitive species, the germination of high marsh plants is strongly inhibited by the high soil salinities routinely encountered in natural bare patches. Watering high marsh soil in the greenhouse to alleviate salt stress resulted in the emergence of up to 600 seedlings/225 cm2. The vast majority of this seed bank consisted of Juncus gerardi, the only common high marsh plant with high seed set. We tested the hypothesis that salt stress limits seedling contributions to marsh patch secondary succession in the field. Watering bare patches with fresh water partially alleviated patch soil salinities and dramatically increased both the emergence and survival of seedlings. Our results show that seedling recruitment by high marsh perennial turfs is limited by high soil salinities and that consequently their population dynamics are determined primarily by clonal growth processes. In contrast, populations of patch-dependent fugitive marsh plants which cannot colonize vegetatively are likely governed by spatially and temporally unpredictable windows of low salinities in bare patches.


Time-matched analysis of DNA adduct formation and early gene expression as predictive tool for renal carcinogenesis in methylazoxymethanol acetate treated Eker rats.
Genotoxic carcinogens pose great hazard to human health. Uncertainty of current risk assessment strategies and long latency periods between first carcinogen exposure and diagnosis of tumors have raised interest in predictive biomarkers. Initial DNA adduct formation is a necessary step for genotoxin induced carcinogenesis. However, as DNA adducts not always translate into tumorigenesis, their predictive value is limited. Here we hypothesize that the combined analysis of pro-mutagenic DNA adducts along with time-matched gene expression changes could serve as a superior prediction tool for genotoxic carcinogenesis. Eker rats, heterozygous for the tuberous sclerosis (Tsc2) tumor suppressor gene and thus highly susceptible towards genotoxic renal carcinogens, were continuously treated with the DNA alkylating carcinogen methylazoxymethanol acetate (MAMAc). Two weeks of MAMAc treatment resulted in a time-dependent increase of O6-methylguanine and N7-methylguanine adducts in the kidney cortex, which was however not reflected by significant expression changes of cyto-protective genes involved in DNA repair, cell cycle arrest or apoptosis. Instead, we found a transcriptional regulation of genes involved in the tumor-related MAPK, FoxO and TGF-beta pathways. Continuous MAMAc treatment for up to 6 months resulted in a mild but significant increase of cancerous lesions. In summary, the combined analysis of DNA adducts and early gene expression changes could serve as a suitable predictive tool for genotoxicant-induced carcinogenesis.


The Identification and Analysis of MicroRNAs Combined Biomarkers for Hepatocellular Carcinoma Diagnosis.
Hepatocellular carcinoma (HCC) is a common malignant tumor with high morbidity and mortality globally. Compared with traditional diagnostic methods, microRNAs (miRNAs) are novel biomarkers with higher accuracy. We aimed to identify combinatorial biomarkers of miRNAs to construct a classification model for the diagnosis of HCC. The mature miRNA expression profile data of six cancers (liver, lung, gastric, breast, prostate, and colon) were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database with accession number GSE36915, GSE29250, GSE99417, GSE41970, GSE64333 and GSE35982. The messenger RNA (mRNA) expression profile data of these six cancers were obtained from TCGA. Three R software packages, student's t-test, and a normalized foldchange method were utilized to identify HCC-specific differentially expressed miRNAs (DEMs). Using all combinations of obtained HCC-specific DEMs as input features, we constructed a classification model by support vector machine searching for the optimal combination. Furthermore, target genes prediction was conducted on the miRWalk 2.0 website to obtain differentially expressed mRNAs (DEmRNAs), and KEGG pathway enrichment was analyzed on the DAVID website. The optimal combination consisted of four miRNAs (hsa-miR-130a-3p, hsa-miR-450b-5p, hsa-miR-136-5p, and hsa-miR-24-1-5p), of which the last one has not been currently reported to be relevant to HCC. The target genes of hsa-miR-24-1-5p (CDC7, ACACA, CTNNA1, and NF2) were involved in the cell cycle, AMPK signaling pathway, Hippo signaling pathway, and insulin signaling pathway, which affect the proliferation, metastasis, and apoptosis of cancer cells. Moreover, the area under the receiver operating characteristic curves of the four miRNAs were all higher than 0.85. These results suggest that the miRNAs combined biomarkers were reliable for the diagnosis of HCC. Hsa-miR-24-1-5p was a novel biomarker for HCC diagnosis identified in this study.


Effect of grain size on mechanical, surface and biological properties of microwave sintered hydroxyapatite.
Hydroxyapatite (HA) compacts having average grain sizes of 168±0.086 nm, 1.48±0.627 μm and 5.01±1.02 μm are processed from synthesized HA powder by microwave sintering at varying sintering temperature for different times. Superior mechanical and biological properties are shown by nano-grain HA compacts as compared to their micron grained counterparts. Compressive strength, indentation hardness, and indentation fracture toughness are increased with the decrease in HA grain size. The highest surface energy and maximum wettability are exhibited by nano-grain HA. HA compacts are assessed for cell-material interaction by SEM, MTT and immunochemistry assays using human osteoblast cell line for 1, 5 and 11 days. MTT assays showed higher number of living cells and faster proliferation on nano-grain HA surface. Osteoblast cells on nano-grain HA surface expressed significantly higher amount of vinculin and alkaline phosphatase (ALP) protein markers for cell adhesion and differentiation respectively. This study shows the effect of grain size on physical, mechanical and in vitro biological properties of microwave sintered HA compacts.


m1A within cytoplasmic mRNAs at single nucleotide resolution: a reconciled transcriptome-wide map.
Following synthesis, RNA can be modified with over 100 chemically distinct modifications. Recently, two studies-one by our group-developed conceptually similar approaches to globally map N1-methyladenosine (m1A) at single nucleotide resolution. Surprisingly, the studies diverged quite substantially in their estimates of the abundance, whereabouts, and stoichiometry of m1A within internal sites in cytosolic mRNAs: One study reported it to be a very rare modification, present at very low stoichiometries, and invariably catalyzed by TRMT6/61A. The other found it to be present at >470 sites, often at high levels, and suggested that the vast majority were highly unlikely to be TRMT6/61A substrates. Here we reanalyze the data from the latter study, and demonstrate that the vast majority of the detected sites originate from duplications, misannotations, mismapping, SNPs, sequencing errors, and a set of sites from the very first transcribed base that appear to originate from nontemplated incorporations by reverse transcriptase. Only 53 of the sites detected in the latter study likely reflect bona-fide internal modifications of cytoplasmically encoded mRNA molecules, nearly all of which are likely TRMT6/TRMT61A substrates and typically modified at low to undetectable levels. The experimental data sets from both studies thus consistently demonstrate that within cytosolic mRNAs, m1A is a rare internal modification where it is typically catalyzed at very low stoichiometries via a single complex. Our findings offer a clear and consistent view on the abundance and whereabouts of m1A, and lay out directions for future studies.


Neutrophil metabolomics in severe COVID-19 reveal GAPDH as a suppressor of neutrophil extracellular trap formation.
Severe COVID-19 is characterized by an increase in the number and changes in the function of innate immune cells including neutrophils. However, it is not known how the metabolome of immune cells changes in patients with COVID-19. To address these questions, we analyzed the metabolome of neutrophils from patients with severe or mild COVID-19 and healthy controls. We identified widespread dysregulation of neutrophil metabolism with disease progression including in amino acid, redox, and central carbon metabolism. Metabolic changes in neutrophils from patients with severe COVID-19 were consistent with reduced activity of the glycolytic enzyme GAPDH. Inhibition of GAPDH blocked glycolysis and promoted pentose phosphate pathway activity but blunted the neutrophil respiratory burst. Inhibition of GAPDH was sufficient to cause neutrophil extracellular trap (NET) formation which required neutrophil elastase activity. GAPDH inhibition increased neutrophil pH, and blocking this increase prevented cell death and NET formation. These findings indicate that neutrophils in severe COVID-19 have an aberrant metabolism which can contribute to their dysfunction. Our work also shows that NET formation, a pathogenic feature of many inflammatory diseases, is actively suppressed in neutrophils by a cell-intrinsic mechanism controlled by GAPDH.


Acyl-Trafficking During Plant Oil Accumulation.
Vegetable oils are an extremely important agricultural commodity. Their use has risen inexorably for the last 50 years and will undoubtedly be even more prevalent in the future. They have a role not only in foodstuffs but also as renewable chemicals. However, our understanding of their metabolism, and particularly its control, is incomplete. In this article we highlight current knowledge and its deficiencies. In particular, we focus on the important role that phosphatidylcholine plays in lipid accumulation and in influencing the quality of the vegetable oils produced.


Innate Immune Responses to Sporothrix schenckii: Recognition and Elimination.
Sporothrix schenckii (S. schenckii), a ubiquitous thermally dimorphic fungus, is the etiological agent of sporotrichosis, affecting immunocompromised and immunocompetent individuals. Despite current antifungal regimens, sporotrichosis results in prolonged treatment and significant mortality rates in the immunosuppressed population. The innate immune system forms the host's first and primary line of defense against S. schenckii, which has a bi-layered cell wall structure. Many components act as pathogen-associated molecular patterns (PAMPs) in pathogen-host interactions. PAMPs are recognized by pattern recognition receptors (PRRs) such as toll-like receptors, C-type lectin receptors, and complement receptors, triggering innate immune cells such as neutrophils, macrophages, and dendritic cells to phagocytize or produce mediators, contributing to S. schenckii elimination. The ultrastructure of S. schenckii and pathogen-host interactions, including PRRs and innate immune cells, are summarized in this review, promoting a better understanding of the innate immune response to S. schenckii and aiding in the development of protective and therapeutic strategies to combat sporotrichosis.


Neoadjuvant chemotherapy for locally advanced transitional cell carcinoma of the bladder: do local findings suggest a potential for salvage of the bladder?
Sixteen patients with locally advanced transitional cell carcinoma of the bladder were given two to four cycles of combination chemotherapy with methotrexate, vinblastine, doxorubicin hydrochloride (Adriamycin), and cisplatin (M-VAC) in an effort to reduce tumor size and enhance the potential for surgical resection. All patients had initial clinical staging (based on cystoscopy and cystoscopic biopsy, urine cytology, computed tomographic scanning, and excretory urography). Before each cycle, all patients had repeat clinical staging tests. Ten patients underwent postchemotherapy bilateral pelvic lymphadenectomy and radical cystoprostatectomy, and their bladders were examined histopathologically by step-sectioning techniques. One patient underwent abdominal exploration, bilateral pelvic lymphadenectomy, and ipsilateral partial cystectomy. Five patients had repeat clinical staging only without removal of their bladders. Of the 16 patients, 5 (31%) had residual invasive tumor and no tumor response. Three patients (19%) had a partial response, two of whom had only carcinoma in situ (one with prostatic duct involvement) and one of whom had stage pT1, NO, MO disease. Five patients (31%) had normal findings on computed tomographic scans, cystoscopy, biopsy, and urine cytology and thus had complete responses. In addition, 3 of 11 patients who underwent pathologic staging had no residual tumor on clinical and surgical staging and were complete responders. The overall (partial + complete) response rate was 69%, and the overall complete remission rate (pathologic + clinical staging) was 50%. These results suggest that the concept of possible salvage of the bladder with the current treatment program might be premature and must be applied selectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Mutational analysis of CD45. A leukocyte-specific protein tyrosine phosphatase.
The cytoplasmic domain of murine CD45 has been expressed using an in vitro transcription/translation system. The recombinant protein was isolated by immunoprecipitation with a specific rabbit antiserum and was shown to have protein tyrosine phosphatase (PTPase) activity. Oligonucleotide-directed mutagenesis was then used to investigate the structural requirements for PTPase activity. Although the cysteine crucial for PTPase activity resides in domain I, this domain was not active alone. Both PTPase domains of CD45 and the membrane proximal region of 77 amino acids were required for enzymatic activity. Deletion of 78 residues at the carboxyl terminus of the cytoplasmic region did not influence activity, but an additional deletion of 13 amino acids from PTPase domain II totally abolished activity. Excision of the 21-residue acidic insert in the second PTPase domain resulted in a decrease of activity of approximately 4-fold. Nine conserved residues around the critical cysteine in the first domain were found to be important for activity. Of the 3 conserved tyrosine residues in domain I, only Tyr729 was specifically required for activity.


Oesophageal intrasquamous IgG4 deposits: an adjunctive marker to distinguish eosinophilic oesophagitis from reflux oesophagitis.
To explore the utility of an IgG4 immunohistochemical stain to help distinguish eosinophilic oesophagitis from gastroesophageal reflux disease. We examined 21 cases of eosinophilic oesophagitis and 25 cases of gastroesophageal reflux disease. The diagnosis of eosinophilic oesophagitis was based on the presence of oesophageal dysfunction, >15 eosinophils per high-power field, and a lack of response to proton pump inhibitors. Gastroesophageal reflux disease showed intraepithelial eosinophils, but a clinical and/or histological response to proton pump inhibitor therapy. We also evaluated an additional cohort of 22 cases with intraepithelial eosinophils. Immunohistochemical staining for IgG4 was performed. Sixteen of 21 (76%) eosinophilic oesophagitis cases showed intrasquamous extracellular IgG4 deposits, whereas all 25 gastroesophageal reflux disease cases were negative. Mucosal IgG4-positive plasma cells were identified in eosinophilic oesophagitis and gastroesophageal reflux disease cases in 58% and 40% of cases, respectively. Eosinophilic oesophagitis patients receiving treatment were less likely to be positive for intraepithelial IgG4 deposits (88% versus 53%). In the validation cohort, the sensitivity and specificity for eosinophilic oesophagitis were 88% and 100%, respectively. The presence of intrasquamous IgG4 deposits is a useful adjunctive marker in the distinction between eosinophilic oesophagitis and gastroesophageal reflux disease.


Subclinical Cushing's syndrome.
Subclinical Cushing's syndrome (SCS) refers to subtle autonomous cortisol hypersecretion that is insufficient to generate the typical, clinically recognizable overt syndrome. Diagnosis of SCS is challenging. The combination of 1 mg overnight dexamethasone suppression test, serum ACTH level, and urinary cortisol level are used to diagnose SCS. Laparoscopic adrenalectomy is the treatment of choice for SCS. Patients with adrenal incidentalomas and SCS should be treated with perioperative steroids to prevent post-operative hypocortisolism.


Defined salmonella antigens for detection of cellular and humoral immune responses in salmonella infected calves.
Intracutaneous injection of a crude supernatant fraction from homogenised Salmonella typhimurium SVA 44 (O 4, 5, 12) or S dublin SVA 47 (O 9, 12) elicited highly significant (P less than 0.005) double skin-fold thickness increases in calves spontaneously infected with salmonella and verified as excretors. The use of isolated structurally defined outer membrane components from salmonella bacteria established that the delayed skin reactions could be elicited by either the lipopolysaccharide which contains O-antigenic polysaccharide chains homologous to the infecting strain, or an outer membrane protein fraction (porin). The porin preparation gave rise to skin reactions regardless of which salmonella serotype the calf was infected with. Histological examination of biopsy material indicated a delayed skin reaction. No such reactions were seen in biopsies from control calves. The use of lipopolysaccharide permitted a salmonella serogroup specific skin test although the endotoxic side effects were marked in doses above 50 micrograms. Purified O-antigen specific polysaccharides devoid of lipid A from S typhimurium (O 4, 12) or S enteritidis (O 9, 12) failed however to elicit skin reactions. Infected calves had humoral antibody titres against the O antigen of the infecting strain which were significantly (P less than 0.005) higher than those found in control calves.


Sampling and Characterization of Bioaerosols in Poultry Houses.
Two poultry Confined Animal Feeding Units (CAFUs), "House A" and "House B", were selected from the TAMU poultry facility for the study, and samples were collected over a five-day period. Bioaerosol sampling was conducted using a Wetted Wall Cyclone (WWC) bioaerosol collector at the two CAFU houses, in which House A housed approximately 720 broiler chickens and roosters, while House B remained unoccupied and served as a reference. Both houses consisted of 24 pens arranged on either side of a central walkway. Bacterial content analysis was conducted using microbial plating, real-time Polymerase Chain Reaction (PCR), and Fatty Acid Methyl Ester (FAME) analysis, while ambient temperature and relative humidity were also monitored. The concentrations of microorganisms in House A showed a highly dynamic range, ranging from 4000 to 60,000 colony forming units (CFU) per cubic meter of air. Second, the WWC samples contained approximately ten-fold more bacterial DNA than the filter samples, suggesting higher levels of viable cells captured by the WWC. Third, significant concentrations of pathogens, including Salmonella, Staphylococcus, and Campylobacter, were detected in the poultry facility. Lastly, the WWC system demonstrated effective functionality and continuous operation, even in the challenging sampling environment of the CAFU. The goal of this study was to characterize the resident population of microorganisms (pathogenic and non-pathogenic) present in the CAFUs and to evaluate the WWC's performance in such an environment characterized by elevated temperature, high dust content, and feathers. This knowledge could then be used to improve understanding microorganism dynamics in CAFUs including the spread of bacterial infections between animals and from animals to humans that work in these facilities, as well as of the WWC performance in this type of environment (elevated temperature, high content of dust and feathers). A more comprehensive understanding can aid in improving the management of bacterial infections in these settings.


Diagnostic and therapeutic considerations of myogenic tumors of the duodenum.
Three cases of duodenal myogenic tumor are described in detail. All the three were surgically treated and the final diagnoses were histologically established. The three consisted of two leiomyomas and one leiomyosarcoma. To make clinical diagnosis, roentgenologic, endoscopic, and angiographic examinations were empolyed. The selective angiography was more reliable than endoscopic biopsy to make a differential diagnosis whether a tumor was benign or malignant. Surgical procedures were required not only for malignant myomatous lesions but also for benign lesions because the latter also produce a high incidence of hemorrhage from ulceration of the tumor. Out of the three cases, one was successfully treated by enucleation but the other two were undergone more extensive surgery such as a Whipple's procedure or wide resection of the duodenal wall with side-to-side duodenojejunostomy. Operative techniques are discussed in detail basing on the biological characteristics, location, and size of the tumor.


Hypertrophic osteopathy associated with hepatocellular carcinoma in a dog.
A 9-year-old spayed female dog diagnosed with hepatocellular carcinoma and hypertrophic osteopathy was negative for additional lesions on computed tomography of the thorax and abdomen. Resection of the affected liver lobe resulted in resolution of clinical signs. This is the first case of hypertrophic osteopathy secondary to hepatocellular carcinoma.


Testosterone promotion effect of Eucommia ulmoides staminate flower via the steroidogenic pathway and potential hormonal mechanism.
Eucommia ulmoides staminate flowers (EUF), a newly approved functional food in China, have great potential for hormonal regulation. Herein, we aim to demonstrate the chemical composition and pharmacological activity of EUF in testosterone production and hormonal regulation. EUF extract and its components, kaempferol and geniposidic acid, exhibited a strong stimulating effect by increasing testosterone secretion, reducing ROS production, or promoting viability in Leydig cells. Meanwhile, the increased testosterone production was related to the upregulation of mRNA and protein expression of the steroidogenic pathway, such as steroidogenic acute-regulatory protein (StAR), 3β -hydroxysteroid dehydrogenase type 1 (HSD3B1), 17α-hydroxylase/17,20-lyase (CYP17A1), and nuclear receptor subfamily 5 group A member 1 (NR5A1). However, PKA inhibitor H89 or adenylyl cyclase inhibitor SQ22536 could block their effect. The results of transgenic yeast models showed the androgenic agonistic effects of kaempferol and naringenin and the estrogenic agonistic effects of rutin. These results indicated that the testosterone promotional effect of EUF was related to the activation of the steroidogenic pathway and potential hormonal regulation. Kaempferol and geniposidic acid might be the key active ingredients.


Effects of Stem Cell Therapy on Diabetic Mellitus Erectile Dysfunction: A Systematic Review and Meta-analysis.
Stem cell is considered a potential therapy for treating erectile dysfunction (ED), including diabetic mellitus erectile dysfunction (DMED), which was investigated in some preclinical studies. Several trials introduced stem cell into clinical practice, but divergences emerged. To further investigate the therapeutic effects of stem cell on DMED in preclinical studies and investigate some possible factors that influence curative effects. The literature research was conducted in Web of Science and PubMed to retrieve studies utilizing stem cell to treat DMED. Revman 5.3 was used to perform subgroup analysis of intracavernosal pressure/mean artery pressure (ICP/MAP) and structural changes. Publication bias was assessed with Egger's test, funnel plot, and sensitivity analysis by Stata 15.0. The ICP/MAP and structural changes before and after stem cell treatment. Of 2,115 studies retrieved, 23 studies are eligible. Plus 10 studies from a meta-analysis published in 2016, 33 studies were enrolled. Pooled analysis showed that stem cell ameliorates damaged ICP/MAP (WMD 0.26; 95% CI 0.23-0.29; P < .001) and structural changes induced by diabetes. Subgroup analysis indicated that adipose-derived mesenchymal stem cell (ADSC) may have better efficacy than bone marrow-derived mesenchymal stem cell (BMSC) (χ2= 4.21, P = .04; ADSC WMD 0.28, 95% CI [0.24-0.32] vs BMSC WMD 0.22 95% CI [0.17-0.26]). Transplantation type, diabetes type, and cell number make no difference to curative effects. Gene modification and therapy combination proved promising in improving the therapeutic effects of stem cell. The evidence reminded that ADSC may be prior to BMSC in clinical trials and autotransplantation is probably not compulsory in the clinical practice of stem cell. The study number and sample size are large enough. However, high degree of heterogeneity remains after subgroup analysis. This meta-analysis suggests the efficacy of stem cell therapy for DMED and the possible superiority of ADSC over BMSC in erection restoration and structure renovation. Yao C, Zhang X, Yu Z, et al., Effects of Stem Cell Therapy on Diabetic Mellitus Erectile Dysfunction: A Systematic Review and Meta-analysis. J Sex Med 2022;19:21-36.


Ligand-induced coupling versus receptor pre-association: cellular automaton simulations of FGF-2 binding.
The binding of basic fibroblast growth factor (FGF-2) to its cell surface receptor (CSR) and subsequent signal transduction is known to be enhanced by heparan sulfate proteoglycans (HSPGs). HSPGs bind FGF-2 with low affinity and likely impact CSR-mediated signaling via stabilization of FGF-2-CSR complexes via association with both the ligand and the receptor. What is unknown is whether HSPG associates with CSR in the absence of FGF-2. In this paper, we determine conditions by which pre-association would impact CSR-FGF-2-HSPG triad formation assuming diffusion-limited surface reactions. Using mean-field rate equations, we show that (i) when [HSPG] is much higher than [CSR], the presence of pre-formed complexes does not affect the steady state of FGF-2 binding, and (ii) when the concentrations are comparable, the presence of pre-formed complexes substantially increases the steady-state concentration of FGF-2 bound to CSR. These findings are supported by explicit cellular automaton simulations, which justify the mean-field treatment. We discuss the advantages of such a two-receptor system compared to a single-receptor model, when the parameters are comparable. Further, we speculate that the observed high concentration of HSPG in intact cells ([HSPG]-100[CSR]) provides a way to ensure that the binding levels of FGF-2 to its signaling receptor remains high, irrespective of the presence of pre-formed CSR-HSPG complexes on the cell surface, while allowing the cell to finely tune the response to FGF-2 via down-regulation of the signaling receptor.


First do no harm: Measuring weight bias beliefs in preschool-age children.
Although the importance of investigating the development of weight bias in young children has been documented, little research has examined potential impacts of children's participation in such research. The purpose of the current study was to assess whether participation in research measuring beliefs about body size may engender changes in the development of weight beliefs in young children. Eighty children (44 boys, 36 girls), ages 3-5 (M = 3.73, SD =0.69) participated in tasks assessing weight bias beliefs and perception of their own body size at two time periods (two weeks apart). Participants' responses at Time 2 were also compared to data collected from a similar sample who completed the measures only once. Results demonstrated main effects of gender (girls reporting greater weight bias) and age (older children reporting greater weight bias)) across time points that are consistent with prior research. Importantly, there was no change in participants' responses from Time 1 to Time 2 and no significant differences between Time 2 data and data collected from participants who only completed the measures at one time period, suggesting that participation in such research may not pose undue risks to young children.


Association of gestational age with MRI-based biometrics of brain development in fetuses.
Reported date of last menstrual period and ultrasonography measurements are the most commonly used methods for determining gestational age in antenatal life. However, the mother cannot always determine the last menstrual period with certainty, and ultrasonography measurements are accurate only in the first trimester. We aimed to assess the ability of various biometric measurements on magnetic resonance imaging (MRI) in determining the accurate gestational age of an individual fetus in the second half of gestation. We used MRI to scan a total of 637 fetuses ranging in age from 22 to 40 gestational weeks. We evaluated 9 standard fetal 2D biometric parameters, and regression models were fitted to assess normal fetal brain development. A stepwise linear regression model was constructed to predict gestational age, and measurement accuracy was determined in a held-out, unseen test sample (n = 49). A second-order polynomial regression model was found to be the best descriptor of biometric measures including brain bi-parietal diameter, head circumference, and fronto-occipital diameter in relation to normal fetal growth. Normal fetuses showed divergent growth patterns for the cerebrum and cerebellum, where the cerebrum undergoes rapid growth in the second trimester, while the cerebellum undergoes rapid growth in the third trimester. Moreover, a linear model based on biometrics of brain bi-parietal diameter, length of the corpus callosum, vermis area, transverse cerebellar diameter, and cerebellar area accurately predicted gestational age in the second and third trimesters (cross-validation R2 = 0.822, p < 0.001). These results support the use of MRI biometry charts to improve MRI evaluation of fetal growth and suggest that MRI biometry measurements offer a potential estimation model of fetal gestational age in the second half of gestation, which is vital to any assessment of pregnancy, fetal development, and neonatal care.


Cellulitis as a manifestation of miliary tuberculosis in a renal transplant recipient.
Cutaneous involvement is an unusual presentation of tuberculosis (TB) and is rarely reported in renal transplant recipients. We describe a 37-year-old renal transplant recipient with disseminated Mycobacterium tuberculosis infection that presented as cellulitis. The organism was isolated from tissue and blood cultures. The patient was treated with quadruple anti-TB therapy for 12 months. Anti-TB therapy led to a complete resolution of TB lesions. We also provide a review of the literature on cutaneous TB in renal transplant recipients. Skin TB in renal transplant recipients usually occurs with nontuberculous mycobacteria. The spectrum of the skin lesions can be quite different and can mimic bacterial infections. Mycobacteriosis should always be included in the differential diagnosis of a skin lesion in renal transplant recipients.


Specificity of asbestos-induced chromosomal aberrations in short-term cultured human mesothelial cells.
Short-term cultured normal human mesothelial cells were exposed for 48 hours to three different asbestos compounds, crocidiolite, chrysotile, and amosite. In the concentration used (0.01 mg/ml) all three asbestiform minerals caused, within a few days, a significant increase of cells showing numerical and/or structural abnormalities. The abnormalities were analyzed in detail using banding techniques. The results were compared with the cytogenetic observations in 52 published cases of mesotheliomas. This comparison revealed only a few similarities as regards numerical deviations. The structural rearrangements in asbestos-exposed cultures, however, in many instances involved chromosome types and chromosome regions preferentially affected in mesotheliomas.


The production of CXCR3-agonistic chemokines by synovial fibroblasts from patients with rheumatoid arthritis.
The inflamed synovial tissue of rheumatoid arthritis (RA) is characterized by an infiltration with Th1 cells that predominantly express the chemokine receptors CXCR3 and CCR5. In this study, we investigated the production of the CXCR3-agonistic chemokines CXCL9, CXCL10, and CXCL11 by synovial tissue cells and synovial fibroblast-cell lines (fourth or fifth passage) from RA patients. Concentrations of all CXCR3 ligands in synovial fluids were markedly higher in RA patients than in osteoarthritis (OA) patients. Synovial tissue cells from RA patients more strongly expressed mRNAs for CXCR3 ligands and spontaneously secreted larger amounts of these chemokine proteins than the cells from OA patients. The mRNA expression of all CXCR3 ligands was induced in synovial fibroblasts from RA patients after stimulation with interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), or interleukin-1 beta (IL-1beta). However, synovial fibroblasts significantly secreted CXCL9 and CXCL10 proteins, but not CXCL11 protein, after IFN-gamma stimulation and secreted only CXCL10 protein after TNF-alpha or IL-1beta stimulation. When stimulated with a combination of IFN-gamma and TNF-alpha, these cells were able to secrete large amounts of all three chemokines. These results indicate that synovial fibroblasts may be involved in perpetuating the Th1 immune response by producing the Th1-associated CXCR3 ligands, and the synergistic effect of IFN-gamma and TNF-alpha may be important for their chemokine production in RA joints.


Improvement in the assessment of diastolic function in a clinical echocardiography laboratory following implementation of a quality improvement initiative.
The aim of this study was to demonstrate improvement in the characterization of diastolic function in the routine practice of a clinical echocardiography laboratory after the implementation of a quality improvement initiative. The echocardiographic analysis of left ventricular (LV) diastolic dysfunction is an inherently complex process involving the integration of multiple indices for accurate assessment. A baseline survey of 50 randomly chosen echocardiographic studies was reviewed for the accuracy of diastolic function assessment. A four-step quality improvement protocol was then initiated: (1) sonographer and physician education; (2) the implementation of data acquisition protocol changes using LV inflow, tissue Doppler velocity of the mitral annulus in early diastole (e'), flow propagation velocity of LV inflow (Vp), and left atrial volume index (LAVI), along with the establishment of uniform criteria for diagnostic interpretation; (3) peer review of performance; and (4) focused interactive case review sessions. At baseline, measurements of LV inflow were most often correct (100% accurate), while measurements of e' (82% accurate), Vp (12% accurate), and LAVI (12% accurate) and the proper classification of diastolic function (44% accurate) were significantly limited. After the quality improvement initiative, there were significant increases in the accuracy of all recorded measurements, with e' 92% accurate (a 10% improvement; P < .10), Vp 67% accurate (a 55% improvement; P < .001), LAVI 80% accurate (a 68% improvement, P < .001), and proper characterization of diastolic function 76% accurate (a 32% improvement, P < .001). A multifaceted quality improvement protocol including staff education, systematic support with enhanced infrastructure, and peer review with feedback can be effective for improving the clinical performance of a nonacademic echocardiography laboratory in the characterization of diastolic function.


Glucagon-like peptide 1 (GLP-1) receptor agonists as a protective factor for incident depression in patients with diabetes mellitus: A systematic review.
Glucagon-like peptide 1 (GLP-1) receptor agonists are widely used for glycemic control in patients with diabetes mellitus (DM) and are primarily indicated for type 2 diabetes mellitus (T2DM). GLP-1 receptor agonists have also been shown to have neuroprotective and antidepressant properties. Replicated evidence suggests that individuals with DM are significantly more likely to develop depression. Herein, we aim to investigate whether GLP-1 receptor agonists can be used prophylactically on patients with DM to lower the risk of incident depression. We conducted a systematic search for English-language articles published on the PubMed/MEDLINE, Scopus, Embase, APA, PsycInfo, Ovid and Google Scholar databases from inception to June 6, 2022. Four retrospective observational studies were identified that evaluated the neuroprotective effects of GLP-1 receptor agonists on incident depression in patients with DM. We found mixed results with regards to lowering the risk of incident depression, with two studies demonstrating a significant reduction in risk and two studies showing no such effect. A single study found that dulaglutide may lower susceptibility to depression. Our results were limited by high interstudy heterogeneity, paucity of literature, and lack of controlled trials. While we did not find evidence of GLP-1 receptor agonists significantly lowering risk of incident depression in patients with DM, promising neuroprotective data presented in two of the included papers, specifically on dulaglutide where information is scarce, provide the impetus for further investigation. Future research should focus on better elucidating the neuroprotective potential of different classes and doses of GLP-1 receptor agonists using controlled trials.


Effects of successful parathyroidectomy on neuropsychological and cognitive status in patients with asymptomatic primary hyperparathyroidism.
Besides typical clinical symptoms, primary hyperparathyroidism (pHPT) is associated with impaired quality of life and cognitive status. The aim of this study was to evaluate the quality of life and cognitive impairment in patients with pHPT, before and after parathyroidectomy. We conducted a panel study, which included asymptomatic pHPT patients scheduled for parathyroidectomy. Besides demographic and clinical data, patients' quality of life and cognitive capacity were recorded before, 1 month, and 6 months following parathyroidectomy using the Short Form 36 questionnaire (RAND-36), Beck Depression Inventory (BDI), Depression Anxiety Stress Scales (DASS), Mini-Mental State Examination (MMSE), and Symptom Check List 90-revised version (SCL90R). During a 2-year follow-up, 101 patients entered the study (88 women), with an average age of 60.7 years. The Global score of RAND-36 test ameliorated by almost 50% 6 months after parathyroidectomy. The most sustained subscores of the RAND-36 test were role functioning/physical and health change, with an improvement of more than 125%. According to the BDI, DASS depression subscore, and SCL90R depression subscore, the extent of depressive symptoms reduction was approximately 60% 6 months postoperatively. The level of anxiety was reduced by 62.4%, measured by both the DASS and SCL90R anxiety subscores. The stress level was almost halved according to the DASS stress subscore (from 10.7 to 5.6 points). The results of the MMSE test showed a significant improvement postoperatively, for 1.2 points (4.4%). A worse preoperative score of each tool was related to the higher magnitude of improvement 6 months after parathyroidectomy. A considerable number of pHPT patients, even without other typical symptoms, show signs of impaired quality of life and neurocognitive status preoperatively. After a successful parathyroidectomy, there is an improvement in quality of life, declined levels of depression, anxiety, and stress, as well as amelioration of cognitive status. Patients with more impaired quality of life and pronounced neurocognitive symptoms may expect more benefits from the surgery.


Hollow fiber-based liquid-liquid-liquid microextraction combined with high-performance liquid chromatography for the speciation of organomercury.
A novel and extremely highly sensitive method for the speciation of organomercury in sea food and environmental water samples was developed by hollow fiber liquid-liquid-liquid microextraction (LLLME) coupled to high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection at 254 nm. By the use of toluene filled the pores of the hollow fiber wall as the organic phase and Na(2)S(2)O(3) aqueous solution in the lumen of hollow fiber as acceptor phase, the simultaneous preconcentration of methylmercury (MeHg), ethylmercury (EtHg), and phenylmercury (PhHg) could be realized, and the target mercury species in the post-extraction acceptor phase were directly injected into HPLC for their separation. The factors affecting on the liquid-liquid-liquid microextraction of three organomercury species, including organic solvent, the pH of donor phase, the concentration of complexing agent, extraction time and stirring rate were investigated and the optimal extraction conditions were established. With the consumption of 3.8 mL of sample solution, the enrichment factors were about 120, 215 and 350 for MeHg, EtHg, and PhHg, respectively. The limits of detection were in the range of 0.3-3.8 ng mL(-1) (as Hg) with precisions (RSDs (%), c=30 ng mL(-1) (as Hg), n=7) ranging from 6.4 to 8.9%. The developed technique was validated by analyzing a certified reference material (DORM-2, dogfish-muscle, NRCC) and an environmental water sample, and the analytical results were satisfactory.


The Ethics of Geoengineering: A Literature Review.
Geoengineering as a technological intervention to avert the dangerous climate change has been on the table at least since 2006. The global outreach of the technology exercised in a non-encapsulated system, the concerns with unprecedented levels and scales of impact and the overarching interdisciplinarity of the project make the geoengineering debate ethically quite relevant and complex. This paper explores the ethical desirability of geoengineering from an overall review of the existing literature on the ethics of geoengineering. It identifies the relevant literature on the ethics of geoengineering by employing a standard methodology. Based on various framing of the major ethical arguments and their subsets, the results section presents the opportunities and challenges at stake in geoengineering from an ethical point of view. The discussion section takes a keen interest in identifying the evolving dynamics of the debate, the grey areas of the debate, with underdeveloped arguments being brought to the foreground and in highlighting the arguments that are likely to emerge in the future as key contenders. It observes the semantic diversity and ethical ambiguity, the academic lop-sidedness of the debate, missing contextual setting, need for interdisciplinary approaches, public engagement, and region-specific assessment of ethical issues. Recommendations are made to provide a useful platform for the second generation of geoengineering ethicists to help advance the debate to more decisive domains with the required clarity and caution.


Correction to: Quality of care evaluation in non-functioning pituitary adenoma with chiasm compression: visual outcomes and timing of intervention clinical recommendations based on a systematic literature review and cohort study.
The original version of the article unfortunately contained an error in Figure 2. The term 'Refer within 3 days' should read 'Refer as soon as possible'. Corrected version of Figure 2 is given below.


Assessment of longitudinal brain development using super-resolution magnetic resonance imaging following fetal surgery for open spina bifida.
Prenatal surgery is offered for selected fetuses with open spina bifida (OSB) to improve long-term outcome. We studied the effect of fetal OSB surgery on brain development using advanced magnetic resonance imaging (MRI) techniques to quantify the volume, surface area and shape of cerebral structures and to analyze surface curvature by means of parameters that correspond to gyrification. We compared MRI data from 29 fetuses with OSB before fetal surgery (mean gestational age (GA), 23 + 3 weeks) and at 1 and 6 weeks after surgery, with that of 36 GA-matched control fetuses (GA range, 21 + 2 to 36 + 2 weeks). Automated super-resolution reconstruction provided three-dimensional isotropic volumetric brain images. Unmyelinated white matter, cerebellum and ventricles were segmented automatically and refined manually, after which volume, surface area and shape parameter (volume/surface area) were quantified. Mathematical markers (shape index (SI) and curvedness) were used to measure gyrification. Parameters were assessed according to lesion type (myelomeningocele vs myeloschisis (MS)), postoperative persistence of hindbrain herniation (HH) and the presence of supratentorial anomalies, namely partial agenesis of the corpus callosum (pACC) and heterotopia (HT). Growth in ventricular volume per week and change in shape parameter per week were higher at 6 weeks after surgery in fetuses with OSB compared with controls (median, 2500.94 (interquartile range (IQR), 1689.70-3580.80) mm3 /week vs 708.21 (IQR, 474.50-925.00) mm3 /week; P < 0.001 and 0.075 (IQR, 0.047-0.112) mm/week vs 0.022 (IQR, 0.009-0.042) mm/week; P = 0.046, respectively). Ventricular volume growth increased 6 weeks after surgery in cases with pACC (P < 0.001) and those with persistent HH (P = 0.002). During that time period, the change in unmyelinated white-matter shape parameter per week was decreased in OSB fetuses compared with controls (0.056 (IQR, 0.044-0.092) mm/week vs 0.159 (IQR, 0.100-0.247) mm/week; P = 0.002), particularly in cases with persistent HH (P = 0.011), MS (P = 0.015), HT (P = 0.022), HT with corpus callosum anomaly (P = 0.017) and persistent HH with corpus callosum anomaly (P = 0.007). At 6 weeks postoperatively, despite OSB fetuses having a lower rate of change in curvedness compared with controls (0.061 (IQR, 0.040-0.093) mm-1 /week vs 0.094 (IQR, 0.070-0.146) mm-1 /week; P < 0.001), reversing the trend seen at 1 week after surgery (0.144 (IQR, 0.099-0.236) mm-1 /week vs 0.072 (IQR, 0.059-0.081) mm-1 /week; P < 0.001), gyrification, as determined using SI, appeared to be increased in OSB fetuses overall compared with controls. This observation was more prominent in fetuses with pACC and those with severe ventriculomegaly (P-value range, < 0.001 to 0.006). Following fetal OSB repair, volume, shape and curvedness of ventricles and unmyelinated white matter differed significantly compared with those of normal fetuses. Morphological brain changes after fetal surgery were not limited to effects on the circulation of cerebrospinal fluid. These observations may have implications for postnatal neurocognitive outcome. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


The impact of influenza on the ability to work, volunteer and provide care: results from an online survey of Canadian adults 50 years and older.
Influenza is associated with a decline in functional abilities among Canadian older adults, although specific impacts on daily life have not been fully explored. In August 2019 and May 2020, we conducted surveys of Canadian adults 50-64 years and 65 years and older through an online market research platform. The survey included questions about the impact of diagnosed influenza or self-reported influenza-like-illness (ILI) on working, volunteering and caregiving. We surveyed 1006 adults in the 50-64 year age group about the 2018/19 season and 1001 about the 2019/20 season. In the 65 years and older age group, we surveyed 3548 and 3500 individuals about the 2018/19 and 2019/20 influenza seasons, respectively. In each season, nearly two-thirds of individuals 50-64 years with influenza/ILI were employed; 51.7% reported absenteeism in 2018/19 and 53.6% in 2019/20. Of the 20% of individuals 65 years and older who were employed, 47.0% of those with influenza/ILI were absent while ill in 2018/19 (39.8% in 2019/20). In 2018/2019, 29.6% of respondents 50-64 years old with influenza/ILI identified as volunteers (29.3% in 2019/2020). In both seasons, nearly half were unable to do so while ill. Of the 164 (32.7%) individuals 65 years and older who volunteered during the 2018/19 season, 80 (48.8%) did not while ill; 224 (37.3%) respondents volunteered in the 2019/20 season, and half were absent while ill. Of those 50-64 years with influenza/ILI, 97 (42.2%) and 57 (22.2%) were caregivers in 2018/19 and 2019/20, respectively. In 2018/19 and 2019/20, 40 (41.2%) and 28 (49.1%) caregivers were unable to provide care when ill, respectively. Of those with influenza/ILI in the 65 years and older age group, 123 (24.6%) and 162 (27.0%) were caregivers in 2018/19 and 2019/20, respectively. In 2018/19, 18 (14.6%) caregivers with influenza/ILI did not provide care while ill (42 [25.9%] in 2019/20). In Canadian older adults, influenza and ILI had notable impacts on ability to volunteer and provide care across two recent seasons. Optimization of influenza prevention in this population may yield important societal benefits.


Older living donors provide excellent quality kidneys: a single center experience (older living donors).
The role of advanced age live donors remains controversial because of decline in glomerular filtration rate and perceived increased risks of perioperative complications. A retrospective review of all live donor transplants performed from January 2000 to December 2003. Seventy-eight live donor transplants were performed during the period of review, 47 (60.3%) female and 31 (39.7%) male. Twenty-two (28.2%) of the donors were >50 yr old, 15 (68%) female and seven (32%) male. Living related donation was performed in 56 (74.4%) and unrelated in 20 (35.6%). Laparoscopic nephrectomy was performed in 29 (37.2%) and open nephrectomy in 49 (62.8%). More donors >50 underwent laparoscopic nephrectomy, 13 of 22 (59.1%) vs. 16 of 56 (28.6%). Overall patient and graft survival at 1 yr are 97 and 97%. One-year patient and graft survival is 100% vs. 96% and 100% vs. 96% in the older vs. young donors. Rejection occurred in nine of 78 (11.5%), but was not different between groups. Older donors had a reduced creatinine clearance 107.5 +/- 3.4 vs. 124.2 +/- 3.1 mL/min (p = 0.002) and a reduced clearance normalized for body surface area 60.6 +/- 3.6 mL/(min m2) vs. 70.2 +/- 2.6 mL/(min m2) (p = 0.045). Recipient serum creatinine was higher on postoperative day 1 in the older donor group 5.4 mg/dL vs. 4.4 mg/dL (p = 0.009). There was no difference in recipient serum creatinine at postoperative day 7, 30, 90, 180, 365 and 730. Donor serum creatinine was not different between groups on postoperative days 1, 7 and 30 but was higher in group 1 vs. group 2 on postoperative day 365, 1.26 +/- 0.26 mg/dL vs. 1.01 +/- 0.18 mg/dL (p = 0.020). Despite a reduced initial creatinine clearance, renal function is comparable in recipients of both young and old donor kidneys. Older donors had a slightly reduced serum creatinine 1 yr post-donation that warrants additional follow-up to determine if the observations continue. The introduction of laparoscopic nephrectomy may provide additional incentive for older donors to present for live donor nephrectomy.


90-Day Return Visit to the Emergency Department After an Initial Neurosurgical Evaluation.
This study evaluated emergency department (ED) neurosurgical reevaluation rates and their causes. Identifying the most significant reasons that make patients return to the ED for a neurosurgical reevaluation can help implement changes to reduce the economic and medical burden of patient turnover. All patients undergoing neurosurgical reevaluation at our institution's ED after an initial neurosurgical evaluation were enrolled in a prospective 3-month longitudinal registry. Inclusion criteria were all adult patients 21 years of age or older previously evaluated by neurosurgery at our institution's ED who return within 90 days for a neurosurgical reevaluation. We found an overall 90-day ED neurosurgical return visit rate of 2.1%. During the study, 34 patients returned to the ED for a neurosurgical reevaluation. Patients returned for a neurosurgical reevaluation at a median of 23.5 days after the initial neurosurgery evaluation. The principal causes for a return visit were altered mental status, headache, and wound infections. Among the returning patients, 59% required hospitalization and 50% required an operation. To our knowledge, this is the first study to prospectively collect data to estimate the 90-day ED return visit rate for a neurosurgical reevaluation following an initial ED neurosurgical evaluation. Some patients still use the ED to get continued care of their condition despite having access to their primary care physician. Better communication, social worker coordination, and prompt follow-up appointments at the neurosurgical outpatient clinic may reduce return visits.


Lipid nanocarriers for microRNA delivery.
Non-coding RNAs (ncRNAs) like microRNAs (miRNAs) or small interference RNAs (siRNAs) with their power to selectively silence any gene of interest enable the targeting of so far 'undruggable' proteins and diseases. Such RNA molecules have gained much attention from biotech and pharmaceutical companies, which led to the first Food and Drug Administration (FDA) approved ncRNA therapeutic in 2018. However, the main barrier in clinical practice of ncRNAs is the lack of an effective delivery system that can protect the RNA molecules from nuclease degradation, deliver them to specific tissues and cell types, and release them into the cytoplasm of the targeted cells, all without inducing adverse effects. For that reason, drug delivery approaches, formulations, technologies and systems for transporting pharmacological ncRNA compounds to achieve a diagnostic or therapeutic effect in the human body are in demand. Here, we review the development of therapeutic lipid-based nanoparticles for delivery of miRNAs, one class of endogenous ncRNAs with specific regulatory functions. We outline challenges and opportunities for advanced miRNA-based therapies, and discuss the complexity associated with the delivery of functional miRNAs. Novel strategies are addressed how to deal with the most critical points in miRNA delivery, such as toxicity, specific targeting of disease sites, proper cellular uptake and endosomal escape of miRNAs. Current fields of application and various preclinical settings involving miRNA therapeutics are discussed, providing an outlook to future clinical approaches. Following the current trends and technological developments in nanomedicine exciting new delivery systems for ncRNA-based therapeutics can be expected in upcoming years.


Regional and segmental differences in the embryonic expression of a putative leech Hox gene, Lox2, by central neurons immunoreactive to FMRFamide-like neuropeptides.
We performed immunofluorescence experiments using a rat polyclonal antibody on formaldehyde-fixed whole-mount embryos to characterize the expression of a putative leech Hox gene, Lox2, during embryonic development. The main goal was to determine whether the differentiation of subsets of FMRFamide-like immunoreactive (FLI) neurons coincide with the expression domain of Lox2. The earliest expression of Lox2 was detected in relatively large, prominent nuclei in the posterior region at embryonic day 4, a very early stage. Lox2 expression was also detected in subsets of central neurons (neurons located in the CNS) located in midbody ganglia 6 (M6)-M21. In addition, Lox2 was expressed by a number of segment-specific and segmentally repeated central FLI neurons. Lox2-positive FLI neurons of interest included some of those previously identified: the rostral most ventral (RMV) neurons, the circular ventral (CV) neurons, and cell 261. The paired RMVs, which are located in all midbody ganglia, expressed Lox2 only in M7-M19. The CV neurons, specialized motor neurons that innervate the circular ventral muscles of the body wall, expressed Lox2 in M7-M19. The putative cell 261 expressed Lox2 in M7-M12, where Lox1 is also expressed. FMRFamide staining in putative segmental homologs of cell 261 was not detected in other segmental ganglia. Our results suggest a role for Lox2 in very early embryonic development (before the formation of the CNS), and in the differentiation of segmentally repeated and region-specific FLI neurons.


Article retracted, but the message lives on.
The retraction of an original article aims to ensure that readers are alerted to the fact that the findings are not trustworthy. However, the present research suggests that individuals still believe in the findings of an article even though they were later told that the data were fabricated and that the article was retracted. Participants in a debriefing condition and a no-debriefing condition learned about the scientific finding of an empirical article, whereas participants in a control condition did not. Afterward, participants in the debriefing condition were told that the article had been retracted because of fabricated data. Results showed that participants in the debriefing condition were less likely to believe in the findings than participants in the no-debriefing condition but were more likely to believe in the findings than participants in the control condition, suggesting that individuals do adjust their beliefs in the perceived truth of a scientific finding after debriefing-but insufficiently. Mediational analyses revealed that the availability of generated causal arguments underlies belief perseverance. These results suggest that a retraction note of an empirical article in a scientific journal is not sufficient to ensure that readers of the original article no longer believe in the article's conclusions.


Cells in the respiratory and intestinal tracts of chickens have different proportions of both human and avian influenza virus receptors.
Avian influenza viruses play a crucial role in the creation of human pandemic viruses. In this study, we have demonstrated that both human and avian influenza receptors exist in cells in the respiratory and intestinal tracts of chickens. We have also determined that primarily cultured chicken lung cells can support the replication of both avian and human influenza viruses.


5-fluorouracil and glaucoma filtering surgery. II. A pilot study.
5-Fluorouracil (5-FU) was injected subconjunctivally after glaucoma filtering surgery in a pilot study of eyes with poor surgical prognoses. Twenty-seven (79%) of the 34 aphakic eyes with glaucoma achieved an intraocular pressure (IOP) of less than or equal to 21 mmHg (range of follow-up on nonreoperated eyes, 91 -468 days). Nine (69%) of 13 eyes with neovascular glaucoma achieved an IOP of less than or equal to 21 mmHg (range of follow-up on nonreoperated eyes, 120-379 days). Eight (89%) of nine phakic eyes with glaucoma following unsuccessful filtering procedures achieved an IOP of less than or equal to 21 mmHg (range of follow-up on nonreoperated eyes, 134-394 days). Visual acuities remained within one line of their preoperative levels or improved in 32 (94%) of the 34 aphakic eyes with glaucoma, eight (62%) of the 13 eyes with neovascular glaucoma, and six (67%) of the nine phakic eyes with glaucoma following unsuccessful filtering procedures. Postoperative corneal epithelial defects occurred in 45% of the cases. Conjunctival wound and conjunctival needle tract leaks were observed in 41% of the cases, but only one eye required wound revision. No other serious side effects that we attributed to 5-FU were observed. It seems that postoperative subconjunctival 5-FU increases the likelihood of achieving IOP control following filtering surgery in eyes with poor surgical prognoses; however, a randomized clinical trial is necessary to confirm this.


[Changes in the levels of non-enzymatic cationic proteins and degree of damage in leukocytes in rabbits with hemorrhage].
We study the contain of non-enzymatic cationic proteins (NCP) and the "degree of damage" in leucocytes in the rabbits with hemorrhages. In the animals with unimportant hemorrhages the contain of NCP in leucocytes increased. But in the rabbits with the considerable and return hemorrhages the contain of NCP in leucocytes lost. The degree of damage in leucocytes increased in the all experiments. The received results proved the presence of leucocytolysis in the rabbits with considerable and return haemorrages. In the rabbits with hemorrhages the contain of NCP in leucocytes changed dependence of the weight of the hemorrhages.


Women, work, and health: employment as a risk factor for coronary heart disease.
Employment as such does not appear to be a risk factor for coronary heart disease and may in fact have a beneficial effect on health. Although there is at present a paucity of reliable data, several key points emerge. In general, working women are in better health than homemakers or unemployed women. Single and married working women are apparently in better health than are divorced, separated, or widowed women. Among working women perception of control over the job environment may be a more important predictor of risk than level of job stress. Health appears to be compromised most among women who perceive little control over their lives. Although multiple social roles of wife, mother, and employee seem to enhance health, too much intensity in any one role may be detrimental.


Pelvic somato-visceral reflexes after spinal cord injury: measures of functional loss and partial preservation.
For people with spinal cord injuries, the impact of bladder, bowel and sexual problems on quality of life and lost opportunities can be devastating. Supra-sacral spinal lesions can cause incontinence by interrupting those pathways that normally coordinate the function of the bladder, bowel and sphincters. From a scientific perspective, neural control of the pelvic organs is one of the most intriguing in the body, involving both somatic and autonomic pathways participating in an exquisitely fine integration of lumbo-sacral reflexes. This chapter aims to review briefly those aspects of neural control of the pelvic organs that are amenable to neurophysiological examination in man. More specifically, it will focus in greater detail on the interactions of somatic and autonomic lumbo-sacral pathways responsible for coordinating the bladder and sphincters. Where appropriate, it will make comparisons with those controlling the bowel. It will describe how measurement of pelvic floor and sphincter reflexes can be used to assess the modulatory effects of sacral autonomic pathways on sacral somatic reflexes and vice versa including the so-called "guarding reflex" and vesical inhibitory reflexes. Aberrant activity following spinal cord injury (SCI), such as bladder hyperreflexia and sphincter dyssynergia, will be discussed in relation to these reflexes. The effects of volitional modulation of pelvic floor reflexes in people with both complete and incomplete lesions will be described. Finally, the chapter will address the possible utility of neurophysiological measures for complementing the established neurological classification and the assessment of somatic sensory-motor impairment in SCI.


Is there a common pathophysiology of erectile dysfunction and how does this relate to new pharmacotherapies?
Many basic and clinical studies show erectile dysfunction (ED) to be caused by a wide variety of factors. Although these factors can be divided into psychological and organic origins and these too can further be subdivided, many patients will show complex patterns of causes for ED ('mixed ED'). Many of these factors will have a direct or indirect impact on the efficacy of centrally and peripherally acting drugs, thus necessitating a variety of drugs with different modes of action and different modes of application to ensure appropriate therapy for many patients. However, some factors will render all imaginable forms of pharmacological options totally inefficient, thus necessitating forms of treatment other than pharmacotherapy.


Carrier detection and X-inactivation studies in the fragile X syndrome. Cytogenetic studies in 63 obligate and potential carriers of the fragile X.
Cytogenetic investigations by three different lymphocyte culture methods in 63 obligate and potential carriers of the fragile X [fra(X)] are reported. A difference was observed between normal and retarded carriers in the manifestation of the fra(X). An inverse relationship between percentage positive cells and age was demonstrated in normal carriers, whereas retarded carriers generally showed higher percentages at all ages. X-inactivation studies in retarded carriers compared with normal carriers showed a tendency towards a skewed inactivation pattern with an excess of early replicating fra(X) in both groups when carriers expressing high percentages of fra(X) positive cells were compared. In normal carriers with low percentage expression the tendency was apparently reversed. The relationship between the replication pattern of the fragile X and the mental status of the individual is more complicated than suggested by previous studies.


Identification of an amino acid determinant of pH regiospecificity in a seed lipoxygenase from Momordica charantia.
Lipoxygenases (LOX) form a heterogeneous family of lipid peroxidizing enzymes, which catalyze specific dioxygenation of polyunsaturated fatty acids. According to their positional specificity of linoleic acid oxygenation plant LOX have been classified into linoleate 9- and linoleate 13-LOX and recent reports identified a critical valine at the active site of 9-LOX. In contrast, more bulky phenylalanine or histidine residues were found at this position in 13-LOX. We have recently cloned a LOX-isoform from Momordica charantia and multiple amino acid alignments indicated the existence of a glutamine (Gln599) at the position were 13-LOX usually carry histidine or phenylalanine residues. Analyzing the pH-dependence of the positional specificity of linoleic acid oxygenation we observed that at pH-values higher than 7.5 this enzyme constitutes a linoleate 13-LOX whereas at lower pH, 9-H(P)ODE was the major reaction product. Site-directed mutagenesis of glutamine 599 to histidine (Gln599His) converted the enzyme to a pure 13-LOX. These data confirm previous observation suggesting that reaction specificity of certain LOX-isoforms is not an absolute enzyme property but may be impacted by reaction conditions such as pH of the reaction mixture. We extended this concept by identifying glutamine 599 as sequence determinant for such pH-dependence of the reaction specificity. Although the biological relevance for this alteration switch remains to be investigated it is of particular interest that it occurs at near physiological conditions in the pH-range between 7 and 8.


The variability of ovum pick-up response and in vitro embryo production from monozygotic twin cows.
Oocytes were recovered by ovum pick up (OPU) from nine pairs of monozygotic twin German Simmental cows. The hypothesis was that there is less variability between identical twins versus among non-related individuals in the variation in the recovery of oocytes by OPU and in the efficiency of in vitro embryo production. Estrous cycles were synchronized with two doses of cloprostenol, 11 days apart. Beginning 3-4 days after synchronized estrus, OPU was done twice weekly (every 3 or 4 days; total of 11 sessions). The influence of repeated OPU on estrous cyclicity was established by estrus detection, plasma progesterone concentrations, and ovarian ultrasonography. There were no differences among days of collection for the number and quality of cumulus oocyte-complexes (COCs), and rates of cleavage and blastocyst formation. A total of 1,661 COCs, including 657 (39.6%) good-quality COCs, were recovered. From 1,457 (87.7%) cultured COCs, 827 zygotes cleaved and 314 blastocysts were produced on Day 7. The total number of COCs and the blastocyst rates varied among pairs of monozygotic twins; within pairs, only slight differences were observed. In conclusion, recovery of COCs and production of embryos had substantially less variation within pairs of monozygotic twins than among non-related cattle.


[The challenges of choosing a name in a transcultural situation].
The arrival of a child is accompanied by a psychological crisis for the future parents. In a context of migration, the parents are exposed to additional factors of vulnerability which further accentuate the intrapsychological and intersubjective change of "becoming a parent". The clinical situation of a family referred for a transcultural consultation shows how the choice of the baby's name can illustrate this issue.


Global surface ultraviolet radiation intensity may modulate the clinical and immunologic expression of autoimmune muscle disease.
To determine if geoclimatic factors may influence the nature and frequency of dermatomyositis (DM), polymyositis, and associated autoantibodies around the world. We assessed, in the first global evaluation of these conditions, the relationship between 13 geoclimatic variables that may modulate disease and the relative proportion of DM and its associated autoantibody anti-Mi-2, directed against an SNF2-superfamily helicase associated with the nucleosome remodeling and histone acetylation and deacetylation complex, in a global myositis population. Altogether, 919 consecutive patients from populations at 15 locations were studied. Univariate and multivariate analyses demonstrated that of the variables evaluated, surface ultraviolet (UV) radiation intensity (irradiance) most strongly contributed to the relative proportion of DM and was strongly related to the proportion of anti-Mi-2 autoantibodies (weighted r = 0.939, P < 4 x 10(-7) and weighted r = 0.69, P = 0.02, respectively). Published ethnogeographic immunogenetic allele frequencies imply that the striking differences in the proportion of DM- and DM-specific autoantibodies observed around the world are not the result of inherent global variations in known genetic risk factors. These data suggest that UV radiation exposure may modulate the clinical and immunologic expression of an autoimmune disease in different populations around the world.


NK cell-based immunotherapy for malignant diseases.
Natural killer (NK) cells play critical roles in host immunity against cancer. In response, cancers develop mechanisms to escape NK cell attack or induce defective NK cells. Current NK cell-based cancer immunotherapy aims to overcome NK cell paralysis using several approaches. One approach uses expanded allogeneic NK cells, which are not inhibited by self histocompatibility antigens like autologous NK cells, for adoptive cellular immunotherapy. Another adoptive transfer approach uses stable allogeneic NK cell lines, which is more practical for quality control and large-scale production. A third approach is genetic modification of fresh NK cells or NK cell lines to highly express cytokines, Fc receptors and/or chimeric tumor-antigen receptors. Therapeutic NK cells can be derived from various sources, including peripheral or cord blood cells, stem cells or even induced pluripotent stem cells (iPSCs), and a variety of stimulators can be used for large-scale production in laboratories or good manufacturing practice (GMP) facilities, including soluble growth factors, immobilized molecules or antibodies, and other cellular activators. A list of NK cell therapies to treat several types of cancer in clinical trials is reviewed here. Several different approaches to NK-based immunotherapy, such as tissue-specific NK cells, killer receptor-oriented NK cells and chemically treated NK cells, are discussed. A few new techniques or strategies to monitor NK cell therapy by non-invasive imaging, predetermine the efficiency of NK cell therapy by in vivo experiments and evaluate NK cell therapy approaches in clinical trials are also introduced.


Metal-Ligand Cooperativity of the Calix[4]pyrrolato Aluminate: Triggerable C-C Bond Formation and Rate Control in Catalysis.
Metal-ligand cooperativity (MLC) had a remarkable impact on transition metal chemistry and catalysis. By use of the calix[4]pyrrolato aluminate, [1]- , which features a square-planar AlIII , we transfer this concept into the p-block and fully elucidate its mechanisms by experiment and theory. Complementary to transition metal-based MLC (aromatization upon substrate binding), substrate binding in [1]- occurs by dearomatization of the ligand. The aluminate trapps carbonyls by the formation of C-C and Al-O bonds, but the products maintain full reversibility and outstanding dynamic exchange rates. Remarkably, the C-C bonds can be formed or cleaved by the addition or removal of lithium cations, permitting unprecedented control over the system's constitutional state. Moreover, the metal-ligand cooperative substrate interaction allows to twist the kinetics of catalytic hydroboration reactions in a unique sense. Ultimately, this work describes the evolution of an anti-van't Hoff/Le Bel species from their being as a structural curiosity to their application as a reagent and catalyst.


Histological and ultrastructural features of gastrointestinal basidiobolomycosis.
Basidiobolus ranarum is a fungus found in the dung of amphibians, reptiles, and insectivorous bats. Its structural elements include both hyphae and zygospores. Patients with B. ranarum infection may present with subcutaneous, gastrointestinal, or systemic lesions. Here we report a case of gastrointesinal badidiomycosis in a 13-year-old male child who presented with acute abdomen. Exploration revealed a mass in the ascending colon. On histology, transmural granulomatous inflammation composed of abundant eosinophils, lymphocytes, histiocytes and giant cells was seen. Histochemical stains revealed broad, non-septate, hyphae-like structures surrounded by an eosinophilic sheath. On an ultrastructural level, fungal hyphae, spores, and macrophage-laden crystalloids were observed. The diagnosis of gastrointestinal basidiobolomycosis was established and the patient received antifungal treatment. This paper reviews the relevant literature regarding basidiomycosis, and discusses its diverse clinicopathological features, as well as distinguishing it from other diseases.


The modified polytetrafluoroethylene Blalock-Taussig shunt: case report of an unusual complication.
A case of excessive serous leak through a modified polytetrafluoroethylene Blalock-Taussig shunt is presented. This relatively rare complication was treated successfully with fibrin glue and collagen fleece.


SARS-CoV-2 in migrant worker dormitories: Geospatial epidemiology supporting outbreak management.
Migrant worker dormitories-residential complexes where 10-24 workers share living spaces-account for the majority of cases of SARS-CoV-2 infection in Singapore. To prevent overspill of transmission to the wider population, starting in early April 2020, residents were confined to their dormitories while measures were put in place to arrest the spread of infection. This descriptive study presents epidemiological data for a population of more than 60 000 migrant workers living in two barracks-style and four apartment-style dormitories located in western Singapore from April 3 to June 10, 2020. Our report draws from data obtained over the first 50 days of outbreak management in order to describe SARS-CoV-2 transmission in high-density housing environments. Cumulative counts of SARS-CoV-2 cases and numbers of housing units affected were analyzed to report the harmonic means of harmonic means of doubling times and their 95% confidence intervals (CI). Multiple transmission peaks were identified involving at least 5467 cases of SARS-CoV-2 infection across six dormitories. Our geospatial heat maps gave an early indication of outbreak severity in affected buildings. We found that the number of cases of SARS-CoV-2 infection doubled every 1.56 days (95% CI 1.29-1.96) in barracks-style buildings. The corresponding doubling time for apartment-style buildings was 2.65 days (95% CI 2.01-3.87). Geospatial epidemiology was useful in shaping outbreak management strategies in dormitories. Our results indicate that building design plays an integral role in transmission and should be considered in the prevention of future outbreaks.


Macroautophagy--a novel Beta-amyloid peptide-generating pathway activated in Alzheimer's disease.
Macroautophagy, which is a lysosomal pathway for the turnover of organelles and long-lived proteins, is a key determinant of cell survival and longevity. In this study, we show that neuronal macroautophagy is induced early in Alzheimer's disease (AD) and before beta-amyloid (Abeta) deposits extracellularly in the presenilin (PS) 1/Abeta precursor protein (APP) mouse model of beta-amyloidosis. Subsequently, autophagosomes and late autophagic vacuoles (AVs) accumulate markedly in dystrophic dendrites, implying an impaired maturation of AVs to lysosomes. Immunolabeling identifies AVs in the brain as a major reservoir of intracellular Abeta. Purified AVs contain APP and beta-cleaved APP and are highly enriched in PS1, nicastrin, and PS-dependent gamma-secretase activity. Inducing or inhibiting macroautophagy in neuronal and nonneuronal cells by modulating mammalian target of rapamycin kinase elicits parallel changes in AV proliferation and Abeta production. Our results, therefore, link beta-amyloidogenic and cell survival pathways through macroautophagy, which is activated and is abnormal in AD.


The use of glucagon in the diagnosis and management of illeocolic intussusception.
Twenty-one of 25 episodes of ileocolic intussusception were successfully reduced by the barium enema hydrostatic technique supplemented by glucagon. No apparent serious complications occurred from the use of this drug. The comfort of the children and the ease of filling the colon and small bowel seemed enhanced by the glucagon.


[Hepatitis (Hep-Net) competence network].
In Germany almost 1 million people are affected by chronic viral hepatitis. Despite of the improved therapy options for the treatment of hepatitis B and C, several questions regarding epidemiology, pathophysiology and therapy are still unclear. Vaccines against hepatitis C and D viruses are still not available. Additionally, many patients and their relatives need information about infectiosity, course of the disease and therapy options. By the integration of doctors' practices and patient advocacy groups, Hep-Net aims at the educational information on the infection and tries to give access to qualified therapy strategies for all patients with an indication for therapy. After 18 months the Hep-Net Homepage already shows more than 9000 hits per day. Consultation hours via telephone, email-services and numerous activities in cooperation with the Deutsche Leberhilfe e.V. are highly frequented. In the Hep-Net study-house high-standard clinical studies with first successful results are centrally organized. Further, basic questions in the fields of epidemiology, virology and immunology are processed in cooperative research projects within the network.


Dynamic changes of dissolved organic matter in membrane bioreactors at different organic loading rates: Evidence from spectroscopic and chromatographic methods.
Excitation emission matrix-parallel factor analysis (EEM-PARAFAC) and size exclusion chromatography (SEC) were utilized to explore the dynamics in extracellular polymeric substances (EPS), soluble microbial products (SMP), and effluent for the membrane bioreactors at two different organic loading rates (OLRs). Combination of three different fluorescent components explained the compositional changes of dissolved organic matter. The lower OLR resulted in a higher production of tryptophan-like component (C1) in EPS, while the opposite trends were found for the other two components (humic-like C2 and tyrosine-like C3), signifying the role of C1 in the endogenous condition. Larger sized molecules were more greatly produced in EPS at the lower OLR. Meanwhile, all the size fractions of SMP were more abundant at the higher OLR particular for the early phase of the operation. Irrespective of the OLR, the higher degrees of the membrane retention were found for relatively large sized and protein-like molecules.


Template-directed synthesis of silica-coated J-aggregate nanotapes.
Self-assembly of porphyrin nanotapes in the presence of alkoxysilane reaction solutions produces hybrid nanofilaments consisting of an optically responsive J-aggregate core encased within an ultrathin shell of amorphous silica.


A Review of Cardiovascular Outcomes Trials of Glucose-Lowering Therapies and Their Effects on Heart Failure Outcomes.
Type 2 diabetes mellitus has long been recognized as a major risk factor for adverse atherosclerotic cardiovascular disease events; however, recent data indicate that heart failure is now emerging as the most common and morbid cardiovascular complication of type 2 diabetes mellitus. When heart failure develops in patients with type 2 diabetes, prognosis is ominous, highlighting the need for glucose-lowering therapies that can prevent heart failure, improve outcomes, or both. Prior to 2008, there was a paucity of randomized controlled trials evaluating long-term cardiovascular outcomes with glucose-lowering therapies. This changed after guidance on the assessment of novel glucose-lowering agents was issued by both the US Food and Drug Administration and the European Medicines Agency. Since then, significant progress has been made as a result of large cardiovascular outcomes trials. Though randomized controlled trials on insulin, sulfonylureas, and metformin are still limited, cardiovascular outcomes trials on newer glucose-lowering agents have included hundreds of thousands of patients with multiple years of follow-up. The increased risk of thiazolidinediones on heart failure had been well theorized and is now established; however, the increase in heart failure hospitalization with certain dipeptidyl peptidase-4 inhibitors was unexpected. The reasons for discrepancies with regard to heart failure risk with different dipeptidyl peptidase-4 inhibitors remain unclear, and further mechanistic studies are ongoing. The role of glucagon-like peptide-1 receptor agonists among patients with heart failure also remains unclear, and their effects may differ in patients with and without established heart failure, particularly those with decompensated heart failure with reduced ejection fraction.


Differential muscle hypertrophy is associated with satellite cell numbers and Akt pathway activation following activin type IIB receptor inhibition in Mtm1 p.R69C mice.
X-linked myotubular myopathy is a congenital myopathy caused by deficiency of myotubularin. Patients often present with severe perinatal weakness, requiring mechanical ventilation to prevent death from respiratory failure. We recently reported that an activin receptor type IIB inhibitor produced hypertrophy of type 2b myofibers and modest increases of strength and life span in the severely myopathic Mtm1δ4 mouse model of X-linked myotubular myopathy. We have now performed a similar study in the less severely symptomatic Mtm1 p.R69C mouse in hopes of finding greater treatment efficacy. Activin receptor type IIB inhibitor treatment of Mtm1 p.R69C animals produced behavioral and histological evidence of hypertrophy in gastrocnemius muscles but not in quadriceps or triceps. The ability of the muscles to respond to activin receptor type IIB inhibitor treatment correlated with treatment-induced increases in satellite cell number and several muscle-specific abnormalities of hypertrophic signaling. Treatment-responsive Mtm1 p.R69C gastrocnemius muscles displayed lower levels of phosphorylated ribosomal protein S6 and higher levels of phosphorylated eukaryotic elongation factor 2 kinase than were observed in Mtm1 p.R69C quadriceps muscle or in muscles from wild-type littermates. Hypertrophy in the Mtm1 p.R69C gastrocnemius muscle was associated with increased levels of phosphorylated ribosomal protein S6. Our findings indicate that muscle-, fiber type-, and mutation-specific factors affect the response to hypertrophic therapies that will be important to assess in future therapeutic trials.


A Systematic Review of the Impact of Juvenile Curfew Laws on Public Health and Justice Outcomes.
Automobile crashes cause more than 800,000 youth injuries and deaths each year. Other youth suffer the consequences from being either a perpetrator or victim of a crime. One type of law that has an effect on youth behavior is juvenile curfew laws. These laws restrict the times that youth may occupy public places or streets. We systematically reviewed studies evaluating the effectiveness of these laws to address the question: Can juvenile curfew laws be used to improve youth public health and juvenile justice outcomes? In 2013, we used a standardized set of keywords to search 24 databases for studies that evaluated effectiveness outcome measures of juvenile curfew laws. After applying the exclusion criteria and removing duplicate studies, 14 studies of juvenile curfews remained. Of the six studies examining the effectiveness of juvenile curfew laws on adverse youth health outcomes, five found a positive impact. Of the eight studies examining the effectiveness of curfew laws on juvenile crime and victimization, four found a positive impact. The studies that found that juvenile curfew laws were effective at reducing adverse youth health outcomes (e.g., trauma transports); juvenile crime; and victimization were of higher quality (e.g., stronger methodologic approaches) than those finding no effects. However, given the limited number of studies and concerns with quality, we conclude that more research is needed before conclusions can be drawn about the effectiveness of juvenile curfew laws.


Fibrin monomer increases platelet adherence to tumor cells in a flowing system: a possible role in metastasis?
Considerable evidence exists linking hemostasis and malignancy. Platelet adhesion to tumor cells has been implicated in the metastatic process. Plasma fibrinogen (Fg) and fibrin (Fn) monomer, increased in cancer, may play a role in tumor biology. Binding of Fn monomer to tumor cells and its effect on platelet-tumor cell adhesion in a flowing system were studied. Fn monomer was produced by adding thrombin (1 micro/mL) to FXIII- and plasminogen-free Fg in the presence of Gly-Pro-Arg-Pro (GPRP) amide. Fn monomer binding to live A375 cells was visualized by confocal laser scanning microscopy (CLSM). Adherent cells were perfused for 1h with Fn monomer, washed and stained in situ with anti-human Fn (American Biogenetic Sciences, Inc.) followed by goat anti-mouse IgG(FITC). Platelet adherence to Fn monomer treated A375 cells was performed under flow conditions by passing platelets (5x10(4)/microl 0.25 mL/min; labeled with the carbocyanine dye DiI) over the tumor cells for 30 min. CLSM images were obtained after washing. There was considerable binding of Fn monomer, but not Fg alone. Platelets adhered relatively weakly to untreated A375 cells and this was not significantly affected by pre-treatment of the tumor cells with fibrinogen or thrombin. However, pre-treatment with Fn monomer resulted in extensive platelet binding to tumor cells, suggesting that coagulation activation and the subsequent increase in circulating Fn monomer may enhance platelet adhesion to circulating tumor cells and thereby facilitate metastatic spread.


Does competition for phosphate supply explain the invasion pattern of Elodea species?
Two invasive aquatic plants, Elodea canadensis and Elodea nuttallii, occurred in north-eastern France. In this study, we examine the influence of phosphorus availability in soft water streams to explain the invasion pattern of exotic species (E. nuttallii and E. canadensis) compared to native plants (Callitriche platycarpa, Ranunculus peltatus). Total phosphorus was measured in these four aquatic macrophytes. Sediment total phosphorus and water-soluble reactive phosphorus were also analysed each season in 2001. Phosphorus content in the two invasive species and in R. peltatus was higher than in C. platycarpa. Elodea species are adapted to the seasonal phosphorus fluctuations as well as R. peltatus and exhibited high phosphorus storage ability. The high fluctuation availability of resources in space or/and time favoured the spread of the invasive plants and confirms the theory of invasibility of Davis et al. [2000. Fluctuating resources in plant communities: a general theory of invasibility. J. Ecol. 88, 528-534]. The eutrophication process increases the invasibility of E. nuttallii's, while inducing competition between E. nuttallii and native macrophyte species.