Intellectual performance correlates of trauma exposure in adolescent psychiatric inpatients.
Half of individuals have experienced a trauma adequate to meet criteria for PTSD. Intelligence may correlate with trauma, with the causal direction unclear. The Childhood Trauma Questionnaire (CTQ) was administered to 733 child and adolescent inpatients. Intelligence and academic achievement was assessed using the Wechsler Scales. Clinician diagnoses came from the electronic medical record, as did data on exposure to substance abuse and other stressors. Multivariate analyses assessed associations between intelligence, diagnoses, experiences, and CTQ. Cases who met criteria for physical and sexual abuse performed more poorly across all intellectual domains. Other than for PTSD, there were no diagnostic differences in CTQ scores. Emotional abuse or neglect were not associated with intelligence, although exposure to substance abuse was associated with increased CTQ scores and lower intelligence. Exposure to substance abuse as a covariate did not eliminate the influence of CTQ scores on intelligence, but was consistently related to intelligence beyond CTQ scores. Intelligence and substance abuse are known to have genomic influences and recent studies have suggested a genomic signature associated with childhood abuse. Future genomic studies of the consequences of trauma exposure could add intelligence polygenic scores into their models, while considering genomic and nongenomic elements of family experiences.


Pure (acute) erythroid leukemia: morphology, immunophenotype, cytogenetics, mutations, treatment details, and survival data among 41 Mayo Clinic cases.
Pure erythroid leukemia (PEL), also known as acute erythroid leukemia (AEL), is recognized as a distinct morphologic entity by both the 2016 and 2022 World Health Organization (WHO) classification system. By contrast, the 2022 International Consensus Classification (ICC) includes PEL under a broader category of "acute myeloid leukemia with mutated TP53". We identified 41 Mayo Clinic cases of PEL (mean age 66 years, range 27-86; 71% males) and provide a comprehensive account of bone marrow morphology, immunophenotype, cytogenetic and mutation profiles. PEL was primary in 14 cases, therapy-related in 14, secondary in 12, and undetermined in one. All cases expressed biallelic TP53 alterations, including TP53 deletion/single TP53 mutation (68%), two TP53 mutations (29%) or two TP53 deletions (3%); additional mutations were infrequent. Karyotype was complex in all cases and monosomal in 90%. Treatment details were available in 29 patients: hypomethylating agent (HMA) alone (n = 5), HMA + venetoclax (n = 12), intensive chemotherapy (n = 4), supportive care/other (n = 8); no responses or allogeneic stem cell transplants were documented, and all patients died at a median 1.8 months (range 0.2-9.3). The current study highlights a consistent and reproducible set of morphologic and genetic characteristics that identify PEL as a distinct AML variant whose dismal prognosis requires urgent attention.


[Construction and expression of recombinant adenovirus encoding MDA-7/IL-24 and its inhibitory effect on proliferation in human hepatocellular carcinoma cells].
To construct recombinant plasmid and adenovirus harboring MDA-7 gene, and to investigate its biological function on the proliferation of human hepatocellular carcinoma cells. The MDA-7 fragments from the T vectors were inserted into pCDNA-3 vector to construct expression plasmids named pCDNA3-MDA-7. To determine its effects on the proliferation of HCC cells, transfected the expression vector into cells and tested the ability of colony formation in cancer cells. Simultaneously, constructed recombinant adenovirus expressing MDA-7, and detected its effect on the proliferation of HCC cells by using MTT assay. Successfully constructed plasmid- and adenovirus-based system to express MDA-7. The data of colony formation assay and M'T test showed that MDA-7 can obviously suppress cell growth in HCC cells. MDA-7 may function as tumor suppressor in HCC cells, and the adenovirus-mediated MDA-7 can be a novel strategy for the anti-HCC therapy. Our study established the foundation for future research on the effect of MDA-7 in HCC.


[Rate of benyzylpenicillin inactivation in native solutions during extraction].
The constants of benzylpenicillin inactivation in acidified fermentation broth filtrates were different in various filtrate batches. Marked inactivation of the antibiotic in the filtrates immediately after their acidification was observed. Possible losses of the antibiotic due to inactivation under conditions of extraction were estimated.


Epilepsy-associated stigma in Zambia: what factors predict greater felt stigma in a highly stigmatized population?
Epilepsy-associated stigma in Africa has been described largely in terms of enacted stigma or discrimination. We conducted a study of 169 adults with epilepsy attending epilepsy clinics in Zambia's Lusaka or Southern province using a three-item instrument (maximum score = 3). Potential determinants of felt stigma including age, gender, education, wealth, disclosure status (meaning whether or how their community members knew of their condition), seizure type (generalized vs partial), seizure frequency, the presence of visible epilepsy-associated stigmata, personal contagion beliefs, and community contagion beliefs. The median stigma score was 2.5, suggesting some ceiling effect in the instrument. People with epilepsy who believed their condition to be contagious, who thought their community believed epilepsy to be contagious, and whose condition had been revealed to their community against their wishes reported more felt stigma. Community and clinic-based educational campaigns to dispel contagion beliefs are needed.


Age-related differences in nest defense in common terns: Relationship to other life-history parameters.
The Common Tern (Sterno hirundo) is a long-lived colonial nesting seabird. Previous studies have shown that chick growth and fledging success vary with age of the parental pair and with laying date, with older parents and those nesting earlier being more successful. This study investigated the dependence of breeding performance and one aspect of behavior, defense against conspecifics, on age and laying date. Nest defense behavior was evaluated by recording individual responses to a mirror placed 20 cm from the nest, simulating an unfamiliar intruder within the territory. Most study birds were of known age (3-21 years) from banding as chicks; they were divided into three groups: ≥12, 8-11 and ≤seven years. Responses to the mirror were examined during incubation and at the time of hatching. Older birds nested earlier than younger birds. Chicks reared by older parents gained mass more quickly and survived better than chicks of younger parents. Using a composite score reflecting both the intensity and duration of aggressive responses to the mirror, older birds responded more strongly than younger birds during incubation, but responses were similar at the time of hatching. Older birds reduced their aggressive responses between incubation and hatching, while younger birds increased their responses. We suggest that this contributes to the greater success of older birds, because younger birds expend more time and energy on territorial defense at a time when they need to feed chicks. Our findings are consistent with previous studies and show that Common Tern colonies are finely structured by age and laying date; older and earlier-nesting birds are superior to younger and later birds on several measures of performance. This study suggests that finely-tuned nest defense behavior is one component of the superior performance of old birds.


Urinary tract infection in infants: the significance of low bacterial count.
In national guidelines for urinary tract infection (UTI) in children, different cut-off levels for defining bacteriuria are used. In this study, the relationship between bacterial count in infant UTI and inflammatory parameters, frequency of vesicoureteral reflux (VUR), kidney damage, and recurrent UTI was analyzed. We conducted a population-based retrospective study of 430 infants age <1 year with symptomatic UTI diagnosed by suprapubic aspiration. Clinical and laboratory parameters, findings on voiding cystourethrography and (99m)technetium dimercapto-succinic acid scintigraphy, and frequency of recurrence were related to bacterial count at the index UTI. Eighty-three (19%) infants had bacterial counts <100,000 colony-forming units (CFU)/ml and 347 (81%) had ≥100,000 CFU/ml. There was similar frequency of VUR (19% in both groups), kidney damage (17 and 23%, p = 0.33) and recurrent UTI (6 and 12%, p = 0.17) in the low and high bacterial group. Non-E. coli species were more prevalent (19 versus 6%, p = 0.0006) and mean C-reactive protein was lower (50 vs. 79 mg/l, p <0.0001) in the low bacteria group. UTI with low bacterial count is common and of importance since it may be associated with VUR and renal damage. Non-E. coli species and low inflammatory response were more prevalent in UTI with low bacterial count.


Toward the creation of NMR databases in chiral solvents: bidentate chiral NMR solvents for assignment of the absolute configuration of acyclic secondary alcohols.
The absolute configuration of acyclic secondary alcohols can be established from analysis of the chemical shift behaviors of the adjacent carbons in bidentate chiral solvents (R,R)- and (S,S)-1d as formulated in the boxed illustration.


Increased tolerance to large hyperosmotic shocks and compensatory solutes in mammalian cultured cells.
L929 and MDCK cells acclimated to sorbitol, proline or taurine media can tolerate a NaCl load that they would be unable to stand when cultured in normal conditions. The protecting effect is observed only at high concentrations, between 100 and 300 mM. In that range, the effect is increasing with increasing concentration. The presence of the compound is not necessary, in the extracellular medium, to induce tolerance. These results are discussed in the framework of the theory considering preferential interactions of proteins with solvent components to explain the protecting effect of such compounds.


Trends and effect of marginalization on diabetes mellitus-related mortality in Mexico from 1990 to 2019.
Diabetes mellitus (DM) is currently one of the leading causes of mortality worldwide. However, the disease evolves differently across countries. This study intends to characterize the trends and assess the potential effects of marginalization on DM mortality between 1990 and 2019 in Mexico. We analyzed death certificates that listed DM as the underlying cause of death (N = 1,907,173), as well as the extent to which DM mortality changes were associated with marginalization through an age-period-cohort analysis. DM mortality increased in Mexico between 1990 and 2019; the change was faster in the first half and slowed down after 2004. The highest marginalization quintiles drove the changes in DM mortality trends during the study period, with a higher risk of dying in these quintiles as age increased. In recent cohorts, the highest marginalization quintiles doubled the risk of dying from DM as compared to the lowest. Renal complications was the main death driver among persons with DM, with a marked increase between 1999 and 2001. In conclusion, Mexico continues to have a substantially high DM mortality, but its pace slowed over time. Moreover, subnational differences in marginalization can partially explain such a trend.


Metabolic rewiring in melanoma drug-resistant cells.
Several evidences indicate that melanoma, one of the deadliest types of cancer, presents the ability to transiently shift its phenotype under treatment or microenvironmental pressure to an invasive and treatment-resistant phenotype, which is characterized by cells with slow division cycle (also called slow-cycling cells) and high-OXPHOS metabolism. Many cellular marks have been proposed to track this phenotype, such as the expression levels of the master regulator of melanocyte differentiation (MITF) and the epigenetic factor JARID1B. It seems that the slow-cycling phenotype does not necessarily present a single gene expression signature. However, many lines of evidence lead to a common metabolic rewiring process in resistant cells that activates mitochondrial metabolism and changes the mitochondrial network morphology. Here, we propose that mitochondria-targeted drugs could increase not only the efficiency of target therapy, bypassing the dynamics between fast-cycling and slow-cycling, but also the sensitivity to immunotherapy by modulation of the melanoma microenvironment.


Percutaneous transhepatic venous angioplasty and stenting in a 9-month-old patient with hepatic vein obstruction after partial liver transplantation.
Hepatic venous outflow obstruction is a rare but serious complication after liver transplantation. We report ultrasound-guided percutaneous transhepatic stent placement in a 9-month-old infant with a left lateral split liver transplantation with near-complete hepatic vein obstruction.


Removal of silver nanoparticles in simulated wastewater treatment processes and its impact on COD and NH(4) reduction.
The increasing utilization of silver nanoparticles in industrial and consumer products has raised concern to wastewater treatment utilities due to its antimicrobial activity. In this work, the removal of citrate stabilized silver nanoparticles (Ag-NPs) during the wastewater treatment processes and its impact on treatment performance were examined. During simulated primary clarification, over 90% of the Ag-NPs remained in the wastewater, indicating that the majority of silver nanoparticles in sewage would enter the subsequent treatment units. During sequencing batch reactor processes, silver nanoparticles were effectively removed in each cycle throughout the 15-d experimental duration. Continuous input of silver nanoparticles into the wastewater did not significantly alter chemical oxygen demand (COD) removal. NH(4) removal was reduced at the beginning of the SBR experiment but quickly recovered at the later stage of the experiment. This study demonstrated that in the near future it is unlikely that citrate-stabilized Ag-NPs released into sewage will cause significant adversary effects on the COD and NH(4) removal of activated sludge processes in municipal wastewater treatment plants.


Monitoring the cellular activity of a cultured single cell by scanning electrochemical microscopy (SECM). A comparison with fluorescence viability monitoring.
The respiratory activities of cultured HeLa cells were monitored at a single cell level using scanning electrochemical microscopy (SECM) that produces images of the localized distribution of oxygen around the cell. The change in the cellular activity was traced after exposures to KCN, ethyl alcohol and the antibiotic drug, Antimycin A. The results were compared with those from the conventional fluorescence monitoring using Calcein-AM that is sensitive to deformation of the cell membrane. The SECM-based measurement follows the decrease in the cellular activity upon exposure to KCN and Antimycin A more rapidly than the fluorescence-based measurements, demonstrating that SECM is suitable for studying the cellular influence of respiration inhibitors.


Epidemiologic and molecular risk factors for contralateral breast cancer among young women.
Women diagnosed with a first breast cancer before the age of 45 years have a greater than 5.0-fold risk of developing a second primary contralateral breast cancer (CBC) than women in the general population have of developing a first breast cancer. Identifying epidemiologic or molecular factors that influence CBC risk could aid in the development of new strategies for the management of these patients. A total of 1285 participants in two case-control studies conducted in Seattle, Washington, who were 21-44 years of age when diagnosed with a first invasive breast carcinoma from 1983 to 1992, were followed through December 2001. Of them, 77 were diagnosed with CBC and 907 tumour tissues from first cancers were analysed. Women with body mass indices (BMIs) >/=30 kg m(-2) had a 2.6-fold greater risk (95% CI: 1.1-5.9) of CBC compared to women with BMIs </=19.9 kg m(-2). Women whose first tumour was c-erbB-2 positive had a 1.7-fold (95% CI: 1.0-3.0) excess CBC risk. Body mass index and c-erbB-2 expression may be risk factors for CBC in young women. Further observational studies are needed to confirm these findings and to evaluate whether testing for c-erbB-2 in this population may help identify those at high risk for CBC.


Integrated analysis of dermal blister fluid proteomics and genome-wide skin gene expression in systemic sclerosis: an observational study.
Skin fibrosis is a hallmark feature of systemic sclerosis. Skin biopsy transcriptomics and blister fluid proteomics give insight into the local environment of the skin. We have integrated these modalities with the aim of developing a surrogate for the modified Rodnan skin score (mRSS), using candidate genes and proteins from the skin and blister fluid as anchors to identify key analytes in the plasma. In this single-centre, prospective observational study at the Royal Free Campus, University College London, London, UK, transcriptional and proteomic analyses of blood and skin were performed in a cohort of patients with systemic sclerosis (n=52) and healthy controls (n=16). Weighted gene co-expression network analysis was used to explore the association of skin transcriptomics data, clinical traits, and blister fluid proteomic results. Candidate hub analytes were identified as those present in both blister and skin gene sets (modules), and which correlated with plasma (module membership >0·7 and gene significance >0·6). Hub analytes were confirmed using RNA transcript data obtained from skin biopsy samples from patients with early diffuse cutaneous systemic sclerosis at 12 months. We identified three modules in the skin, and two in blister fluid, which correlated with a diagnosis of early diffuse cutaneous systemic sclerosis. From these modules, 11 key hub analytes were identified, present in both skin and blister fluid modules, whose transcript and protein levels correlated with plasma protein concentrations, mRSS, and showed statistically significant correlation on repeat transcriptomic samples taken at 12 months. Multivariate analysis identified four plasma analytes as correlates of mRSS (COL4A1, COMP, SPON1, and TNC), which can be used to differentiate disease subtype. This unbiased approach has identified potential biological candidates that might be drivers of local skin pathogenesis in systemic sclerosis. By focusing on measurable analytes in the plasma, we generated a promising composite plasma protein biomarker that could be used for assessment of skin severity, case stratification, and as a potential outcome measure for clinical trials and practice. Once fully validated, the biomarker score could replace a clinical score such as the mRSS, which carries substantial variability. GlaxoSmithKline and UK Medical Research Council.


Rhabdomyolysis induced by simvastatin-fluconazole combination.
Rhabdomyolysis is a potential adverse consequence of statin therapy. Here, we report a patient with prostate cancer being treated with simvastatin who developed rhabdomyolysis after coadministration with fluconazole. The rhabdomyolysis promptly resolved after discontinuation of fluconazole, suggesting the possible role of drug interaction in the development of rhabdomyolysis with coadministration of the two medications. Both simvastatin and fluconazole were promptly discontinued, and the patient was admitted to the intensive care unit, where vigorous hydration along with urine alkalinization led to resolution of rhabdomyolysis. Since statins are commonly prescribed treatments for individuals with hyperlipidemia, caution is advised in coadministration with azoles such as fluconazole. Although supportive treatment remains the mainstay of therapy for patients with rhabdomyolysis, fatal consequences can arise from hyperkalemia, cardiac arrhythmia, renal failure and disseminated intravascular coagulation.


Effect of the COVID-19 Pandemic on Postacute Care Decision Making.
The response to the coronavirus disease 2019 (COVID-19) pandemic in the United States has resulted in rapid modifications in the delivery of health care. Key among them has been surge preparation to increase both acute care hospital availability and staffing while using state and federal waivers to provide appropriate and efficient delivery of care. As a large health system in New York City, the epicenter of the pandemic in the United States, we were faced with these challenges early on, including the need to rapidly transition patients from acute care beds to provide bed capacity for the acute care hospitals. Rehabilitation medicine has always played an essential role in the continuum of care, establishing functional goals while identifying patients for postacute care planning. During this crisis, this expertise and the overwhelming need to adapt and facilitate patient transitions resulted in a collaborative process to efficiently assess patients for postacute care needs. We worked closely with our skilled nursing facility, home care partners, and an acute inpatient rehabilitation hospital to adapt their admissions processes to the patient population with COVID-19, all the while grappling with varying access to vital supplies, testing, and manpower. As the patient criteria were established, rapid pathways were created to postacute care, and we were able to create much needed bed capacity in our acute care hospitals.


Specific Ag-guiding nano-vaccines attenuate neutrophil-dominant allergic asthma.
Polymorphonuclear neutrophils (PMN) are one fraction of the major inflammatory cells in allergic asthma (asthma, in short); the role of PMN in the asthma pathogenesis is not fully understood yet. This study aims to investigate the effects of specific Ag-guiding exosomes on suppressing the neutrophil-dominant airway inflammation. In this study, BALB/c mice were immunized with ovalbumin plus complete Freund adjuvant to induce an asthma model featured with neutrophil-dominant lung inflammation. The Ag specific PMN (sPMN)-targeting exosomes (tExo), that were exosomes carrying a complex of specific Ag/anti-CD64 Ab and Fas ligand, were constructed to be used to alleviate neutrophilic asthma in mice. We found that sPMNs were the major cellular component in bronchoalveolar lavage fluid (BALF) in asthma mice, while less than 3% PMNs in naive control mice. The sPMNs expressed higher levels of CD64, which formed complexes with Ag-specific IgG (sIgG). The sIgG/CD64 complex-carrying PMNs could be activated upon exposing to specific Ags. Exposure to tExos induced Ag-specific PMNs apoptosis. Administration of tExos efficiently suppressed experimental asthma. We conclude that a fraction of sPMN was identified in the airway of asthma mice. The sPMNs could be activated upon exposure to specific Ags. tExos could induce sPMNs apoptosis, that show the translational potential in the treatment of asthma.


The distribution of lipids and sterols in cell types from the marine sponge Pseudaxinyssa sp.
The sponge Pseudaxinyssa sp., unique in sterol and fatty acid composition, was cellularly dissected into fractions enriched in each of the major cell types present in the sponge: microbial symbionts (cyanobacteria), small sponge cells (pinacocytes and choanocytes), and large sponge cells (archeocytes and cyanophytes). Three phototrophic microbial symbionts were also isolated from the cell fractions and grown in culture. An unsymmetrical distribution of fatty acids and sterols was observed for the sponge cells: small cells contained larger quantities of long chain fatty acids (greater than C24) and smaller quantities of sterols than were present in the larger sponge cells. Moreover, the rare sterols 24-isopropylcholesterol predominated in the smaller sponge cells, whereas its 22-dehydro analog predominated in the larger sponge cells. Long chain fatty acids and sterols were not detected in the cultured microbial symbionts. This constitutes the first report of lipid variability according to cell type for this most primitive group of Metazoa.


Pharmacokinetic and pharmacodynamic modeling of the metastin/kisspeptin analog, TAK-448, for its anti-tumor efficacy in a rat xenograft model.
TAK-448 is the investigational metastin/kisspeptin analog, which is known to have an anti-tumor effect through suppression of androgen hormones (luteinizing hormone and testosterone) levels. This study developed pharmacokinetic-pharmacodynamic (PK/PD) models of TAK-448 and leuprorelin acetate (TAP-144) in a rat vertebral-cancer of the prostate (VCaP) androgen-sensitive prostate cancer xenograft model to quantitatively assess and compare the anti-tumor effects of both drugs. A potential contribution of the hormone-independent direct effects of TAK-448 to the tumor growth inhibition was also investigated in the in vivo rat xenograft model, because our in vitro experiments revealed that TAK-448 may also directly suppress VCaP cellular proliferation. The PK/PD model successfully described the time course of tumor growth inhibition after drug treatment as well as the development of resistance to the inhibition of androgen hormones, following drug treatment or castration. The EC50 of the hormone-dependent inhibitory effect of TAK-448 was much lower than that of TAP-144, and TAK-448 also has a faster onset of anti-tumor effect than TAP-144, demonstrating that TAK-448 has a stronger overall anti-tumor effect than TAP-144. In addition, model inference, by incorporating a hormone-independent inhibition pathway of TAK-448 into the PK-PD model, suggested that such a direct inhibition pathway for TAK-448 cannot be excluded, as also indicated by in vitro studies, but its EC50 would be approximately three orders of magnitude higher than that of the hormone-dependent pathway. This study helps to understand the potential and mechanism of TAK-448 as a prostate cancer treatment.


Estrogen-2/4-hydroxylase activities in rat brain and liver microsomes exhibit different substrate preferences and sensitivities to inhibition.
NADPH-dependent estrogen-2/4-hydroxylase activities in rat brain and liver microsomes were compared with respect to the utilization of different estrogens as substrates and the inhibitory effects of alpha-naphthoflavone, metyrapone and steroids. Of 6 different estrogens used as substrates, only 17 beta- and 17 alpha-estradiol were transformed relatively effectively by brain microsomes. In contrast liver microsomes utilized these two estrogens as well as ethynyl estradiol, estrone and diethylstilbestrol effectively. Estriol was a poor substrate for estrogen-2/4-hydroxylase activity in both tissues. With 40 microM 17 beta-estradiol as substrate the estrogen-2/4-hydroxylase activities in brain and liver were inhibited by alpha-naphthoflavone, metyrapone, progesterone, 17 alpha-hydroxyprogesterone and testosterone. The brain enzyme activity appeared to be more sensitive than the liver enzyme to inhibition by alpha-naphthoflavone and metyrapone. Testosterone propionate (50-100 microM) stimulated the brain enzyme activity significantly. Progesterone and 17 alpha-hydroxyprogesterone were the most effective steroidal inhibitors of brain estrogen-2/4-hydroxylase activity. In the liver the inhibitory potencies of 3 different steroids varied, depending on the estrogen used as substrate. With 17 beta-estradiol, for example, progesterone was the most potent steroidal inhibitor, while corticosterone was the most potent inhibitor when diethylstilbestrol was used as substrate. These findings indicate that rat liver microsomes can utilize a wider range of different estrogens for catecholestrogen formation than brain microsomes and suggest that the profiles of catecholestrogen-forming P-450 isozymes in the two organs differ.


The distribution and origin of mutagens in airborne particulates, detected by the salmonella/microsome assay in relation to levels of lead, vanadium and PAH.
At three stations in central Copenhagen, Denmark, samples of particulate matter were collected simultaneously with different contributions from automobile exhaust products. Samples were obtained at street level, 22 m above street level and within a hospital zone; 32 samples were analysed for levels of polycyclic aromatic hydrocarbons (PAH) and elements, as well as for mutagenicity towards S. typhimurium TA1538. Two classes of mutagens were quantified: a non-polar extract rich in PAH and, other promutagens, and a polar extract containing direct acting mutagens (not requiring microsomal activation). Covariances between lead and mutagenicity, and the varying distribution of the polar and non-polar mutagens at the stations, indicate that at all stations the mutagenicity of the non-polar extract is dominated by automobile exhaust products. The polar extract is relatively less influenced by primary traffic emissions; a considerable part of the activity of this extract is attributed to secondary emissions, transformed by atmospheric reactions, and primary emissions from stationary sources.


Soil weathering dynamics and erosion in a dry oceanic area of the southern hemisphere (Otago, New Zealand).
Landscape evolution is driven by tectonics, climate and surface denudation. In New Zealand, tectonics and steep climatic gradients cause a dynamic landscape with intense chemical weathering, rapid soil formation, and high soil losses. In this study, soil, and elemental redistribution along two adjacent hillslopes in East Otago, New Zealand, having different landscape settings (ridge versus valley) are compared to identify soil weathering and erosion dynamics. Fallout radionuclides (239+240Pu) show that over the last ~ 60 years, average soil erosion rates in the valley (~ 260 [t km-2 year-1]) are low compared to the ridge (~ 990 [t km-2 year-1]). The ridge yields up to 26% lower soil weathering intensity than the topographical-protected valley. The lowest soil weathering intensity is found at both hilltop positions, where tors (residual rocks) are present and partially disintegrate. The soil weathering intensity increases with distance from tors, suggesting that tors rejuvenate the chemical weathering signature at the hilltop positions with fresh material. The inversed and decreasing weathering degree with all soil depth indicates that the fresh mineral contribution must be higher at the soil surface than at the bedrock weathering front. Higher erosion rates at the exposed ridge may be partially attributed to wind, consistent with rock abrasion of tors, and low local river sediment yields (56 [t km-2 year-1]). Thus, the East Otago spatial patterns of soil chemistry and erosion are governed by tor degradation and topographic exposure.


Dynamical interactions reconfigure the gradient of cortical timescales.
The functional organization of the brain is usually presented with a back-to-front gradient of timescales, reflecting regional specialization with sensory areas (back) processing information faster than associative areas (front), which perform information integration. However, cognitive processes require not only local information processing but also coordinated activity across regions. Using magnetoencephalography recordings, we find that the functional connectivity at the edge level (between two regions) is also characterized by a back-to-front gradient of timescales following that of the regional gradient. Unexpectedly, we demonstrate a reverse front-to-back gradient when nonlocal interactions are prominent. Thus, the timescales are dynamic and can switch between back-to-front and front-to-back patterns.


Surgery for constipation: systematic review and clinical guidance: Paper 1: Introduction & Methods.
This manuscript provides the introduction and detailed methodology used in subsequent reviews to assess the outcomes of surgical interventions with the primary intent of treating chronic constipation in adults and to develop recommendations for practice. PRISMA guidance was adhered to throughout. A literature search was performed in public databases between January 1960 and February 2016. Studies that fulfilled strictly-defined PICOS (patients, interventions, controls, outcome, and study design) criteria were included. The process involved two groups of participants: (i): 'a clinical guidance group' of 18 UK experts (including junior support) who performed the systematic reviews and produced summary evidence statements (SES) based strictly on data synthesis in each review. The same group then produced prototype graded practice recommendations (GPRs) based on coalescence of SES and expert opinion; (ii): a European Consensus group of 18 ESCP (European Society of Coloproctology) nominated experts from nine European countries evaluated the appropriateness of each prototype GPR based on published RAND/UCLA methodology. An overview of the search results is provided in this manuscript. A total of 156 studies from 307 full text articles (from 2551 initially screened records) were included, providing data on procedures characterized by: (i) colonic resection (n = 40); (ii) rectal suspension (n = 18); (iii) rectal wall excision (n = 44); (iv) rectovaginal septum reinforcement (n = 47); (v) sacral nerve stimulation (n = 7). The overall quality of evidence was poor with 113/156 (72.4%) studies providing only Oxford level IV evidence. The best evidence was extracted for rectal excisional procedures, where the majority of studies were Oxford level I or II. The five subsequent reviews provide a total of 99 SES (reflecting perioperative variables, efficacy, harms and prognostic variables) that contributed to 100 prototype GPRs covering patient selection, procedural considerations and patient counselling. The final manuscript details the 85/100 GPRs that were deemed appropriate by European Consensus (remaining 15 were all uncertain) and future research recommendations. This manuscript and the following 6 papers suggest that the evidence base for surgical management of chronic constipation is currently poor although some expert consensus exists on best practice. Further studies are required to inform future commissioning of treatments and of research funding.


Telomeres expand sphere of influence: emerging molecular impact of telomeres in non-telomeric functions.
Although the impact of telomeres on physiology stands well established, a question remains: how do telomeres impact cellular functions at a molecular level? This is because current understanding limits the influence of telomeres to adjacent subtelomeric regions despite the wide-ranging impact of telomeres. Emerging work in two distinct aspects offers opportunities to bridge this gap. First, telomere-binding factors were found with non-telomeric functions. Second, locally induced DNA secondary structures called G-quadruplexes are notably abundant in telomeres, and gene regulatory regions genome wide. Many telomeric factors bind to G-quadruplexes for non-telomeric functions. Here we discuss a more general model of how telomeres impact the non-telomeric genome - through factors that associate at telomeres and genome wide - and influence cell-intrinsic functions, particularly aging, cancer, and pluripotency.


Informative title: Guided bone regeneration with and without rhBMP-2: 17-year results of a randomized controlled clinical trial.
To assess long-term outcomes of implants placed in conjunction with guided bone regeneration (GBR) with or without recombinant human bone morphogenetic protein-2 (rhBMP-2). Eleven patients with at least two lateral bone defects (split-mouth design) received a total of 34 implants. The defects were treated with a xenogenic bone substitute with (test) or without (control) rhBMP-2 and covered with a collagen membrane. Eight patients could be reexamined after at least 17 years. Wilcoxon signed-rank tests were performed to assess differences between test and control groups. The implant survival rate was 100% for all test and control sites. Mean marginal bone levels were 2.51 mm (SD ±1.64) (mesial test), 1.83 mm (SD ±0.93) (mesial control) (p = .055), 2.36 mm (SD ±1.70) (distal test), and 2.13 mm (SD ±0.84) (distal control) (p = 1.000). Compared with the mean values at baseline, a mean bone loss of 1.16 mm (SD ±1.60) (test) and 0.70 mm (SD ±1.02) (control) was found. The mean buccal bone gain after 17 years was 5.38 mm (test) and 3.14 mm (control) based on the comparison between the measurements at the cone beam CT after 17 years and the data from the intraoperative measurements at baseline. Further, mean values for (i) bone thickness ranged from 1.36 to 3.09 mm (test) and 1.18 to 3.39 mm (control) and for (ii) mucosal thickness of 1.24 mm (test) and 1.26 mm (control). Implants placed in conjunction with GBR applying a xenogenic bone substitute and a collagen membrane with and without the addition of rhBMP-2 demonstrate excellent clinical and radiographic results after at least 17 years.


Challenging the Portrait of the Unhealthy Gamer-The Fitness and Health Status of Esports Players and Their Peers: Comparative Cross-Sectional Study.
Esports players are often referred to as sedentary athletes, as gaming requires prolonged sedentary screen exposure. As sedentary behavior and physical inactivity are major causes of noncommunicable diseases and premature death, esports players may be at an increased risk for health implications. Prior research has established esports players as having higher levels of body fat and lower levels of lean body mass versus age-matched controls, suggesting the need to assess further health and fitness outcomes of this demographic. However, while research interest is undoubtedly increasing, the majority of studies has focused on subjective self-report data and has lacked relevant objective health and fitness measurements. This study aimed to assess the health and fitness status of a group of competitive esports players in relation to an age- and sex-matched comparison group. In total, 51 competitive esports players (mean 23, SD 3 years, 2 female) and 51 nonesports players (mean 24, SD 3 years, 2 female) were enrolled in this cross-sectional laboratory study. The esports players and the nonesports players completed a questionnaire assessing demographic data and self-reported physical activity levels. Furthermore, physical parameters including BMI, waist-to-height ratio, body fat percentage, systolic blood pressure, diastolic blood pressure, pulse wave velocity, maximal grip strength, and maximal oxygen consumption were assessed. There were no significant differences in BMI (t100=1.54; P=.13; d=0.30), waist-to-height ratio (t100=1.44; P=.16; d=0.28), body fat percentage (t100=-0.48; P=.63; d=-0.09), systolic blood pressure (t100=-0.06; P=.93; d=-0.01), diastolic blood pressure (t100=0.37; P=.71; d=0.07), pulse wave velocity (t93=-2.08; P=.15; d=-0.43), maximal grip strength (t100=-.08; P=.94; d=-0.02), maximal oxygen consumption (t100=-0.11; P=.92; d=-0.02), and physical activity (PA) levels (t86=2.17; P=.08; d=0.46) between the groups. While the health narrative directed toward esports players has been mainly negative, this laboratory-based study indicated that esports players are not less healthy or fit compared to their peers. However, it seems that esports players are very heterogeneous and seem to span across the whole range of the fitness and health spectrum. Thus, the generalized statements of the esports athlete as an obese and unhealthy individual may need to be reconsidered.


[Value of Glasgow-Pittsburgh Coma Scale scoring in childhood coma].
To investigate the value of Glasgow Coma Scale (GCS) and Glasgow-Pittsburgh Coma Scale (GCS-P) scoring in predicting the prognosis of coma in children. Clinical data of 17 comatose children were retrospectively reviewed. The results of GCS and GCS-P scoring, electroencephalogram (EEG) and cranial imaging were analyzed. Dynamic curves of GCS-P score were drawn. Seven patients received EEG examination and four showed low potential. The four patients had poor prognosis. Cranial CT and MRI were performed in 12 patients. Of these three showed cerebral hemorrhage and ischemia and had a poor prognosis. The accuracy rate for predicting the prognosis of GCS and GCS-P scoring was 85.71% and 88.57% respectively. A continuous GCS-P scoring was performed in 13 patients. A dynamic GCS-P curve showed an ascent in seven cases with good prognosis but a flat or declined tendency in six cases with poor prognosis. GCS-P scoring is valuable for predicting prognosis in children with coma. Combined with EEG and cranial imaging examinations, the accuracy for predicting prognosis of GCS-P scoring will increase.


Structure function studies on phytochrome. Identification of light-induced conformational changes in 124-kDa Avena phytochrome in vitro.
Light-mediated conformational changes in highly purified 124-kDa phytochrome preparations from etiolated oat seedlings have been identified by steric exclusion high performance liquid chromatography and limited proteolytic studies. Steric exclusion high performance liquid chromatography studies of oat and rye phytochromes show photoreversible changes in retention times, with the red absorbing form of phytochrome (Pr form) eluting later than the far red absorbing form of phytochrome produced by saturating red light illumination of Pr (Pfr form) in a variety of different mobile phase buffers. Molecular mass calibration with globular protein standards in Tris-glycol buffers provides estimates of 318-349 and 363-366 kDa for the molecular sizes of the Pr and Pfr forms, respectively. These analyses support earlier studies that phytochrome is a nonglobular homodimer of 124-kDa subunits in vitro. Limited proteolytic dissection of phytochrome in nondenaturing buffers with seven different endoproteases provides evidence for two "operational" domains within the 124-kDa subunit with molecular mass values of 69-72 and 52-55 kDa. The larger 69-72-kDa domain contains the site for the chromophore attachment as shown by gel electrophoresis derived enzyme-linked immunosorbent assay utilizing site-directed rabbit antiserum to a synthetic undecapeptide which is homologous with the chromophore binding site on oat phytochrome. This chromophore domain exhibits a compact structure, resistant to further proteolysis except near its N terminus. By contrast, the 52-55-kDa nonchromophore domain contains multiple sites for further proteolytic cleavage as revealed by rapid cleavage to smaller polypeptide fragments. Detailed kinetic analyses of the limited proteolytic cleavage of phytochrome with four endoproteases, subtilisin BPN', thermolysin, trypsin, and clostripain, has mapped specific regions within the 124-kDa subunit that participate in light-induced conformational changes. These include a 4-10-kDa region near the N terminus of the chromophore binding domain and at least two regions within the nonchromophore domain. A comprehensive peptide map of the oat phytochrome subunit is presented, which incorporates the results of these proteolytic studies with the recent, yet unpublished sequence analyses of Avena phytochrome cDNA clones which show the N-terminal localization of the chromophore binding site (Hershey, H. P., Colbert, J. T., Lissemore, J. L., Barker, R. F., and Quail, P. H. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 2332-2336).


A Novel EMD Mutation Identified by Whole-Exome Sequencing in Twins with Emery-Dreifuss Muscular Dystrophy.
This case reports a novel hemizygous frameshift EMD mutation (c.487delA, p.Ser163fs) in twins of an Emery-Dreifuss muscular dystrophy family with severe cardiac involvement and mild muscle weakness. Their mother carried the same heterozygous mutation.


Clinical Features, Treatment, Prognosis, and Mortality in Paraquat Poisonings: A Hospital-Based Study in Iran.
The aim of the present study was to evaluate the demographics, clinical characteristics, fatal dose, the efficacy of treatments, and prognosis in paraquat (PQ) poisoning in the Kerman Province of Iran. This analytical cross-sectional study was conducted on 126 PQ poisoned patients who were referred to Afzalipour Hospital during 2006-2015. Demographic variables such as age and gender, signs and symptoms of poisoning, the estimated ingested dosage of PQ, and clinical outcome were extracted from medical records. Patients were compared and categorized into two groups considering the outcome: survivors and nonsurvivors. Patients with nonoral exposures, combined drug exposures, PQ exposures more than 24 h before the presentation, and critical underlying diseases were not included in the study. Our results indicated that the mean dose of PQ used by all patients was 2358 mg, which was reported as 1846 and 2812 mg in females and males, respectively. Moreover, the results showed that the highest mortality rate was in patients with respiratory distress, followed by oral ulceration and excess salivation. In all PQ-poisoned patients, the dose of greater than approximately 2250 mg predicted death with 86.2% specificity and 75.7% sensitivity. Based on the results of the present study, the mortality rate in PQ-poisoned patients depended on the dose of poison, blood sugar level, and aspartate transaminase levels. Our results suggest that these parameters have excellent prognostic value for the prediction of mortality.


Common infections in clinical practice: dealing with the daily uncertainties.
Common infections we see every day in the office--urinary tract infections, vaginitis, upper respiratory tract infections, and soft-tissue infections--present a number of diagnostic and treatment uncertainties. In this age of growing antibiotic resistance, these include if and when to start antibiotic therapy, and which agents to use.


B lymphocyte activation during cognate interactions with CD4+ T lymphocytes: molecular dynamics and immunologic consequences.
Productive interaction between T and B lymphocytes is required for humoral immune responses to many foreign protein antigens and production of pathogenic antibodies characteristic of several autoimmune conditions. Thus, much attention has been given in recent years to understand the dynamic molecular interactions and signal transduction required for productive T-B interaction. In this review we highlight current knowledge of signaling and biologic responses that occur in B cells during cognate interactions with helper T cells, focusing on the dynamic function of B cell-surface molecules in T-B synapses.


Intranasal co-administration of recombinant active fragment of Zonula occludens toxin and truncated recombinant EspB triggers potent systemic, mucosal immune responses and reduces span of E. coli O157:H7 fecal shedding in BALB/c mice.
Escherichia coli O157:H7 with its traits such as intestinal colonization and fecal-oral route of transmission demands mucosal vaccine development. E. coli secreted protein B (EspB) is one of the key type III secretory system (TTSS) targets for mucosal candidate vaccine due to its indispensable role in the pathogenesis of E. coli O157:H7. However, mucosally administered recombinant proteins have low immunogenicity which could be overcome by the use of mucosal adjuvants. The quest for safe, potent mucosal adjuvant has recognized ΔG fragment of Zonula occludens toxin of Vibrio cholerae with such properties. ΔG enhances mucosal permeability via the paracellular route by altering epithelial tight junction structure in a reversible, ephemeral and non-toxic manner. Therefore, we tested whether recombinant ΔG intranasally co-administered with truncated EspB (EspB + ΔG) could serve as an effective mucosal adjuvant. Results showed that EspB + ΔG group induced higher systemic IgG and mucosal IgA than EspB alone. Moreover, EspB alone developed Th2 type response with IgG1/IgG2a ratio (1.64) and IL-4, IL-10 cytokines whereas that of EspB + ΔG group generated mixed Th1/Th2 type immune response evident from IgG1/IgG2a ratio (1.17) as well as IL-4, IL-10 and IFN-γ cytokine levels compared to control. Sera of EspB + ΔG group inhibited TTSS mediated haemolysis of murine RBCs more effectively compared to EspB, control group and sera of both EspB + ΔG, EspB group resulted in similar levels of efficacious reduction in E. coli O157:H7 adherence to Caco-2 cells compared to control. Moreover, vaccination with EspB + ΔG resulted in significant reduction in E. coli O157:H7 fecal shedding compared to EspB and control group in experimentally challenged streptomycin-treated mice. These results demonstrate mucosal adjuvanticity of ΔG co-administered with EspB in enhancing overall immunogenicity to reduce E. coli O157:H7 shedding.


Axonal transport of thiamine in frog sciatic nerves in vitro.
Thiamine has an essential and unknown function in nerve membranes. Administration of thiamine can alleviate symptoms of thiamine deficiency within a few hours. The time course is consistent with a fast axonal transport of the vitamin. Very little is known about axonal transport of low-molecular-weight substances with a preferential localization to the axon membrane. We investigated if labeled thiamine could be transported in the frog sciatic nerve. Radioactivity accumulated proximal to a ligature on the sciatic nerve after supplying the dorsal ganglia with [35S]thiamine in vitro. The accumulation was reduced by inhibition of the energy metabolism with dinitrophenol and by inhibition of protein synthesis in the ganglia with cycloheximide. Vinblastine did not affect the accumulation of thiamine at a concentration which was sufficient to block transport of [3H]leucine-labeled proteins. Accumulation distal to a ligature could be demonstrated in vivo but not in vitro after injecting the gastrocnemius muscle with labeled thiamine. Axonal transport of [3H]leucine-labeled proteins was inhibited by thiamine at millimolar concentrations in the incubation medium. A transient reduction of the compound action potential was obtained at these concentrations. Thiamine was migrating at a fast rate in frog sciatic nerves in both orthograde and retrograde directions. The uptake and/or transport was dependent on energy metabolism and a concomitant protein synthesis. The lack of effect by vinblastine suggests that the transported fraction of thiamine differs in subcellular localization from the bulk of transported [3H]leucine-labeled proteins.


Erratum to: Development of novel multiplex microsatellite polymerase chain reactions to enable high-throughput population genetic studies of Schistosoma haematobium.
Unfortunately, the original version of this article [1], contained a mistake. In Table 1, the primers for Sh6 and Sh9 were included incorrectly. Instead of GGGATGTATGCAGACTTG TTGTTTGGCTGCAGTAAC and GCTGAGCTTGAGATTG CTTCTGTCCCATCGATACC they should have been Sh6 Forward Primer GGTGGATTACGCAATAG, Sh6 Reverse Primer TTTAATCAACCGGGTGTC and Sh9 Forward Primer GGGATGTATGCAGACTTG, Sh9 Reverse Primer TTGTTTGGCTGCAGTAAC respectively. A corrected version of Table 1 is included below


ABC-training as a new intervention for hazardous alcohol drinking: Two proof-of-principle randomized pilot studies.
ABC-training is a new intervention to encourage health behavior change that targets the automatic activation of adaptive beliefs (i.e. automatic inferences). The aim of this proof-of-principle study was to test the effectiveness of web-based ABC-training to change outcome expectancies of alcohol drinking in a sample of hazardous drinkers. One exploratory and one confirmatory experiment with two between-subject conditions (online ABC- and control-training) and assessments at baseline and 1 week later (after three sessions of training). Participants recruited on Prolific Academic completed the web-based study. Adults with self-reported hazardous alcohol drinking (Experiment 1: 193 adults, United Kingdom, age mean = 46.7 years; Experiment 2: 282 adults, different nationalities, age mean = 38.3 years). ABC-training involved completing an online task that required choosing personally relevant alternative behaviors to drinking alcohol in personally relevant antecedent contexts to attain personally important outcomes. Comparator was control-training, in which participants selected both the alternative behaviors and alcohol drinking an equal number of times. Training was completed at baseline, after 3 days and after 1 week. Primary outcome was change in automatic and self-reported (negative/positive) outcome expectancies of alcohol drinking from baseline to after 1 week. Secondary outcomes were change in weekly alcohol consumption, self-efficacy, craving and motivation (and approach-alcohol associations in Experiment 1). Moderators were baseline outcome scores, motivation, age and alcohol dependency. Findings of this study are as follows: stronger increase in negative outcome expectancies after ABC- than control-training (Experiment 1: self-report, 95% confidence interval of difference scores (CIdiff ) = [0.04, Inf]; automatic, CIdiff = [0.01, Inf]; Experiment 2: self-report, CIdiff = [0.16, Inf]; automatic, CIdiff = [0.002, Inf]). Stronger reduction in self-reported positive outcome expectancies after ABC- than control-training (Experiment 1: CIdiff = [-Inf, -0.01]; Experiment 2: CIdiff = [-Inf, -0.21]) but mixed findings on automatic positive outcome expectancies (Experiment 1: CIdiff = [-Inf, 0.02]; Experiment 2: CIdiff = [-Inf, -0.001]). ABC-training may change outcome expectancies of alcohol consumption, but testing of clinically relevant effects in other samples is warranted.


Generation of two iPSC lines from patient with Mucopolysaccharidosis IV B type and autosomal recessive non-syndromic hearing loss 12.
We generated two human induced pluripotency stem cell (hiPSC) lines, RCMGi011-A and 11-B, from skin fibroblast from patient with Mucopolysaccharidosis IV B type and autosomal recessive non-syndromic hearing loss 12 using non-integrating, viral CytoTune™-iPS 2.0 Sendai Reprogramming Kit. We verified variant c.808 T > G and insertion in GLB1 gene, as well as two mutations, c.6992 T > C and c.805C > T, in CDH23 gene which lead to autosomal recessive hearing loss type 12. We have demonstrated normal karyotype of hiPSCs and capacity for cell differentiation into three germ layers.


Draining implant for neovascular glaucoma.
We treated 12 eyes with advanced neovascular glaucoma with a modification of drainage implant surgery. All 12 eyes had rubeosis iridis and severe pain and nine had undergone previous glaucoma surgery. After follow-up periods of two to 24 months (mean, 11.3 months), nine of 12 eyes had intraocular pressures of less than 24 mm Hg (mean preoperative value, 49.5 +/- 8.2 mm Hg; mean postoperative value, 22.2 +/- 12.9 mm Hg). Surgery was unsuccessful in three eyes, in two because the anterior chamber remained flat postoperatively and in one because a large hyphema blocked the tube 15 months postoperatively. Our procedure, which uses a Y-shaped Teflon tube, is easy to perform, is well tolerated by the eye, and is associated with a low risk of serious complications.


Modeling and control of non-square MIMO system using relay feedback.
This paper proposes a systematic approach for the modeling and control of non-square MIMO systems in time domain using relay feedback. Conventionally, modeling, selection of the control configuration and controller design of non-square MIMO systems are performed using input/output information of direct loop, while the output of undesired responses that bears valuable information on interaction among the loops are not considered. However, in this paper, the undesired response obtained from relay feedback test is also taken into consideration to extract the information about the interaction between the loops. The studies are performed on an Air Path Scheme of Turbocharged Diesel Engine (APSTDE) model, which is a typical non-square MIMO system, with input and output variables being 3 and 2 respectively. From the relay test response, the generalized analytical expressions are derived and these analytical expressions are used to estimate unknown system parameters and also to evaluate interaction measures. The interaction is analyzed by using Block Relative Gain (BRG) method. The model thus identified is later used to design appropriate controller to carry out closed loop studies. Closed loop simulation studies were performed for both servo and regulatory operations. Integral of Squared Error (ISE) performance criterion is employed to quantitatively evaluate performance of the proposed scheme. The usefulness of the proposed method is demonstrated on a lab-scale Two-Tank Cylindrical Interacting System (TTCIS), which is configured as a non-square system.


Fat boosts, while androgen receptor activation counteracts, BPH-associated prostate inflammation.
Metabolic syndrome (MetS) and benign prostate hyperplasia (BPH) are often comorbid. Chronic inflammation, a determinant pathogenic factor for BPH, is a putative link between the two conditions. In a multi-center cohort of BPH patients (n = 244) who underwent prostatectomy, we evaluated whether MetS is associated with prostatic inflammation in BPH specimens. In addition, we investigated the in vitro inflammatory effects of metabolic insults on human prostatic myofibroblastic cells (hBPH). Inflammatory infiltrates score (IS) in prostatectomy specimens showed a step-wise association with the number of MetS factors present (P = 0.001). After adjusting for age, reduced HDL cholesterol, and elevated triglycerides were the only factors significantly associated with IS. Increased IS was also significantly associated with hypogonadism. In an age- and testosterone (T)-adjusted model, dyslipidemia was still associated with IS. To investigate whether metabolic factors could directly trigger prostate inflammation, we performed preliminary studies in myofibroblastic hBPH. Among the different factors, oxidized low-density lipoprotein (oxLDL) showed the highest secretion of IL-8 (>10-fold)-a surrogate marker of prostate inflammation--as well as IL-6, and bFGF. Co-treatment with DHT significantly inhibited oxLDL-induced secretion of IL-8, whilst an AR-antagonist, bicalutamide, reversed DHT effects. DHT suppresses oxLDL receptor (LOX-1) expression. Our data suggest that fats and insulin could have a detrimental effect on prostate health, boosting inflammation, a key pathogenic factor in BPH. Conversely, beneficial effects of DHT in counteracting lipid- and insulin-induced prostatic alterations, suggest that T-via its conversion into DHT-may have unexpected beneficial effects on prostate health.


Multicenter phase II study of brequinar sodium in patients with advanced breast cancer.
In this study, 34 patients with advanced breast cancer were treated with brequinar sodium: 75% of the patients were postmenopausal, and 94% had received chemotherapy previously; 50% had previously received an anthracycline-containing regimen. Brequinar was administered intravenously at a median weekly dose of 1,200 mg/m2. The toxicity was moderate, with 17 patients (50%) experiencing grade 3 or 4 toxicity. There were 33 patients evaluable for response: 4 patients (12%; 95% confidence interval, 3.4-28.2%) achieved partial responses, 10 patients (30%) were stable, and 19 patients (58%) had progressive disease. We conclude that, at this dose and schedule, brequinar has only modest activity in patients with advanced breast cancer.


A 28-Year-Old Man from India with SARS-Cov-2 and Pulmonary Tuberculosis Co-Infection with Central Nervous System Involvement.
BACKGROUND Tuberculosis (TB) is a great mimic of central nervous system (CNS) tumors. This mimicry may pose a challenge, as the management of both diseases is quite different. Furthermore, the temporal association of initiating treatment affects prognosis. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mainly infects the pulmonary system. However, in a patient with concomitant pulmonary tuberculosis, it can be a diagnostic challenge. CASE REPORT A 28-year-old man of Indian origin presented with headache and vomiting. He had a brain mass on imaging suggestive of a glioma. He also had lung infiltrates and was diagnosed with a co-infection by SARS-CoV-2, by a reverse-transcription polymerase chain reaction (RT-PCR) using the GeneXpert system. The mass was excised and was found to be a tuberculoma, diagnosed by Xpert MTB. He received first-line anti-TB and treatment for COVID-19 pneumonia based on local guidelines. CONCLUSIONS This report highlights that COVID-19 can co-exist with other infectious diseases, such as TB. A high degree of clinical suspicion is required to detect TB with atypical presentation. A co-infection of pulmonary and CNS TB with COVID-19 can present a diagnostic challenge, and appropriate patient management relies on an accurate and rapid diagnosis. Surgery may be necessary if there are compressive signs and symptoms secondary to CNS TB. A diagnosis of COVID-19 should not delay urgent surgeries. Further studies are needed to understand the effects of COVID-19 on the clinical course of TB.


Interference of therapeutic antibodies used in desensitization protocols on lymphocytotoxicity crossmatch results.
Therapeutic antibodies used to desensitize patients awaiting a human leukocyte antigen (HLA) or ABO-mismatched graft are suspected to interfere with the lymphocytotoxicity crossmatch (LCT-XM) test when they are present in the tested sera because of their potential ability to activate or inhibit the complement. The most frequent therapeutic antibodies (Abs) used in desensitization protocols (intravenous immunoglobulins, rituximab, basiliximab, eculizumab, antithymocyte globulin) were added to a negative- or a positive-control serum at various concentrations, and tested in vitro in a LCT-XM test. Rituximab turned the LCT-XM positive on B cells at 0.2 μg/mL and antithymocyte globulin turned the LCT-XM positive with T and B cells at 20 μg/mL and 200 μg/mL, respectively. Treatment with dithiothreitol sera, supplemented with rituximab (0.2 and 2 μg/mL) and antithymocyte globulins (20 and 200 μg/mL), partially or totally reduced this positive interference. Intravenous immunoglobulin, eculizumab, and basiliximab did not trigger any interference with the negative control serum. In a positive LCT-XM, eculizumab did not annihilate activation of the rabbit complement. Intravenous immunoglobulins (25 g/L) could partially or totally reduced lysis score of positive crossmatch with weak lysis scores. If eculizumab within the serum did not annihilate rabbit complement activation and basiliximab did not interfere with the crossmatch reaction, treatments based on rituximab, antithymocyte globulin and intravenous immunoglobulins need to be taken into account when interpreting a positive or negative crossmatch test.


Discharge properties of dorsal medullary inspiratory neurons in newborn pigs.
The discharges of medullary inspiratory neurons were recorded in newborn pigs. They were classified by discharge pattern; response to lung inflation; synaptic relation to phrenic motoneurons. Our results showed: these neurons have similar discharge patterns and responses to lung inflation as adult cats; most neurons do not project to phrenic motoneurons. It is suggested that our sampled population of neurons is involved in integrating pulmonary afferent inputs.


Characterization of the O-antigen gene clusters of Yersinia pseudotuberculosis and the cryptic O-antigen gene cluster of Yersinia pestis shows that the plague bacillus is most closely related to and has evolved from Y. pseudotuberculosis serotype O:1b.
One of the most virulent and feared bacterial pathogens is Yersinia pestis, the aetiologic agent of bubonic plague. Characterization of the O-antigen gene clusters of 21 serotypes of Yersinia pseudotuberculosis and the cryptic O-antigen gene cluster of Y. pestis showed that the plague bacillus is most closely related to and has evolved from Y. pseudotuberculosis serotype O:1b. The nucleotide sequences of both gene clusters (about 20.5 kb each) were determined and compared to identify the differences that caused the silencing of the Y. pestis gene cluster. At the nucleotide sequence level, the loci were 98.9% identical and, of the 17 biosynthetic genes identified from the O:1b gene cluster, five were inactivated in the Y. pestis cluster, four by insertions or deletions of one nucleotide and one by a deletion of 62 nucleotides. Apparently, the expression of the O-antigen is not beneficial for the virulence or to the lifestyle of Y. pestis and, therefore, as one step in the evolution of Y. pestis, the O-antigen gene cluster was inactivated.


Alterations of aqueous flare and cells detected by laser flare-cell photometry in patients with Behcet's disease.
To quantitatively evaluate aqueous flare and cells in patients with Behcet's disease. This study included 30 Behcet's patients (52 eyes) with active uveitis. The patients were treated with immunosuppressive agents. Aqueous flare and cells were quantified using the laser flare-cell photometry before treatment and 1 and 2 months after treatment. Before treatment, mean aqueous flare (ph/ms) in Behcet's eyes was 25.7 ± 20.5. After treatment, flare values were significantly reduced after 1 and 2 months compared with those before treatment. No significant difference was found between flare values after 1 and 2 months. Before treatment, mean cell counts (cells/0.5 mm(3)) in Behcet's eyes were 23.2 ± 29.4. After treatment, cell counts were also significantly reduced after 1 and 2 months compared with those before treatment. Cell counts were further significantly reduced from 1 to 2 months. Both aqueous flare and cells were significantly increased in Behcet's patients with active uveitis and improved after a two-month treatment. Breakdown of the blood-aqueous barrier lasts longer than aqueous cells in these patients.


Thoracic spine disc-related abnormalities: longitudinal MR imaging assessment.
To describe and characterize the temporal changes in disc-related disorders of the thoracic spine using MR imaging. A retrospective longitudinal cohort study was carried out of 40 patients with two sequential thoracic spine MR images at variable intervals. The images were assessed for baseline presence of, new incidence of and changes in disc herniation, degenerative disc disease, endplate marrow signal alteration and Schmorl nodes. The range of follow-up was 4-149 weeks. Baseline presence was: disc herniation, 10% (49/480); degenerative disc disease, 14% (66/480); endplate marrow signal alteration, 2.3% (11/480); Schmorl nodes 9.6% (46/480). Most pre-existing lesions tended to remain unchanged. Herniations showed the most change, tending to improve in 27%. New incidence was: disc herniation, 1.5% (7/480), degenerative disc disease, 2% (10/480); endplate marrow signal alteration, 1.6% (8/480); Schmorl nodes, 2.1% (10/480). Disc degeneration was first visible at an 11-week interval and once established almost never changed over many weeks to months. Endplate signal alterations (Modic changes) were uncommon. Schmorl nodes show no change from baseline for up to 2 1/2 years. All findings predominated in the lower intervertebral levels from T6 to T10. The most prevalent thoracic spine disc-related findings are degeneration and herniation. Disc herniations predominate in the lower segments and are a dynamic phenomenon. Disc degeneration can be rapidly evolving but tends to remain unchanged after occurrence. Endplate marrow signal changes were an uncommon manifestation of thoracic disc disease. Schmorl nodes showed the least change over time.


Exploring the diversity of blood-sucking Diptera in caves of Central Africa.
Caves house pathogenic microorganisms, some of which are transmitted by blood-sucking arthropods. In Africa, previous studies identified mosquitoes, sand flies and biting midges as the main potential vectors of cave-dwelling pathogens. However, to understand their involvement in pathogen spillover, it is crucial to characterize their diversity, community composition and dynamics. Using CDC light traps, we collected hematophagous Diptera in six caves of Gabon during one-shot or longitudinal sampling, and investigated their species diversity and dynamics in relation with external rainfall. Overall, we identified 68 species of mosquitoes, sand flies and biting midges, including 45 new records for Gabon. The dominant species were: Uranotaenia nigromaculata, Anopheles smithii s.l., Culex. rima group and Culex quasiguiarti for mosquitoes, Spelaeophlebotomus gigas and Spelaeomyia emilii for sand flies and the Culicoides trifasciellus group and Culicoides fulvithorax for biting midges. The survey revealed that species assemblages were cave-specific and included mainly troglophilous and trogloxenous species. Both diversity and abundance varied according to the cave and sampling time, and were significantly associated with rainfall. These associations were modulated by the cave specific environmental conditions. Moreover, the presence of trogloxenous and troglophilous species could be of high significance for pathogen transfers between cave and epigeous hosts, including humans.


[Hereditary muscular dystrophy: bioengineering approaches to muscle fiber repair].
Restoration of disturbed functions of the organs and tissues is the main task of contemporary genetic and cellular biotechnology, including genetic and cellular therapy. Duchenne dystrophy, one of the most widespread human genetic diseases, is at the same time the most extensively studied from the viewpoint of both genetic and histological changes leading to muscle fiber degeneration. Although many studies carried out on models, recognized analogous to Duchenne dystrophy, gave hopeful results, clinical tests with the use of developed methods gave no expected success and the rate of mortality from this disease amounts to 100%. Based on the world experience and analysis of the authors' data, possible influence of the intensity of regeneration on success of genetic and cellular therapy has been considered.


Continuous flow left ventricular assist device outcomes in commercial use compared with the prior clinical trial.
A multicenter clinical trial conducted from 2005 to 2008 of a continuous flow left ventricular assist device (LVAD) resulted in Food and Drug Administration approval for bridge to transplantation. The purpose of this analysis was to determine changes in posttrial outcomes in widespread commercial use since the clinical trial. We compared outcomes of 486 patients who received a continuous flow LVAD as a bridge to transplantation at 36 centers during the clinical trial (March 2005 to April 2008) with outcomes of 1,496 posttrial patients who received a continuous flow LVAD at 83 centers (April 2008 to September 2010 as reported to the Interagency Registry for Mechanically Assisted Circulatory Support). Baseline data were comparable between groups. Cumulative follow-up was 511 and 1,082 patient-years for trial and posttrial patients, respectively, and average support duration was 12.6 ± 14.0 and 8.7 ± 7.1 months. Kaplan-Meier survival improved at 1 year from 76% (trial) to 85% (posttrial). The percentage of patients undergoing transplantation in the first year decreased from 48% in the trial period to 39% in the posttrial period. Quality of life metrics improved by 3 months in both groups. The survival rate of a large group of continuous flow LVAD patients in a real-world setting after Food and Drug Administration market approval for bridge to transplantation has improved since the clinical trial. These data show that excellent outcomes have been maintained with dissemination of new LVAD technology from a clinical trial phase to more broad based use in the period after market approval.


Comprehensive ESI-Q TRAP-MS/MS based characterization of metabolome of two mango (Mangifera indica L) cultivars from China.
Polyphenols based bioactive compounds from vegetables and fruits are known for impressive antioxidant activity. Ingestion of these antioxidants may promote human health against cardiovascular diseases and cancer. Mango is a popular tropical fruit with special taste, high nutritional value and health-enhancing metabolites. The aim was to investigate the diversity of phytochemicals between two mango cultivars of china at three stages of fruit maturity. We used ESI-QTRAP-MS/MS approach to characterize comprehensively the metabolome of two mango cultivars named Hongguifei (HGF) and Tainong (TN). HPLC was used to quantify selected catechin based phenolic compounds. Moreover, real-time qPCR was used to study the expression profiles of two key genes (ANR and LAR) involved in proanthocyanidin biosynthesis from catechins and derivatives. A total of 651 metabolites were identified, which include at least 257 phenolic compounds. Higher number of metabolites were differentially modulated in peel as compared to pulp. Overall, the relative quantities of amino acids, carbohydrates, organic acids, and other metabolites were increased in the pulp of TN cultivar. While the contents of phenolic compounds were relatively higher in HGF cultivar. Moreover, HPLC based quantification of catechin and derivatives exhibited cultivar specific variations. The ANR and LAR genes exhibited an opposite expression profile in both cultivars. Current study is the first report of numerous metabolites including catechin-based derivatives in mango fruit. These findings open novel possibilities for the use of mango as a source of bioactive compounds.


Depression and cognition: how do they interrelate in old age?
To disentangle the reciprocal effects between depressive symptoms and cognitive functioning over time and to study the association between changes in their trajectories using 13 years of follow-up. Data were used from five waves of the population-based Longitudinal Aging Study Amsterdam. Subjects were included if data was present on depressive symptoms and cognitive performance on at least two occasions, which resulted in a study sample of N = 2,299. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale. Cognitive functioning was assessed using the Mini-Mental State Examination (general cognitive functioning) and timed coding task (speed of information processing). Cross-domain latent change analyses showed that depression at baseline predicted both decline of general cognitive functioning and information processing speed, independent of relevant covariates. Conversely, information processing speed at baseline, but not general cognitive functioning was related to the course of depressive symptoms. The course of cognitive functioning was not significantly associated with the course of depressive symptoms. Depressive symptoms in older patients flag an increased likelihood of cognitive decline. This effect is considerable and may be due to several underlying mechanisms. The likelihood of the relationship reflecting either a causal effect of depression on cognitive decline, or a common cause, or both, should be estimated. Likewise, older persons with more limitations in information processing speed specifically are more vulnerable to increases in depression.


[High-dose trivalent influenza vaccine: safety and immunogenicity].
Adults aged 65 years or older suffer the most severe health effects of seasonal flu. Although the influenza vaccine is effective in preventing influenza virus infection and its complications, it is not as effective in the elderly due to age-associated immunosenescence phenomenon. Since 2009, a high-dose trivalent influenza vaccine has been approved in the United States for the immunization of people ≥ 65 years with an antigen concentration four times higher than the standard vaccine. Multiple clinical trials carried out over different seasons, and using different methodologies, have shown that the high-dose trivalent influenza vaccine is not only more effective, but it also has a similar safety profile and is more immunogenic than the standard dose vaccine in the prevention of flu and its complications in the elderly. This document reviews the current scientific evidence on the safety and immunogenicity of high-dose influenza vaccine in people aged 65 years and over, and includes information from randomized clinical trials, observational studies with data from real clinical practice, and systematic reviews, and meta-analysis.


The case for supporting basic research in gerontology.
Basic research on aging has moved well beyond describing the aging of physiological systems and developing theories of aging, to the pursuit of mechanistic answers to questions such as: Why do we age? Why do individuals within a population age differently? Why do different species have such different life spans? How do aging changes increase the risk of developing age-related disease? and Can we develop safe and effective interventions to reduce age-related disability? Two general areas of research promise to provide answers to these questions. One is the attempt to understand the mechanisms by which caloric restriction extends longevity and delays the onset of age-related disease. The other is the identification of genes which strongly influence the rate of aging in various animal model systems. Recent results in the latter area of research are providing new insights into the answers to these central aging questions and may help us understand how caloric restriction retards aging.


OEEF-Driven Intramolecular Self-Redox of Superalkali Rb3BeB6Be'Rb'3: A High-Performance Candidate for NLO Molecular Switch.
To provide a novel intramolecular self-redox switch, a boron-based sandwich-like complex Rb3BeB6Be'Rb'3 is achieved by using theoretical computations. An applicable oriented external electric field (OEEF) can result in the occurrence of intramolecular self-redox (IMSR) with a long-range electron transfer from tetrahedral Be'Rb'3 to Rb3Be and subsequently [Rb3Be]3+[B6]6-[Be'Rb'3]3+ (D3d) changes to [Rb3Be]2+[B6]6-[Be'Rb'3]4+ (C3v), accompanying high-performance NLO switchable effect for both static and dynamic first hyperpolarizability (β0). [Rb3Be]3+[B6]6-[Be'Rb'3]3+ (off-form) owns zero of dipole moment (μ0) and β0, while [Rb3Be]2+[B6]6-[Be'Rb'3]4+ (on-form) exhibits a μ0 of 3.36 D and a β0e of 2.18 × 105 au. The different dynamic first hyperpolarizabilities between [Rb3Be]3+[B6]6-[Be'Rb'3]3+ and [Rb3Be]2+[B6]6-[Be'Rb'3]4+ are also significant. This indicates that Rb3BeB6Be'Rb'3 is a potential candidate for an IMSR NLO switch.


Substance P-like immunoreactivity in the parietal eye visual system of the lizard Uta stansburiana.
We examined the parietal eye visual system of the iguanid lizard Uta stansburiana for the presence of substance P-like immunoreactivity by use of both immunofluorescence and peroxidase-antiperoxidase techniques. In the parietal eye no substance P-containing somata were found; however, its plexiform layer contained small (ca. 1 micron diam) immunoreactive fibers. These fibers apparently originate outside the parietal eye. Immunoreactive fibers also were found in the parietal nerve, the dorsal sac, and the leptomeninx of the pineal gland. No labeled somata were observed in any of these regions in either normal or colchicine treated animals. Previously we demonstrated that a system of centrifugal fibers to the parietal eye originates from neurons in the dorsal sac (Engbretson et al. 1981). The apparent absence of substance P-containing neurons in the dorsal sac suggests that the substance P-containing fibers in the parietal eye are not the previously observed centrifugal fibers. The source of the substance P-containing fibers in the parietal eye is unknown. The pars dorsolateralis of the left medial habenular nucleus receives a dense substance P-positive projection. No such projection was seen in the right habenula. Simultaneous visualization of the terminals of ganglion cells of the parietal eye (labeled with orthograde intraaxonally transported horseradish peroxidase) and substance P-like immunofluorescence showed that the locus of habenular immunoreactivity is distinct from the projection field of the parietal eye. Thus the substance P-positive terminals in the habenula do not originate in the parietal eye. Transection of the parietal nerve confirmed this conclusion.


Disposition and pharmacokinetics of a lubricant contaminant, 2,6-di-tert-butyl 4-nitrophenol, in grafted human skin.
Disposition and uptake/elimination profiles of topical 2,6-di-t-butyl, 4-nitrophenol (DBNP), the nitrated metabolite of an antioxidant additive of lubricant and hydraulic fluids was quantified in human skin grafted on athymic mice after a single topical 75 microg dose in corn oil. DBNP was quantified throughout the stratum corneum (SC), epidermis (E) and dermis (D) in punch biopsies collected from treated skin 0.5, 1, 2, 4, 8 and 24 h after application. SC samples were harvested from the treated skin with 20 adhesive discs. E and D were generated from the biopsy using a manual sectioning method. Detectable DBNP concentrations were measured in all skin compartments at all time points investigated. The Cmax of DBNP in SC was 1663 +/- 602 microg cm(-3), and approximately 30 and approximately 300 fold greater than the Cmax for E and D, respectively. Tmax occurred at 1.0, 0.5 and 1.0 in the SC, E and D, respectively. Over a 24 h interval (AUC0-24 h) there was 52 and 520 fold more DBNP in the SC than E and D, respectively. The elimination half-life of DBNP was 11 h from the SC and 9 h from both E and D. Thus, DBNP was quickly absorbed into the outermost layer of skin and established a steep concentration profile through human skin. The data are consistent with the vast majority of DBNP remaining on the surface (77%) or within human skin (15%) in vivo with only 0.2% of the DBNP dose quantified in the systemic blood circulation.


Heparin cryoprecipitation reduces plasma levels of non-traditional risk factors for atherosclerosis in vitro.
To show that heparin cryoprecipitation (HCP), an in vitro method of plasma purification, reduces the levels of in vivo modified proteins and non-traditional risk factors from plasma of atherosclerotic hemodialysis (HD) patients. HCP was applied to plasma obtained from HD patients and controls, forming a precipitate--cryogel. Levels of fibrinogen, albumin, CRP, TNF-alpha, IL-6, advanced oxidation protein products, carbonylated fibrinogen and carbonylated albumin were determined in plasma before and after applying HCP and in the cryogel. Treatment of HD plasma with HCP, beyond the significant reduction of the increased levels of all the above-mentioned molecules, reduced fibrinogen, TNF-alpha, carbonylated fibrinogen and carbonylated albumin to control levels which were simultaneously found in the cryogel. HCP applied to plasma enables the simultaneous precipitation of modified molecules and circulating non-traditional risk factors for atherosclerosis. This study may serve as a base for the future development of a clinical purification technique.


The effect of tamoxifen on cervical squamous maturation in Papanicolaou stained cervical smears of post-menopausal women.
Using cervical smears obtained as part of routine gynaecological examinations, a retrospective study of the effects of the drug tamoxifen on squamous epithelial maturation of the cervix of post-menopausal women being treated for advanced breast cancer was made. The degree of squamous epithelial maturation was quantitated by using the Maturation Index and the Maturation Value. Although tamoxifen is a synthetic, non-steroidal compound classified as anti-oestrogenic, the findings indicate that this drug commonly produces a level of squamous maturation indicative of oestrogenic stimulation in Papanicolaou stained cervical smears from post-menopausal patients receiving this drug. Knowledge of the oestrogenic effect of tamoxifen in the cervix can obviate clinical concern about endometrial carcinoma.


A testicular germ cell-associated serine-threonine kinase, MAK, is dispensable for sperm formation.
A member of the mitogen-activated protein kinase superfamily, MAK, has been proposed to have an important role in spermatogenesis, since Mak gene expression is highly restricted to testicular germ cells. To assess the biological function of MAK, we have established MAK-deficient (Mak(-/-)) mice. Mak(-/-) mice developed normally, and no gross abnormalities were observed. Spermatogenesis of the Mak(-/-) mice was also intact, and most of the mice were fertile. However, Mak(-/-) male-derived litter sizes and their sperm motility in vitro were mildly reduced. These data show that function of MAK is not essential for spermatogenesis and male fertility.


Suctioning versus traditional minimally invasive percutaneous nephrolithotomy to treat renal staghorn calculi: A case-matched comparative study.
Staghorn calculi remain a treatment challenge for urologists. The aim of the study was to compare the treatment outcomes of suctioning minimally invasive percutaneous nephrolithotomy (MPCNL) and traditional MPCNL for renal staghorn stones. Between April 2018 and June 2019, we included patients suffering from renal staghorn stones who were treated with modified MPCNL with a suctioning system. The outcomes of these patients were compared with those of a cohort of patients undergoing traditional MPCNL (between January 2017 and March 2018) using a 1:1 scenario matched-pair analysis. Cases were matched sequentially according to stone burden, stone branches, and stone hardness as well as age and sex. A total of 512 patients were included in this study (256 patients in each group). The baseline characteristics were equally distributed between the two groups. The suctioning MPCNL group achieved a significantly higher stone-free rate (SFR) (78.5% vs 69.1%; P = 0.016) after a single procedure and had a significantly shorter operative time (106.2 ± 18.4 vs. 132.1 ± 22.2 min; P < 0.001) than the traditional MPCNL group. The traditional MPCNL group experienced a significantly higher rate of overall complications than the suctioning MPCNL group (27.3% vs. 16.8%; P = 0.004). Regarding individual complications, a significantly higher rate of fever (13.7% vs. 7.4%; P = 0.021) and urosepsis requiring only additional antibiotics (8.2% vs. 3.5%; P = 0.024) was observed in the traditional MPCNL group than in the suctioning MPCNL group; there was a trend that the suctioning MPCNL group conferred a decreased risk of urosepsis shock (1.2% vs. 2.3%), but this trend failed to achieve statistical significance (P = 0.313). There was no significant difference between the two groups regarding the incidence of severe hemorrhage, the mean number of tracts used during a single procedure and the postoperative hospital stay. The use of suctioning MPCNL for staghorn calculi had advantages over the use of traditional MPCNL in terms of a higher SFR after a single procedure and fewer postoperative infectious complications. Further well-designed studies are needed to confirm the results.


Is serum uric acid level associated with all-cause mortality in high-functioning older persons: MacArthur studies of successful aging?
To explore the effect of serum uric acid level on subsequent all-cause mortality in high-functioning community-dwelling older persons. It is controversial whether high serum uric acid level is a true independent risk factor for cardiovascular and total mortality or the association is due to other confounding variables. Furthermore, it remains unclear whether the predictive value of uric acid level on mortality observed in younger cohorts can be extended to older people. Prospective cohort study. A sample of community-dwelling older people. A cohort of 870 participants from the MacArthur Studies of Successful Aging. Baseline information was obtained for serum uric acid level, C-reactive protein (CRP), interleukin-6 (IL-6), prevalent medical conditions, and health behaviors. Crude and multivariate logistic regression analyses were used to examine the association between serum uric acid levels and 7-year all-cause mortality, while adjusting for potential confounders. In men, the multiply adjusted risk ratios for 7-year total mortality were 1.07 (95% CI=0.61-1.88) for the mid tertile of uric acid level and 1.24 (95% CI=0.70-2.20) for the top tertile. In women, the multiply adjusted risk ratios were 0.58 (95% CI=0.29-1.18) and 0.47 (95% CI=0.22-0.99), for the mid and top tertiles respectively. CRP and IL-6 were important confounders in the relationship between serum uric acid and overall mortality. High serum uric acid level is not independently associated with increased total mortality in high-functioning older men and women. When evaluating the association between serum uric acid and mortality, the potential confounding effect of underlying inflammation and other risk factors must be considered.


Integration of 3D digital mammography with tomosynthesis for population breast-cancer screening (STORM): a prospective comparison study.
Digital breast tomosynthesis with 3D images might overcome some of the limitations of conventional 2D mammography for detection of breast cancer. We investigated the effect of integrated 2D and 3D mammography in population breast-cancer screening. Screening with Tomosynthesis OR standard Mammography (STORM) was a prospective comparative study. We recruited asymptomatic women aged 48 years or older who attended population-based breast-cancer screening through the Trento and Verona screening services (Italy) from August, 2011, to June, 2012. We did screen-reading in two sequential phases-2D only and integrated 2D and 3D mammography-yielding paired data for each screen. Standard double-reading by breast radiologists determined whether to recall the participant based on positive mammography at either screen read. Outcomes were measured from final assessment or excision histology. Primary outcome measures were the number of detected cancers, the number of detected cancers per 1000 screens, the number and proportion of false positive recalls, and incremental cancer detection attributable to integrated 2D and 3D mammography. We compared paired binary data with McNemar's test. 7292 women were screened (median age 58 years [IQR 54-63]). We detected 59 breast cancers (including 52 invasive cancers) in 57 women. Both 2D and integrated 2D and 3D screening detected 39 cancers. We detected 20 cancers with integrated 2D and 3D only versus none with 2D screening only (p<0.0001). Cancer detection rates were 5.3 cancers per 1000 screens (95% CI 3.8-7.3) for 2D only, and 8.1 cancers per 1000 screens (6.2-10.4) for integrated 2D and 3D screening. The incremental cancer detection rate attributable to integrated 2D and 3D mammography was 2.7 cancers per 1000 screens (1.7-4.2). 395 screens (5.5%; 95% CI 5.0-6.0) resulted in false positive recalls: 181 at both screen reads, and 141 with 2D only versus 73 with integrated 2D and 3D screening (p<0.0001). We estimated that conditional recall (positive integrated 2D and 3D mammography as a condition to recall) could have reduced false positive recalls by 17.2% (95% CI 13.6-21.3) without missing any of the cancers detected in the study population. Integrated 2D and 3D mammography improves breast-cancer detection and has the potential to reduce false positive recalls. Randomised controlled trials are needed to compare integrated 2D and 3D mammography with 2D mammography for breast cancer screening. National Breast Cancer Foundation, Australia; National Health and Medical Research Council, Australia; Hologic, USA; Technologic, Italy.


Infecting kidney organoids with a cDNA reporter clone of SARS-CoV-2.
Induced pluripotent stem cell (iPSC)-derived kidney organoids can be used for disease modeling and drug testing. Here, we describe a protocol to prepare stocks of an infectious clone of SARS-CoV-2 expressing a stable mNeonGreen reporter (icSARS-CoV-2-mNG). We demonstrate the infection of kidney organoids, primarily at the proximal tubular cells, with icSARS-CoV-2-mNG. Using a TCID50 (tissue culture infectious dose 50) assay and confocal microscopy, we show the quantification of SARS-CoV-2-mNG signal in proximal tubular cells of the kidney organoids. For complete details on the use and execution of this protocol, please refer to Rahmani et al. (2022).


A coach's political use of video-based feedback: a case study in elite-level academy soccer.
This paper examines the video-based pedagogical practices of Terry (pseudonym), a head coach of a professional junior academy squad. Data were collected through 6 in-depth, semi-structured interviews and 10 field observations of Terry's video-based coaching in situ. Three embracing categories were generated from the data. These demonstrated that Terry's video-based coaching was far from apolitical. Rather, Terry strategically used performance analysis technologies to help fulfil various objectives and outcomes that he understood to be expected of him within the club environment. Kelchtermans' micropolitical perspective, Callero's work addressing role and Groom et al.'s grounded theory were primarily utilised to make sense of Terry's perceptions and actions. The findings point to the value of developing contextually grounded understandings of coaches' uses of video-based performance analysis technology. Doing so could better prepare coaches for this aspect of their coaching practice.


Effect of VDR polymorphisms on growth and bone mineral density in homozygous beta thalassaemia.
We examined the effect of vitamin D receptor (VDR) polymorphisms at exon 2 (FokI) and intron 8 (BsmI) on the stature and bone mineral density at femoral neck (FBMD) and lumbar spine (LBMD) in 108 prepubertal and pubertal homozygous beta thalassaemic patients, regularly treated. We found significantly shorter stature and lower LBMD and FBMD in all patients with CC VDR genotype, and significant shorter height and lower LBMD in prepubertal and pubertal female patients with BB VDR genotype. Because homozygous CC and BB VDR genotypes influence Vitamin D activity, they can be considered additional risk factors for bone disease in beta thalassaemia.


Can the Timed Up & Go Test and Montreal Cognitive Assessment predict outcomes in patients waitlisted for renal transplant?
Frail patients who undergo renal transplantation (RT) have more complications; however, little is known if these patients can sustain the wait to RT. We used the Timed Up and Go Test (TUGT) and Montreal Cognitive Assessment (MoCA) to determine outcomes of RT candidates. In this retrospective study, 526 RT candidates underwent TUGT and MoCA (2015-2019) and were divided into "favorable" (transplanted or remained on the list) or "unfavorable" (not listed, removed from list, or died) outcome. Demographics, education, language, comorbidities, dialysis type, use of a walking device, TUGT, and MoCA were compared by outcome. Overall, 230 patients (43.7%) passed TUG, 268 (51%) passed MoCA, 133 (25.3%) passed both, and 161 (30.6%) failed both tests. Multivariate analysis demonstrated age ≥ 65 (OR 1.58, CI 1.03-2.43), cardiac disease (OR 3.09, CI 2.02-4.72), ≥36 months on dialysis (OR 1.80, CI 1.24-2.69), EPTS < 20% at time of MoCA (OR 0.26, CI 0.07-0.98), and failing TUGT (OR 2.14, CI 1.43-3.19) were associated with unfavorable outcome. Failing MoCA was not associated with outcome. MoCA test results were not associated with RT waitlist outcomes; however, passing the TUGT was associated with receiving RT or remaining on the list. Additional studies are needed to validate this and determine outcome after RT.


Dependence of long-term potentiation on the interval between A- and C-responses of the spinal dorsal horn neurons in rats.
We investigated whether tetanic stimulation (TS) of peripheral afferent nerves induced long-term potentiation (LTP) in the spinal dorsal horn of rats. Extracellular recordings from a wide dynamic range of neurons in the lumbosacral enlargement were performed using urethane-anaesthetized rats. High frequency electrical TS of sciatic nerves has revealed three groups of neurons based on their responses: LTP-induced, no-change and long-term depression-induced neurons. The firing pattern of LTP-induced neurons showed a short interval between A- and C-responses in comparison to the no-change neurons, which displayed longer intervals between A- and C-responses. During TS, coincident depolarization increased the probability of LTP induction. It can be suggested that coincident depolarization or increase in excitability of the postsynaptic dorsal horn neurons during TS may be necessary for successful induction of LTP through the dorsal horn.


Clinical spectrum and predictive risk factors of major infections in hospitalized children with nephrotic syndrome.
This observational study was conducted with the primary objective of studying the incidence of major infections in nephrotic syndrome (NS), while the secondary objectives were to evaluate the risk factors for and the etiological spectrum of major infections. Eighty six children up to 13 years of age fulfilling the International Study of Kidney Disease in Children (ISKDC) criteria for NS, who required 101 hospital admissions were recruited from November 2010 to July 2012. Major infections were defined as those that are disseminated, affecting deep organs, requiring hospitalization or potentially life-threatening. The incidence of major infections was 36.6%. Among the major infections, peritonitis and pneumonia together accounted for 72.9%, while urinary tract infections and cellulitis accounted for 16.2%. On logistic regression, severe ascites and more severe clinical types of NS independently predicted major infections, while serum cholesterol >400 mg/dL was the sole predictor of peritonitis.