Enrichment of biofertilizer-type hydrogen-oxidizing bacteria on urea containing Cu(II).
With the utilization of pesticides and fertilizers (e.g. urea), the presence of nitrogen and heavy metals (e.g. copper) can enter and pollute the environment. Biofertilizers can be used to replace chemical fertilizers to increase crop yields and reduce environmental stress. The utilization of hydrogen-oxidizing bacteria (HOB) to be biofertilizers has recently attracted more attention. However, the enrichment of HOB on urea and the effect of copper are undetermined. HOB were successfully enriched using urea in this investigation. The average urea conversion rate (AUCR) was 180.08 mgN/L/d with a hydraulic retention time of 10 h. Microbial community (R1) was dominated by Hydrogenophaga (83.92%), a biofertilizer-type HOB. After addition of 5.47 mg/L Cu2+, the AUCR was decreased by 16%-151.18 mgN/L/d, and the growth of HOB was inhibited by 48%. Meanwhile, inhibition was also reflected by the increase of polysaccharide content (20.27 ± 0.57 to 33.45 ± 2.53 mg/gVSS) and protein content (106.19 ± 19.39 to 125.14 ± 24.73 mg/gVSS) of extracellular polymeric substances in the HOB. The resulting microbial community (R2) was changed to Azospiralium-dominated flora (91.33%). Both enriched microbial communities (R1 and R2) exhibited the abilities of ACC degradation and phosphate solubilization. This study demonstrates that employing urea can directly enrich biofertilizer-type HOB and copper-tolerant HOB can be obtained in a 5.47 mg/L Cu2+ environment. The results provide potential methods to obtain biofertilizer from copper-containing urea wastewater via HOB.


Wave-Like Dose-Dependence of the Stimulating Effects of Dimebon on Cognition in a Wide Dose Range.
Comparison of the cognition-stimulating effects of Dimebon in a wide dose range revealed a non-monotonic and nontrivial wave-like dose-dependence of its activity. Positive results were obtained at low (0.02-0.05 mg/kg) or high (5-10 mg/kg) doses of Dimebon, while intermediate doses were ineffective. This type of the dose dependence of the pharmacological effect can indicate that the substance has several targets. This fact should be taken into consideration when selecting the doses and concentrations of the substance and its analogues for further studies, and for planning treatment schemes and administration doses in clinical studies.


Purification and properties of a protamine kinase from bovine kidney microsomes.
About an eightfold increase in protamine kinase activity was detected following extraction of highly purified microsomes from bovine kidney with 1% Triton X-100. Relative to the soluble fraction, the microsomes contained about 30% protamine kinase activity. The microsomal protamine kinase was purified to apparent homogeneity. The purified enzyme exhibited an apparent M(r) approximately 45,000 as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by gel permeation chromatography on Sephacryl S-200. Relative to protamine, the purified kinase exhibited about 100% activity with the synthetic peptide RRLSSLRA and about 5, 8, and less than 0.1% activity with casein, histone H2B, and histone H1, respectively. The purified kinase phosphorylated several 40 S ribosome polypeptides. One of these polypeptides was identified as ribosomal protein S6 by N-terminal sequencing. About 2.5 mol of phosphoryl groups was incorporated per mole of ribosomal protein S6 following incubation of the 40 S ribosomes with the purified kinase. Following incubation with protein phosphatase 2A2, purified preparations of the protamine kinase were inactivated. These properties were identical to those of purified preparations of a protamine kinase from extracts of bovine kidney cytosol (Z. Damuni, G.D. Amick, and T.R. Sneed, 1989, J. Biol. Chem. 264, 6412-6418). Near identical peptide patterns were obtained following incubation of purified preparations of the microsomal and cytosolic protamine kinases with Staphylococcus aureus V8 proteinase. The results indicate that a form of the cytosolic protamine kinase is present in microsomes.


Surgical decompression of a tension pneumomediastinum. A ventilatory complication of status asthmaticus.
A case of status asthmaticus was associated with cardiorespiratory arrest, illustrating rarely reported complications of ventilatory therapy including tension pneumomediastinum and coronary air embolization. Proposed pathophysiologic mechanisms and recommendations for surgical management are discussed.


Diffusion tensor imaging of the nigrostriatal fibers in Parkinson's disease.
Parkinson's disease (PD) is histopathologically characterized by the loss of dopamine neurons in the substantia nigra pars compacta. The depletion of these neurons is thought to reduce the dopaminergic function of the nigrostriatal pathway, as well as the neural fibers that link the substantia nigra to the striatum (putamen and caudate), causing a dysregulation in striatal activity that ultimately leads to lack of movement control. Based on diffusion tensor imaging, visualizing this pathway and measuring alterations of the fiber integrity remain challenging. The objectives were to 1) develop a diffusion tensor tractography protocol for reliably tracking the nigrostriatal fibers on multicenter data; 2) test whether the integrities measured by diffusion tensor imaging of the nigrostriatal fibers are abnormal in PD; and 3) test whether abnormal integrities of the nigrostriatal fibers in PD patients are associated with the severity of motor disability and putaminal dopamine binding ratios. Diffusion tensor tractography was performed on 50 drug-naïve PD patients and 27 healthy control subjects from the international multicenter Parkinson's Progression Marker Initiative. Tractography consistently detected the nigrostriatal fibers, yielding reliable diffusion measures. Fractional anisotropy, along with radial and axial diffusivity of the nigrostriatal tract, showed systematic abnormalities in patients. In addition, variations in fractional anisotropy and radial diffusivity of the nigrostriatal tract were associated with the degree of motor deficits in PD patients. Taken together, the findings imply that the diffusion tensor imaging characteristic of the nigrostriatal tract is potentially an index for detecting and staging of early PD.


Death on the table. Some thoughts on how to handle an anaesthetic-related death.
This describes one way to handle the aftermath of anaesthetic catastrophe. The techniques of how to share bad news, interview relatives, complete official forms, deal with the legal process and debrief colleagues are outlined. It is hoped that this article will promote discussion on this topic and improve communication with all those affected by mishaps in the operating suite.


Ultrasonography of the shoulder. Static and dynamic imaging.
High-resolution, real-time ultrasonography is an effective diagnostic technique for evaluating rotator cuff movements and is useful in detecting aberrations that correlate with rotator cuff biomechanics and impingement syndrome.


Comparative study of serum and synovial fluid interleukin-11 levels in patients with various arthritides.
To determine the levels of serum and synovial fluid (SF) interleukin (IL)-11 in patients with various arthritides and estimate the contribution of IL-11 to acute phase response (APR). Serum and SF IL-11 were measured by ELISA in patients with rheumatoid arthritis (RA, n = 31), seronegative spondyloarthritis (SSA, n = 23), gout (GT, n = 14) and osteoarthritis (OA, n = 20) and were correlated with ESR and acute phase proteins as well as with cytokines IL-1 alpha, IL-1 beta, IL-6, and TNF alpha. IL-11 was detected in both serum and SF in each group, with IL-11 being statistically higher in SF than serum in all groups, suggesting reduced catabolism or increased synthesis of IL-11 intra-articularly. Median SF IL-11 levels were higher in OA patients than in other groups and in the treated than in the untreated RA subgroup. Moreover, serum and SF IL-11 were correlated significantly with each other, and moderately with the other cytokines examined in RA, SSA, and GT, but not in OA patients, while a significant negative correlation was found with a few of the inflammatory markers examined in each group. Our findings provide evidence of extensive intra-articular expression of IL-11 in arthritides, especially in OA and treated RA patients, suggesting a protective role for IL-11 in joints, probably through the induction of tissue inhibitor of metalloproteinases.


Degradation of paper mill water components in laboratory tests with pure cultures of bacteria.
The degradation of dissolved and colloidal substances from thermomechanical pulp (TMP) by bacteria isolated from a paper mill was studied in a laboratory slide culture system. Burkholderia cepacia strains hydrolysed triglycerides to free fatty acids, and the liberated unsaturated fatty acids were then degraded to some extent. Saturated fatty acids were not notably degraded. However, the branched anteiso-heptadecanoic fatty acid was degraded almost like the unsaturated fatty acids. About 30% of the steryl esters were degraded during 11 days, increasing the concentrations of free sterols. Approximately 25% of the dehydroabietic, and 45% of the abietic and isopimaric resin acids were degraded during 11 days. The degree of unsaturation seemed to be of greater importance for the degradation of fatty acids than the molar mass. No degradation of dissolved hemicelluloses could be observed with any of the nine bacterial strains studied. Burkholderia cepacia strains and one Bacillus coagulans strain degraded monomeric fructose and glucose in winter TMP water, but in summer TMP water, with much lower sugar concentrations, also other Bacillus strains degraded monomeric sugars.


End-to-end anastomosis after segmental esophagectomy for early stage cervical esophageal carcinoma.
Surgical procedures are still controversial for patients with cervical esophagus carcinoma. Conventional surgical procedures of cervical esophagectomy or total esophagectomy and esophageal reconstruction are invasive and time taking, which contributes to higher morbidity and mortality. Here, we describe a technique of local esophagectomy for the treatment of early stage cervical esophageal carcinoma. The cervical esophagus is circumferentially mobilized and transected segmentally at the appropriate level, followed by direct end-to-end anastomosis of esophagus. The procedure has been performed in 7 patients aged 59 to 82 years old, with minor postoperative complications.


Cerebellar pilocytic astrocytoma in childhood: Investigating the long-term impact of surgery on cognitive performance and functional outcome.
Previous studies differ regarding the long-term effects of surgically removed pediatric cerebellar pilocytic astrocytomas (CPA). Thus, the aim of this study was to investigate the long-term impact on neurocognitive and functional outcome and to analyze age as an influencing factor. Fourteen CPA patients were compared to the age norm and to a group of 14 high-achieving peers regarding cognitive functioning, health-related quality of life (HRQoL), and stress regulation. Mean follow-up time after diagnosis was 13.29 years (range: 3-21 years). Patients showed satisfactory academic achievement and did not differ from the norm except for the bodily dimension of HRQoL. However, there were marked differences in specific neurocognitive functions between patients and high achievers. Age at diagnosis did not influence neurocognitive outcome. CPA patients treated with surgery only seem to have a favorable long-term outcome, yet, in comparison with high achievers specific cognitive impairments become apparent.


Tumor infiltrating lymphocytes in head and neck squamous cell carcinoma - Evaluation and clinical impact.
Head-and-neck squamous cell carcinomas (HNSCCs) are one of the most common malignancies worldwide. Emerging evidence reveals that tumor-infiltrating lymphocytes (TIL) provide valuable prognostic information in various malignancies, including HNSCC. The present study aimed to evaluate a simple yet accurate method of counting TILs in HNSCCs. It was also done to determine if there is any correlation between different clinicopathological parameters of HNSCC and TIL counts. A. retrospective institutional-based, observational study was undertaken for 1 year. Patients with histologically proven HNSCCs were included. All clinicopathological parameters were noted, and evaluation of TIL was meticulously done both in the stromal and intratumoral regions for each case. Standard statistical methods were employed for data analysis. The present study included 81 patients, among which 51 (63%) were male and the rest (30, 37%) were female. The mean age of the patients was 55.3 ± 10.5 years. Most tumors were located in the oral cavity (73, 90.1%). The most common histologic type was moderately differentiated (MD) squamous cell carcinoma (SCC) (50 cases, 61.7%). Stromal TIL score was high in 45 cases (55.6%). In 69 cases (85.2%), the intratumoral TIL level was low. A statistically significant correlation was found between TIL levels (both stromal and intratumoral TIL) and tumor differentiation, pT stage, and lymphovascular invasion. The correlation between intratumoral TIL level, age of patients, and pN stage was also statistically significant. TIL evaluation is an inexpensive, simple, and reproducible method, which furnishes relevant prognostic data. It has the potential for consideration of its inclusion in routine histopathological reports of HNSCCs.


A multiphysics model of photo-sensitive hydrogels in response to light-thermo-pH-salt coupled stimuli for biomedical applications.
This paper aims to unveil the fundamental response mechanism of photo-sensitive hydrogels subject to light-thermo-pH-salt coupled stimuli, for their potential biomedical uses such as cell scaffolds and extracellular matrices, where biological activity largely depends on internal electrochemical changes. To mimic the microenvironment of biomolecules or cells, we focus on a spirobenzopyran-modified N-isopropylacrylamide hydrogel incorporating acrylic acid as a proton generator and develop a multiphysics model to characterize its behaviour within aqueous solution in response to light intensity, temperature, buffer pH, and salt concentration. The model allows for concurrent chemical reactions, ionic diffusion, electrostatic effects and large mechanical deformation, as well as interaction with the solution domain. Validation was performed by comparison with the published experimental results and showed good agreement. It is demonstrated by the simulation results that the photo-sensitive hydrogel exhibits a varied sensitivity to the external stimuli if incorporated with different molar ratios of acrylic acid. The electrical and pH response characteristics of the hydrogel, especially those in neutral solution, may inspire some potential biomedical applications, such as photo-controlled drug release and cell growth.


Differential necrosis despite similar perfusion in mouse strains after ischemia.
Numerous mouse models have been used to study the tissue response to ischemia, but multiple technical differences make comparisons difficult. We have comprehensively characterized the mouse hind limb ischemia model and determined how different genetic backgrounds of mice affect recovery. Severity of tissue necrosis and restoration of perfusion after femoral artery excision or femoral artery transection, using five different surgical procedures, were evaluated using laser Doppler imaging in a mouse model of hind limb ischemia. Severity of necrosis was concurrently measured using a five-point scale. Significant differences were observed depending upon the surgical procedure used to initiate ischemia as well as the strain of mouse used. First, a progressively delayed and incomplete recovery of vascular perfusion occurred in relation to the anatomical position and extent of the arterial defect. Second, among mouse strains, the severity of tissue necrosis varied despite similar restoration of perfusion. Thus, DBA/1J mice had significantly increased severity and incidence of tissue loss as compared with either C57Bl/6J (P = 0.01) or BALB/c (P = 0.01) mice. Finally, contrary to previous reports, T-cell-mediated immune events did not modify ischemia-induced hind limb perfusion and necrosis as responses in nude mice were not different than controls on either BALB/c or C57Bl/6J backgrounds. Surgical approach, mouse strain, and measures of hind limb perfusion and tissue injury are crucial considerations in the study of ischemia. Understanding how different genetic backgrounds in mice can affect necrosis may provide insights into the diverse healing responses observed in humans.


A study on the association between C1GALT1 polymorphisms and the risk of Henoch-Schönlein purpura in a Chinese population.
Henoch-Schönlein purpura (HSP) is the most common systemic vasculitis of childhood. The molecular etiology of HSP is not well understood. The purpose of this study is to investigate the association between polymorphisms in C1GALT1 gene and the risk of HSP in a Chinese population. A total of unrelated 542 northern Chinese were enrolled in this study. PCR-RFLP method was used to genotype the five tagging SNPs in the C1GALT1 gene. Chi-squared test and logistic regression analysis were used for the comparison of genotype distribution between cases and controls. The five tagging SNPs were all in Hardy-Weinberg equilibrium in controls. SNP7 was significantly associated with HSP risk, P = 0.005. The DI genotype, compared with the DD genotype, was associated with a significantly higher risk of developing HSP (OR 1.72; 95 % CI 1.11-2.67). The II genotype, compared with the DD genotype, was associated with a significantly higher risk of developing HSP (OR 3.39; 95 % CI 1.16-9.30). Other SNPs were not associated with HSP risk. Variations in the C1GALT1 gene were found to be associated with HSP risk. Further studies are warranted to validate our findings and to investigate into its underlining mechanism.


Toy story: A cross-sectional survey of toy populations in tertiary neonatal units.
Thousands of babies are given toys for their zeroth birthday … But what happens if that baby is admitted to neonatal intensive care? In a global first, we describe the population of toys found in incubators on neonatal intensive care unit.


Prevalence of liver cirrhosis in individuals with hepatitis B virus infection in sub-Saharan Africa: Systematic review and meta-analysis.
Chronic hepatitis B virus (HBV) infection accounts for 30%-50% of cirrhosis related deaths in sub-Saharan Africa (SSA). Since HBV-related cirrhosis is an indication for immediate antiviral therapy and cancer surveillance, we aimed to estimate the prevalence of cirrhosis among treatment-naïve patients with chronic HBV infection in SSA. We performed a systematic review of published articles which evaluated liver fibrosis stage among treatment-naïve HBV-infected individuals who presented to care in SSA. Our primary outcome was the prevalence of cirrhosis in HBsAg-positive persons, which was estimated using random-effects meta-analysis. Risk factors for cirrhosis were explored using subgroup-analyses and multivariable meta-regression. Of 2129 articles identified, 17 met our eligibility criteria. The studies described 22 cohorts from 13 countries, including 13 cohorts (3204 patients) with chronic HBV mono-infection and nine cohorts (688 patients) with HIV/HBV-coinfection. Liver fibrosis was assessed using transient elastography (10 cohorts), APRI score (11 cohorts), and Fibrotest (one cohort). The pooled prevalence of cirrhosis was 4.1% (95% confidence interval [CI] 2.6-6.4) among studies from primary care facilities or general population, compared to 12.7% (95% CI 8.6-18.3) in studies performed in referral or tertiary care facilities (adjusted odds ratio 0.29, 95% CI 0.15-0.56). We found no association between cirrhosis and age, gender, fibrosis test used or HIV-coinfection. Depending on the setting, between 4% and 13% of HBV-infected individuals in SSA have cirrhosis and need immediate antiviral therapy. These estimates should be considered when planning HBV treatment strategies and resource allocation.


Perceived emotion regulation and emotional distress tolerance in patients with hoarding disorder.
Emotional distress tolerance (EDT) and emotion regulation (ER) appear to be highly relevant to hoarding pathology, as excessive saving and/or acquiring may be motivated by emotional avoidance or other attempts to regulate negative affect. While findings with nonclinical samples have suggested and EDT/ER predicts hoarding symptoms, there is little data on clinical samples. The aim of the current study was to examine several self-report measures of EDT and ER in individuals with HD (n = 87) and age-matched nonclinical controls (n = 46), and to explore whether this was predictive of treatment compliance and/or outcome in group CBT for HD. Results suggested that, the Difficulties in Emotion Regulation Scale (DERS; Gratz & Roemer, 2004) total score, DERS goals and awareness subscales, and Intolerance of Uncertainty Scale (IUS; Buhr & Dugas, 2002) were predictive of hoarding severity. However, EDT/ER did not change with treatment, did not mediate treatment outcome, and did not predicted treatment retention, compliance, or outcome. Results suggest that some EDT/ER constructs, such as uncertainty intolerance, difficulty persisting in goal behaviors when upset, and low emotional awareness, may explain significant variance in HD symptoms, although they did not appear to be mechanisms of change in CBT for HD.


Collateral bladder duplication with exstrophy of one moiety in a female infant.
Complete bladder duplication with exstrophy of one moiety is an extremely rare condition. We report an unusual case of complete bladder duplication with exstrophy of one moiety, in which each bladder received one ureter and the internal bladder drained into a urogenital sinus. The patient was treated by combining the two bladder halves and using the bladder neck of the internal bladder, with excellent cosmetic result. This case underscores the importance of ultrasonography and computed tomography to detect the anatomy of the patient with exstrophy in whom the ureteric orifices cannot be clearly identified on both sides of the trigone.


Endovascular Retrograde Reconstruction of the Left Renal Artery through the False Lumen of a Postdissection Thoracoabdominal Aortic Aneurysm-A Case Report.
Postdissection aneurysm is an indication for intervention due to high risk of rupture. However, the reconstruction of visceral branches involved in this disease, especially those perfused by a false lumen, is a tough and challenging task. In this article, we describe a case of successful total endovascular repair via retrograde reconstruction of the left renal artery through the false lumen of a postdissection thoracoabdominal aortic aneurysm.


Flower-like surface modification of titania materials by lithium hydroxide solution.
Surface modification of titania materials to give flower-like structures has been achieved simply by the treatment in lithium hydroxide aqueous solution under mild conditions. The flower-like structured materials were characterized by X-ray diffraction, thermogravimetric analysis, and Raman scattering. The analyses indicate that the flower-like materials are composed of layered hydrous lithium titanate. It is suggested that the unique intercalation behavior of lithium ions into titania allows dissolution and re-precipitation of titania to form the flower-like structure. The obtained flower-like structure can be retained up to 700 °C, while the crystal phase transforms into Li(4)Ti(5)O(12).


Longitudinal white matter change in frontotemporal dementia subtypes and sporadic late onset Alzheimer's disease.
Degradation of white matter microstructure has been demonstrated in frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). In preparation for clinical trials, ongoing studies are investigating the utility of longitudinal brain imaging for quantification of disease progression. To date only one study has examined sample size calculations based on longitudinal changes in white matter integrity in FTLD. To quantify longitudinal changes in white matter microstructural integrity in the three canonical subtypes of frontotemporal dementia (FTD) and AD using diffusion tensor imaging (DTI). 60 patients with clinical diagnoses of FTD, including 27 with behavioral variant frontotemporal dementia (bvFTD), 14 with non-fluent variant primary progressive aphasia (nfvPPA), and 19 with semantic variant PPA (svPPA), as well as 19 patients with AD and 69 healthy controls were studied. We used a voxel-wise approach to calculate annual rate of change in fractional anisotropy (FA) and mean diffusivity (MD) in each group using two time points approximately one year apart. Mean rates of change in FA and MD in 48 atlas-based regions-of-interest, as well as global measures of cognitive function were used to calculate sample sizes for clinical trials (80% power, alpha of 5%). All FTD groups showed statistically significant baseline and longitudinal white matter degeneration, with predominant involvement of frontal tracts in the bvFTD group, frontal and temporal tracts in the PPA groups and posterior tracts in the AD group. Longitudinal change in MD yielded a larger number of regions with sample sizes below 100 participants per therapeutic arm in comparison with FA. SvPPA had the smallest sample size based on change in MD in the fornix (n = 41 participants per study arm to detect a 40% effect of drug), and nfvPPA and AD had their smallest sample sizes based on rate of change in MD within the left superior longitudinal fasciculus (n = 49 for nfvPPA, and n = 23 for AD). BvFTD generally showed the largest sample size estimates (minimum n = 140 based on MD in the corpus callosum). The corpus callosum appeared to be the best region for a potential study that would include all FTD subtypes. Change in global measure of functional status (CDR box score) yielded the smallest sample size for bvFTD (n = 71), but clinical measures were inferior to white matter change for the other groups. All three of the canonical subtypes of FTD are associated with significant change in white matter integrity over one year. These changes are consistent enough that drug effects in future clinical trials could be detected with relatively small numbers of participants. While there are some differences in regions of change across groups, the genu of the corpus callosum is a region that could be used to track progression in studies that include all subtypes.


The impact of epistasis in the heterosis and combining ability analyses.
The current theoretical knowledge concerning the influence of epistasis on heterosis is based on a simplified multiplicative model. The objective of this study was to assess how epistasis affects the heterosis and combining ability analyses, assuming additive model, hundreds of genes, linkage disequilibrium (LD), dominance, and seven types of digenic epistasis. We developed the quantitative genetics theory for supporting the simulation of the individual genotypic values in nine populations, the selfed populations, the 36 interpopulation crosses, 180 doubled haploids (DHs), and their 16,110 crosses, assuming 400 genes on 10 chromosomes of 200 cM. Epistasis only affects population heterosis if there is LD. Only additive × additive and dominance × dominance epistasis can affect the components of the heterosis and combining ability analyses of populations. Epistasis can have a negative impact on the heterosis and combining ability analysis of populations, leading to wrong inferences regarding the identification of superior and most divergent populations. However, this depends on the type of epistasis, percentage of epistatic genes, and magnitude of their effects. Except for duplicate genes with cumulative effects and non-epistatic genic interaction, there was a decrease in the average heterosis by increasing the percentage of epistatic genes and the magnitude of their effects. The same results are generally true for the combining ability analysis of DHs. The combining ability analyses of subsets of 20 DHs showed no significant average impact of epistasis on the identification of the most divergent ones, regardless of the number of epistatic genes and magnitude of their effects. However, a negative effect on the assessment of the superior DHs can occur assuming 100% of epistatic genes, but depending on the epistasis type and the epistatic effect magnitude.


The 13p HSR in a human neuroblastoma cell line does not contain rRNA genes.
We have studied a human neuroblastoma cell line containing a homogeneously staining region (HSR) on the short (p) arm of chromosome #13. The HSRs are believed to represent sites of gene amplification, containing multiple copies of one or a small number of genes. The 18S and 28S ribosomal RNA genes are the only structural genes so far assigned to the p arms of the human acrocentric chromosomes, which include number #13. Using two recombinant DNA probes specific for sequences in the 18S/28S ribosomal RNA (rRNA) gene complex for in situ hybridization, we have been able to establish that the 13pHSR in this line does not contain rRNA genes.


"Did I get into the twilight zone somehow?": sexual and gender minority cancer caregiver experiences during COVID.
The COVID-19 pandemic created new challenges for cancer patients and caregivers. Little is known about the confluence of the pandemic and people with multiple marginalized identities, such as those in the Sexual and Gender Minority (SGM) community. We conducted a mixed-methods pilot study using semi-structured interviews to elicit experiences of cancer among a diverse population of SGM patients and caregivers and a matched set of cisgender heterosexual (cishet) individuals. Here, we present qualitative findings focused on caregiver experiences as ascertained from the broader study. We discovered differences between SGM and cishet caregiving experiences, with SGM caregivers reporting less comfort in the cancer center environment; dissatisfaction with patient-provider communication; feeling excluded from their loved ones' care; and increased social isolation resulting from the caregiver experience. SGM and cishet caregivers described the detrimental impact of the pandemic. Our data suggest SGM caregivers experience additional burdens to cancer caregiving when compared to cishet peers. Although SGM and cishet caregivers reported challenges stemming from the COVID-19 pandemic, challenges appeared greater and more acute for SGM caregivers. Pandemic-related findings point to overall gaps in SGM cancer caregiver supports that may be remedied by additional research and targeted intervention development.


High urinary sulfate concentration is associated with reduced risk of renal disease progression in type 2 diabetes.
Diabetes is associated with a high incidence of microvascular disease, including nephropathy. Diabetic nephropathy is the most common cause of chronic kidney disease in the Western world. Sulfate in the urine is the metabolic end product of hydrogen sulfide (H2S), a recent discovered gaseous signaling molecule. Urinary sulfate has earlier shown beneficial predictive properties in renal transplant recipients. Based on the protective role of exogenous H2S in experimental models of diabetic nephropathy, we aimed to cross-sectionally investigate the association of sulfate with renal risk markers, and to prospectively investigate its predictive value for renal events in patients with diabetic nephropathy. Post-hoc analysis on data of the sulodexide macroalbuminuria (Sun-MACRO) trial and the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study was performed. A total of 1004 patients with type 2 diabetes were included. Urinary sulfate concentration was measured and cross-sectionally associated to renal risk markers by linear regression. Multivariable Cox regression analysis was performed to assess the prospective association of sulfate with renal events, which was defined as end stage renal disease or a doubling of baseline serum creatinine. Mean age was 63 ± 9 years, median sulfate concentration was 8.0 (IQR 5.8-11.4) mmol/L. Urinary sulfate positively associated with male gender, hemoglobin, and negatively associated with albuminuria at baseline. During follow-up for 12 (IQR 6-18) months, 38 renal events occurred. Each doubling of urinary sulfate was associated with a 19% (95%CI 1%-34%) lower risk of renal events, independent of adjustment for potential confounders, including age, estimated glomerular filtration rate (eGFR), and albuminuria. To conclude, higher urinary sulfate concentration is associated with a more beneficial profile of renal risk markers, and is independently associated with a reduced risk for renal events in type 2 diabetes patients with nephropathy.


Inositol 1,4,5-trisphosphate receptor immunoreactivity in SH-SY5Y human neuroblastoma cells is reduced by chronic muscarinic receptor activation.
Inositol 1,4,5-trisphosphate (InsP3) receptor immunoreactivity in SH-SY5Y human neuroblastoma cells was monitored with a monoclonal antibody raised against the mouse cerebellar InsP3 receptor. Recognition of a protein corresponding to the InsP3 receptor (molecular mass, approximately 275 kDa) was inhibited markedly following exposure of cells to 0.1 mM carbachol. This effect was half-maximal and maximal at approximately 2 and approximately 6 h, respectively; was blocked by atropine; but was not mimicked by thapsigargin, K+, or phorbol 12-myristate 13-acetate. However, the decrease in immunoreactivity following exposure of cells to carbachol for 5 h was blocked if the extracellular Ca2+ concentration was reduced from 1.3 mM to 200 nM. This manipulation also reduced markedly carbachol-induced increases in InsP3 concentration at 5 h. These data indicate that chronic muscarinic stimulation of phosphoinositide hydrolysis reduces InsP3 receptor concentration in SH-SY5Y cells, perhaps via a mechanism that involves prolonged elevation of InsP3 levels.


Subjective Perception of Sports Performance, Training, Sleep and Dietary Patterns of Malaysian Junior Muslim Athletes during Ramadan Intermittent Fasting.
To examine the subjective perception of daily acute fasting on sports performance, training, sleep and dietary patterns of Muslim athletes during the Ramadan month. Seven hundred and thirty-four (411 male and 323 female) Malaysian Junior-level Muslim athletes (mean age 16.3 ± 2.6 y) participated in the survey which was designed to establish the personal perception of their sport performance, sleep pattern, food and fluid intake during Ramadan fasting. The survey was conducted during and immediately after the month of Ramadan in 2009. Twenty-four percent of the athletes perceived that there was an adverse effect of the Ramadan fast on their sporting performance and 29.3% reported that quality of training during Ramadan was also negatively influenced. Majority (48.2%) of the athletes stated that Ramadan fasting did not affect their normal sleep pattern but 66.6% of them complained of sleepiness during the daytime. Half of the athletes (41.4%) maintained the caloric intake during Ramadan as they normally would with the majority of them (76.2%) reporting that they consumed more fluids during Ramadan. Overall, Malaysian Junior-level Muslim athletes showed diverse views in their perception of changes in their training, sleep and dietary patterns during Ramadan fast. These individual differences probably indicate differences in the athletes' adaptability and coping strategies during fasting and training in Ramadan.


Age-dependent effects of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP).
The neurotoxic effects of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) have been shown to be dependent upon its conversion to 1-methyl-4-phenyl pyridine ion (MPP+) by monoamine oxidase. Since central monoamine oxidase activity increases with age, the neurotoxic effects of MPTP should be age-dependent. This hypothesis was evaluated by administering MPTP to three groups of rats differing in age. It was observed that both the lethality and neurotoxicity of MPTP were age-dependent.


Downregulation of PHGDH expression and hepatic serine level contribute to the development of fatty liver disease.
Supplementation with serine attenuates alcoholic fatty liver by regulating homocysteine metabolism and lipogenesis. However, little is known about serine metabolism in fatty liver disease (FLD). We aimed to investigate the changes in serine biosynthetic pathways in humans and animal models of fatty liver and their contribution to the development of FLD. High-fat diet (HFD)-induced steatosis and methionine-choline-deficient diet-induced steatohepatitis animal models were employed. Human serum samples were obtained from patients with FLD whose proton density fat fraction was estimated by magnetic resonance imaging. 3-Phosphoglycerate dehydrogenase (Phgdh)-knockout mouse embryonic fibroblasts (MEF) and transgenic mice overexpressing Phgdh (Tg-phgdh) were used to evaluate the role of serine metabolism in the development of FLD. Expression of Phgdh was markedly reduced in the animal models. There were significant negative correlations of the serum serine with the liver fat fraction, serum alanine transaminase, and triglyceride levels among patients with FLD. Increased lipid accumulation and reduced NAD+ and SIRT1 activity were observed in Phgdh-knockout MEF and primary hepatocytes incubated with free fatty acids; these effects were reversed by overexpression of Phgdh. Tg-Phgdh mice showed significantly reduced hepatic triglyceride accumulation compared with wild-type littermates fed a HFD, which was accompanied by increased SIRT1 activity and reduced expression of lipogenic genes and proteins. Human and experimental data suggest that reduced Phgdh expression and serine levels are closely associated with the development of FLD.


Optimization of lipase-catalyzed synthesis of sorbitan acrylate using response surface methodology.
In this study, we have synthesized sorbitan acrylate through response surface methodology, using sorbitan and vinyl acrylate that catalyze immobilized lipase. In order to optimize the enzymatic synthesis of the sorbitan acrylate, we applied response surface techniques to determine the effects of five-level-four-factors and their reciprocal interactions with the biosynthesis of sorbitan acrylate. Our statistical model predicted that the highest conversion yield of sorbitan acrylate would be approx 100%, under the following optimized reaction conditions: a reaction temperature of 40.1 degrees C, a reaction time of 237.4 min, an enzyme concentration of 8%, and a 4.49:1 acyl donor/acceptor molar ratio. Using these optimal conditions in three independent replicates, the conversion yield reached 97.6+/-1.3%.


A novel and sensitive dual signaling ratiometric electrochemical aptasensor based on nanoporous gold for determination of Ochratoxin A.
Ochratoxin A (OTA) is a toxic pollutant in foods, and its actual detection is crucial. A novel and sensitive dual signaling ratiometric electrochemical aptasensor based on nanoporous gold (NPG) was proposed to determine OTA. NPG, with high specific surface area and conductivity, improved the sensitivity by immobilizing more aptamers. Meanwhile, the dual signaling ratiometric strategy improved the detection reproducibility through self-referencing and built-in correction. NPG and ratiometric strategy multi-amplified the dual signal changes. The sensitivity of OTA was evaluated by the ratio of methylene to ferrocene current values. Under the optimal conditions, the NPG-based aptasensor demonstrated excellent sensitivity with a wide linear range of 1 pg/mL to 2 ng/mL and the limit of detection (LOD) of 0.4 pg/mL for OTA. This developed aptasensor also effectively detected OTA in spiked Cordyceps sinensis and grape juice samples, with recovery values falling in the 98.49-108.0% range.


The impact of serum acid, arterial stiffness, and hypertension as a mediating factor: A cohort study.
Serum uric acid (SUA) has been associated with arterial stiffness. However, previous studies were limited to contradicting cross-sectional studies. This study aimed to examine the longitudinal association between SUA and the progression of arterial stiffness and the potential mechanisms. Based on the Kailuan study, arterial stiffness progression was assessed by the annual growth rate of repeatedly measured brachial-ankle pulse wave velocity (baPWV). Generalized linear regression models were used to estimate the association of SUA with baseline arterial stiffness (n = 37,659) and arterial stiffness progression (n = 16,506), and Cox regressions were used to investigate the risk of incident arterial stiffness (n = 13,843). Mediation analysis was used to explore the potential mediators of the associations. Per standard deviation increase in SUA was associated with an 11.89 cm/s increment (95% confidence interval [CI], 8.60-15.17) in baseline baPWV and a 2.67 cm/s/yr increment in the annual growth rate of baPWV. During the 5.77-year follow-up, there were 1953 cases of incident arterial stiffness. Participants in the highest quartile of SUA had a 39% higher risk of arterial stiffness (HR, 1.39; 95% CI, 1.21-1.60), as compared with those in the lowest quartile of SUA. Furthermore, the observed associations were more pronounced in women than in men (Pint<0.05). The pathological pathway from high SUA to arterial stiffness was mainly mediated through hypertension (mediated proportion: 24.74%). Our study indicates that SUA was positively associated with the risk of arterial stiffness and its progression, especially in women. The association was mainly mediated through hypertension.


Ritanserin, a 5-HT2 receptor antagonist, does not modify ECT-induced prolactin release.
The effect of pretreatment with ritanserin, a potent and selective serotonin-S2 (5-HT2) receptor antagonist, on the prolactin (PRL) response to electroconvulsive therapy (ECT) was studied in seven female patients suffering from major depressive disorder. They were given either ECT alone, or ECT after 10 or 20 mg ritanserin PO, and PRL was estimated in blood samples taken at times -5, 0, +5, +15, +30 and +60 min. The PRL responses after drug administration were not different from the responses after ECT alone. We conclude that, if serotonergic mechanisms are involved in the ECT-induced PRL increase, this neuroendocrine response seems to be rather a 5-HT1 than 5-HT2 receptor mediated event.


Comparison of rates of infection by the Lyme disease spirochete in selected populations of Ixodes dammini and Amblyomma americanum (Acari: Ixodidae).
At a major endemic focus in New Jersey, 50% of 290 adult Ixodes dammini collected in the fall of 1984 were infected with the Lyme disease spirochete (Borrelia burgdorferi), which was statistically higher than the rate found in the 202 adult ticks (39.6%) examined during the spring. Neither sex nor site of collection within the focus significantly affected the infection rate. The observed infection rates were similar to those reported in endemic areas of New York and Connecticut. Borrelia burgdorferi also infected all active stages of Amblyomma americanum ticks. Rates of infection were 5.4% in adults (n = 467) and 3.4% in nymphs (n = 289); 15.6% of clusters of unengorged larvae harbored B. burgdorferi, suggesting transovarial passage of the spirochete. Comparison of the rates of infection in I. dammini and A. americanum and their potential impact on Lyme disease transmission is discussed.


Total pancreatectomy for chronic pancreatitis.
A survey of six British centres collected data on 83 patients undergoing total pancreatectomy (TP) for chronic pancreatitis between 1977 and 1986. There were 57 men and 26 women with a median age of 38 years (range 19-61 years). Half were alcoholics and half had had previous acute pancreatitis. Besides jaundice (14 per cent) severe pain was the indication for the operation; regular opiates had been needed in 82 per cent of patients and 37 per cent were addicted to these drugs. All but 12 had had previous pancreatic or biliary surgery, with a median of two operations and a maximum of six. TP was a one-stage procedure in 32 patients, 42 had had distal resections and 9 proximal resections in the past; the pylorus was preserved in 30. Median operation time was 4 h (range 2-18 h) and median blood loss was 3 units (1-21 units). Intraoperative complications in 11 patients included haemorrhage in 9. Four deaths occurred within 30 days from bleeding (2), respiratory failure (1) and Roux-loop infarction (1). All but one of the 79 survivors required full pancreatic supplementation and 38 per cent had difficulties in endocrine control. At a median follow-up of 1.5 years (range 0.25-10 years), 57 patients (72 per cent) were pain-free and 9 (11 per cent) needed only occasional analgesia. Though 13 (17 per cent) still took regular analgesics, all were symptomatically improved. There have been 10 late deaths (13 per cent), all but one of which are attributable to the operation.


Incomes, attitudes, and occurrences of invasive species: an application to signal crayfish in Sweden.
This article analyzes and carries out an econometric test of the explanatory power of economic and attitude variables for occurrences of the nonnative signal crayfish in Swedish waters. Signal crayfish are a carrier of plague which threatens the native noble crayfish with extinction. Crayfish are associated with recreational and cultural traditions in Sweden, which may run against environmental preferences for preserving native species. Econometric analysis is carried out using panel data at the municipality level with economic factors and attitudes as explanatory variables, which are derived from a simple dynamic harvesting model. A log-normal model is used for the regression analysis, and the results indicate significant impacts on occurrences of waters with signal crayfish of changes in both economic and attitude variables. Variables reflecting environmental and recreational preferences have unexpected signs, where the former variable has a positive and the latter a negative impact on occurrences of waters with signal crayfish. These effects are, however, counteracted by their respective interaction effect with income.


Mitochondrial dysfunction in schizophrenia: With a focus on postmortem studies.
Among the many brain abnormalities in schizophrenia are those related to mitochondrial functions such as oxidative stress, energy metabolism and synaptic efficacy. The aim of this paper is to provide a brief review of mitochondrial structure and function and then to present abnormalities in mitochondria in postmortem brain in schizophrenia with a focus on anatomy. Deficits in expression of various mitochondrial genes have been found in multiple schizophrenia cohorts. Decreased activity of complexes I and IV are prominent as well as abnormal levels of individual subunits that comprise the complexes of the electron transport chain. Ultrastructural studies have shown layer, input and cell specific decreases in mitochondria. In cortex, there are fewer mitochondria in axon terminals, neuronal somata of pyramidal neurons and oligodendrocytes in both grey and white matter. In the caudate and putamen mitochondrial number is linked with symptoms and symptom severity. While there is a decrease in the number of mitochondria in astrocytes, mitochondria are smaller in oligodendrocytes. In the nucleus accumbens and substantia nigra, mitochondria are similar in density, size and structural integrity in schizophrenia compared to controls. Mitochondrial production of ATP and calcium buffering are essential in maintaining synaptic strength and abnormalities in these processes could lead to decreased metabolism and defective synaptic activity. Abnormalities in mitochondria in oligodendrocytes might contribute to myelin pathology and underlie dysconnectivity in the brain. In schizophrenia, mitochondria are affected differentially depending on the brain region, cell type in which they reside, subcellular location, treatment status, treatment response and predominant symptoms.


Generic composition and physiological and cultural properties of heterotrophic bacteria isolated from soil, rhizosphere and mycorrhizosphere of pine (Pinus silvestris L.).
Among the bacteria studied Arthrobacter globiformis was predominating in the root zone, while in the non-rhizosphere soil most numerous were Bacillus circulans and A. globiformis. Ammonifiers were more numerous among the root zone bacteria than among the root free soil organisms. The reverse was noted with bacteria capable of hydrolysing starch, cellulose, pectin and chitin.


Surgical treatment is better than non-surgical treatment for primary patellar dislocation: a meta-analysis of randomized controlled trials.
At present, the best treatment for primary patellar dislocation (PPD) has not been unified. Moreover, meta-analyses comparing the non-surgical and surgical treatments of PPD are lacking. Thus, we aimed to compare the clinical efficacy of surgical or non-surgical treatment of PPD. Randomized controlled studies of surgical and non-surgical treatments of PPD from 1966 to 2018 were retrieved from the following databases: PubMed, EMBASE, Cochrane Library, Wanfang Database, China Knowledge Network, Google Scholar, and Weipu Database. We screened for literature that met the inclusion criteria and extracted useful data for our meta-analysis. Nine studies, involving 492 patients, met the inclusion criteria and were analyzed in this study. The recurrence rate of patellar dislocation in the surgical group was lower than that in the non-surgical group (P = 0.04]). Subgroup analysis according to the follow-up time showed that the Kujala score (P < 0.001) and lower recurrence rate of dislocation (P = 0.05) than the non-surgical group in the short term. Subgroup analysis according to surgical year showed that the surgical group get higher Kujala score (P < 0.001) and lower recurrence rate of dislocation (P = 0.01) than the non-surgical group in recent years. Surgical treatment can provide better clinical results in a short period of time, and patients may achieve good results within 10 years owing to the advances in surgical techniques and instruments. Thus, we recommend surgical treatment as the preferred treatment for primary patellar dislocation.


The sleep EEG envelope is a novel, neuronal firing-based human biomarker.
Sleep EEG reflects voltage differences relative to a reference, while its spectrum reflects its composition of various frequencies. In contrast, the envelope of the sleep EEG reflects the instantaneous amplitude of oscillations, while its spectrum reflects the rhythmicity of the occurrence of these oscillations. The sleep EEG spectrum is known to relate to demographic, psychological and clinical characteristics, but the envelope spectrum has been rarely studied. In study 1, we demonstrate in human invasive data from cortex-penetrating microelectrodes and subdural grids that the sleep EEG envelope spectrum reflects neuronal firing. In study 2, we demonstrate that the scalp EEG envelope spectrum is stable within individuals. A multivariate learning algorithm could predict age (r = 0.6) and sex (r = 0.5) from the EEG envelope spectrum. With age, oscillations shifted from a 4-5 s rhythm to faster rhythms. Our results demonstrate that the sleep envelope spectrum is a promising biomarker of demographic and disease-related phenotypes.


Immunoperoxidase localization of chlamydial antigens in acute salpingitis.
Seventy surgically excised fallopian tubes in which there was originally a diagnosis of acute salpingitis were reviewed histologically and screened for chlamydial antigens by the immunoperoxidase technique. Chlamydial antigens were localized within tubal epithelial cells in two of the 70 cases (3%). Endometrial specimens from these two patients were also positive for chlamydial antigens. There was no definite correlation between the histologic features of the salpingitis and chlamydial immunoperoxidase positivity.


Molecular cloning and functional characterization of duck Janus kinase 1.
Janus kinase 1 (JAK1) is a member of JAK family of non-receptor protein tyrosine kinases that plays critical roles in transducing cytokine signals via JAK-signal transducer and activator of transcription (STAT) signaling pathway. The importance of JAK1 in innate immunity has been well-studied in mammals and fish, yet in avian remains largely unknown. Here, we cloned the full-length of the duck JAK1 (duJAK1) gene for the first time. DuJAK1 encoded a protein of 1152 amino acids and possessed high amino acid identity with goose and budgerigar JAK1s. The duJAK1 was expressed in all detected tissues, especially high in the thymus and bursa of Fabricius. Overexpression of duJAK1 significantly activated ISRE promoter activity and induced duck viperin, 2', 5'-OAS, MX, PKR and ZAP expression. Knockdown of duJAK1 by small interfering RNA significantly inhibited duck Tembusu virus (DTMUV)-, duck Enteritis virus (DEV)-, poly (I:C)-, poly (dA:dT)- or Sendai virus (SeV)-induced ISRE promoter activation. Furthermore, duJAK1 exhibited antiviral activity against DTMUV infection. These results will help us understand the function of JAK family proteins in duck antiviral immunity.


Exercise combined with a probiotics treatment alters the microbiome, but moderately affects signalling pathways in the liver of male APP/PS1 transgenic mice.
It has been demonstrated that physical exercise and probiotic supplementation delay the progress of Alzheimer's Disease (AD) in male APP/PS1TG mice. However, it has also been suggested that both exercise and AD have systemic effects. We have studied the effects of exercise training and probiotic treatment on microbiome and biochemical signalling proteins in the liver. The results suggest that liver is under oxidative stress, since SOD2 levels of APP/PS1 mice were decreased when compared to a wild type of mice. Exercise training prevented this decrease. We did not find significant changes in COX4, SIRT3, PGC-1a or GLUT4 levels, while the changes in pAMPK/AMPK, pmTOR/mTOR, pS6/S6 and NRF2 levels were randomly modulated. The data suggest that exercise and probiotics-induced changes in microbiome do not strongly affect mitochondrial density or protein synthesis-related AMPK/mTOR/S6 pathways in the liver of these animals.


Deubiquitinating enzyme BAP1 is involved in the formation and maintenance of the diapause embryos of Artemia.
The modification of proteins by ubiquitination and deubiquitination plays an important role in various cellular processes. BRCA1-associated protein-1 (BAP1) is a deubiquitinating enzyme whose function in the control of the cell cycle requires both its deubiquitinating activity and nuclear localization. In the present study, a ubiquitin carboxyl-terminal hydrolase belonging to the BAP1 family was identified and characterized from Artemia parthenogenetica, a member of a family of brine shrimp that, under certain conditions, produce and release diapause embryos in which cell division and turnover of macromolecules are arrested. Western blot analysis and in vitro enzyme activity assay revealed ArBAP1 to be a cytoplasmic protein with typical ubiquitin hydrolase activity. Northern blot analysis revealed that ArBAP1 was abundant in the abdomen of Artemia producing diapause-destined embryos. Furthermore, by in situ hybridization, ArBAP1 was located exclusively in the embryos. In vivo knockdown of ArBAP1 by RNA interference resulted in the formation of embryos with split shells and abortive nauplii. The present findings suggest that ArBAP1, the first reported cytoplasmic BAP1, participates in the formation of diapause embryos and plays an important role in the control of cell cycle arrest in these encysted embryos.


HAA by the first {Mn(iii)OH} complex with all O-donor ligands.
There is considerable interest in MnOHx moieties, particularly in the stepwise changes in those O-H bonds in tandem with Mn oxidation state changes. The reactivity of aquo-derived ligands, {MOHx}, is also heavily influenced by the electronic character of the other ligands. Despite the prevalence of oxygen coordination in biological systems, preparation of mononuclear Mn complexes of this type with all O-donors is rare. Herein, we report several Mn complexes with perfluoropinacolate (pinF)2- including the first example of a crystallographically characterized mononuclear {Mn(iii)OH} with all O-donors, K2[Mn(OH)(pinF)2], 3. Complex 3 is prepared via deprotonation of K[Mn(OH2)(pinF)2], 1, the pKa of which is estimated to be 18.3 ± 0.3. Cyclic voltammetry reveals quasi-reversible redox behavior for both 1 and 3 with an unusually large ΔEp, assigned to the Mn(iii/ii) couple. Using the Bordwell method, the bond dissociation free energy (BDFE) of the O-H bond in {Mn(ii)-OH2} is estimated to be 67-70 kcal mol-1. Complex 3 abstracts H-atoms from 1,2-diphenylhydrazine, 2,4,6-TTBP, and TEMPOH, the latter of which supports a PCET mechanism. Under basic conditions in air, the synthesis of 1 results in K2[Mn(OAc)(pinF)2], 2, proposed to result from the oxidation of Et2O to EtOAc by a reactive Mn species, followed by ester hydrolysis. Complex 3 alone does not react with Et2O, but addition of O2 at low temperature effects the formation of a new chromophore proposed to be a Mn(iv) species. The related complexes K(18C6)[Mn(iii)(pinF)2], 4, and (Me4N)2[Mn(ii)(pinF)2], 5, have also been prepared and their properties discussed in relation to complexes 1-3.


Multivariate analysis of factors related to the absence of musculoskeletal degenerative disease in middle-aged and older people.
Musculoskeletal degenerative disease (MSD; osteoporosis, knee arthritis and lumbar spondylosis) decreases the quality of life (QOL) of older people. The objective of the present study was to identify the factors related to the absence of MSD in multivariate logistic regression analysis. The participants were 1034 volunteers (444 men, 590 women, mean age 63.5 years) in the Yakumo study. Osteoporosis (percentage of young adult mean ≤70%), knee arthritis (Kellgren-Lawrence grade ≥2), and lumbar spondylosis (Nathan class ≥3) were prospectively examined. Participants were divided into those with and without MSD. Age, sex, body mass index, muscle strength, gait ability, pain, body balance, spinal sagittal alignment, geriatric syndrome (locomotive syndrome, frailty and sarcopenia) and QOL (Short Form Health Survey) were compared between these groups to identify the factors associated with the absence of MSD. Significantly lower age, body mass index and pain; higher gait speed, grip and back muscle strength; more stable body balance; better sagittal spinal alignment; and lower rates of locomotive syndrome, frailty and sarcopenia were observed in the group without MSD (n = 445, 43%), with significantly better QOL (P < 0.0001). In multivariate logistic regression analysis adjusted for age and sex, lower body mass index (odds ratio [OR] 1.10, P < 0.001), lower spinal inclination (OR 1.08, P < 0.01), higher back muscle strength (OR 1.01, P < 0.05), no locomotive syndrome (OR 1.80, P < 0.05) and good body balance (OR: 1.12, P < 0.05) were significant factors for the absence of MSD. Factors related to an absence of MSD are also related to good QOL, and should be a focus of health interventions in healthy middle-aged and older people. Geriatr Gerontol Int 2019; 19: 1141-1146.


Persons with multiple disabilities exercise adaptive response schemes with the help of technology-based programs: three single-case studies.
The present three single-case studies assessed the effectiveness of technology-based programs to help three persons with multiple disabilities exercise adaptive response schemes independently. The response schemes included (a) left and right head movements for a man who kept his head increasingly static on his wheelchair's headrest (Study I), (b) left- and right-arm movements for a woman who tended to hold both arms/hands tight against her body (Study II), and (c) touching object cues on a computer screen for a girl who rarely used her residual vision for orienting/guiding her hand responses. The technology involved microswitches/sensors to detect the response schemes and a computer/control system to record their occurrences and activate preferred stimuli contingent on them. Results showed large increases in the response schemes targeted for each of the three participants during the intervention phases of the studies. The importance of using technology-based programs as tools for enabling persons with profound and multiple disabilities to practice relevant responses independently was discussed.


Noninvasive method for measuring respiratory system compliance during pressure support ventilation.
To date, few methods have been accepted for assessing the respiratory system compliance (C(rs)) in patients under assisted ventilation at the bedside. The aim of this study was to evaluate our adaptive time slice method (ATSM) to continuously calculate the C(rs). One breath is divided into several time periods (slices). For each slice, a compliance value C(i) is calculated. The slice width is adapted according to the confidence interval of C(i). After all C(i) values are obtained and the outliers are eliminated, the C(rs) of this breath is calculated as the mean value of the remainder of C(i)'s. Seven patients with Chronic Obstructive Pulmonary Disease were evaluated during pressure support ventilation. The results are compared with the values calculated with the transdiaphragmatic pressure (P(di)). 95 ± 4% of the recorded data could be analyzed with ATSM. In 6 patients out of 7, the results delivered with ATSM and with P(di) had similar variation (standard deviation) and accuracy (difference<20%). They were strongly correlated (weighted correlation coefficient = 0.86, p<10(-5)) with a mean difference of 3.22 ml/mbar. The ATSM is a robust method and able to provide accurate C(rs) in spontaneously breathing patients during pressure support ventilation noninvasively without extra instrumentation or complicated maneuvers.


Quantitative real-time RT-PCR analysis in desert locusts reveals phase dependent differences in neuroparsin transcript levels.
In different parts of the world, locust swarms cause severe ecological and economic damage. However, the physiological mechanisms underlying this gregarization process remain elusive. In this study, we present a detailed quantitative analysis of two neuroparsin precursor (Scg-NPP1 and Scg-NPP2) transcripts in the brain, fat body, gut, gonads and accessory glands of male and female, gregarious and solitarious desert locusts (Schistocerca gregaria). These transcripts are generally more abundant in solitarious than in gregarious animals. In contrast to their gregarious congeners, solitarious locusts contain detectable Scg-NPP1 and Scg-NPP2 transcript levels in the fat body. Moreover, our data reveal temporal changes of neuroparsin mRNA levels in the brains and fat bodies of adult isolated-reared locusts. This paper provides the first scientific evidence for phase-dependent transcriptional regulation of neuropeptide hormone encoding genes.


Sex-Related Outcomes of Medical, Percutaneous, and Surgical Interventions for Coronary Artery Disease: JACC Focus Seminar 3/7.
Biological and sociocultural differences between men and women are complex and likely account for most of the variations in the epidemiology and treatment outcomes of coronary artery disease (CAD) between the 2 sexes. Worse outcomes in women have been described following both conservative and invasive treatments of CAD. For example, increased levels of residual platelet reactivity during treatment with antiplatelet drugs, higher rates of adverse cardiovascular outcomes following percutaneous coronary revascularization, and higher operative and long-term mortality after coronary bypass surgery have been reported in women compared with in men. Despite the growing recognition of sex-specific determinants of outcomes, representation of women in clinical studies remains low and sex-specific management strategies are generally not provided in guidelines. This review summarizes the current evidence on sex-related differences in patients with CAD, focusing on the differential outcomes following medical therapy, percutaneous coronary interventions, and coronary artery bypass surgery.


Effect of isometric horizontal abduction on pectoralis major and serratus anterior EMG activity during three exercises in subjects with scapular winging.
The aim of this study was to determine the effect of isometric horizontal abduction using Thera-Band during three exercises (forward flexion, scaption, and wall push-up plus) in subjects with scapular winging by investigating the electromyographic (EMG) amplitude of the pectoralis major, serratus anterior and the pectoralis major/serratus anterior activity ratio. Twenty-four males with scapular winging participated in this study. The subjects performed the forward flexion, scaption, and wall push-up plus with and without isometric horizontal abduction using Thera-Band. Surface EMG was used to collect the EMG data of the pectoralis major and serratus anterior during the three exercises. Two-way repeated analyses of variance with two within-subject factors (isometric horizontal abduction condition and exercise type) were used to determine the statistical significance of pectoralis major and serratus anterior EMG activity and the pectoralis major/serratus anterior EMG activity ratio. Pectoralis major EMG activity was significantly lower during forward flexion and wall push-up plus with isometric horizontal abduction, and serratus anterior EMG activity was significantly greater with isometric horizontal abduction. Additionally, the pectoralis major/serratus anterior activity ratio was significantly lower during the forward flexion and wall push-up plus with isometric horizontal abduction. The results of this study suggest that isometric horizontal abduction using Thera-Band can be used as an effective method to facilitate the serratus anterior activity and to reduce excessive pectoralis major activity during exercises for activating serratus anterior.


[Benefits and risks of current pharmacotherapy in the treatment of type 2 diabetes].
The development of new drugs for the treatment of type 2 diabetes (T2DM) and metabolic disorders is currently one of the most innovative areas of drug development. However, a considerable number of newly developed drugs have either not reached the market and were stopped late in development or have been withdrawn after initial approval soon after market authorization due to serious safety concerns. How can drug safety problems be anticipated and, even more important, how can adverse events definitely caused by a drug be differentiated from incidences of naturally occurring diseases? This review article will provide an update about the state of the art treatment of type 2 diabetes and reflect on the newest available study evidence on glitazones, incretin mimetics (GLP-1 agonists and DPP-4 inhibitors), SGLT-2 inhibitors (gliflocines) and pan-PPAR agonists (glitazars). Furthermore, new and still experimental approaches for the treatment of T2DM, such as bardoxolone, salsalate and anakinra will be briefly reviewed.


Increased generation of intracellular reactive oxygen species initiates selective cytotoxicity against the MCF-7 cell line resultant from redox active combination therapy using copper-thiosemicarbazone complexes.
The combination of cytotoxic copper-thiosemicarbazone complexes with phenoxazines results in an up to 50-fold enhancement in the cytotoxic potential of the thiosemicarbazone against the MCF-7 human breast adenocarcinoma cell line over the effect attributable to drug additivity-allowing minimization of the more toxic copper-thiosemicarbazone component of the therapy. The combination of a benzophenoxazine with all classes of copper complex examined in this study proved more effective than combinations of the copper complexes with related isoelectronic azines. The combination approach results in rapid elevation of intracellular reactive oxygen levels followed by apoptotic cell death. Normal fibroblasts representative of non-cancerous cells (MRC-5) did not display a similar elevation of reactive oxygen levels when exposed to similar drug levels. The minimization of the copper-thiosemicarbazone component of the therapy results in an enhanced safety profile against normal fibroblasts.


[Familial thyroid carcinomas].
Approximately 5% of differentiated thyroid carcinomas with follicular cell differentiation, papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) and 25-30% of medullary thyroid carcinoma (MTC) are hereditary. They occur either as part of a defined syndrome or are confined to the thyroid gland. Compared to their sporadic non-hereditary counterparts hereditary thyroid carcinomas generally develop earlier and regularly show multifocal tumour growth. With the exception of familial MTC, which is preceded by neoplastic C cell hyperplasia, no precursor lesions of hereditary thyroid carcinoma are known. In strong correlation with the localisation of the germline mutation of the RET protooncogene, familial MTC shows a distinct clinical course which allows precise clinical decision-making for prophylactic thyroidectomy to prevent invasive MTC. According to current knowledge prophylactic thyroidectomy of all other types of hereditary thyroid carcinoma is not justified.


Factors affecting body temperatures of toads.
Factors influencing levels and rates of variation of body temperature (T b) in montane Bufo boreas boreas and in lowland Bufo boreas halophilus were investigated as an initial step toward understanding the role of natural thermal variation in the physiology and energetics of these ectothermic animals. Body temperatures of boreas can vary 25-30° C over 24-h periods. Such variation is primarily due to both nocturnal and diurnal activity and the physical characteristics of the montane environment. Bufo boreas halophilus are primarily nocturnal except during breeding and are voluntarily active at body temperatures ranging between 10 and 25° C. Despite variation in T b encountered in the field, boreas select a narrow range of T b in a thermal gradient, averaging 23.5 and 26.2° C for fasted individuals maintained under field conditions or acclimated to 20° C, respectively. In a thermal gradient the mean T b of fasted halophilus acclimated to 20° C is 23.9° C. Skin color of boreas varies in the field from very dark to light. The dark skins absorb approximately 4% more radiation than the light ones. Light colored boreas should absorb approximately 5% more radiation than similarly colored halophilus. Evaporative water losses increase directly with skin temperatures and vapor pressure deficit in both subspecies. Larger individuals heat and cool more slowly than smaller ones. Calculation of an enery budget for boreal toads suggests that they could sit in direct sunlight for long periods without fatally overheating, providing the skin was continually moist.


Effects of camonagrel, a selective inhibitor of platelet thromboxane synthase, on the platelet-subendothelium interaction.
The aim of this study was to compare the effects of a new thromboxane synthase inhibitor, camonagrel, on platelet aggregation and platelet-subendothelium interaction under flow conditions, in comparison with a standard thromboxane synthase inhibitor (dazoxiben) and a cyclooxygenase inhibitor (acetylsalicylic acid). With respect to platelet aggregation in whole blood, the 50% inhibitory concentrations (IC(50)) of camonagrel were between 318 and 797 micromol/l after induction with collagen and adenosine 5'-diphosphate, respectively. For inhibition of thromboxane B(2) synthesis, the IC(50) values were 868 +/- 68 micromol/l; prostaglandin E(2) was inhibited only by acetylsalicylic acid (IC(50) for camonagrel >2,000 micromol/l), and the leukocyte 6-keto-PGF(1alpha) level was increased by camonagrel. The greatest reduction in percentage subendothelial surface occupied by platelets (mainly in the thrombi) after blood perfusion was seen after incubation with camonagrel in the range of concentrations that inhibited collagen-induced platelet aggregation. In conclusion, camonagrel reduced platelet-subendothelium interaction under flow conditions, showing this effect in a range of concentrations lower than in inhibition of platelet aggregation.


Leptin intake during lactation prevents obesity and affects food intake and food preferences in later life.
Breast milk is practically the only food ingested during the first months of life in fully breastfed infants and it is assumed to match the infant's nutritional needs. Epidemiological data suggest that breastfeeding compared with infant formula feeding confers protection against several chronic diseases later on in life and, particularly, against obesity and related medical complications. However, causality has not been related to any specific compound of breast milk. Recent data in our laboratory have identified leptin as the specific compound that is responsible for some of these beneficial effects of breastfeeding. The hormone leptin was identified as a key candidate because it is present in breast milk, but is not present in infant formula, and when ingested during the suckling period can be absorbed by the immature stomach exerting biological effects. Evidence of the beneficial effects of breast milk leptin was obtained from human studies, showing that milk-borne maternal leptin appeared to give moderate protection to infants from excess weight gain. Direct cause-effect evidence was obtained in rats, where oral leptin supplementation during the suckling period resulted in a decrease in food intake, affected food preferences in favour of carbohydrates versus fat, and protected against overweight in adulthood, with an improvement of related parameters such as leptin and insulin sensitivity. These findings open a new area of research on the use of leptin in the design of more appropriate infant formula, which is significant considering the increasing incidence of obesity and its associated medical complications.


A highly sensitive strand-specific multiplex RT-qPCR assay for quantitation of Zika virus replication.
Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) is widely used to quantify viral RNA genomes for diagnostics and research, yet conventional RT-qPCR protocols are unable to accurately distinguish between the different viral RNA species that exist during infection. Here we show that false-priming and self-priming occur during reverse transcription with several published Zika virus (ZIKV) primer sets. We developed a RT-qPCR assay using tagged primers and thermostable reverse transcriptase, which greatly reduced the occurrence of nonspecific cDNA products. Furthermore, we optimized the assay for use in multiplex qPCR which allows for simultaneous quantitative detection of positive-strand and negative-strand ZIKV RNA along with an internal control from both human and mosquito cells. Importantly, this assay is sensitive enough to study early stages of virus infection in vitro. Strikingly, using this assay, we detected ZIKV negative-strand RNA as early as 3 h post-infection in mammalian cell culture, at a time point prior to the onset of positive-strand RNA synthesis. Overall, the strand-specific RT-qPCR assay developed herein is a valuable tool to quantify ZIKV RNA and to study viral replication dynamics during infection. The application of these findings has the potential to increase accuracy of RNA detection methods for a variety of viral pathogens.


Nutritional deficiency post esophageal and gastric cancer surgery: A quality improvement study.
Esophagectomy or gastrectomy for malignant tumors can have a profound effect on nutritional status of patients undergoing the procedure. Hence, postoperative nutritional status is an important prognostic factor to consider in ensuring optimal recovery. In this study, we looked at assessing the prevalence of micronutrient deficiencies post esophagectomy or gastrectomies and the efficiency of Allied Health Professionals (AHP) led clinics in identifying and appropriately managing the deficiencies. Between February 2017 and February 2018, all patients who attended the AHP clinic, had micronutrient screening, which includes ferritin, folate, vitamin B12 and vitamin D. Patients were screened for exocrine pancreatic insufficiency (EPI) through series of questions related to symptoms of EPI including steatorrhea, flatulence and urgency to defecate. All patients included in the study were started on A-Z multivitamin tablets from their first visit. Patients reporting symptoms indicative of EPI were started on Creon. Patients found deficient in any micronutrients were invited for a follow-up measurement of the respective deficiency. A total of 63 patients were included in the study period with a median follow-up of 18 months (range: 2-60 months) post esophagectomy and/or subtotal/total gastrectomy for malignant tumors. Proportion of patients with deficiency in ferritin, folate, vitamin B12 and vitamin D were 42.86%, 9.52%, 6.35% and 36.67% respectively. The proportion of patients identified with symptoms indicative of EPI was 31.75%. At re-test follow-up, 66.67% patient noticed settlement of symptoms of EPI. Ferritin, Folate, Vitamin B12 and D levels significantly improved post initial AHP follow-up (significance level p < 0.05). This study highlights that nutritional deficiencies post esophagectomy and/or subtotal/total gastrectomy for malignant tumors are prevalent. AHP run follow-up clinics in our unit helps identify these deficiencies and manage them accordingly. This study shows statistically significant improvement in deficiencies thereby making AHP led follow-up clinics to be cost effective and improve patient outcome.


Implications of the PAPP-A-IGFBP-IGF-1 pathway in the pathogenesis and treatment of polycystic kidney disease.
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic diseases implicated in the development of end stage renal disease (ESRD). Although FDA has recently approved a drug against ADPKD, there is still a great need for development of alternative management strategies for ADPKD. Understanding the different mechanisms that lead to cystogenesis and cyst expansion in ADPKD is imperative to develop new therapies against ADPKD. Recently, we demonstrated that caloric restriction can prevent the development of cystic disease in animal models of ADPKD and through these studies identified a new role for pregnancy associated plasma protein-A (PAPP-A), a component of the insulin-like growth factors (IGF) pathway, in the pathogenesis of this disease. The PAPP-A-IGF pathway plays an important role in regulation of cell growth, differentiation, and transformation and dysregulation of this pathway has been implicated in many diseases. Several indirect studies support the involvement of IGF-1 in the pathogenesis of ADPKD. However, it was only recently that we described a direct role for a component of this pathway in pathogenesis of ADPKD, opening a new avenue for the therapeutic approaches for this cystic disease. The present literature review will critically discuss the evidence that supports the role of components of IGF pathway in the pathogenesis of ADPKD and discuss the pharmacological implications of PAPP-A-IGF axis in this disease.


P53 tumor suppressor gene mutations in laryngeal cancer and in recurrent disease following radiation therapy.
In this study we performed p53 sequencing based mutation analysis in laryngeal cancers and matched recurrent disease following irradiation. The question is if irradiation affects the DNA and introduces or deletes mutations so that p53 cannot be used as a clonal marker anymore. P53 mutations were identified in fresh-frozen laryngectomy specimens with either primary laryngeal cancers, treated by surgery and irradiation post-operative with local failure during follow-up, or with recurrent laryngeal cancers following primary irradiation. In 21 tumors the p53 status was analyzed by direct sequencing full-length mRNA through RT-PCR. DNA sequencing analysis of exons 2 through 11 was performed when RNA isolation could not be performed. The marker mutation identified in this way was detected by DNA sequencing of the corresponding exon in formalin-fixed deparaffinized tumor biopsy samples in respectively matched recurrent disease following surgery and irradiation or primary tumor before irradiation. DNA sequencing analysis of the corresponding exon of peripheral blood leukocytes excluded the presence of germline mutations or polymorphisms. In 16 out of 21 tumors (71%), a mutation was identified. Fifteen of these marker mutations were detected in the matched tumor biopsy sample (94%). The only case lacking the marker mutation probably was a second primary tumor. We conclude that we find no direct evidence for induction or loss of p53 mutations following irradiation. Consequently, p53 may be used as a diagnostic tool when histological examination fails, for example in discriminating between the presence of a second primary tumor in the same area versus recurrent disease.


Onsager's conjecture in bounded domains for the conservation of entropy and other companion laws.
We show that weak solutions of general conservation laws in bounded domains conserve their generalized entropy, and other respective companion laws, if they possess a certain fractional differentiability of order one-third in the interior of the domain, and if the normal component of the corresponding fluxes tend to zero as one approaches the boundary. This extends various recent results of the authors.


Establishing cytogenetic biodosimetry laboratory in Saudi Arabia and producing preliminary calibration curve of dicentric chromosomes as biomarker for medical dose estimation in response to radiation emergencies.
In cases of public or occupational radiation overexposure and eventual radiological accidents, it is important to provide dose assessment, medical triage, diagnoses and treatment to victims. Cytogenetic bio-dosimetry based on scoring of dicentric chromosomal aberrations assay (DCA) is the "gold standard" biotechnology technique for estimating medically relevant radiation doses. Under the auspices of the National Science, Technology and Innovation Plan in Saudi Arabia, we have set up a biodosimetry laboratory and produced a national standard dose-response calibration curve for DCA, pre-required to estimate the doses received. For this, the basic cytogenetic DCA technique needed to be established. Peripheral blood lymphocytes were collected from four healthy volunteers and irradiated with radiation doses between 0 and 5 Gy of 320 keV X-rays. Then, lymphocytes were PHA stimulated, Colcemid division arrested and stained cytogenetic slides were prepared. The Metafer4 system (MetaSystem) was used for automatic and manually assisted metaphase finding and scoring of dicentric chromosomes. Results were fit to the linear-quadratic dose-effect model according to the IAEA EPR-Biodosimetry-2011 report. The resulting manually assisted dose-response calibration curve (Y = 0.0017 + 0.026 × D + 0.081 × D2) was in the range of those described in other populations. Although the automated scoring over-and-under estimates DCA at low (<1 Gy) and high (>2 Gy) doses, respectively, it showed potential for use in triage mode to segregate between victims with potential risk to develop acute radiotoxicity syndromes. In conclusion, we have successfully established the first biodosimetry laboratory in the region and have produced a preliminary national dose-response calibration curve. The laboratory can now contribute to the national preparedness plan in response to eventual radiation emergencies in addition to providing information for decision makers and public health officials who assess the magnitude of public, medical, occupational and accidental radiation exposures.


Acute fatty liver of pregnancy complicated by coagulopathy: A case report.
We present the case of a rare obstetric emergency, which is usually fatal. Our case highlights suspicion of AFLP in patients presenting with jaundice in the third trimester with good maternal and fetal outcomes after a timely intervention. Acute fatty liver of pregnancy (AFLP) is a rare, obstetric emergency characterized by maternal liver dysfunction that can lead to maternal and fetal complications. We report a case of 28-year-old primigravida 39 weeks gestation diagnosed with AFLP complicated by coagulopathy with good maternal and fetal outcomes after a timely intervention.


[Giant anal fibroepithelial polyp during pregnancy: a case study].
Anal fibroepithelial polyp is a benign tumor rarely reported during pregnancy. We here report a case of giant anal fibroepithelial polyp in a 31-year old multiparous woman. It developed progressively over the previous 3 years. Clinical examination showed firm sessile bud formation, at the anal margin. The patient had normal ongoing pregnancy (31 weeks of amenorrhea). Endoanal examination was normal. Surgical resection was preformed under spinal anesthesia. The specimen measured 21x12x7cm and was covered by the skin. Histological examination showed anal fibroepithelial polyp without signs of malignancy. The postoperative course was uneventful.


Stimulation of methemoglobin reduction by selenium: a comparative study with erythrocytes of various animals.
The extent of stimulation of methemoglobin (metHb) reduction by selenite depends upon the level of reduced glutathione (GSH) in the erythrocytes. The reason for the species difference in the effect of selenite was discussed with respect to species differences in the GSH levels in erythrocytes.


Electrophysiologic effects of intravenous timolol.
We evaluated the electrophysiologic effects and dose response of the long-acting beta-blocking drug timolol given intravenously to 12 patients during intracardiac electrophysiologic study. Electrophysiologic parameters were measured during control and immediately, 30 minutes, and 48 hours following infusion. Significant changes in electrophysiologic parameters were only observed in the five patients (Group B) who received 0.05 mg/kg and not in the seven patients who received 0.02 mg/kg (Group A). In Group B patients immediately after timolol infusion sinus cycle length increased from 840 +/- 254 msec to 1048 +/- 63 msec (P less than 0.01), A-H interval during normal sinus rhythm increased from 94 +/- 42 msec to 101 +/- 45 msec (P less than 0.05), paced cycle length to A-V nodal Wenckebach increased from 370 +/- 45 msec to 430 +/- 76 msec (P less than 0.05), and A-V nodal effective refractory period increased from 284 +/- 63 msec to 360 +/- 83 msec (P less than 0.01). Significant increases in these electrophysiologic parameters were also noted at 30 minutes following timolol infusion. Other conduction times, atrial and ventricular refractory periods, and corrected sinus node recovery. time were unaltered by timolol. All electrophysiologic parameters returned to control in 48 hours. No adverse effects were observed. We conclude that intravenous timolol in doses of 0.05 mg/kg significantly increases sinus cycle length and prolongs A-V nodal conduction and refractoriness, demonstrates peak effects immediately after intravenous administration, and is well tolerated.


Excretion patterns of alkylating metabolites in urine following cyclophosphamide treatment of tumor patients: influence of application route, dosage, liver and kidney function.
The excretion patterns of cyclophosphamide (CP) in urine were studied in 54 tumor patients aged between 21 and 61 years, using the nitrobenzyl-pyridine (NBP) reaction, with regard to the route of application (i.v., i.m. or oral), the CP dose and the functional state of the liver and kidney. The studies were carried out in nephrectomized patients and patients with liver affections caused by the basic disease, in particular with malignant lymphomas and mammary carcinomas. The following results were obtained: 1. There exists a direct relationship between the dose of CP applied and the quantitative excretion of alkylating metabolites in urine. According to these studies in which the patients received up to 2.8 g CP/m2 body surface, the upper CP dose was limited by the generally toxic side effects rather than by the metabolization rate. 2. At comparable CP doses the route of application (i.v., i.m. or oral) has no appreciable influence on the excreted NBP activity. 3. Disorders of the liver function without signs of icterus are not a contraindication to CP treatment. 4. The functional failure of one kidney has no statistically significant influence on the excretion of alkylating metabolites in urine.


Triticale crisp bread enriched with selected bioactive additives: volatile profile, physical characteristics, sensory and nutritional properties.
The effect of selected plant additives (couch grass, artichoke, kale, nettle, ground buckwheat husks, broad beans, fenugreek seeds, and extracts of yellow tea and mulberry leaf) on the volatile compounds, color, texture, sensory attributes, polyphenols, and antioxidant properties of triticale crisp bread was studied. The volatile profile of control bread was dominated by lipid oxidation products with hexanal and (E)-2-nonenal predominant. The additives strongly modified the volatile profile of the extruded crisp bread. The greatest differences were recorded in the case of products with artichoke and kale additions, which had respectively about 12 and 8 times higher levels of total volatile compounds than the control crisp bread. The samples containing kale, buckwheat, and fenugreek as well as yellow tea extract characterized high levels of sulfur compounds, with methanethiol predominant. The additives, especially kale, nettle, and artichoke affected the color of the crisp breads, in most cases making them darker. In terms of texture only the crisp bread with addition of buckwheat husk was significantly harder than the control sample. On the basis of sensory evaluation it was stated that among all the additives, the artichoke and fenugreek resulted in dramatic deterioration in the extruded product taste. The used additives also affected the antioxidant properties of triticale crisp bread. The greatest content of total phenolic compounds and the highest antioxidant activity were observed for the bread with yellow tea extract addition (3.5- and 6.5-fold higher, respectively, than in control sample).


Corrigendum: Discriminative analysis of schizophrenia patients using graph convolutional networks: a combined multimodal MRI and connectomics analysis.
[This corrects the article DOI: 10.3389/fnins.2023.1140801.].


Strong memory CD8+ T cell responses against immunodominant and three new subdominant HLA-B27-restricted influenza A CTL epitopes following secondary infection of HLA-B27 transgenic mice.
We previously showed that the known HLA-B27-restricted influenza A epitope identified from human studies, NP.383-391, was recognized by CTLs following influenza A infection of transgenic (Tg) HLA-B27/H2 class I-deficient (H2 DKO) mice. Here, we examined the kinetics of the primary NP.383-391-specific response in Tg HLA-B27/H2 DKO mice at the site of respiratory infection, along with the profile of additional influenza A epitopes recognized. While the temporal kinetics of the Tg HLA-B27/NP.383-391-specific CD8+ T cell response paralleled the H2-D(b)/NP.366-374-specific response of non-Tg H2b mice, the magnitude was less. Using epitope prediction programs, we identified three novel B27-restricted influenza A epitopes, PB2.702-710, PB1.571-579, and PB2.368-376, recognized during both the primary and secondary response to infection. Although the secondary NP.383-391-specific response was dominant, PB1.571-579 and PB2.368-376 stimulated stronger proliferative expansion in memory T cells. Our results indicate a broader B27/influenza A CTL repertoire than previously known. Together with results for other HLA class I alleles, this information will become important in improving vaccine strategies for influenza A and other human pathogens.


Transmission and prevalence of drug-resistant tuberculosis in a Brazilian setting under a directly observed therapy short-course strategy.
We aimed to estimate the prevalence and transmission of drug-resistant tuberculosis in a high-burden Brazilian setting under directly observed therapy short-course strategy. Isolates of culture-confirmed pulmonary tuberculosis patients from Guarulhos, Brazil, diagnosed in October 2007-2011 were subjected to drug susceptibility and IS6110-restriction fragment length polymorphism testing. The overall resistance prevalence was 11.5% and the multi-drug resistance rate was 4.2%. Twenty-six (43.3%) of 60 drug-resistant isolates were clustered. Epidemiological relationships were identified in 11 (42.3%) patients; 30.8% of the cases were transmitted in households. Drug-resistant tuberculosis was relatively low and transmitted in households and the community.


Detection of response-predicting mutations in the kinase domain of the epidermal growth factor receptor gene in cholangiocarcinomas.
Epidermal growth factor receptor (EGFR) signalings have recently been implicated in the genesis and progression of cholangiocarcinomas. Thus, the EGFR kinase inhibitor appears to be promising in the treatment of this cancer. The response-predicting mutations in the tyrosine kinase domain of EGFR gene have recently been detected in non-small cell lung cancers. This study was, therefore, to investigate if these mutations are also found in cholangiocarcinomas. Twenty-two consecutive cholangiocarcinoma patients who underwent surgical resection were enrolled. Their resected paraffin-embedded cholangiocarcinoma specimens were used for mutation analysis, which was performed by DNA sequencing of exons 18, 19 and 21 in the EGFR gene. Clinical characteristics were compared between each group according to the presence or absence of mutations. Three patients (13.6%) harbored EGFR mutations. All the mutations found were deletions in exon 19. Mutations were more common in intra-hepatic or poorly differentiated tumors. Differences in age, sex, stage at diagnosis and survival were not observed between mutation-positive and -negative patients. This study, for the first time, demonstrates that a subset of cholangiocarcinoma patients has response-predicting EGFR mutations. Therefore, a highly selected application of the EGFR kinase inhibitor would be therapeutically effective in these patients.


Influence of regular exercise on subjective sense of burden and physical symptoms in community-dwelling caregivers of dementia patients: a randomized controlled trial.
With an aim to improve quality of life in caregivers of dementia patients, we examined the effect of regular exercise on caregivers' sense of burden and their physical symptoms. Participants were 31 elderly caregivers living with older patients diagnosed with Alzheimer's-type dementia. They were randomly assigned to either the intervention group, who were prescribed regular exercise with moderate-intensity: 3 metabolic equivalents (3METs), 3 times per week for 12 weeks, or the control group, who did not receive any prescription. In the intervention group, significant reductions in the Zarit caregiver burden interview (ZBI) score and in the frequency of feeling fatigued, and an improvement in quality of sleep were observed at follow-up (p < 0.05), while no such changes were observed in the control group. These results suggest that obtaining sustainable habit of moderate exercise may improve quality of life in caregivers of demented patients.


Have the Government's prescription algorithm and the 2013 American College of Cardiology/American Heart Association guidelines for managing dyslipidaemia influenced the management of dyslipidaemia? The MEJORALO-CV Project.
To determine the management of dyslipidaemia in primary care after the publication of the American College of Cardiology/American Heart Association (ACC/AHA) 2013 guidelines and Valencian government's algorithm. We conducted a cross-sectional descriptive study that employed a survey of primary care physicians of the Community of Valencia between January and October 2016. A total of 199 physicians (mean age, 48.9±11.0 years; experience, 21.3±11.1 years) participated in the survey. The most followed guidelines were those of the European Society of Cardiology (37.5% of respondents) and Valencian government (23.4% of respondents). Some 6.3% of the respondents followed the 2013 ACC/AHA guidelines, and 88.0% established objectives based on LDL cholesterol and cardiovascular risk. The choice of lipid-lowering drug was based on its LDL cholesterol lowering capacity (28.6% of respondents), on the Valencian government's algorithm (23.4%) and on the drug's safety (20.4%). Statins, ezetimibe and fibrates were the preferred hypolipemiant agents, and their combination (51% of respondents) and dosage increases (35%) were the strategies employed for poor control. Lipid profile and transaminase and creatine kinase levels were measured every 6 (59.5%, 52.3% and 54.3% of respondents, respectively) or 12 months (25.1%, 29.2% and 30.3%, respectively). Forty-one percent of the respondents were aware of the controversy surrounding the 2013 ACC/AHA guidelines. Although 60% of the respondents acknowledged its relevance, only 21% changed their daily practices accordingly. The Valencian government's algorithm had a greater impact than the 2013 ACC/AHA guidelines in primary care in Valencia. Areas for improvement included the low use of validated guidelines and risk tables and the streamlining of laboratory test periodicity.