Vishniacozyma changhuana sp. nov., and Vishniacozyma taiwanica sp. nov., two novel yeast species isolated from mangrove forests in Taiwan.
Mangroves grow in the intertidal zone, which alternates between fresh water and sea water, with abundant bioresources. In mangrove habitats, yeasts play an important role in the decomposition of organic matter, and such nutrient cycling has high ecological importance. During a study of the diversity of yeast from Taiwan mangroves, seven strains of basidiomycetous yeasts were isolated and these yeasts represent two novel yeast species belonging to the genus Vishniacozyma. According to the sequences of the D1/D2 domain of large subunit (LSU) rRNA and the internal transcribed spacer (ITS) region, these seven strains could be clearly classified into two groups representing two individual, distinct species. Strains HM5L06, HM6L07, HM11L11 and BJ3S01, differed from their closest relative species Vishniacozyma phoenicis by 4-5 nt substitutions (no gaps) in the sequences of the D1/D2 domain of LSU rRNA and by 23 nt substitutions (10 gaps) in the ITS region. Strains HM6L11, HM7L02 and HM8L19, differed from their closest relative species Vishniacozyma penaeus by 7 nt substitutions (one gap) in the sequences of the D1/D2 domain of LSU rRNA and by 27 nt substitutions (12 gaps) in the ITS region. The scientific names of Vishniacozyma taiwanica sp. nov. and Vishniacozyma changhuana sp. nov. are proposed for these strains. The holotypes are Vishniacozyma taiwanica BCRC 23477T (ex-type HM5L06=CBS 16558; MycoBank number MB837428) and Vishniacozyma changhuana BCRC 23478T (ex-type HM6L11=CBS 16556; MycoBank number MB837429).


Disaster waste management after the 2016 Kumamoto Earthquake: A mini-review of earthquake waste management and the Kumamoto experience.
Millions of tons of debris can be generated by natural disasters, impacting the surrounding environment and posing health risks to the public. Proper handling and treatment of such waste is essential to overcome potential hazards as well as to reduce the burden on natural resources during the reconstruction phase. Disaster waste management can have social, economic, and environmental benefits if planned effectively. This mini-review focuses on the destruction caused and debris generated by the 2016 Kumamoto Earthquake in Japan. In addition, it elaborates upon the treatment of debris in Kumamoto at temporary and secondary storage sites by segregation and the adoption of a full-scale recycling system. It also shows that cooperative networks involving numerous organizations are important in managing a large amount of disaster waste. Finally, it presents comparative discussions of different aspects of disaster waste management in the Kumamoto Earthquake event and other disasters. The experience gained from the Kumamoto Earthquake is important for future disaster waste management planning.


Location: root architecture structures rhizosphere microbial associations.
Root architectural phenotypes are promising targets for crop breeding, but root architectural effects on microbial associations in agricultural fields are not well understood. Architecture determines the location of microbial associations within root systems, which when integrated with soil vertical gradients, determines the functions and the metabolic capability of rhizosphere microbial communities. We argue that variation in root architecture in crops has important implications for root exudation, microbial recruitment and function, and the decomposition and fate of root tissues and exudates. Recent research has shown that the root microbiome changes along root axes and among root classes, that root tips have a unique microbiome, and that root exudates change within the root system depending on soil physicochemical conditions. Although fresh exudates are produced in larger amounts in root tips, the rhizosphere of mature root segments also plays a role in influencing soil vertical gradients. We argue that more research is needed to understand specific root phenotypes that structure microbial associations and discuss candidate root phenotypes that may determine the location of microbial hotspots within root systems with relevance to agricultural systems.


African swine fever virus structural protein p54 is essential for the recruitment of envelope precursors to assembly sites.
The assembly of African swine fever virus (ASFV) at the cytoplasmic virus factories commences with the formation of precursor membranous structures, which are thought to be collapsed cisternal domains recruited from the surrounding endoplasmic reticulum (ER). This report analyzes the role in virus morphogenesis of the structural protein p54, a 25-kDa polypeptide encoded by the E183L gene that contains a putative transmembrane domain and localizes at the ER-derived envelope precursors. We show that protein p54 behaves in vitro and in infected cells as a type I membrane-anchored protein that forms disulfide-linked homodimers through its unique luminal cysteine. Moreover, p54 is targeted to the ER membranes when it is transiently expressed in transfected cells. Using a lethal conditional recombinant, vE183Li, we also demonstrate that the repression of p54 synthesis arrests virus morphogenesis at a very early stage, even prior to the formation of the precursor membranes. Under restrictive conditions, the virus factories appeared as discrete electron-lucent areas essentially free of viral structures. In contrast, outside the assembly sites, large amounts of aberrant zipper-like structures formed by the unprocessed core polyproteins pp220 and pp62 were produced in close association to ER cisternae. Altogether, these results indicate that the transmembrane structural protein p54 is critical for the recruitment and transformation of the ER membranes into the precursors of the viral envelope.


[Therapy of malignant systemic diseases: hemoblastoses and malignant lymphomas].
Recent progress in the treatment of acute leukemias in adults includes combination chemotherapy (TAD) and the use of high-dose antimetabolites (methotrexate plus citrovorum rescue or high-dose cytosine-arabinoside). The role of post-induction chemotherapy is still controversial especially with regard to the maintenance chemotherapy. The German AML (acute myeloid leukemia) Cooperative Group started a cooperative multi-center comparative trial to evaluate the validity of maintenance chemotherapy in patients with AML. A complete remission rate of 61% was achieved. The median time to complete remission was 33 days, and a complete remission was obtained in 68% of responders after only 1 course of therapy. Patients in complete remission were eligible for randomization for TAD consolidation with or without monthly maintenance chemotherapy. The up-dated life-table analysis revealed a predicted rate of continuous complete remission at 2 1/2 years of 30% for the maintenance and 17% for the non-maintenance group of patients (p = 0.003). On the basis of these results post-induction myelosuppressive chemotherapy appears to be substantial for achieving long-term remissions in AML. In addition, consolidation chemotherapy together with monthly maintenance seems to be superior to consolidation in prolonging the remission duration. In adult ALL/AUL (acute lymphatic/undifferentiated leukemia) complete remission rates amount to 60-85% and remission durations of 9-25 months have been reported.(ABSTRACT TRUNCATED AT 250 WORDS)


Medical and life-style risk factors affecting fetal mortality, 1989-90.
This report presents fetal mortality data by medical and life-style risk factors of the mother and the fetus. Deaths and fetal mortality rates are presented in this descriptive report. Data sources used are vital statistics data for fetal deaths and live births. The data that became available with the revision of the U.S. Standard Report of Fetal Death in 1989 expanded the medical and health data available on mothers and fetuses. Reporting of medical conditions is probably incomplete for fetal deaths as well as for live births. Therefore, caution should be exercised in using this data. Reported occurrences of medical and life-style risk factors of mother and fetus for fetal deaths and live births and fetal mortality rates are presented. Maternal medical conditions most often associated with having a fetal death were problems with amniotic fluid levels and blood disorders. Fetal mortality was 35 percent greater when tobacco was used during pregnancy and 77 percent higher when alcohol was consumed during pregnancy. The complication of labor most often associated with fetal mortality was abruptio placenta. Although a very small proportion of all deliveries have specific congenital anomalies reported, fetal mortality was close to 50 percent for anencephalus, about 25 percent for renal agenesis, and slightly more than 20 percent for hydrocephalus.


Towards the immunoproteome of Neisseria meningitidis.
Despite the introduction of conjugated polysaccharide vaccines for many of the Neisseria meningitidis serogroups, neisserial infections continue to cause septicaemia and meningitis across the world. This is in part due to the difficulties in developing a, cross-protective vaccine that is effective against all serogroups, including serogroup B meningococci. Although convalescent N. meningitidis patients develop a natural long-lasting cross-protective immunity, the antigens that mediate this response remain unknown. To help define the target of this protective immunity we identified the proteins recognized by IgG in sera from meningococcal patients by a combination of 2D protein gels, western blots and mass spectrometry. Although a number of outer membrane antigens were identified the majority of the antigens were cytoplasmic, with roles in cellular processes and metabolism. When recombinant proteins were expressed and used to raise sera in mice, none of the antigens elicited a positive SBA result, however flow cytometry did demonstrate that some, including the ribosomal protein, RplY were localised to the neisserial cell surface.


[New directions in GABAergic pharmacology of anxiety and depression].
New prospects in the use of drugs affecting central GABAergic system for the treatment of anxiety and depressive states are critically assessed. Both clinical (human) and experimental (animal) data on the mutual influence of various GABA-receptor modulators as well as the interaction of GABAergic system with neurohumoral mechanisms of stress are considered. Based on this analysis, new strategies in the GABAergic pharmacotherapy of anxiety and depression spectrum disorders are outlined.


The biosynthesis of phospholipids is linked to the cell cycle in a model eukaryote.
The structural challenges faced by eukaryotic cells through the cell cycle are key for understanding cell viability and proliferation. We tested the hypothesis that the biosynthesis of structural lipids is linked to the cell cycle. If true, this would suggest that the cell's structure is important for progress through and perhaps even control of the cell cycle. Lipidomics (31P NMR and MS), proteomics (Western immunoblotting) and transcriptomics (RT-qPCR) techniques were used to profile the lipid fraction and characterise aspects of its metabolism at seven stages of the cell cycle of the model eukaryote, Desmodesmus quadricauda. We found considerable, transient increases in the abundance of phosphatidylethanolamine during the G1 phase (+35%, ethanolamine phosphate cytidylyltransferase increased 2·5×) and phosphatidylglycerol (+100%, phosphatidylglycerol synthase increased 22×) over the G1/pre-replication phase boundary. The relative abundance of phosphatidylcholine fell by ~35% during the G1. N-Methyl transferases for the conversion of phosphatidylethanolamine into phosphatidylcholine were not found in the de novo transcriptome profile, though a choline phosphate transferase was found, suggesting that the Kennedy pathway is the principal route for the synthesis of PC. The fatty acid profiles of the four most abundant lipids suggested that these lipids were not generally converted between one another. This study shows for the first time that there are considerable changes in the biosynthesis of the three most abundant phospholipid classes in the normal cell cycle of D. quadricauda, by margins large enough to elicit changes to the physical properties of membranes.


Management of small and diminutive colorectal polyps: a review of the literature.
Major advances in biomedical optics have increased our ability to detect more colorectal polyps. Increased small (6-9 mm) and diminutive (<6 mm) polyp detection has been reported however the impact of these increases in terms of colorectal cancer prevention is unknown. The same advances that have allowed increased detection have also made in vivo determination of polyp histology possible. As our in-vivo assessment accuracy improves, the need for resection of non neoplastic polyps and pathologic confirmation of low risk adenomas may eventually diminish. The clinical significance of small and diminutive polyps continues to be debated however both retrospective and prospective studies support a low prevalence of advanced pathology in colorectal polyps <10mm in size. Furthermore, natural history studies suggest these polyps exhibit little or slow growth and some may in fact regress over time. Though the overall risk of colonoscopy is low, polypectomy remains the single greatest risk factor, driving interest in methods to avoid polypectomy of non-neoplastic polyps thereby improving safety without reducing cancer prevention effectiveness. A "diagnose and discard" strategy for diminutive adenomas and a "diagnose and leave behind" strategy for diminutive hyperplastic polyps may offer risk and cost reduction without compromising effectiveness but will require the ability to make both accurate high confidence in-vivo polyp assessment and agreement in setting post-polypectomy surveillance intervals. As both our technology and our knowledge increase, we will be better equipped to confidently provide a complete colorectal screening, to manage detected polyps according to their chance for neoplasia, and to provide an accurate assessment of lifetime colorectal cancer risk and need for future surveillance examinations.


Trust in public health institutions moderates the effectiveness of COVID-19 vaccine discussion groups on Facebook.
Distrust and partisan identity are theorized to undermine health communications. We examined the role of these factors on the efficacy of discussion groups intended to promote vaccine uptake. We analyzed survey data from unvaccinated Facebook users (N = 371) living in the US between January and April 2022. Participants were randomly assigned to Facebook discussion groups (intervention) or referred to Facebook's COVID-19 Information Center (control). We used Analysis of Covariance to test if the intervention was more effective at changing vaccination intentions and beliefs compared to the control in subgroups based on participants' partisan identity, political views, and information trust views. We found a significant interaction between the intervention and trust in public health institutions (PHIs) for improving intentions to vaccinate (P = .04), intentions to encourage others to vaccinate (P = .03), and vaccine confidence beliefs (P = .01). Among participants who trusted PHIs, those in the intervention had higher posttest intentions to vaccinate (P = .008) and intentions to encourage others to vaccinate (P = .002) compared to the control. Among non-conservatives, participants in the intervention had higher posttest intentions to vaccinate (P = .048). The intervention was more effective at improving intentions to encourage others to vaccinate within the subgroups of Republicans (P = .03), conservatives (P = .02), and participants who distrusted government (P = .02). Facebook discussion groups were more effective for people who trusted PHIs and non-conservatives. Health communicators may need to segment health messaging and develop strategies around trust views.


Lifestyle, environmental, and genetic predictors of bulky DNA adducts in a study population nested within a prospective Danish cohort.
Bulky DNA adducts are considered a potential biomarker of cancer risk. In this study, the association between various lifestyle, environmental, and genetic factors and the levels of bulky DNA adducts in peripheral leukocytes was examined in a study group nested within a population-based prospective Danish cohort. At enrollment, blood samples were collected and information on lifestyle, including dietary and smoking habits, obtained. Previously, bulky DNA adducts were measured in 245 individuals who developed lung cancer and 255 control members of the cohort. Of these 500 individuals, data on 375 individuals were included in this study, excluding 125 cases, which developed lung cancer within the first 3 yr after blood sampling. Bulky DNA adduct levels were measured by 32P-postlabeling technique and polymorphisms in carcinogen metabolism and DNA repair genes were determined. Potential predictors of bulky DNA adduct levels were analyzed by univariate and multivariate regression analyses. Women tended to have higher adduct levels than men. Living in central Copenhagen and surface darkness of fried meat and fish were associated with quantitative higher adduct levels. No significant associations were found between dietary factors or smoking and DNA adduct levels. Further, the results showed no prominent associations between any of 12 genetic polymorphisms and adduct levels. Overall, our study showed only few associations between dietary, environmental, and genetic factors and levels of bulky DNA adducts measured in peripheral leukocytes in a general Danish population.


Association of an extended haplotype in the tau gene with progressive supranuclear palsy.
We describe two extended haplotypes that cover the human tau gene. In a total of approximately 200 unrelated caucasian individuals there is complete disequilibrium between polymorphisms which span the gene (which covers approximately 100 kb of DNA). This suggests that the establishment of the two haplotypes was an ancient event and either that recombination is suppressed in this region, or that recombinant genes are selected against. Furthermore, we show that the more common haplotype (H1) is significantly over-represented in patients with progressive supranuclear palsy (PSP), extending earlier reports of an association between an intronic dinucleotide polymorphism and PSP.


In vivo confocal microscopy and tear cytokine analysis in post-LASIK ectasia.
Corneal keratectasia is one of the complications associated with laser in situ keratomileusis (LASIK) that results in vision impairment. The pathogenesis of post-LASIK ectasia (PLE) remains underexplored. We report the tear cytokine profile and in vivo confocal microscopy (IVCM) findings in eyes with PLE. This retrospective study included age-matched 7 (14 eyes) post-LASIK controls (PLCs) and 6 (12 eyes) PLE subjects. Corneal topography was used to categorise the subjects into PLC and PLE groups. Ocular Surface Disease Index (OSDI) scores obtained were based on standard questionnaire and IVCM images were used to determine corneal dendritic cells density (DCD) and sub-basal nerve plexus morphology. Inflammatory cytokines/chemokines in the tears were quantified using flow cytometry based cytometric bead array. Pentacam-based scores, OSDI scores and corneal DCD were significantly (p<0.05) higher in patients with PLE compared with PLC. Discomfort-related subscale of OSDI score exhibited a positive correlation with total corneal DCD in the PLE cohort. The fold difference of chemokine (C-C motif) ligand/monocyte chemotactic protein-1 (CCL2/MCP1) (3.4±0.6) was found to be significantly (p<0.05) higher in the PLE cohorts and a positive correlation between CCL2/MCP1 levels and total corneal DCD was also observed in the PLE cohort. The current study found a significant difference in the tear film cytokine profile between normal and PLE eyes. Presence of increased corneal dendritic cells and altered tear cytokines suggests an ongoing inflammatory response in PLE.


Effect of Fe and C Contents on the Microstructure and High-Temperature Mechanical Properties of IN625 Alloy Processed by Laser Powder Bed Fusion.
Two alloys with different Fe and C contents were studied to assess the influence of their compositions on the microstructure and mechanical properties of Ni-based Inconel 625 superalloy processed by laser powder bed fusion and subjected to stress relief annealing (870 °C) and a solution treatment (1120 °C). It was concluded that the alloy with a higher Fe content (~4 wt.% as compared to ~1 wt.%) manifests a greater propensity to segregate Nb and Mo elements during printing and form δ phase particles during the stress relief annealing. On the other hand, the alloy with a higher C content (~0.04 wt.% compared to ~0.02 wt.%) exhibits a greater tendency to form M6C carbides during the solution treatment. No effects of the Fe and C content variations on the room temperature mechanical properties were observed. On the contrary, an increase in the C content resulted in a 40% lower high-temperature (760 °C) ductility of the laser powder bed fused and post-processed IN625 alloy, without affecting its strength characteristics.


Adiponectin stimulates autophagy and reduces oxidative stress to enhance insulin sensitivity during high-fat diet feeding in mice.
Numerous studies have characterized the antidiabetic effects of adiponectin, yet the precise cellular mechanisms in skeletal muscle, in particular, changes in autophagy, require further clarification. In the current study, we used a high-fat diet (HFD) to induce obesity and insulin resistance in wild-type (WT) or adiponectin knockout (Ad-KO) mice with and without adiponectin replenishment. Temporal analysis of glucose tolerance and insulin sensitivity using hyperinsulinemic-euglycemic clamp and muscle insulin receptor substrate and Akt phosphorylation demonstrated exaggerated and more rapid HFD-induced insulin resistance in skeletal muscle of Ad-KO mice. Superoxide dismutase activity, the reduced glutathione-to-glutathione disulfide ratio, and lipid peroxidation indicated that HFD-induced oxidative stress was corrected by adiponectin. Gene array analysis implicated several antioxidant enzymes, including Gpxs, Prdx, Sod, and Nox4, in mediating this effect. Adiponectin also attenuated palmitate-induced reactive oxygen species production in cultured myotubes and improved insulin-stimulated glucose uptake in primary muscle cells. Increased LC3-II and decreased p62 expression suggested that HFD induced autophagy in muscle of WT mice; however, these changes were not observed in Ad-KO mice. Replenishing adiponectin in Ad-KO mice increased LC3-II and Beclin1 and decreased p62 protein levels, induced fibroblast growth factor-21 expression, and corrected HFD-induced decreases in LC3, Beclin1, and ULK1 gene expression. In vitro studies examining changes in phospho-ULK1 (Ser555), LC3-II, and lysosomal enzyme activity confirmed that adiponectin directly induced autophagic flux in cultured muscle cells in an AMPK-dependent manner. We overexpressed an inactive mutant of Atg5 to create an autophagy-deficient cell model, and together with pharmacological inhibition of autophagy, demonstrated reduced insulin sensitivity under these conditions. In summary, adiponectin stimulated skeletal muscle autophagy and antioxidant potential to reduce insulin resistance caused by HFD.


Inhibition of RPE65 Retinol Isomerase Activity by Inhibitors of Lipid Metabolism.
RPE65 is the isomerase catalyzing conversion of all-trans-retinyl ester (atRE) into 11-cis-retinol in the retinal visual cycle. Crystal structures of RPE65 and site-directed mutagenesis reveal aspects of its catalytic mechanism, especially retinyl moiety isomerization, but other aspects remain to be determined. To investigate potential interactions between RPE65 and lipid metabolism enzymes, HEK293-F cells were transfected with expression vectors for visual cycle proteins and co-transfected with either fatty acyl:CoA ligases (ACSLs) 1, 3, or 6 or the SLC27A family fatty acyl-CoA synthase FATP2/SLCA27A2 to test their effect on isomerase activity. These experiments showed that RPE65 activity was reduced by co-expression of ACSLs or FATP2. Surprisingly, however, in attempting to relieve the ACSL-mediated inhibition, we discovered that triacsin C, an inhibitor of ACSLs, also potently inhibited RPE65 isomerase activity in cellulo. We found triacsin C to be a competitive inhibitor of RPE65 (IC50 = 500 nm). We confirmed that triacsin C competes directly with atRE by incubating membranes prepared from chicken RPE65-transfected cells with liposomes containing 0-1 μM atRE. Other inhibitors of ACSLs had modest inhibitory effects compared with triascin C. In conclusion, we have identified an inhibitor of ACSLs as a potent inhibitor of RPE65 that competes with the atRE substrate of RPE65 for binding. Triacsin C, with an alkenyl chain resembling but not identical to either acyl or retinyl chains, may compete with binding of the acyl moiety of atRE via the alkenyl moiety. Its inhibitory effect, however, may reside in its nitrosohydrazone/triazene moiety.


Short communication: Genomic selection using a multi-breed, across-country reference population.
Three breeds (Fleckvieh, Holstein, and Jersey) were included in a reference population, separately and together, to assess the accuracy of prediction of genomic breeding values in single-breed validation populations. The accuracy of genomic selection was defined as the correlation between estimated breeding values, calculated using phenotypic data, and genomic breeding values. The Holstein and Jersey populations were from Australia, whereas the Fleckvieh population (dual-purpose Simmental) was from Austria and Germany. Both a BLUP with a multi-breed genomic relationship matrix (GBLUP) and a Bayesian method (BayesA) were used to derive the prediction equations. The hypothesis tested was that having a multi-breed reference population increased the accuracy of genomic selection. Minimal advantage existed of either GBLUP or BayesA multi-breed genomic evaluations over single-breed evaluations. However, when the goal was to predict genomic breeding values for a breed with no individuals in the reference population, using 2 other breeds in the reference was generally better than only 1 breed.


Antimicrobial sensitivity of aerobic gram-negative rods isolated from bovin udder infections.
Antimicrobial sensitivity of 214 aerobic gram-negative rods recovered from infected bovine mammary glands was determined. Seventeen antimicrobial agents were used. More than 90% of the cultures were sensitive to chloramphenicol, gentamicin, and polymyxin B. These 3 antimicrobials are not approved for infusion into the bovine mammary gland. Escherichia coli was most sensitive to the 17 antimicrobials, and in decreasing sequence, Klebsiella pneumoniae, Citrobacter spp, Enterobacter spp, and Proteus spp were sensitive to fewer antimicrobials. Pseudomonas spp were most resistant.


Molecular markers in blood as surrogate prognostic indicators of melanoma recurrence.
Improvement is needed in the ability to evaluate the prognosis of melanoma patients who are clinically disease-free but likely to develop recurrent metastatic disease. The detection of circulating melanoma cells in blood is a potential surrogate marker of subclinical residual disease. We assessed the prognostic clinical utility of a multimarker melanoma reverse transcriptase-PCR (RT-PCR) assay using blood of 46 patients who were clinically disease-free. All patients were followed up for more than 4 years for disease recurrence. There was a significant correlation between number of RT-PCR markers present in blood and American Joint Committee on Cancer stage (P = 0.009). The number of RT-PCR markers detected in blood was an independent prediction factor of disease recurrence in a Cox proportional hazard model (P = 0.02). A risk factor model using American Joint Committee on Cancer stage and number of positive RT-PCR markers significantly predicted disease recurrence in 2, 3, and 4 years of follow-up. These studies demonstrate that molecular detection of circulating melanoma cells may be of significant prognostic value in determining early disease recurrence and may be useful for stratifying patients for adjuvant therapy.


Oral fluoroquinolone use and risk of peripheral neuropathy: a pharmacoepidemiologic study.
To quantify the risk of peripheral neuropathy (PN) with oral fluoroquinolone (FQ) use. We conducted a case-control study within a cohort of men aged 45 to 80 years in the United States followed from 2001 to 2011. Cases were defined as those with the first physician visit diagnosis of PN, polyneuropathy, or drug-induced polyneuropathy. Four controls were matched to each case by age, follow-up, and calendar time using density-based sampling. As a sensitivity analysis, we also quantified the risk of PN with finasteride use, a drug that is not expected to increase the risk of PN. Rate ratios (RRs) for current users of FQs were computed using conditional logistic regression, which was adjusted for chronic renal failure, chronic liver disease, hypothyroidism, postherpetic neuralgia, and the use of nitrofurantoin and metronidazole. We identified 6,226 cases and 24,904 controls. Current users of FQs were at a higher risk of developing PN (RR = 1.83, 95% confidence interval [CI] 1.49-2.27). Current new users had the highest risk (RR = 2.07, 95% CI 1.56-2.74). No risk was observed for current users of finasteride (RR = 1.21, 95% CI 0.97-1.51). Current users, especially new users of FQs, are at a higher risk of developing PN. Despite the increase in the use of FQs, clinicians should weigh the benefits against the risk of adverse events when prescribing these drugs to their patients.


Effects of iron and multimicronutrient supplementation on geophagy: a two-by-two factorial study among Zambian schoolchildren in Lusaka.
Geophagy has been associated with iron deficiency and anaemia, but no causal relationship has been established. To clarify this, we conducted a two-by-two factorial randomised, controlled trial on the effect of iron and multimicronutrient supplementation on geophagy in Zambian schoolchildren in Lusaka, from February to December 2001. Of the 406 children, 212 (52.2%) were girls and the mean (range) age was 10.2 (7-15) years. Geophagy was reported by 302 (74.4%) and more often in girls than in boys (80.2 vs. 67.7%, P = 0.007). The mean (range) daily earth intake was 25.2 (1-200) g. Geophageous children had more often geophageous relatives than non-geophageous children (79.5 vs. 1.9%, P < 0.001). Geophageous children had lower serum ferritin (20.5 vs. 25.0 microg/l, P = 0.032) but not haemoglobin (Hb) (129.2 vs. 130.4 g/l, P = 0.59), than non-geophageous. Among those with Hb < 130 g/l, geophageous children had significantly higher prevalence (53.7 vs. 30.6%, P = 0.024) of Ascaris lumbricoides infection than non-geophageous. The prevalence of geophagy (74.4 to 51.6%) and the intake of earth (25.3 to 15.0 g/day) declined (P = 0.001 and P < 0.001, respectively) among the 220 (54.2%) children followed-up. In bivariate analysis, non-iron supplementation reduced the prevalence of geophagy more than iron supplementation did, but this was not confirmed in the multiple logistic regression analysis. Multimicronutrients had no effect on either geophagy prevalence or earth intake. Geophagy was prevalent and associated with iron deficiency, but iron supplementation had no effects on geophageous behaviour. Geophagy could be a copied behaviour and the association between geophagy and iron deficiency due to impaired iron absorption following earth eating.


Pharmacokinetics of methylphenidate in man, rat and monkey.
The pharmacokinetics and bioavailability of methylphenidate (MPH) and a metabolite, ritalinic acid (RA), were studied in normal adults, children with hyperactivity, monkeys and rats. Adult males received 0.15 or 0.3 mg/kg of MPH orally and MPH and RA were analyzed in plasma samples obtained at various times after treatment. Maximal MPH concentrations in plasma were found to occur 2.2 hr after administration of either dose (range: 1.0-4.0). The mean (+/-S.E.) maximal concentration in plasma for MPH was 3.5 +/- 0.4 ng/ml after 0.15 mg/kg and 7.8 +/- 0.8 ng/ml after 0.3 mg/kg. MPH clearances were high (10.1 liters/hr/kg) and variable (range: 3.6-23.2) for the 0.3 mg/kg dose. Pharmacokinetic parameters for children receiving 0.3 mg/kg were essentially the same as for adults. RA plasma levels were 50 to 100 times greater than MPH levels in normal adults. The clearance of RA is less than that of MPH. The absolute bioavailability of MPH was found to be 0.19 in the rat and 0.22 in the monkey, suggesting substantial presystemic elimination of MPH.


Characterization of Atherosclerotic Plaque Coating for Thrombosis Microfluidics Assays.
Studying arterial thrombus formation by in vitro flow assays is a widely used approach. Incorporating human atherosclerotic plaque material as a thrombogenic surface in these assays represents a method to model the pathophysiological environment of thrombus formation upon plaque disruption. Up until now, achieving a homogeneous coating of plaque material and subsequent reproducible platelet adhesion has been challenging. Here, we characterized a novel method for coating of plaque material on glass coverslips for use in thrombosis microfluidic assays. A homogenate of human atherosclerotic plaques was coated on glass coverslips by conventional manual droplet coating or by spin coating. Prior to coating, a subset of coverslips was plasma treated. Water contact angle measurements were performed as an indicator for the hydrophilicity of the coverslips. Homogeneity of plaque coatings was determined using profilometric analysis and scanning electron microscopy. Thrombogenicity of the plaque material was assessed in real time by microscopic imaging while perfusing whole blood at a shear rate of 1500 s-1 over the plaque material. Plasma treatment of glass coverslips, prior to spin coating with plaque material, increased the hydrophilicity of the coverslip compared to no plasma treatment. The most homogeneous plaque coating and highest platelet adhesion was obtained upon plasma treatment followed by spin coating of the plaque material. Manual plaque coating on non-plasma treated coverslips yielded lowest coating homogeneity and platelet adhesion and activation. Spin coating of atherosclerotic plaque material on plasma treated coverslips leads to a more homogenous coating and improved platelet adhesion to the plaque when compared to conventional droplet coating on non-plasma treated coverslips. These properties are beneficial in ensuring the quality and reproducibility of flow experiments. The online version contains supplementary material available at 10.1007/s12195-021-00713-9.


Heparanase inhibitors restrain mesothelioma.
Malignant mesothelioma is a highly aggressive form of cancer with poor prognosis due to lack of markers for early diagnosis and resistance to conventional therapies. Heparanase, the sole heparan sulfate (HS) degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, metastasis, angiogenesis, and inflammation. Heparanase accomplishes this by degrading HS and thereby facilitating cell invasion and regulating the bioavailability of heparin-binding proteins. Applying pre-clinical and clinical models of human mesothelioma and potent inhibitors of heparanase enzymatic activity (PG545, Defibrotide) we investigated the significance of heparanase in the pathogenesis of mesothelioma. We found that mesothelioma tumor growth was markedly attenuated by heparanase gene silencing and by heparanase inhibitors. Furthermore, heparanase inhibitors were more potent in vivo than conventional chemotherapy. Clinically, heparanase levels in patients' pleural effusions could distinguish between malignant and benign effusions, and heparanase H-score (immunostaining of tumor specimens) above 90 was associated with reduced patient survival. These results strongly imply that heparanase plays an important role in mesothelioma tumor progression, thus encouraging the use of heparanase inhibitors in combination with existing drugs as a new therapeutic modality in mesothelioma clinical trials.


Reactive oxygen species play a critical role in collagen-induced platelet activation via SHP-2 oxidation.
The collagen-stimulated generation of reactive oxygen species (ROS) regulates signal transduction in platelets, although the mechanism is unclear. The major targets of ROS include protein tyrosine phosphatases (PTPs). ROS-mediated oxidation of the active cysteine site in PTPs abrogates the PTP catalytic activity. The aim of this study was to elucidate whether collagen-induced ROS generation leads to PTP oxidation, which promotes platelet stimulation. SH2 domain-containing PTP-2 (SHP-2) is oxidized in platelets by ROS produced upon collagen stimulation. The oxidative inactivation of SHP-2 leads to the enhanced tyrosine phosphorylation of spleen tyrosine kinase (Syk), Vav1, and Bruton's tyrosine kinase (Btk) in the linker for the activation of T cells signaling complex, which promotes the tyrosine phosphorylation-mediated activation of phospholipase Cγ2 (PLCγ2). Moreover, we found that, relative to wild-type platelets, platelets derived from glutathione peroxidase 1 (GPx1)/catalase double-deficient mice showed enhanced cellular ROS levels, oxidative inactivation of SHP-2, and tyrosine phosphorylation of Syk, Vav1, Btk, and PLCγ2 in response to collagen, which subsequently led to increased intracellular calcium levels, degranulation, and integrin αIIbβ3 activation. Consistent with these findings, GPx1/catalase double-deficiency accelerated the thrombotic response in FeCl3-injured carotid arteries. The present study is the first to demonstrate that SHP-2 is targeted by ROS produced in collagen-stimulated platelets and suggests that a novel mechanism for the regulation of platelet activation by ROS is due to oxidative inactivation of SHP-2. We conclude that collagen-induced ROS production leads to SHP-2 oxidation, which promotes platelet activation by upregulating tyrosine phosphorylation-based signal transduction.


[3D/4D strategic lymph node diagnostics : The 4D representation of the human lymph node enables the observation and interpretation of the immune system in space and time].
Lymph-node diagnostics is performed using thin sections, with help of immunohistochemistry by light microscopy and supplemented by molecular pathology. Which are the scientific and diagnostic perspectives of 3D and 4D lymph node investigations, using laser, scanning, and computer technologies? What is the impact of machine learning in complex data analysis. It was shown in different investigations that the analysis in space and time (3D/4D) of lymph node tissue is able to provide a lot of new information concerning biology and diagnostics and enable excellent evaluations applying machine learning. 3D and 4D analysis of human lymphoid tissue gives new insights into immunologic mechanisms and malignant lymphomas.


Exosomes derived from mesenchymal stem cells improved core symptoms of genetically modified mouse model of autism Shank3B.
Partial or an entire deletion of SHANK3 are considered as major drivers in the Phelan-McDermid syndrome, in which 75% of patients are diagnosed with autism spectrum disorder (ASD). During the recent years, there was an increasing interest in stem cell therapy in ASD, and specifically, mesenchymal stem cells (MSC). Moreover, it has been suggested that the therapeutic effect of the MSC is mediated mainly via the secretion of small extracellular vesicle that contains important molecular information of the cell and are used for cell-to-cell communication. Within the fraction of the extracellular vesicles, exosomes were highlighted as the most effective ones to convey the therapeutic effect. Exosomes derived from MSC (MSC-exo) were purified, characterized, and given via intranasal administration to Shank3B KO mice (in the concentration of 107 particles/ml). Three weeks post treatment, the mice were tested for behavioral scoring, and their results were compared with saline-treated control and their wild-type littermates. Intranasal treatment with MSC-exo improves the social behavior deficit in multiple paradigms, increases vocalization, and reduces repetitive behaviors. We also observed an increase of GABARB1 in the prefrontal cortex. Herein, we hypothesized that MSC-exo would have a direct beneficial effect on the behavioral autistic-like phenotype of the genetically modified Shank3B KO mouse model of autism. Taken together, our data indicate that intranasal treatment with MSC-exo improves the core ASD-like deficits of this mouse model of autism and therefore has the potential to treat ASD patients carrying the Shank3 mutation.


Integrative genomic analysis in African American children with asthma finds three novel loci associated with lung function.
Bronchodilator (BD) drugs are commonly prescribed for treatment and management of obstructive lung function present with diseases such as asthma. Administration of BD medication can partially or fully restore lung function as measured by pulmonary function tests. The genetics of baseline lung function measures taken before BD medication have been extensively studied, and the genetics of the BD response itself have received some attention. However, few studies have focused on the genetics of post-BD lung function. To address this gap, we analyzed lung function phenotypes in 1103 subjects from the Study of African Americans, Asthma, Genes, and Environment, a pediatric asthma case-control cohort, using an integrative genomic analysis approach that combined genotype, locus-specific genetic ancestry, and functional annotation information. We integrated genome-wide association study (GWAS) results with an admixture mapping scan of three pulmonary function tests (forced expiratory volume in 1 s [FEV1 ], forced vital capacity [FVC], and FEV1 /FVC) taken before and after albuterol BD administration on the same subjects, yielding six traits. We identified 18 GWAS loci, and five additional loci from admixture mapping, spanning several known and novel lung function candidate genes. Most loci identified via admixture mapping exhibited wide variation in minor allele frequency across genotyped global populations. Functional fine-mapping revealed an enrichment of epigenetic annotations from peripheral blood mononuclear cells, fetal lung tissue, and lung fibroblasts. Our results point to three novel potential genetic drivers of pre- and post-BD lung function: ADAMTS1, RAD54B, and EGLN3.


Effectiveness of the Australian MATES in Construction Suicide Prevention Program: a systematic review.
Suicide is a major public health issue globally. The World Health Organization has called for nations to create comprehensive national suicide prevention strategies including multisectoral collaboration, awareness raising, advocacy and capacity building. The workplace provides opportunity and structure for suicide prevention programs. However, many of these programs are poorly documented and evaluated. The MATES in Construction (MATES) program is a multimodal workplace-based suicide prevention program designed for and by the construction industry. This systematic review examined the available evidence for the effectiveness of the MATES program and is reported according to PRISMA guidelines. A literature search resulted in the inclusion of 12 peer-reviewed articles published between January 2010 and February 2023 containing primary data of evaluations of MATES. There was evidence of the effectiveness of the MATES program in improving mental health and suicide prevention literacy, helping intentions and reducing stigma. The results highlighted the importance of worker-to-worker peer approaches with workers consistently stating that supervisors were the least trusted resources for mental health and suicide concerns. Favourable results were found in relation to reduced suicide risk in the construction industry. The evidence base for MATES is limited in terms of causal inference with very few controlled evaluations and no experimental studies having been conducted to date. Improved understanding of how the program motivates volunteers, their experiences and research on the longer-term impacts of the program on the industry is required.


Estimation of glycogen levels in human colorectal cancer tissue: relationship with cell cycle and tumor outgrowth.
In this study, we quantitatively measured glycogen levels in tissue samples obtained from tumors, regions adjacent to tumor, and regions of normal colorectum to determine whether the levels were related to cell cycle and cancer growth. Glycogen levels were analyzed in relation to histopathological factors, (tumor size and stage of disease) and cell cycle progression. The glycogen level was found to be highest in the cancer tissue, lower in normal tissue, and lowest in the adjacent tissue. The difference in glycogen level between the cancer tissue and the other two regions was significant (P < 0.05). There was a negative correlation between glycogen level and tumor size, but it was not significant. The level of glycogen in cancer tissues decreased as the stage of the disease progressed, but a significant difference was not found between stages. There was a negative correlation between the glycogen level and the proliferation index. There was a positive correlation between the glycogen level and the proportion of cancer cells in G1 phase, while there was a negative correlation with S and G2M phases. Glycogen levels were highest in cancers with a high proportion of cells in G1, and decreased with progression to S phase. It may be that glycogen is utilized in the progression to S phase, and the cancer tissues are supplied with glycogen from the tumors themselves as well as their adjacent tissues. Cancer growth may be inhibited by artificial control of the glycogen level in the G1 phase of cancer cells.


Detection and prognostic impact of micrometastasis in colorectal cancer.
Review of literature was performed on studies with prognostic impact of micrometastasis in colorectal cancer. Among 16 studies included, micrometastasis was detected in 26.5% of patients. Most analysis revealed that micrometastasis carries a poorer prognosis compared to node negative disease (NND). The results of those studies were compared with our pilot study of 109 patients with colon cancer, showing improved prognosis of micrometastasis after being upstaged and treated with chemotherapy when compared with NND.


[Prevention and control of HIV infection in the Osh region of the Kyrgyz Republic].
A total of 178 cases of HIV infection were diagnosed in the Osh region of the Kyrgyz Republic for January 1, 2003, the intensity of the prevalence of HIV infection being 14.5 per 100,000 of the population with this figure for the whole republic being equal to 5.9. In the dynamics of the HIV infection epidemic two periods were detected. During the first 3 years (1998-2000) a few individual imported cases of HIV infection were registered in the region. During the last 2 years (2001-2002) 98.8% of all cases of HIV infection registered in the region, as well as the presence of an epidemic outbreak among injection drug users (IDU), were detected. The risk factors of getting HIV infection were the intravenous use of drugs and a low level of information among young people concerning the routes of transmission of this infection and means of protection from HIV/AIDS: the promotion of healthy life style among young people, the introduction of the programs of "harm reduction" among IDU and the rules of safe sex.


[The long road home: a discussion of the autonomy of schizophrenia patients after their discharge from the hospital].
Every adult has the right to self-determination and to have his or her autonomy respected. While schizophrenia patients have the right to be discharged from the hospital, their needs subject their caregivers to high care loadings. This situation presents a dilemma for the medical team. The authors justify the patient's autonomy to request and to be granted a discharge. Then, present the decision-making process related to discharge for the reference of medical teams. Capacity is necessary to autonomy. There is currently no standard for assessing the capacity of patients that clearly defines their competence. A sliding scale approach to decision making distinguishes between decisions involving significant potential risk and, therefore, involving higher level of capacity requirements and decisions on minimal potential risk. In order to protect the interests of patients, the sliding scale approach takes into account different decisions. Cases in which schizophrenia patients choose to self-discharge involve a high-level of risk. Poor preparations for follow-up care lead to poor-quality patient care and may cause harm to the patients. In a share decision model, the medical team plays the role of negotiator between the patient and the family and respects the autonomy of the patient while supporting the family through the hospital discharge process. Medical team must have a discharge planning for the patient and family, follow-up care system, and support network. During hospitalization, the discharge plan aims to facilitate the life adaptation and disease recovery for patients with the goal of restoring their normal home life.


Analysis of a telephone hotline for palliative care patients at home and their families.
To describe the use of a telephone consultation (TC) hotline for palliative care (PC) patients and their families at home provided by a PC service, during the COVID-19 lockdown. Observational and cross-sectional study of a TC hotline performed by a PC service from 1 January to 31 December 2020. Data was collected through a record sheet completed during the call. Descriptive analyses were performed using the SPSS software (V.21 for Windows). A total of 494 calls were retrieved (n=187 patients; 6500 minutes recorded). Compared to 2019, incoming calls increased 33.8%. Most callers were a family member (n=419) or a community health worker (n= 60). The peak of calls was registered in April (13.5%), May (13.2%) and October (15.0%). Main problems included uncontrolled symptoms (81.9%), need for medication (8.6%), information (4.8%) and consultation rescheduling (2.6%). In 81.9% of the cases, the call occurred during a crisis. The PC team solved 92.9% of the problems. Only 20 patients were admitted in the emergency department (this was 30.5% less compared to 2019). The TC is a feasible alternative to traditional in-person follow-ups. Callers considered it very useful, especially during the COVID-19 lockdown. Communication was improved and admissions to emergency services were reduced.


Laparoscopic and robotic nephroureterectomy: does lymphadenectomy have an impact on the clinical outcome?
To evaluate the effect of lymphadenectomy (LND) in conjunction with nephroureterectomy on cancer-specific mortality (CSM) and overall survival (OS) for patients with muscle-invasive UTUC. A retrospective, multicenter study of patients with UTUC, clinical stage N0M0, who underwent nephroureterectomy between January 2008 and December 2014 was conducted. Outcome measures were OS and CSM. In total, 298 patients underwent robot-assisted or laparoscopic radical nephroureterectomy with a final histological diagnosis of UTUC. LND was performed in 46 (15.4%). One hundred and seventy-two patients (62%) had non-muscle-invasive disease (NMID); 105 patients (38%) had muscle-invasive disease (MID). Median time of follow-up was 43.5 months (95% CI 36.0-47.2). For patients with MID, the 5-year cumulative incidence of all-cause mortality and CSM was 73.5% (95% CI 60.4-86.6) and 52.4% (95% CI 38.9-65.9), respectively (p < 0.0001). There was no significant difference in OS between patients with N1 and patients with N0 disease (p = 0.53). The 5-year OS rates were 30.5% (95% CI 6.6-54.4) and 25.7% (95% CI 10.9-40.5), respectively. This study is limited by its retrospective nature. There may also have been bias in the selection of patients undergoing LND. Five-year OS and CSM are comparable between patients with N1 and N0 MID. This evidence may support the use of the LND procedure in patients with muscle-invasive UTUC.


Increasing fire frequency and severity will increase habitat loss for a boreal forest indicator species.
Climate change will lead to more frequent and more severe fires in some areas of boreal forests, affecting the distribution and availability of late-successional forest communities. These forest communities help to protect globally significant carbon reserves beneath permafrost layers and provide habitat for many animal species, including forest-dwelling caribou. Many caribou populations are declining, yet the mechanisms by which changing fire regimes could affect caribou declines are poorly understood. We analyzed resource selection of 686 GPS-collared female caribou from three ecotypes and 15 populations in a ~600,000 km2 region of northwest Canada and eastern Alaska. These populations span a wide gradient of fire frequency but experience low levels of human-caused habitat disturbance. We used a mixed-effects modeling framework to characterize caribou resource selection in response to burns at different seasons and spatiotemporal scales, and to test for functional responses in resource selection to burn availability. We also tested mechanisms driving observed selection patterns using burn severity and lichen cover data. Caribou avoided burns more strongly during winter relative to summer and at larger spatiotemporal scales relative to smaller scales. During the winter, caribou consistently avoided burns at both spatiotemporal scales as burn availability increased, indicating little evidence of a functional response. However, they decreased their avoidance of burns during summer as burn availability increased. Burn availability explained more variation in caribou selection for burns than ecotype. Within burns, caribou strongly avoided severely burned areas in winter, and this avoidance lasted nearly 30 years after a fire. Caribou within burns also selected higher cover of terrestrial lichen (an important caribou food source). We found a negative relationship between burn severity and lichen cover, confirming that caribou avoidance of burns was consistent with lower lichen abundance. Consistent winter avoidance of burns and severely burned areas suggests that caribou will experience increasing winter habitat loss as fire frequency and severity increase. Our results highlight the potential for climate-induced alteration of natural disturbance regimes to affect boreal biodiversity through habitat loss. We suggest that management strategies prioritizing protection of core winter range habitat with lower burn probabilities would provide important climate-change refugia for caribou.


Pathologic significance of nephromegaly in pediatric disease.
Ultrasonic renal volume and length measurements are easily performed in pediatric patients. Increases in volume over the normal level provide a potentially attractive method of assessing the severity and progression or regression of renal diseases. However, an analysis of data on 59 children with clinical renal disease and nephromegaly did not demonstrate any correlation with severity of the disease. We conclude that increases in renal length and volume in pediatric patients may indicate the presence of disease but not its severity.


Three-Dimensional Endoscopic Magnification for Treatment of Thoracic Spinal Dural Arteriovenous Fistulas: Technical Note.
Treatment of thoracic spinal dural arteriovenous fistulas (DAVFs) by microsurgery has recently been approached using minimally invasive spine surgery (MISS). The advantages of such an approach are offset by difficult maneuverability within the tubular retractor and by the creation of "tunnel vision" with reduced luminosity to a remote surgical target. To demonstrate how the pitfalls of MISS can be addressed by applying 3-D endoscopy to the minimally invasive approach of spinal DAVFs. We present 2 cases of symptomatic thoracic DAVFs that were not amenable to endovascular treatment. The DAVFs were excluded solely via a minimally invasive approach using a 3-D endoscope. Two patients underwent exclusion of a DAVF following laminotomy, one through a midline 5-cm incision and the other through a paramedian 3-cm incision using minimally invasive nonexpandable tubular retractors. The dura opening, intradural exploration, fistula exclusion, and closure were performed solely under endoscopic 3-D magnification. No incidents were recorded and the postoperative course was marked by clinical improvement. Postoperative imaging confirmed the exclusion of the DAVFs. Anatomical details are exposed using intraoperative videos. When approaching DAVFs via MISS, replacing the microscope with the endoscope remedies the limitations related to the "tunnel vision" created by the tubular retractor, but at the expense of losing binocular vision. We show that the 3-D endoscope resolves this latter limitation and provides an interesting option for the exclusion of spinal DAVFs.


Abdominal Obesity and Type 2 Diabetes Mellitus are Associated With Higher Seric Levels of IL 4 in Adults.
Study of IL4 in relation to the anthropometric, biochemical and immunological parameters in patients with obesity and/or diabetes. The relationship between IL4 and clinical and biological parameters was studied in 76 patients divided into 4 groups: obese diabetics (OD), n = 25; obese without diabetes (O), n = 25; non obese diabetics (NOD), n = 11; controls (M), n = 15. IL4 was determined using the ELISA method. Statistical analysis was done using the MedCalc statistical software, version 16.1. Serum IL4 was 0.38 ±0,40 pg / mL in the Control group, 0.366 (0,100-2,35) pg / ml in group O, 4.66±3.73 pg / ml in group OD, 0.30 (0.10-1.35) pg / ml in NOD. When IL4 levels were compared between the four groups, statistical significance was reached for the comparison between groups OD and M. Statistically significant correlations were detected between IL4 and age, waist circumference and hip circumference, blood glucose, glycated hemoglobin (HbA1c), VLDL, triglycerides and serum protein fraction β1. In univariate regression, the IL4 level predictors were age, height, BMI, abdominal circumference, hip circumference, beta 1% glucose, HbA1c, total lipids, total cholesterol, VLDL triglycerides, CRP. In multivariate regression, waist circumference and glycemia were significant predictors of levels of IL4 (p = 0.0001).


Healthcare epidemiology: Ventilator-associated pneumonia: preventing the inevitable.
Ventilator-associate pneumonia (VAP) is the most common nosocomial infection in patients in intensive care units (ICU). Because of its association with unwanted clinical outcomes, preventive measures have been studied intensively in the past 25 years. Unfortunately, a large amount of clinical trials yielded disappointingly few clear-cut answers. Furthermore, because of the difficulties in reliably diagnosing VAP, we should be very reluctant in embracing measures that have been associated with VAP reductions in small-sized studies, but with no benefits on patient outcome documented in sufficiently powered well-designed trials. Only topical antimicrobial prophylaxis (either alone in the oropharynx or in combination with intestinal decontamination) has been demonstrated to improve patient outcome resulting from prevention of VAP. However, this was demonstrated in not-so-average circumstances-in ICUs with extremely low levels of antibiotic resistance. Despite the obvious challenges with using antibiotics as preventive measures, careful evaluation of these strategies in settings with higher drug-resistance levels is now justified, and future studies should be designed to demonstrate outcome benefits rather than reductions in VAP rates.


Expression of the Arabidopsis vacuolar H⁺-pyrophosphatase gene (AVP1) improves the shoot biomass of transgenic barley and increases grain yield in a saline field.
Cereal varieties with improved salinity tolerance are needed to achieve profitable grain yields in saline soils. The expression of AVP1, an Arabidopsis gene encoding a vacuolar proton pumping pyrophosphatase (H⁺-PPase), has been shown to improve the salinity tolerance of transgenic plants in greenhouse conditions. However, the potential for this gene to improve the grain yield of cereal crops in a saline field has yet to be evaluated. Recent advances in high-throughput nondestructive phenotyping technologies also offer an opportunity to quantitatively evaluate the growth of transgenic plants under abiotic stress through time. In this study, the growth of transgenic barley expressing AVP1 was evaluated under saline conditions in a pot experiment using nondestructive plant imaging and in a saline field trial. Greenhouse-grown transgenic barley expressing AVP1 produced a larger shoot biomass compared to null segregants, as determined by an increase in projected shoot area, when grown in soil with 150 mM NaCl. This increase in shoot biomass of transgenic AVP1 barley occurred from an early growth stage and also in nonsaline conditions. In a saline field, the transgenic barley expressing AVP1 also showed an increase in shoot biomass and, importantly, produced a greater grain yield per plant compared to wild-type plants. Interestingly, the expression of AVP1 did not alter barley leaf sodium concentrations in either greenhouse- or field-grown plants. This study validates our greenhouse-based experiments and indicates that transgenic barley expressing AVP1 is a promising option for increasing cereal crop productivity in saline fields.


Lurasidone for the acute treatment of adults with schizophrenia: what is the number needed to treat, number needed to harm, and likelihood to be helped or harmed?
To describe the efficacy, safety and tolerability of lurasidone for the acute treatment of schizophrenia using the metrics number needed to treat (NNT) and number needed to harm (NNH). Study data were pooled from six Phase II and III, 6-week, randomized, placebo-controlled trials that were conducted to test the efficacy and safety of lurasidone for the acute treatment of schizophrenia. Included were the following interventions: fixed doses of lurasidone 20, 40, 80, 120 and 160 mg/d; haloperidol 10 mg/d; olanzapine 15 mg/d; quetiapine extended-release 600 mg/d; placebo. The following outcomes were assessed: responder rates as defined by a reduction of ≥20, 30, 40 or 50% from baseline on the Positive and Negative Syndrome Scale (PANSS) total score; study completion; discontinuation due to an adverse event (AE); weight gain ≥7% from baseline; incidence of spontaneously reported AEs; incidence of total cholesterol ≥240 mg/dL, low-density lipoprotein cholesterol ≥160 mg/dL, fasting triglycerides ≥200 mg/dL and glucose ≥126 mg/dL at endpoint. NNT for the efficacy outcomes were calculated after excluding one failed study. NNH for the safety/tolerability outcomes were calculated using all six studies. Likelihood of being helped or harmed (LHH) was also calculated to illustrate trade-offs between outcomes of improvement ≥30% on the PANSS vs. incidence of akathisia, nausea, sedation, somnolence and parkinsonism. NNT vs. placebo for PANSS reductions ≥30% were 6, 6, 7 and 4 for lurasidone doses of 40, 80, 120 and 160 mg/d, respectively, and 4 and 3 for olanzapine 15 mg/d and quetiapine extended-release 600 mg/d, respectively. Lurasidone was not associated with any statistically significant disadvantages over placebo for weight gain or metabolic abnormalities; NNH vs. placebo for weight gain ≥7% from baseline was 4 for olanzapine and 9 for quetiapine extended-release in contrast to a NNH for this outcome ranging from 43 to 150 for lurasidone 40-160 mg/d. The 5 most consistently encountered adverse events attributable to lurasidone were akathisia, nausea, sedation, somnolence and parkinsonism, with NNH vs. placebo for lurasidone 40-120 mg/d ranging from 6 (akathisia with 120 mg/d) to 30 (parkinsonism with 80 mg/d). Lurasidone 160 mg/d appeared better tolerated than doses of 40, 80 or 120 mg/d for akathisia, nausea, sedation or somnolence, with no NNH values for these adverse events for 160 mg/d vs. placebo being statistically significant. LHH was favorable for lurasidone when contrasting PANSS reductions vs. adverse events. NNT and NNH can help quantify efficacy, safety and tolerability outcomes and place lurasidone into clinical perspective. Advantages for lurasidone include a low propensity for weight gain and metabolic abnormalities. More commonly encountered adverse events include akathisia, nausea, sedation, somnolence and parkinsonism, but NNH values are generally in the double digits, reflecting an overall tolerable profile. Individual patient characteristics, values and preferences will need to be considered when selecting lurasidone over other antipsychotics.


The EMBL-EBI bioinformatics web and programmatic tools framework.
Since 2009 the EMBL-EBI Job Dispatcher framework has provided free access to a range of mainstream sequence analysis applications. These include sequence similarity search services (https://www.ebi.ac.uk/Tools/sss/) such as BLAST, FASTA and PSI-Search, multiple sequence alignment tools (https://www.ebi.ac.uk/Tools/msa/) such as Clustal Omega, MAFFT and T-Coffee, and other sequence analysis tools (https://www.ebi.ac.uk/Tools/pfa/) such as InterProScan. Through these services users can search mainstream sequence databases such as ENA, UniProt and Ensembl Genomes, utilising a uniform web interface or systematically through Web Services interfaces (https://www.ebi.ac.uk/Tools/webservices/) using common programming languages, and obtain enriched results with novel visualisations. Integration with EBI Search (https://www.ebi.ac.uk/ebisearch/) and the dbfetch retrieval service (https://www.ebi.ac.uk/Tools/dbfetch/) further expands the usefulness of the framework. New tools and updates such as NCBI BLAST+, InterProScan 5 and PfamScan, new categories such as RNA analysis tools (https://www.ebi.ac.uk/Tools/rna/), new databases such as ENA non-coding, WormBase ParaSite, Pfam and Rfam, and new workflow methods, together with the retirement of depreciated services, ensure that the framework remains relevant to today's biological community.


Patient values in breast cancer surgical decision-making - The WhySurg study.
The objective of this study was to describe patient values and personality traits associated with breast surgery choice for patients with breast cancer. A survey based on qualitative patient interviews and the Big-Five personality trait profile was distributed to Love Research Army volunteers aged 18-70 years old who underwent breast cancer surgery from 2009 to 2020. Multivariable logistic regression analysis was used to determine independent patient values and personality traits for the choice of breast-conserving surgery (BCS), unilateral mastectomy (UM) and bilateral mastectomy (BM). 1497 participants completed the survey. Open-mindedness was associated with UM and sociability was associated with BM. A majority of patients prioritized cancer outcomes. Compared to BM patients, BCS and UM patients were significantly more likely to choose values associated with maintaining their self-image, optimizing surgical recovery, and following their doctor's recommendation. Other values besides cancer outcomes differentiate patient surgical choice for BCS or mastectomy.


A 5-Year Observational Study of Patients With Treatment-Resistant Depression Treated With Vagus Nerve Stimulation or Treatment as Usual: Comparison of Response, Remission, and Suicidality.
The Treatment-Resistant Depression Registry investigated whether adjunctive vagus nerve stimulation (VNS) with treatment as usual in depression has superior long-term outcomes compared with treatment as usual only. This 5-year, prospective, open-label, nonrandomized, observational registry study was conducted at 61 U.S. sites and included 795 patients who were experiencing a major depressive episode (unipolar or bipolar depression) of at least 2 years' duration or had three or more depressive episodes (including the current episode), and who had failed four or more depression treatments (including ECT). Patients with a history of psychosis or rapid-cycling bipolar disorder were excluded. The primary efficacy measure was response rate, defined as a decrease of ≥50% in baseline Montgomery-Åsberg Depression Rating Scale (MADRS) score at any postbaseline visit during the 5-year study. Secondary efficacy measures included remission. Patients had chronic moderate to severe depression at baseline (the mean MADRS score was 29.3 [SD=6.9] for the treatment-as-usual group and 33.1 [SD=7.0] for the adjunctive VNS group). The registry results indicate that the adjunctive VNS group had better clinical outcomes than the treatment-as-usual group, including a significantly higher 5-year cumulative response rate (67.6% compared with 40.9%) and a significantly higher remission rate (cumulative first-time remitters, 43.3% compared with 25.7%). A subanalysis demonstrated that among patients with a history of response to ECT, those in the adjunctive VNS group had a significantly higher 5-year cumulative response rate than those in the treatment-as-usual group (71.3% compared with 56.9%). A similar significant response differential was observed among ECT nonresponders (59.6% compared with 34.1%). This registry represents the longest and largest naturalistic study of efficacy outcomes in treatment-resistant depression, and it provides additional evidence that adjunctive VNS has enhanced antidepressant effects compared with treatment as usual in this severely ill patient population.


Do public health clinics reduce rehospitalizations?: the urban diabetes study.
Safety-net health clinics have been shown to reduce hospitalizations for ambulatory care-sensitive conditions. Their impact on rehospitalization after hospital discharge is unknown. We hypothesized that use of publicly-funded safety-net health clinics would reduce rates of rehospitalization among patients with diabetes. We expected this effect to be most evident among the most vulnerable patients. Linking data from the Philadelphia Health Care Centers (HCCs) with statewide hospital discharge data for 1994-2001 for patients with diabetes, we found that patients enrolled in the HCCs prior to hospitalization were rehospitalized 22% of the time, the same rate as other Philadelphians. Among those at higher risk of rehospitalization because pre-existing diabetes was not noted in hospital records, odds of rehospitalization were reduced by 24% for HCC patients. Given that patients in the HCCs are overwhelmingly poor and uninsured or underinsured, these findings suggest that access to primary care through the HCCs may have a protective effect against the poor health outcomes typically associated with lower socioeconomic status. Enrollment in publicly-funded safety-net health clinics may have prevented rehospitalizations for some vulnerable patients with diabetes.


Secondary intracranial neoplasia in the dog: 177 cases (1986-2003).
This study investigates the frequency, location, and clinical findings associated with 177 secondary brain tumors in dogs. Secondary intracranial neoplasia is more common than primary intracranial neoplasia in dogs during the time period studied, and hemangiosarcoma (HSA) is the most common secondary intracranial tumor. One hundred and seventy-seven client-owned dogs presented to the Matthew J. Ryan Veterinary Hospital between 1986 and 2003. Medical records were searched for a diagnosis of intracranial neoplasia in dogs who underwent complete postmortem examination. Of these dogs, those with a diagnosis of primary intracranial neoplasia were excluded. Of the 177 secondary brain tumors, 51 (29%) were HSAs, 44 (25%) were pituitary tumors, 21 (12%) were lymphosarcomas, and 21 (12%) were metastatic carcinomas. The average age at diagnosis was 9.6 +/- 3.0 years. Most tumors were located in the cerebrum, and a mentation change was the most common presenting clinical sign. On postmortem examination, the same tumor that was in the brain was also present in the lung in 84 cases (47%), in the kidney in 62 cases (35%), and in the heart in 55 cases (31%). Secondary intracranial neoplasia in dogs was more common than primary intracranial neoplasia during the time period studied. Many of these dogs had related disease in other body systems that was apparent on diagnostic tests such as thoracic radiography.


The nonlinear viscoelasticity of hyaluronic acid and its role in joint lubrication.
Hyaluronic acid solutions have been widely studied due to their relevance to the rheological behavior of synovial fluid and joint lubrication. Ambulatory joint motion is typically large oscillatory deflections; therefore, large amplitude oscillatory shear strain experiments are used to examine the relevant non-linear viscoelastic properties of these solutions. Using the sequence of physical processes method to analyze data provides time dependent viscoelastic moduli, which exhibit a clear physiologically relevant behavior to hyaluronic acids non-linear viscoelasticity. In particular, it is seen that during peak strain/acceleration, the time dependent elastic modulus peaks and the loss modulus is at a minimum. The hyaluronic acid can provide an immediate elastic response to sudden forces, acting like a shock absorber during sudden changes in direction of motion or maximum deflection. However, during peak rate, the elastic modulus is at a minimum and the loss modulus is at a maximum, which provides greater efficacy to hydrodynamic shear lubrication.


Organophosphate pesticide exposure and work in pome fruit: evidence for the take-home pesticide pathway.
Organophosphate (OP) pesticides are commonly used in the United States, and farmworkers are at risk for chronic exposure. Using a sample of 218 farmworkers in 24 communities and labor camps in eastern Washington State, we examined the association between agricultural crop and OP pesticide metabolite concentrations in urine samples of adult farmworkers and their children and OP pesticide residues in house and vehicle dust samples. Commonly reported crops were apples (71.6%), cherries (59.6%), pears (37.2%), grapes (27.1%), hops (22.9%), and peaches (12.4%). Crops were grouped into two main categories: pome fruits (apples and pears) and non-pome fruits. Farmworkers who worked in the pome fruits had significantly higher concentrations of dimethyl pesticide metabolites in their urine and elevated azinphos-methyl concentrations in their homes and vehicles than workers who did not work in these crops. Among pome-fruit workers, those who worked in both apples and pears had higher urinary metabolites concentrations and pesticide residue concentrations in dust than did those who worked in a single pome fruit. Children living in households with pome-fruit workers were found to have higher concentrations of urinary dimethyl metabolites than did children of non-pome-fruit workers. Adult urinary concentrations showed significant correlations with both the vehicle and house-dust azinphos-methyl concentrations, and child urinary concentrations were correlated significantly with adult urinary concentrations and with the house-dust azinphos-methyl concentration. The results provide support for the take-home pathway of pesticide exposure and show an association between measures of pesticide exposure and the number of pome-fruit crops worked by farmworkers.


Thermodynamics of Membrane Insertion and Refolding of the Diphtheria Toxin T-Domain.
The diphtheria toxin translocation (T) domain inserts into the endosomal membrane in response to the endosomal acidification and enables the delivery of the catalytic domain into the cell. The insertion pathway consists of a series of conformational changes that occur in solution and in the membrane and leads to the conversion of a water-soluble state into a transmembrane state. In this work, we utilize various biophysical techniques to characterize the insertion pathway from the thermodynamic perspective. Thermal and chemical unfolding measured by differential scanning calorimetry, circular dichroism, and tryptophan fluorescence reveal that the free energy of unfolding of the T-domain at neutral and mildly acidic pH differ by 3-5 kcal/mol, depending on the experimental conditions. Fluorescence correlation spectroscopy measurements show that the free energy change from the membrane-competent state to the interfacial state is approximately -8 kcal/mol and is pH-independent, while that from the membrane-competent state to the transmembrane state ranges between -9.5 and -12 kcal/mol, depending on the membrane lipid composition and pH. Finally, the thermodynamics of transmembrane insertion of individual helices was tested using an in vitro assay that measures the translocon-assisted integration of test sequences into the microsomal membrane. These experiments suggest that even the most hydrophobic helix TH8 has only a small favorable free energy of insertion. The free energy for the insertion of the consensus insertion unit TH8-TH9 is slightly more favorable, yet less favorable than that measured for the entire protein, suggesting a cooperative effect for the membrane insertion of the helices of the T-domain.


Varicella-zoster virus productively infects mature dendritic cells and alters their immune function.
Mature dendritic cells (DCs) are potent antigen-presenting cells essential for initiating successful antiviral immune responses and would therefore serve as an ideal target for viruses seeking to evade or delay the immune response by disrupting their function. We have previously reported that VZV productively infects immature DCs (A. Abendroth, G. Morrow, A. L. Cunningham, and B. Slobedman, J. Virol. 75:6183-6192, 2001), and in the present study we assessed the ability of VZV to infect mature DCs. Mature DCs were generated from immature monocyte-derived DCs by lipopolysaccharide treatment before being exposed to VZV-infected fibroblasts. On day 4 postexposure, flow cytometry analysis revealed that 15 to 45% of mature DCs were VZV antigen positive, and immunofluorescent staining together with infectious-center assays demonstrated that these cells were fully permissive for the complete VZV replicative cycle. VZV infection of mature DCs resulted in a selective downregulation of cell surface expression of the functionally important immune molecules major histocompatibility complex (MHC) class I, CD80, CD83, and CD86 but did not alter MHC class II expression. Immunofluorescent staining showed that the downregulation of cell surface CD83 was concomitant with a retention of CD83 in cytoplasmic vesicles. Importantly, VZV infection of mature DCs significantly reduced their ability to stimulate the proliferation of allogeneic T lymphocytes. These data demonstrate that mature DCs are permissive for VZV and that infection of these cells reduces their ability to function properly. Thus, VZV has evolved yet another immune evasion strategy that would likely impair immunosurveillance and enhance the chances for lifelong persistence in the human population.


Scaled preparation of extracellular vesicles from conditioned media.
Extracellular vesicles (EVs) especially of mesenchymal stem/stomal cells (MSCs) are increasingly considered as biotherapeutic agents for a variety of different diseases. For translating them effectively into the clinics, scalable production processes fulfilling good manufacturing practice (GMP) are needed. Like for other biotherapeutic agents, the manufacturing of EV products can be subdivided in the upstream and downstream processing and the subsequent quality control, each of them containing several unit operations. During upstream processing (USP), cells are isolated, stored (cell banking) and expanded; furthermore, EV-containing conditioned media are produced. During downstream processing (DSP), conditioned media (CM) are processed to obtain concentrated and purified EV products. CM are either stored until DSP or are directly processed. As first unit operation in DSP, clarification removes remaining cells, debris and other larger impurities. The key operations of each EV DSP is volume-reduction combined with purification of the concentrated EVs. Most of the EV preparation methods used in conventional research labs including differential centrifugation procedures are limited in their scalability. Consequently, it is a major challenge in the therapeutic EV field to identify appropriate EV concentration and purification methods allowing scale up. As EVs share several features with enveloped viruses, that are used for more than two decades in the clinics now, several principles can be adopted to EV manufacturing. Here, we introduce and discuss volume reducing and purification methods frequently used for viruses and analyze their value for the manufacturing of EV-based therapeutics.


Development of a Costa Rican version of the Childhood Health Assessment Questionnaire.
To validate a Spanish language version of the Childhood Health Assessment Questionnaire (CHAQ) for use in Costa Rica and to evaluate the feasibility, reliability, and cross cultural equivalency of this version. The original questionnaire, translated without modification into Spanish, was administered to 12 children, all above 10 years of age, with the diagnosis of juvenile chronic arthritis (JCA) and to their parents. There were several problems in comprehension, and self-administration with this version was not possible. For this reason a teacher and a psychologist were consulted to create a modified Costa Rican version. We administered this 2nd version to 46 children with JCA and 62 of their parents. The modified Costa Rican HAQ (CR-CHAQ) was self-administered by 93.5% of the patients and 84% of the parents. The median time to complete the questionnaire was 12 min for the children, 10 min for the parents. The main difficulty in comprehension was the pain score for both groups. Test-retest (Spearman R = 0.73) and interobserver (Spearman R = 0.70) reliability were good. Validity of the instrument was confirmed by the high correlation between the disability and discomfort scores and conventional clinical variables. There was satisfactory correlation between the disability score and conventional clinical variables. Discriminant validity was confirmed by the capacity of the CR-CHAQ to evaluate patients as being in different categories of disease activity. After modifications, the CR-CHAQ achieved cross cultural equivalency.


Comment on 'expectancy of life at birth in 36 nationalities of the Soviet Union: 1958-60'.
Abstract In D. Peter Mazur's recent article, 'Expectancy of Life at Birth in 36 Nationalities of the Soviet Union: 1958-1960', crude rates of death and expectancies of life for nationalities are derived from a scant base of data that includes crude rates of natural increase for administrative units and various ratios of composition of the populations of both administrative units and nationalities. Students of Soviet demography genuinely appreciate Mazur's attempt to derive rich results from meagre data. Of course, to do this strong assumptions are required and Mazur warns that 'the quantitative results ... are valid only to the extent that the underlying methodology is theoretically sound'. One way to test the quantitative results is to examine how well the crude death rates for the nationalities calculated by Mazur reproduce the crude death rates for administrative units with which Mazur started. Mazur feels that the estimated death rates for nationalities closely agree with the death rates for administrative areas. The present author is sceptical. Application of the method described below does not show close correspondence, and this matter, which is crucial in the evaluation of Mazur's results, seems problematical.


Effect of salicylic acid treatment on postharvest quality, antioxidant activities, and free polyamines of asparagus.
The effects of salicylic acid (SA) on the quality and antioxidant activity of asparagus stored at 18 ± 2 °C were investigated by analyzing the color, chlorophyll, shear force, and the activity of antioxidant compounds such as ascorbic acid, phenolics, flavonoids, 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity ferric reducing antioxidant power (FRAP), and polyamines (PAs). The results showed that SA improved the color and maintained the chlorophyll, phenolic, flavonoid, and ascorbic acid content of asparagus. High concentrations of SA caused a deterioration in asparagus would harm to color and had no effect on shear force within 6 d. SA induced the maximum concentration of phenolics in postharvest asparagus, promoted the increase in total flavonoids before 6 to 9 d, affected the antioxidant activity positively as indicated by the resultant increase in FRAP concentration; however, SA was only active with regard to DPPH scavenging activity within 6 d of treatment. Spermidine (Spd) is the most common form of PA in asparagus, and free putrescine (Put) contents increased over the first 3 d following harvest and then decreased. Spd and Spm concentrations evolved in a similar way and decreased during storage. Higher Spd and Spm contents in the SA pre-treatment Put was inhabited and its peaks appeared later.


Novel immunosuppressive agent, FK506. In vitro effects on the cloned T cell activation.
The present study shows the in vitro effects of a novel immunosuppressive agent, FK506, in comparison with cyclosporin A (CsA). FK506 inhibited concanavalin A response and allo-mixed lymphocyte reaction of murine splenic lymphocytes in a dose-dependent manner, and at 40- to 200-fold lower concentrations than CsA. Allo-cytolytic T lymphocyte induction from murine thymocytes was also inhibited by FK506, whereas the ability of cytolytic T lymphocyte to lyse targets was not affected by the agent. Immunosuppressive effects of FK506 were further characterized by using antigen specific-proliferative T lymphocyte clones, BC.21 and KO.6. FK506 inhibited the proliferation of T cell clones stimulated with specific antigens in a dose-dependent manner, and at about 100-fold lower concentrations than CsA. However, cloned T cells, once activated, were scarcely affected by the agent; interleukin-2 (IL-2) driven proliferation of cloned T cells was not inhibited. On the other hand, it was found that FK506 inhibited both IL-2 secretion and IL-2 receptor expression of BC.21 after stimulation with the specific antigen. FK506 also inhibited the proliferation of BC.21 stimulated with phorbol 12-myristate 13-acetate plus calcium ionophore, indicating that it directly affected the signaling pathway downward from the perturbation of the Ti/T3 complex. Finally, it was suggested that FK506 and CsA synergistically inhibited the antigen-driven proliferation of cloned T cells. These results indicate that the novel immunosuppressive agent, FK506, affects T cell activation with mechanisms similar to those of CsA but at considerably lower concentrations.


Further evidence to show population specificity of discriminant function equations for sex determination using the talus of South African blacks.
Several studies have shown that osteometric differences exist between different population groups. Thus, discriminant function equations derived for the determination of sex from skeletal elements are population specific. In a previous study, the authors derived such equations from nine measurements of the talus of South African whites with high levels of average accuracies. The validity of some of the equations was tested on data collected from a South African black sample that consisted of 120 tali, equally distributed by sex, derived from the Raymond A. Dart Collection of Human Skeletons. The average accuracies dropped significantly. This necessitated the derivation of new equations for the South African black population and the average accuracies obtained ranged between 80% and 89%. The validity of the equations derived from the present study was tested using the leave-one-out classification and two independent samples (1 and 2). The applicability of the equations with very high classification rate from the present study was tested on Independent sample 1 of 10 white tali with poor results. The result of the validity of these equations on an Independent sample 2 of 10 black tali revealed acceptably high average accuracies in correct classification thereby supporting earlier observations on population specificity of discriminant function equations.


Predictors of early and delayed recovery in peripartum cardiomyopathy: a prospective study of 52 Patients.
Background: Predictors of early or delayed recovery are unclear in peripartum cardiomyopathy (PPCM). Therefore, we aimed to assess the prognostic value of serial assessment of clinical, echocardiographic, and biochemical markers in patients with PPCM.Methods: Fifty-two consecutive women with PPCM were enrolled in this prospective study. Each patient underwent transthoracic echocardiography, B-type natriuretic peptide (BNP) and C-reactive protein (CRP) measurement at admission, and every 3 months. Early recovery was defined as resolution of heart failure at 6 months postdiagnosis, delayed recovery was defined if the length of time required for recovery of left ventricular function was longer than 6 months, and persistent left ventricular dysfunction (PLVD) was defined as an ejection fraction of less than 50% at the end of follow-up.Results: Thirty patients (57.7%) recovered completely, 10 died (19.2%), and 12 (23.1%) had PLVD. There were no significant differences in baseline BNP and CRP values between patients who recovered completely and who did not recover. However, patients with complete recovery were more likely to have a higher left ventricular ejection fraction, smaller left ventricle end-systolic dimensions at baseline, and lower CRP and BNP levels at follow-up. Elevated levels of BNP and CRP on follow up at 3 and 6 months were associated with nonrecovery. Third and sixth month BNP values were significantly lower in patients with rapid recovery, compared to patients with delayed recovery. Bromocriptine therapy was also associated with early recovery.Conclusions: Persistent elevation of plasma CRP and BNP levels at follow-up portend a slower response or nonrecovery in patients with PPCM. Bromocriptine therapy was an independent predictor of early recovery.


Clinical electrophysiology in myasthenia gravis.
Effective diagnostic methods are of great importance in order to recognise myasthenic patients among those with muscle fatigability. Intracellular recordings are useful for research work within the field and for detailed description of the motor end-plate's physiology in the individual case. The method is not used for the routine diagnosis of myasthenia gravis. The decrement of the electrical muscle response with nerve stimulation is the most commonly used method. The diagnostic yield is higher in proximal muscles, in warmed muscles, after exercise, and after ischaemia. A significant number of patients may be undiagnosed with this technique. The mechanical response with nerve stimulation shows the same type of decrement but also an abnormal response to long stimulation. The diagnostic value of this is under dispute. Single fibre ENG needs more patient cooperation than do these tests. The diagnostic yield is significantly higher. Some patients considered to have myasthenia gravis do not show any abnormalities with this technique, particularly those with the pure ocular form. Conventional EMG is not useful for the diagnosis of myasthenia, but may be indicated in these patients when concurrent nerve or muscle disease is in question. Tests for eye movement fatique have not proved useful. Stapedius reflex fatigability is demonstrated in about the same proportion of patients as have positive SFEMG findings. The technique is not uncomfortable for the patient and requires minimal cooperation. The general usefulness must be assessed by further routine use. Even with the advent of immunological tests, neurophysiological investigations are indispensable in helping establish the diagnosis of myasthenia gravis. Discrepancies between the results comparing electrophysiological and immunological tests may indicate that myasthenia gravis is a heterogenous entity within which subgroups may be identified.


Sheehan's Syndrome A Case Report and Literature Review.
Post-partum pituitary necrosis (Sheehan's syndrome) is a rare complication of post-partum hemorrhage. The diagnosis can be erratic and often delayed. In this case report of Sheehan's syndrome in the post-partum period, the signs were characterized by agalactia, severe hypoglycemia, and low serum levels of thyroid hormones, cortico-adrenal hormones, and gonadotrophin (FSH, LH). The hypophyseal magnetic resonance imaging confirmed the diagnosis of hypopituitarism secondary to pituitary necrosis.


Early host-pathogen interactions in a marine bivalve: Crassostrea virginica pallial mucus modulates Perkinsus marinus growth and virulence.
Perkinsus marinus is an important protistan parasite of the eastern oyster Crassostrea virginica. Recent findings showed that oyster pallial organs (mantle, gills) are a major portal of entry for the parasite. Therefore, mucus covering these organs represents the first host effectors encountered by P. marinus. This study consisted of several experiments designed to investigate the effect of oyster pallial mucus on the growth, protease production and infectivity of P. marinus. In each experiment, P. marinus performance in cultures supplemented with pallial mucus (mantle, gill, or both) was compared to that of parasite cells grown in unsupplemented media or in cultures supplemented with oyster plasma or digestive extracts. P. marinus grown in media supplemented with C. virginica mantle mucus showed a significantly higher growth rate than cultures enriched with the other supplemental extracts, while cultures grown in gill mucus promoted higher protease production. Conversely, P. marinus grown in cultures supplemented with pallial mucus of the non-compatible host Crassostrea gigas (Pacific oyster) were dramatically inhibited. Challenge experiments showed a significant increase in P. marinus virulence in cultures supplemented with C. virginica pallial mucus as compared to unsupplemented cultures or to those supplemented with digestive extract or plasma. These results suggest that C. virginica mucus plays a significant role in the pathogenesis of P. marinus by enhancing the proliferation and the infectivity of this devastating parasite. The contrasting results obtained with both oyster species indicate that P. marinus host specificity may begin in the mucus.


Salt intake and blood pressure response to percutaneous renal denervation in resistant hypertension.
The effect of lowering sympathetic nerve activity by renal denervation (RDN) is highly variable. With the exception of office systolic blood pressure (BP), predictors of the BP-lowering effect have not been identified. Because dietary sodium intake influences sympathetic drive, and, conversely, sympathetic activity influences salt sensitivity in hypertension, we investigated 24-hour urinary sodium excretion in participants of the SYMPATHY trial. SYMPATHY investigated RDN in patients with resistant hypertension. Both 24-hour ambulatory and office BP measurements were end points. No relationship was found for baseline sodium excretion and change in BP 6 months after RDN in multivariable-adjusted regression analysis. Change in the salt intake-measured BP relationships at 6 months vs baseline was used as a measure for salt sensitivity. BP was 8 mm Hg lower with similar salt intake after RDN, suggesting a decrease in salt sensitivity. However, the change was similar in the control group, and thus not attributable to RDN.


The disease burden associated with overweight and obesity.
Overweight and obesity are increasing dramatically in the United States and most likely contribute substantially to the burden of chronic health conditions. To describe the relationship between weight status and prevalence of health conditions by severity of overweight and obesity in the US population. Nationally representative cross-sectional survey using data from the Third National Health and Nutrition Examination Survey (NHANES III), which was conducted in 2 phases from 1988 to 1994. A total of 16884 adults, 25 years and older, classified as overweight and obese (body mass index [BMI] > or =25 kg/m2) based on National Institutes of Health recommended guidelines. Prevalence of type 2 diabetes mellitus, gallbladder disease, coronary heart disease, high blood cholesterol level, high blood pressure, or osteoarthritis. Sixty-three percent of men and 55% of women had a body mass index of 25 kg/m2 or greater. A graded increase in the prevalence ratio (PR) was observed with increasing severity of overweight and obesity for all of the health outcomes except for coronary heart disease in men and high blood cholesterol level in both men and women. With normal-weight individuals as the reference, for individuals with BMIs of at least 40 kg/m2 and who were younger than 55 years, PRs were highest for type 2 diabetes for men (PR, 18.1; 95% confidence interval [CI], 6.7-46.8) and women (PR, 12.9; 95% CI, 5.7-28.1) and gallbladder disease for men (PR, 21.1; 95% CI, 4.1-84.2) and women (PR, 5.2; 95% CI, 2.9-8.9). Prevalence ratios generally were greater in younger than in older adults. The prevalence of having 2 or more health conditions increased with weight status category across all racial and ethnic subgroups. Based on these results, more than half of all US adults are considered overweight or obese. The prevalence of obesity-related comorbidities emphasizes the need for concerted efforts to prevent and treat obesity rather than just its associated comorbidities.