Evaluation of a peer counselling programme to sustain breastfeeding practice in Hong Kong.
Peer counselling is reported to increase breastfeeding rates. We evaluated an intervention consisting of mainly telephone contact peer counselling programme on breastfeeding duration and exclusivity. Peer counsellors (PCs) were mothers who had successfully breastfed and had received formal training. Following a postnatal visit, they provided scheduled telephone consultations (Days 1, 4, 7, Weeks 2, 4, 8, and Month 4) to PC group mothers (n = 100) who continued breastfeeding their infants after discharge. Control group mothers (n = 100) received routine care. After adjusting for mothers' previous breastfeeding experiences, mothers' working status and breastfeeding problems, no statistical differences in mothers' feeding methods (exclusive, almost exclusive or predominant breastfeeding) were noted at the three follow-up times for intervention and control mothers respectively (Day 5: 37%/38%, 46%/53%, 57%/63%; Month 3: 10%/9%, 17%/23%, 20%/26%; Month 6: 2%/1%, 18%/18%, 18%/19%). All differences between the groups were not significant. Also, there was no evidence to suggest that PC intervention prolonged breastfeeding duration. The lack of effect of our PC intervention may reflect the low baseline breastfeeding rate and low value placed on breastfeeding in our population, the type of PC intervention or group allocation biases. ISRCTN93605280.


Toe Amputation After Minor Surgery in a Patient with Behçet's Disease: A Case Report.
Behçet's disease is a systemic autoimmune vasculitis. Although various clinical findings can be observed depending on the pathologic features caused by the blood vessels involved, the classic triad of the disease includes oral aphthae, genital ulcers, and uveitis. Although complications involving the aorta or the vena cava inferior can prove fatal, thrombophlebitis in the superficial veins of the lower extremities are more commonly observed. Some patients can remain asymptomatic for a long period after the diagnosis. In patients with positive pathergy test findings, trauma can trigger the inflammatory cascade. This case report presents a patient with vasculitis that occurred subsequent to minor surgery and led to amputation of the great toe in a female patient with a 14-year old history of Behçet's disease.


Transfer of 125I to eggs in hens fed on diets containing rapeseed meal.
1. Transfer of 125I into the egg in hens fed on diets containing rapeseed meal and a source of myrosinase, to liberate the antithyroid compounds from the glucosinolates, was studied. 2. It was found that less 125I was transferred if the diet contained a myrosinase source and rapeseed meal.


Hyperhomocysteinemia and mortality after coronary artery bypass grafting.
The independent prognostic impact, as well as the possible causal role, of hyperhomocysteinemia (HHcy) in coronary artery disease (CAD) is controversial. No previous study specifically has addressed the relationship between HHcy and mortality after coronary artery bypass grafting (CABG) surgery. The aim of this study is to evaluate the prognostic impact of HHcy after CABG surgery. We prospectively followed 350 patients who underwent elective CABG between May 1996 and May 1999. At baseline, fasting total homocysteine (tHcy) levels were measured in all participants, and a post-methionine loading (PML) test was performed in 77.7% of them (n = 272). After a median follow-up of 58 months, 33 patients (9.4%) had died, 25 because of cardiovascular events. HHcy, defined by levels higher than the 90th percentile (25.2 micromol/L) of the population's distribution, was significantly associated to total and cardiovascular mortality (P = 0.018 [log-rank test 5.57]; P = 0.002 [log-rank test 9.76], respectively). The PML test had no prognostic value. After multiple adjustment for other univariate predictors by Cox regression, including statin therapy (the most powerful predictor in uni-/multivariate analyses), high-sensitivity C Reactive Protein (hs-CRP) levels, and all known major genetic (MTHFR 677C-->T polymorphism) and non-genetic (B-group vitamin status and renal function) tHcy determinants, HHcy remained an independent prognostic factor for mortality (HRs: 5.02, 95% CIs 1.88 to 13.42, P = 0.001). HHcy is an important prognostic marker after CABG, independent of modern drug therapy and biomarkers.


Body fat of rats of different age groups and nutritional states: assessment by micro-CT and skinfold thickness.
Obesity presents a growing public health problem. Therefore the analysis of body composition is important in clinical practice as well as in animal research models of obesity; hence precise methods for the assessment of body fat would be essential. We aimed to evaluate in vivo abdominal microcomputed tomography scan restricted to the L1-L3 region [micro-CT(L1-L3)], a skinfold thickness-based method (STM), and postmortem body composition analysis (PMA) with regard to whole body micro-CT scan in rats. Male Wistar rats of different age groups (from 3 to 24 mo) and nutritional states (normally fed, high-fat diet-induced obese, and calorie-restricted) were used. The fat percentage was determined with micro-CT(L1-L3) and whole body scan in anesthetized rats. Their skinfold thickness was measured in five locations with a Lange caliper. Wet weights of epididymal and retroperitoneal fat pads were determined via PMA. With regard to fat mass, the strongest correlation was observed between abdominal and whole body micro-CT. The other methods showed weaker associations with whole body micro-CT and with each other. Micro-CT(L1-L3) and PMA showed similar age-associated increase in fat mass between 3 and 18 mo. Micro-CT(L1-L3), STM, and PMA were efficient to detect differences in fat mass values in groups of different nutritional states. Micro-CT(L1-L3) appears to be a useful method for body fat assessment in rats with reduced scanning time. In rats, STM may also be a useful, low priced, noninvasive, and simple in vivo technique to assess obesity. NEW & NOTEWORTHY Body fat of rats assessed by in vivo abdominal microcomputed tomography of the L1-L3 region strongly correlates with values determined by whole body scan. Therefore, it is a useful method for fat assessment with reduced scanning time. Skinfold thickness measurement is an in vivo technique to assess progression of obesity in rats.


Treated, hospital-onset Clostridiodes difficile infection: An evaluation of predictors and feasibility of benchmarking comparing 2 risk-adjusted models among 265 hospitals.
To evaluate the incidence of a candidate definition of healthcare facility-onset, treated Clostridioides difficile (CD) infection (cHT-CDI) and to identify variables and best model fit of a risk-adjusted cHT-CDI metric using extractable electronic heath data. We analyzed 9,134,276 admissions from 265 hospitals during 2015-2020. The cHT-CDI events were defined based on the first positive laboratory final identification of CD after day 3 of hospitalization, accompanied by use of a CD drug. The generalized linear model method via negative binomial regression was used to identify predictors. Standardized infection ratios (SIRs) were calculated based on 2 risk-adjusted models: a simple model using descriptive variables and a complex model using descriptive variables and CD testing practices. The performance of each model was compared against cHT-CDI unadjusted rates. The median rate of cHT-CDI events per 100 admissions was 0.134 (interquartile range, 0.023-0.243). Hospital variables associated with cHT-CDI included the following: higher community-onset CDI (CO-CDI) prevalence; highest-quartile length of stay; bed size; percentage of male patients; teaching hospitals; increased CD testing intensity; and CD testing prevalence. The complex model demonstrated better model performance and identified the most influential predictors: hospital-onset testing intensity and prevalence, CO-CDI rate, and community-onset testing intensity (negative correlation). Moreover, 78% of the hospitals ranked in the highest quartile based on raw rate shifted to lower percentiles when we applied the SIR from the complex model. Hospital descriptors, aggregate patient characteristics, CO-CDI burden, and clinical testing practices significantly influence incidence of cHT-CDI. Benchmarking a cHT-CDI metric is feasible and should include facility and clinical variables.


ADAMTS13 Deficiency Worsens Colitis and Exogenous ADAMTS13 Administration Decreases Colitis Severity in Mice.
Inflammatory bowel disease (IBD) affects 1.6 million people in the United States. IBD is associated with an increased risk of thrombosis, which rises with disease activity. The pathogenesis of IBD and its increased thrombotic risk is not completely understood. Ultra large von Willebrand factor (ULVWF) multimers are secreted from activated endothelium, leading to recruitment of platelets and leukocytes. A disintegrin and metalloproteinase with thrombospondin type I repeats motif 13 (ADAMTS13) cleaves highly adhesive ULVWF into smaller, less bioactive, multimers, releasing them into circulation. Mice deficient in ADAMTS13 (ADAMTS13-/-) have heightened inflammatory and thrombotic responses. We hypothesized that upon colitis induction, ADAMTS13-/- mice would have more severe symptoms compared with wild-type (WT) mice, and rhADAMTS13 administration to mice with colitis would improve their condition. Dextran sodium sulfate-induced colitis was worse in ADAMTS13-/- mice than WT. ADAMTS13-/- showed increased weight loss, worse anemia, and increased clinical and histologic colitis severity, compared with WT mice. ADAMTS13-/- mice had increased VWF release, with accumulation at inflamed colonic sites. Also, the majority of mice showed one or more submucosal colonic thrombi. ADAMTS13 deficiency worsened colitis and propagated intestinal inflammation, most likely through increased platelet-leukocyte recruitment by VWF. Treatment of WT mice with rhA-DAMTS13 decreased colitis severity without worsening anemia. Additionally, several immune-mediated chronic murine colitis models, and inflamed colon tissue specimens from IBD patients, showed increased VWF release at inflamed sites, suggesting a generalizability of our findings. Measuring VWF/ADAMTS13 levels could have clinical utility. When applicable, the administration of ADAMTS13, in addition to primary treatment, may improve outcomes for IBD patients.


PsRobot: a web-based plant small RNA meta-analysis toolbox.
Small RNAs (smRNAs) in plants, mainly microRNAs and small interfering RNAs, play important roles in both transcriptional and post-transcriptional gene regulation. The broad application of high-throughput sequencing technology has made routinely generation of bulk smRNA sequences in laboratories possible, thus has significantly increased the need for batch analysis tools. PsRobot is a web-based easy-to-use tool dedicated to the identification of smRNAs with stem-loop shaped precursors (such as microRNAs and short hairpin RNAs) and their target genes/transcripts. It performs fast analysis to identify smRNAs with stem-loop shaped precursors among batch input data and predicts their targets using a modified Smith-Waterman algorithm. PsRobot integrates the expression data of smRNAs in major plant smRNA biogenesis gene mutants and smRNA-associated protein complexes to give clues to the smRNA generation and functional processes. Besides improved specificity, the reliability of smRNA target prediction results can also be evaluated by mRNA cleavage (degradome) data. The cross species conservation statuses and the multiplicity of smRNA target sites are also provided. PsRobot is freely accessible at http://omicslab.genetics.ac.cn/psRobot/.


Phenotypic and Molecular Characterization of Enteroaggregative Escherichia coli Isolated in Kawasaki, Japan.
Enteroaggregative Escherichia coli (EAEC), an enteric pathogen, causes persistent diarrhea in children, HIV-infected individuals, and travelers in economically developing countries. However, the pathogenesis of EAEC infection is not well understood. This study aimed to characterize EAEC in Japan. Between 2012 and 2014, we identified 40 EAEC strains carrying the aggR gene at the Kawasaki City Institute for Public Health, Japan. We characterized these strains using O:H-antigen typing, polymerase chain reaction (for pCVD432, astA, extended-spectrum beta-lactamase, and 4 aggregative adherence fimbriae genes), HEp-2 cell adherence, clump formation, and antimicrobial susceptibility testing. We were able to classify the 40 EAEC strains into 20 O:H types. Although specific O:H types were not correlated with HEp-2 cell aggregative adherence, all the O99:H10, O131:H27, and O176:H34 EAEC strains that were the most frequent O:H types detected in this study showed co-resistance to ampicillin, sulfamethoxazole-trimethoprim, and tetracycline. Based on results of the adhesion assay and detection of virulence-related genes, no significant difference was found between asymptomatic and symptomatic cases. Irrespective of the origin, their potential for virulence was retained. Further characterization is vital to determine whether EAEC is virulent in Japan.


Quadruple synchronous primary cancers in a single patient.
Patients diagnosed with quadruple synchronous primary cancers are extremely rare and we present here, to the best of our knowledge, the first case report of this combination of primary cancers. A 70-year-old woman was diagnosed with cervical adenocarcinoma, melanoma on the right leg, invasive ductal cell carcinoma metastasis in the left axilla with no primary breast tumour detected and multiple basal cell carcinomas on the limbs, all within 2 months. The management was conducted in collaboration with six medical specialties. The cancers were surgically managed, with further adjuvant chemotherapy and ongoing hormone therapy for her breast cancer. Four years after the diagnosis, no signs of recurrence or further metastases from any of the cancers are present.


Assay of trehalose with acid trehalase purified from Saccharomyces cerevisiae.
An enzymatic end-point assay of trehalose using acid trehalase from yeast is described. After quantitative hydrolysis of trehalose by acid trehalase, the resulting glucose is assayed with the commercially available glucose oxidase/peroxidase dye system. Pre-existing glucose is determined in a control reaction from which acid trehalase is omitted. When intact cells are analysed for trehalose, pre-existing glucose can be washed out with ice-cold water without reducing the trehalose content of the cells. A convenient method for extraction of trehalose from intact yeast cells is heating for 20 min at 95 degrees C followed by centrifugation. The specificity of the assay is determined by the specificity of the acid trehalase preparation used. As described previously (Mittenbühler, K. and Holzer, H., 1988, J. Biol. Chem. 263, 8537-8543; Mittenbühler, K., 1988, Thesis, University of Freiburg), the following sugars and sugar derivatives do not form glucose when incubated with purified acid trehalase: sucrose, cellobiose, mellobiose, raffinose, maltose, lactose, glucose-6-phosphate, glucose-1-phosphate, galactose. The application of the new trehalose assay to yeast cells grown to different growth stages and at various temperatures is presented.


α-Adducin gene promoter DNA methylation and the risk of essential hypertension.
This study was conducted to test the association between promoter DNA methylation of α-Adducin (ADD1) gene and the risk of essential hypertension (EH). A total of 150 EH patients and 100 aged- and gender-matched controls were investigated. DNA methylation levels of five cytosine-phosphate-guanine (CpG) dinucleotides on ADD1 promoter were measured employing bisulfite pyrosequencing technology. Our results showed that females have a higher ADD1 DNA methylation than males and a significantly lower CpG1 methylation level is associated with increased risk of EH among them. As for males, a significant association between lower CpG2-5 methylation levels and increased risk of EH was shown. In addition, CpG2-5 methylation was found to be a highly significant predictor for EH among males. In females, CpG1 methylation was considered a predictor of hypertension. No significant correlations were found with biochemical measures, apart from the concentration of aspartate aminotransferase which was inversely correlated with ADD1 CpG2-5 methylation levels among female controls (r = -0.703). These findings highlight that ADD1 methylation may have a contributing role in the pathogenesis of EH with varying implications for both genders.


[Evaluation of cartilage degeneration by near infrared spectroscopy (NIRS): methodical description and systematic literature review].
Damage to hyaline cartilage is the most important pathophysiological tool in the development of osteoarthritis. Cartilage lesions are the most frequent pathological findings during arthroscopic operations. Arthroscopies as well as magnetic resonance tomography are gold standards for detection of cartilage lesions. But the arthroscopic evaluation of cartilage lesions is descriptive and subjective only. The surgeon is able to differentiate between intact cartilage surface, softening, superficial or deep fissure or flake and finally a complete defect. In routine arthroscopy the grading mostly is made by use of different scores [e.g. ICRS (International Cartilage Repair Society), Outerbridge, Insall, Jäger-Wirth or others]. Because the arthroscopic evaluation is subjective the reliability of this method is poor. Spectroscopic methods are established for evaluation of different tissue diseases in different indications. NIRS (near infrared spectroscopy) has become an important method for medical diagnostics in the last years. NIR is very energy-rich and suitable for glass fibre transport without relevant reduction. Insofar this technology may be ideal for endoscopic procedures. Our systematic literature review reveals that NIRS is a sufficient method for an objective diagnosis of cartilage lesions. In the current work we demonstrate an NIRS-based device for intraoperative, real-time cartilage evaluation. Furthermore, we discuss the possible clinical consequences from such measurements.


Correlates of impulsivity among female sex workers in Mexico.
Impulsivity is a trait characteristic that is associated with sexual risk behavior. We examined correlates of impulsivity among 602 female sex workers (FSWs) enrolled in a sexual risk reduction intervention in Mexico (2016-2020). Impulsivity was positively associated with condomless sex with clients. Higher levels of impulsivity were associated with greater use of alcohol and heavy drugs, use of illicit drugs with clients, sexual/physical abuse history, and clinical depression. Global public health policy that supports free substance abuse treatment in combination with psychotherapeutic treatments (e.g. regulation management skills) and behavioral-focused therapy may help to reduce HIV/STI incidence in this vulnerable population.


Medial Meniscus Posterior Root Tear Repair Using a 2-Simple-Suture Pullout Technique.
Medial meniscus posterior root tear is one of the underestimated knee injuries in terms of incidence. Despite its grave sequelae, using simple but effective technique can maintain the native knee joint longevity. In the current note, a 2-simple-suture pullout technique was used to effectively reduce the meniscus posterior root to its anatomic position. The success of the technique depended on proper tool selection as well as tibial tunnel direction that allowed easier root suturing and better suture tensioning, without inducing any iatrogenic articular cartilage injury or meniscal tissue loss. Using anterior knee arthroscopy portals, anterolateral as a viewing portal and anteromedial as a working portal, a 7-mm tibial tunnel starting at Gerdy tubercle and ending at the medial meniscus posterior root bed was created. The 2 simple sutures were retrieved through the tunnel and tensioned and secured over a 12-mm-diameter washer at the tibial tunnel outer orifice. Anatomic reduction of the medial meniscus posterior root tear was confirmed arthroscopically intraoperatively and radiologically by postoperative magnetic resonance imaging.


Significance of high C-reactive protein levels in pre-dialysis patients.
An elevated serum C-reactive protein (CRP) has been shown to be strongly predictive of morbidity and mortality in dialysis patients. However, the significance of high CRP levels in the pre-dialysis period has not been studied extensively. The aim of our study was to analyse the evolution of our pre-dialysis population according to their basal levels of CRP. A cohort of 66 pre-dialysis patients was followed for 1 year, after initial determination of serum CRP. The evolution of blood pressure (BP) control, CRP levels, nutritional data (body mass index, serum albumin, prealbumin, transferrin, cholesterol), proteinuria, calcium-phosphorus product, bicarbonate, haemoglobin (Hb), the weekly dose of erythropoietin (Epo)/kg body weight, and the Hb/Epo dose ratio were measured and compared between patients with high (>6 mg/l) or low (<6 mg/l) CRP levels at baseline. The decline in renal function, hospitalization, and death also were measured and compared between the two groups. At baseline, 23 patients (35%) showed high (>6 mg/l) CRP levels. CRP was higher in patients with a previous history of cardiovascular disease (P<0.01), as well as in patients in whom ischaemic nephropathy or nephrosclerosis was the cause of end-stage renal disease (P<0.01). There were no differences between diabetic and non-diabetic patients. During the study period, patients with higher CRP levels at baseline maintained higher levels (P<0.001). During this period, these patients showed lower (P<0.05) albumin concentration, higher bicarbonate levels, lower Hb concentration, and lower Hb/Epo ratio and needed higher Epo doses. There were no differences in systolic BP, the degree of proteinuria, and the decline in renal function between groups; diastolic BP was lower in patients with high CRP levels. Hospitalization was higher (P<0.005) in this group. Only one patient died. The prevalence of inflammation is high in pre-dialysis patients. High serum CRP levels predict a constant inflammatory state on follow-up. As occurs in dialysis patients, pre-dialysis inflammation predicts lower serum albumin concentration, poorer response to Epo, and a higher hospitalization rate. The decline in renal function does not seem to be related to the inflammatory state. Mortality was not affected on short-term follow-up.


Segregation of Incomplete Achromatopsia and Alopecia Due to PDE6H and LPAR6 Variants in a Consanguineous Family from Pakistan.
We report on two brothers with visual impairment, and non-syndromic alopecia in the elder proband. The parents were first-degree Pakistani cousins. Whole exome sequencing of the elder brother and parents, followed by Sanger sequencing of all four family members, led to the identification of the variants responsible for the two phenotypes. One variant was a homozygous nonsense variant in the inhibitory subunit of the cone-specific cGMP phosphodiesterase gene, PDE6H:c.35C>G (p.Ser12*). PDE6H is expressed in the cones of the retina, which are involved in perception of color vision. This is the second report of a homozygous PDE6H:c.35C>G variant causing incomplete achromatopsia (OMIM 610024), thus strongly supporting the hypothesis that loss-of-function variants in PDE6H cause this visual deficiency phenotype. The second variant was a homozygous missense substitution in the lysophosphatidic acid receptor 6, LPAR6:c.188A>T (p.Asp63Val). LPAR6 acts as a G-protein-coupled receptor involved in hair growth. Biallelic loss-of-function variants in LPAR6 cause hypotrichosis type 8 (OMIM 278150), with or without woolly hair, a form of non-syndromic alopecia. Biallelic LPAR6:c.188A>T was previously described in five families from Pakistan.


Effects of ethanol on ethylmorphine metabolism in isolated rat hepatocytes: characterization by means of a multicompartmental model.
Hepatic cytochrome P-450 enzymes mediate at least two important biotransformation pathways of codeine and ethylmorphine starting with either N-demethylation or O-dealkylation, producing polar metabolites which are then subsequently glucuronidated. The present study was designed to characterise the acute effects of ethanol on the metabolism of ethylmorphine and to compare it with the effects on codeine in suspensions of freshly isolated rat hepatocytes. Isolated rat hepatocytes from male Wistar rats were prepared by a collagenase perfusion method. Ethylmorphine, codeine and their metabolites were quantified by HPLC with UV detection. The total ethylmorphine elimination rate was reduced by 12% at 5mM and 38% at 100 mM ethanol. The corresponding percentages for codeine were 16 and 43%. In the presence of ethanol the concentrations of several intermediate and end products of ethylmorphine and codeine changed markedly from the control situation. The experimental data were applied to a mathematical compartmental linear model to estimate the influence of ethanol on the separate reaction rates in the two main metabolic pathways. The ratios between reaction rate constants in the ethylmorphine experiments at 100 and 0 mM ethanol were 0.65 for ethylmorphine-->norethylmorphine, 0.63 for norethylmorphine-->normorphine, 0.56 for ethylmorphine-->morphine, 0.49 for morphine-->normorphine, 0.31 for normorphine-->normorphine-3-glucuronide and 0.49 for morphine-->morphine-3-glucuronide. Almost similar effects of ethanol on codeine metabolism were found. In additional experiments, norethylmorphine or norcodeine (50 microM) was incubated with 5 mM to 100 mM of ethanol and the metabolism of both norethylmorphine and norcodeine was found to be inhibited by ethanol in a concentration-dependent manner. The glucuronidation of morphine and normorphine added in separate experiments was also inhibited by ethanol, from 22 to 36% for morphine-3-glucuronide and 30 to 60% for normorphine-3-glucuronide, respectively, in the presence of 5 mM to 100 mM of ethanol. It was concluded that all steps in the metabolism of ethylmorphine (and codeine) leading to the end products morphine-3-glucuronide and normorphine-3-glucuronide were inhibited by ethanol, and that the glucuronidation process were the ones most affected by ethanol.


Stab wound of the neck: potential pitfalls in management.
The authors describe the case history of a patient who was stabbed in the back of his neck with a knife and who later presented with a Brown-Séquard syndrome attributable to cervical spinal cord damage. Myelography and CT revealed a compressive extradural lesion shown at exploratory operation to be a loculus of cerebrospinal fluid (CSF). The loculus had formed as a consequence of leakage of CSF through a dural tear caused by the knife. Evacuation of this loculus resulted in some neurological improvement. The necessity of obtaining a clear history and of performing a thorough clinical examination is explained. The need to admit patients in whom stab wounds of the neck have transgressed subcutaneous fat is reiterated. Early referral to a neurosurgeon is advised for those patients with neurological deficits.


Numerical solution of a spatio-temporal predator-prey model with infected prey.
A spatio-temporal eco-epidemiological model is formulated by combining an available non-spatial model for predator-prey dynamics with infected prey [D. Greenhalgh and M. Haque, Math. Meth. Appl. Sci., 30 (2007), 911-929] with a spatio-temporal susceptible-infective (SI)-type epidemic model of pattern formation due to diffusion [G.-Q. Sun, Nonlinear Dynamics, 69 (2012), 1097-1104]. It is assumed that predators exclusively eat infected prey, in agreement with the hypothesis that the infection weakens the prey, making it available for predation otherwise we assume that the predator has essentially no access to healthy prey of the same species. Furthermore, the movement of predators is described by a non-local convolution of the density of infected prey as proposed in [R.M. Colombo and E. Rossi, Commun. Math. Sci., 13 (2015), 369-400]. The resulting convection-diffusion-reaction system of three partial differential equations for the densities of susceptible and infected prey and predators is solved by an efficient method that combines weighted essentially non-oscillatory (WENO) reconstructions and an implicit-explicit Runge-Kutta (IMEX-RK) method for time stepping. Numerical examples illustrate the formation of spatial patterns involving all three species.


Mitochondrial genetics and hearing loss: the missing link between genotype and phenotype.
Mitochondrial DNA mutations have been implicated in a great variety of diseases, including such common ones as diabetes, Parkinson's disease and Alzheimer's, but the pathophysiological pathway leading from a specific mutation to a specific phenotype has remained elusive. Individuals with the same mutation can fall along a clinical spectrum ranging from asymptomatic to severely affected, and can even have completely different diseases. Much of this phenotypic heterogeneity has been attributed to the heteroplasmic nature of mitochondrial mutations, with both normal and mutated mitochondrial chromosomes being present in different proportions and tissue distributions. Isolated hearing loss is one of the only mitochondrial disorders that can be caused by homoplasmic mutations (e.g., only mutated mitochondrial mutations are present in all tissues). This review will outline the relationship between mitochondrial mutations and hearing loss while showing that even in a homoplasmic model, the two basic questions of mitochondrial genetics, penetrance and tissue specificity, remain unanswered: Why does the same mutation cause severe hearing loss in some family members but not in others, and why is the ear the only organ affected?


Lapachol and lapachone analogs: a journey of two decades of patent research(1997-2016).
Lapachol (1), β-lapachone (2) and α-lapachone (3) are three well-studied natural products isolated from Tabebuia impetiginosa having most interesting chemodiversity and demonstrating diverse biological effects. Areas covered: The current review summarizes the recent and past discovery of chemotherapeutic agents based on the compounds 1-3. This review presents an overview of patents filed over the past two decades (1997 to 2016) mostly relating to the anticancer effects of these lapachol and lapachone analogues. Expert opinion: The large number of interesting patents published on the therapeutic potential of quinones 1-3 and their synthetic derivatives lends credence to the importance of these molecules. Moreover, these quinones demonstrated potent anticancer effects towards various cancer cell lines and chemical modification of these quinones have led to products displaying enhanced anticancer effects. It is noteworthy that the majority of patents published are on the anticancer effects of quinones 1-3 and their synthetic derivatives along with a limited number of additional biological effects. It is our opinion that in order to get lead compounds, there needs to be a greater focus on the elucidation of the precise mechanism of action of these compounds including SAR and in vivo studies.


Extreme Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA): a discrete group of patients.
Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in children; by definition, episodes occur every 2 to 8 weeks. However, in a subset of our patients, we noticed a higher frequency of attacks, of less than 2 weeks, which we refer to as extreme PFAPA (ePFAPA). This group consisted of patients who were extreme upon presentation of PFAPA, and those who became extreme after initiation of abortive corticosteroid treatment. We aimed to characterize demographic and clinical features of ePFAPA, including the two groups, and to compare them to patients with non-extreme PFAPA (nPFAPA). The medical records of 365 patients with PFAPA who attended Schneider Children's Medical Center of Israel from March 2014 to April 2021 were reviewed. Patients with concomitant familial Mediterranean fever were excluded. Characteristics of the ePFAPA (including subgroups) and nPFAPA groups were compared using Wilcoxon rank sum, Pearson's chi-squared, and Fisher's exact tests. Forty-seven patients (12.9%) were identified as having ePFAPA. Among patients with ePFAPA, compared to patients with nPFAPA, the median (interquartile range) age at disease onset was earlier: 1.5 years (0.7-2.5) vs. 2.5 years (1.5-4.0), P < 0.001; and diagnosis was younger: 2.6 years (2.0-3.6) vs. 4.5 years (3.0-6.2), P < 0.001. A higher proportion of patients with ePFAPA than nPFAPA were treated with colchicine prophylaxis (53% vs. 19%, P < 0.001), but symptoms and signs during flares did not differ significantly between these groups. Demographic and clinical characteristics were similar between patients with ePFAPA from presentation of PFAPA (22, 47% of those with ePFAPA) and ePFAPA from after corticosteroid treatment. About half the patients categorized with ePFAPA syndrome already had extreme features upon presentation. Patients with ePFAPA compared to nPFAPA presented and were diagnosed at an earlier age.


Quinupristin-dalfopristin-resistant Enterococcus faecium on chicken and in human stool specimens.
The combination of the streptogramins quinupristin and dalfopristin was approved in the United States in late 1999 for the treatment of vancomycin-resistant Enterococcus faecium infections. Since 1974, another streptogramin, virginiamycin, has been used at subtherapeutic concentrations to promote the growth of farm animals, including chickens. To determine the frequency of quinupristin-dalfopristin-resistant E. faecium, we used selective medium to culture samples from chickens purchased in supermarkets in Georgia, Maryland, Minnesota, and Oregon and stool samples from outpatients. Between July 1998 and June 1999, samples from 407 chickens from 26 stores in four states were cultured, as were 334 stool samples from outpatients. Quinupristin-dalfopristin-resistant E. faecium was isolated from 237 chicken carcasses and 3 stool specimens. The resistant isolates from stool had low-level resistance (minimal inhibitory concentration [MIC], 4 microg per milliliter; resistance was defined as a MIC of at least 4 microg per milliliter). The resistant isolates from chickens in general had higher levels of resistance (MICs ranging from 4 to 32 microg per milliliter; MIC required to inhibit 50 percent of isolates, 8 microg per milliliter). Quinupristin-dalfopristin-resistant E. faecium contaminates a large proportion of chickens sold in U.S. supermarkets. However, the low prevalence and low level of resistance of these strains in human stool specimens suggest that the use of virginiamycin in animals has not yet had a substantial influence. Foodborne dissemination of resistance may increase, however, as the clinical use of quinupristin-dalfopristin increases.


Multidrug-resistant Staphylococcus cohnii and Staphylococcus urealyticus isolates from German dairy farms exhibit resistance to beta-lactam antibiotics and divergent penicillin-binding proteins.
Non-aureus staphylococci are commonly found on dairy farms. Two rarely investigated species are Staphylococcus (S.) cohnii and S. urealyticus. Since multidrug-resistant S. cohnii and S. urealyticus are known, they may serve as an antimicrobial resistance (AMR) gene reservoir for harmful staphylococcal species. In our study, nine S. cohnii and six S. urealyticus isolates from German dairy farms were analyzed by whole-genome sequencing and AMR testing. The isolates harbored various AMR genes (aadD1, str, mecA, dfrC/K, tetK/L, ermC, lnuA, fexA, fusF, fosB6, qacG/H) and exhibited non-wildtype phenotypes (resistances) against chloramphenicol, clindamycin, erythromycin, fusidic acid, rifampicin, streptomycin, tetracycline, tiamulin and trimethoprim. Although 14/15 isolates lacked the blaZ, mecA and mecC genes, they showed reduced susceptibility to a number of beta-lactam antibiotics including cefoxitin (MIC 4-8 mg/L) and penicillin (MIC 0.25-0.5 mg/L). The specificity of cefoxitin susceptibility testing for mecA or mecC gene prediction in S. cohnii and S. urealyticus seems to be low. A comparison with penicillin-binding protein (PBP) amino acid sequences of S. aureus showed identities of only 70-80% with regard to PBP1, PBP2 and PBP3. In conclusion, S. cohnii and S. urealyticus from selected German dairy farms show multiple resistances to antimicrobial substances and may carry unknown antimicrobial resistance determinants.


The role of macronutrient intake in reducing the risk of obesity and overweight among carriers of different polymorphisms of FTO gene. A review
Obesity is a growing problem worldwide. The risk of the excessive body weight occurrence is a multifactorial issue. Environmental factors, lifestyle habits, diet, physical activity level, as well as genetic predisposition can increase obesity risk. One of the genes studied – the FTO gene - plays a crucial role in obesity occurrence. Individuals who carry risk alleles of specific single nucleotide polymorphisms (SNP) have a greater risk of being overweight. Recent studies revealed that specific macronutrient diet composition can influence differently on the FTO expression. The aim of this article is to review the recent literature on the topic of the FTO gene, its influence on overweight and obesity prevalence and the role of diet in modifying its impact on the risk of the excessive body weight occurrence. There are not many studies focusing on the dietary intervention influence on the FTO gene expression. As far as it has been researched it seems that the proper dietary habits can modify the FTO gene risk allele influence on obesity susceptibility.


Gynecologic and reproductive issues in women on dialysis.
Most women on dialysis are amenorrheic and do not ovulate, but little information about menstrual patterns in women on dialysis exists, especially since the introduction and use of recombinant human erythropoietin, a therapy that may improve sexual interest and function. In this study, women who were < or = 55 years of age at the start of dialysis (n = 76) completed questionnaires and form the study group. Women older than 55 years at the start of dialysis did not complete the entire questionnaire (n = 115), but their medication records were reviewed for estrogen replacement therapy. The questionnaire asked about pregnancies, menstrual periods (regularity, frequency, duration, character of flow, menopause), and menopause before beginning dialysis and currently. Women also responded to questions about sexual activity, use of birth control, contraception counseling by physicians, yearly Papanicolaou smears, and mammograms. Demographic data (age, race, age at the time dialysis started, mode of dialysis, use of recombinant human erythropoietin, and history of renal transplant) were also obtained through the questionnaires. Fifty-nine percent of the 76 women who completed the study were white and had been on dialysis a median of 3 years (range, 0.1 to 18 years). The median age was 43 years, 68% were on hemodialysis, 90% were receiving recombinant human erythropoietin, and 70% had been pregnant (a total of 179 pregnancies; four pregnancies in four women occurred after the start of dialysis). Significantly more women were menstruating before dialysis started than currently (63% v 42%; P < 0.025), but the difference could be explained by patient age: currently menstruating women were younger (37 +/- 9 v 46 +/- 11 years; P = 0.0002). More women reported menstrual regularity before beginning dialysis (75% v 42% currently; P < 0.005), but there were no differences in number of days between or number of days of menstruation before beginning dialysis and currently. Menstrual flow was reported as heavier currently by more women (64% heavy flow with clots v 38% before dialysis started; P < 0.05). The median age at menopause was 47 years; 28% of the women were postmenopausal. Fifty percent of the women were sexually active, but only 36% used birth control. Discussions between the women and their nephrologist about possible pregnancy and contraception were reported by only 13% of women. Sixty-three percent of the women reported having yearly Papanicolaou smears and 73% had had a mammogram. Only 5% of the 113 women who were older than 55 years when they began dialysis were receiving estrogen replacement therapy. Amenorrhea was reported in this study by a smaller proportion of women than in studies conducted before the introduction of recombinant human erythropoietin. The possibility that erythropoietin may restore normal hormonal cyclic function in women with end-stage renal disease requires further study. Nephrologists as well as primary care physicians and gynecologists need to focus more on the gynecologic concerns of women on dialysis, including the potential for pregnancy. The effects of estrogen replacement on atherosclerosis and osteoporosis, and consideration of such therapy in women on dialysis warrants attention.


Multi-sensory weights depend on contextual noise in reference frame transformations.
During reach planning, we integrate multiple senses to estimate the location of the hand and the target, which is used to generate a movement. Visual and proprioceptive information are combined to determine the location of the hand. The goal of this study was to investigate whether multi-sensory integration is affected by extraretinal signals, such as head roll. It is believed that a coordinate matching transformation is required before vision and proprioception can be combined because proprioceptive and visual sensory reference frames do not generally align. This transformation utilizes extraretinal signals about current head roll position, i.e., to rotate proprioceptive signals into visual coordinates. Since head roll is an estimated sensory signal with noise, this head roll dependency of the reference frame transformation should introduce additional noise to the transformed signal, reducing its reliability and thus its weight in the multi-sensory integration. To investigate the role of noisy reference frame transformations on multi-sensory weighting, we developed a novel probabilistic (Bayesian) multi-sensory integration model (based on Sober and Sabes, 2003) that included explicit (noisy) reference frame transformations. We then performed a reaching experiment to test the model's predictions. To test for head roll dependent multi-sensory integration, we introduced conflicts between viewed and actual hand position and measured reach errors. Reach analysis revealed that eccentric head roll orientations led to an increase of movement variability, consistent with our model. We further found that the weighting of vision and proprioception depended on head roll, which we interpret as being a result of signal dependant noise. Thus, the brain has online knowledge of the statistics of its internal sensory representations. In summary, we show that sensory reliability is used in a context-dependent way to adjust multi-sensory integration weights for reaching.


Perioperative Outcomes of Laparoscopic Radical Nephrectomy for Renal Mass in Patients on Dialysis or with Renal Transplant in Place Compared to Normal Controls.
Background: The risk of renal cell carcinoma (RCC) development in the native kidney of patients on dialysis or with a renal transplant is increased compared to the general population. This study examines perioperative outcomes of laparoscopic radical nephrectomy (LN) in dialysis patients or renal transplant patients compared to normal controls. Methods: Four hundred twelve consecutive LN were evaluated (July 2007 to October 2018). Patients were divided into three groups (control, dialysis, and transplant). Perioperative outcomes, including operating room time (OT), postoperative complications, hospital length of stay, and 90-day readmission rates, were evaluated for the three groups. Results: There were 62 patients in the dialysis group, 20 renal transplants, and 330 normal controls. Dialysis patients were younger (median: 58 years versus 67 years; P = .002) and predominantly male (73% versus 59%, P = .047). Dialysis patients compared to controls had shorter total OT (median: 133 versus 149; P = .022), more papillary RCC (27% versus 10%; P < .001), and fewer high grade tumors (73% [8/11] versus 94% [100/106]; P = .038). Renal transplant patients had a higher rate of 90-day readmission (20% versus 6%; P = .034) and more papillary RCC (30% versus 10%; P = .016) compared to controls. Conclusion: LN on dialysis patients does not alter expected perioperative outcomes compared to a large cohort of control LN. LN on renal transplant patients carries a higher 90-day readmission rate than control LN.


Dietary Phytochemicals and Endrocrine-related Activities: An Update.
Phytochemicals are non-nutrient bioactive compounds occurring in plants and food, which possess the capacity to modulate one or more metabolic processes or pathways in the body, resulting to health benefits and promotion of well-being. The interest of the scientific community continues to grow, powered by progressive research efforts to identify properties and potential applications of bioactive substances, and coupled with public interest and consumer demand. However, the natural derivation of these compounds is not a feature of harmlessness, over that of therapeutic efficacy, to which is also added the absence of post-marketing monitoring which does not allow to evaluate the occurrence of adverse effects related to the use of their related products. The literature is particularly rich of studies concerning phytochemicals as environmental estrogens, which result in infertility, reproductive abnormalities, and tumors but also in some endocrine-related health effects. Nevertheless, further studies have been performed to better understand the bioavailability, pharmacokinetics and mode of action of these compounds which seems to go beyond their ability to bind to oestrogen receptors and either stimulate or inhibit the activity of endogenous oestrogens, highlighting new interesting target molecules and signaling pathways. The present review summarizes the latest developments and knowledge concerning the assessment of endocrine activities of dietary phytochemicals focusing on pharmacological aspects.


[Protective effect of quercetin against immunological liver injury through activating Nrf2/ARE signaling pathway].
Objective To observe the protective effect of quercetin against immunological liver injury induced by triptolide, and investigate the involvement of Nrf2/ARE signaling pathway in the protection. Methods Fifty C57BL/6J mice were randomly divided into five groups: control group, model group, (20, 50, 80) mg/kg quercetin pre-treatment groups. Each group included 10 mice. The mice were treated with different doses of quercetin once daily for consecutive 10 days. At the end of the experiment, triptolide (500 μg/kg) was given intragastrically to induce immunological liver injury in all groups except for the control group. Twenty-two hours later, the levels of serum ALT , AST were detected. The contents of GSH, SOD and MDA in liver tissue homogenates were measured through commercial kits. HE staining was performed to observe pathologic changes of the liver. The mRNA expressions of heme oxygenase-1 (HO-1), NQO1, glutamate-cysteine ligase catalytic subunit (GCLC) was tested by quantitative real-time PCR, and the protein expression of Nrf2 was detected by Western blotting. Results Compared with the model group, the serum activities of ALT and AST as well as MDA content remarkably decreased by the administration of quercetin (80 mg/kg), while GSH, SOD contents were elevated in liver tissues; pathologic changes of the liver was ameliorated evidently by quercetin; Nrf2 protein expression in the nucleus as well as mRNA expressions of HO-1, NQO1, GCLC increased. Moreover, the protective effect of 50 mg/kg quercetin was not as good as that of 80 mg/kg quercetin, and 20 mg/kg quercetin did little against the immunological liver injury. Conclusion High-dose quercetin can inhibit immunological liver injury induced by triptolide, and the mechanism may be associated with the activation of Nrf2/ARE signaling pathway.


Magnetic exchange couplings from noncollinear spin density functional perturbation theory.
We propose a method for the evaluation of magnetic exchange couplings based on noncollinear spin density functional calculations. The method employs the second derivative of the total Kohn-Sham energy of a single reference state, in contrast to approximations based on Kohn-Sham total energy differences. The advantage of our approach is twofold: It provides a physically motivated picture of the transition from a low-spin to a high-spin state, and it utilizes a perturbation scheme for the evaluation of magnetic exchange couplings. The latter simplifies the way these parameters are predicted using first principles: It avoids the nontrivial search for different spin states that needs to be carried out in energy difference methods, and it opens the possibility of "black-boxifying" the extraction of exchange couplings from density functional theory calculations. We present proof of concept calculations of magnetic exchange couplings in the H-He-H model system and in an oxovanadium bimetallic complex where the results can be intuitively rationalized.


Improving face identification of mask-wearing individuals.
Research has consistently shown that concealing facial features can hinder subsequent identification. The widespread adoption of face masks due to the COVID-19 pandemic has highlighted the critical and urgent need to discover techniques to improve identification of people wearing face coverings. Despite years of research on face recognition and eyewitness identifications, there are currently no evidence-based recommendations for lineup construction for cases involving masked individuals. The purpose of this study was to examine identification accuracy of a masked perpetrator as a function of lineup type (i.e., unmasked or masked lineups) and perpetrator presence (i.e., absent or present). In both experiments, discriminability was superior for masked lineups, a result that was due almost exclusively to higher hits rates in target-present conditions. These data suggest that presenting a masked lineup can enhance identification of masked faces, and they have important implications for both eyewitness identification and everyday face recognition of people with face coverings.


Measuring Deformability and Red Cell Heterogeneity in Blood by Ektacytometry.
Decreased red cell deformability is characteristic of several disorders. In some cases, the extent of defective deformability can predict severity of disease or occurrence of serious complications. Ektacytometry uses laser diffraction viscometry to measure the deformability of red blood cells subject to either increasing shear stress or an osmotic gradient at a constant value of applied shear stress. However, direct deformability measurements are difficult to interpret when measuring heterogenous blood that is characterized by the presence of both rigid and deformable red cells. This is due to the inability of rigid cells to properly align in response to shear stress and results in a distorted diffraction pattern marked by an exaggerated decrease in apparent deformability. Measurement of the degree of distortion provides an indicator of the heterogeneity of the erythrocytes in blood. In sickle cell anemia, this is correlated with the percentage of rigid cells, which reflects the hemoglobin concentration and hemoglobin composition of the erythrocytes. In addition to measuring deformability, osmotic gradient ektacytometry provides information about the osmotic fragility and hydration status of erythrocytes. These parameters also reflect the hemoglobin composition of red blood cells from sickle cell patients. Ektacytometry measures deformability in populations of red cells and does not, therefore, provide information on the deformability or mechanical properties of individual erythrocytes. Regardless, the goal of the techniques described herein is to provide a convenient and reliable method for measuring the deformability and cellular heterogeneity of blood. These techniques may be useful for monitoring temporal changes, as well as disease progression and response to therapeutic intervention in several disorders. Sickle cell anemia is one well-characterized example. Other potential disorders where measurements of red cell deformability and/or heterogeneity are of interest include blood storage, diabetes, Plasmodium infection, iron deficiency, and the hemolytic anemias due to membrane defects.


[Clinical Analysis of Surgery for Recurrent Cervical Cancer: A Review of 45 Cases].
Objective: To study the efficacy of surgery for recurrent cervical cancer and the influencing factors on prognosis. Methods: To retrospectively analyze the clinical data of 45 patients with recurrent cervical cancer undergoing surgical treatment in our hospital from January 1980 to October 2015, and study their clinical features and prognosis. Results: The Recurrence Free Interval (RFI) of these 45 patients was 3~120 months, and their median RFI was 15 months. Of the 45 cases, 21 recurred inside the radiotherapy field, including 18 with central recurrence and 3 with non-central recurrence; and 24 recurred outside the radiotherapy field, including 16 with pelvic recurrence who did not receive radiotherapy and 8 with distant recurrence. The overall survival time after recurrence of these 45 cases was (39.1±1.0) months, and their 2-year and 5-year survival rates were 55.6% and 22.2%, respectively. The univariate analysis showed that clinical stage, RFI, recurrent site, and initial treatment method affected the survival rate of the patients with recurrent cervical cancer (P<0.05), while the multivariate analysis revealed that recurrent site was an independent prognostic factor for recurrent cervical cancer (P=0.047). Conclusions: Appropriate surgery should be chosen for recurrent cervical cancer according to initial treatment and recurrent site. For patients with central recurrence inside their radiotherapy field, surgery is an effective treatment. Surgery is also suitable for patients without previous radiotherapy and with isolated recurrence, and adjuvant radiotherapy and chemotherapy can improve their survival.


Analysis of food advertising to children on Spanish television: probing exposure to television marketing.
We aimed to assess longitudinal changes in television (TV) food advertising during 2013 compared to 2007, measuring children's exposure to healthy and unhealthy advertisements, after the new European and Spanish Public Health laws published in 2011. Two thematic channels for children (TC), and 2 generalist channels (GC) for all ages were recorded, between April and May 2013, on 2 week and 2 weekend days. Food advertisements were classified as core (CFA) (nutrient dense, low energy), non-core (NCFA) (unbalanced energy profile or high in energy), or others (OFA) (supermarkets and special food). One thousand two hundred sixty-three food advertisements were recorded (TC: 579/GC: 684) in 2013. NCFA were the most shown (54.9%) in the regular full day TV programming (p < 0.001). In 2013, children watching GC had a higher relative risk of being exposed to fast food advertisements than when watching TC (RR = 2.133, 95% CI: 1.398-3.255); CFA were broadcast most frequently in 2013 (GC: 23.7%; and TC: 47.2%) vs. 2007 (TC: 22.9%) (p < 0.001). The proportion of broadcasting between NCFA/CFA and OFA food advertisements in children's peak time slots was higher on TC (203/162) during 2013 than on GC (189/140), and significantly higher than that shown on TC in 2007 (180/36, p < 0.001). Broadcasting of unhealthy TV food advertising on TC is lower today than six years ago; but, children's exposure to TV advertising of unhealthy food is worrying in Spain, and there is more exposure to unhealthy than healthy food by TV. Watching GC in 2013 had higher risk of being exposed to fast food advertisements than watching TC.


Cyclophilin A Is Overexpressed in Hepatocellular Carcinoma and Is Associated with the Cell Cycle.
To investigate the expression of cyclophilin A (CypA) in human hepatocellular carcinoma (HCC) and explore the effects of CypA on the cell cycle in HCC. CypA expression was assessed by immunohistochemistry in 48 cases of HCC tissues and paired adjacent tissues. CypA plasmid was transfected into HCC cells and the cell cycle was analyzed. Positivity for CypA was higher in HCC tissues than in adjacent tissues (79.1% vs. 12.5%, p<0.05). Positivity for CypA was significantly higher in stage III and IV HCC than in stage I and II (p<0.05). Elevated CypA induced an increase of the percentage of S-phase cells (from 34.79% to 42.14%) and a decrease of G0-G1 phase cells (from 58.10% to 50.64%). CypA is overexpressed in HCC and is associated with TNM stage. CypA also appears to promote the transition of the cell cycle from G1 to S phase.


On the correlation between composition and site-specific evolutionary rate: implications for phylogenetic inference.
Model-based phylogenetic reconstruction methods traditionally assume homogeneity of nucleotide frequencies among sequence sites and lineages. Yet, heterogeneity in base composition is a characteristic shared by most biological sequences. Compositional variation in time, reflected in the compositional biases among contemporary sequences, has already been extensively studied, and its detrimental effects on phylogenetic estimates are known. However, fewer studies have focused on the effects of spatial compositional heterogeneity within genes. We show here that different sites in an alignment do not always share a unique compositional pattern, and we provide examples where nucleotide frequency trends are correlated with the site-specific rate of evolution in RNA genes. Spatial compositional heterogeneity is shown to affect the estimation of evolutionary parameters. With standard phylogenetic methods, estimates of equilibrium frequencies are found to be biased towards the composition observed at fast-evolving sites. Conversely, the ancestral composition estimates of some time-heterogeneous but spatially homogeneous methods are found to be biased towards frequencies observed at invariant and slow-evolving sites. The latter finding challenges the result of a previous study arguing against a hyperthermophilic last universal ancestor from the low apparent G + C content of its rRNA sequences. We propose a new model to account for compositional variation across sites. A Gaussian process prior is used to allow for a smooth change in composition with evolutionary rate. The model has been implemented in the phylogenetic inference software PHASE, and Bayesian methods can be used to obtain the model parameters. The results suggest that this model can accurately capture the observed trends in present-day RNA sequences.


Occipital, parietal, and frontal cortices selectively maintain task-relevant features of multi-feature objects in visual working memory.
Previous studies have shown that information held in visual working memory is represented in the occipital, parietal, and frontal cortices. However, less is known about whether the mnemonic information of multi-feature objects is modulated by task demand in the parietal and frontal regions. To address this question, we asked participants to remember either color or orientation of one of the two colored gratings for a delay. Using fMRI and an inverted encoding model, we reconstructed population-level, feature-selective responses in the occipital, parietal and frontal cortices during memory maintenance. We found that not only orientation but also color information can be maintained in higher-order parietal and frontal cortices as well as the early visual cortex when it was cued to be remembered. Conversely, neither the task-irrelevant feature of the cued object, nor any feature of the uncued object was maintained in the occipital, parietal, or frontal cortices. These results suggest a highly selective mechanism of visual working memory that maintains task-relevant features only.


Chip-based Brillouin radio frequency photonic phase shifter and wideband time delay.
We report a chip-based true-time-delay unit based on stimulated Brillouin scattering that uses an on-off Brillouin gain of 52 dB to enable 4 ns delay over a bandwidth of 100 MHz and a phase shift of ∼200°. To verify these operations, we use a two-tap microwave filter configuration and observed changes in the free spectral range of the filter and shift in the spectrum of the filter. The realization of these functionalities on chip-scale devices is critical for phased-array antennas, multibeam satellites, delay lines, arbitrary waveform generation, and reconfigurable microwave photonic filters.


Sistani population: a different spectrum of β-thalassemia mutations from other ethnic groups of Iran.
This study aimed to characterize the molecular spectrum of β-thalassemia (β-thal) mutations and evaluate the services available for prenatal diagnosis (PND) among the Sistani population of Iran. Mutations were analyzed with amplification refractory mutation system (ARMS), gap-polymerase chain reaction (gap-PCR), multiplex ligation-dependent probe amplification (MLPA) analysis and direct sequencing. Fetal diagnosis was also confirmed by linkage analysis. Over a 9-year period (2002-2011), 405 at-risk Sistani couples were referred for mutation analysis and/or PND. Of the referred couples, 18.5% had one to three affected children with β-thal major (β-TM) and the remainder had no children or were not married. Most of the couples (73.3%) lived in urban areas and the rate of consanguineous marriage was 76.8%. Twenty-one mutations were identified, of which the most frequent ones were IVS-I-5 (G>C) with a frequency of 74.1%, followed by codon 15 G>A (5.0%), codon -88 (C>T) (3.8%), IVS-II-1 (G>A) (3.4%), codons 8/9 (+G) (2.9%) and IVS-I-1 (G>T) (2.7%), which accounted for about 91.9% of the total β-thal mutations for this region. Furthermore, fetal DNA was obtained from chorionic villus sampling (CVS) for 266 pregnant women and 68 (25.5%) fetuses were diagnosed as affected. In summary, β-thal mutations are very heterogeneous and significantly different from those found in other parts of Iran and are similar to those of Pakistani and Indian populations. These results could greatly facilitate timely and accurate PND.


Biofouling Removal and Protein Detection Using a Hypersonic Resonator.
Nonspecific binding (NSB) is a general issue for surface based biosensors. Various approaches have been developed to prevent or remove the NSBs. However, these approaches either increased the background signals of the sensors or limited to specific transducers interface. In this work, we developed a hydrodynamic approach to selectively remove the NSBs using a microfabricated hypersonic resonator with 2.5 gigahertz (GHz) resonant frequency. The high frequency device facilitates generation of multiple controlled microvortexes which then create cleaning forces at the solid-liquid interfaces. The competitive adhesive and cleaning forces have been investigated using the finite element method (FEM) simulation, identifying the feasibility of the vortex-induced NSB removal. NSB proteins have been selectively removed experimentally both on the surface of the resonator and on other substrates which contact the vortexes. Thus, the developed hydrodynamic approach is believed to be a simple and versatile tool for NSB removal and compatible to many sensor systems. The unique feature of the hypersonic resonator is that it can be used as a gravimetric sensor as well; thus a combined NSB removal and protein detection dual functional biosensor system is developed.


Determinants of Cochlear Implant Satisfaction and Decisional Regret in Adult Cochlear Implant Users.
Determine associations expected and actual cochlear implant (CI) outcomes, decisional regret, and satisfaction in experienced adult CI users. Cross-sectional cohort study. Tertiary medical center. Thirty-nine adult CI users meeting traditional bilateral hearing loss indications with ≥12 months CI experience. Patients completed the validated Satisfaction with Amplification in Daily Living and Decisional Regret instruments. Pre- and post-CI outcomes (CI Quality of Life [CIQOL]-Expectations; CIQOL-35 Profile; CNC words, AzBio Sentences) were obtained from a prospectively maintained clinical database. Using established cutoff scores, 29% of patients reported a substantial degree of post-CI decisional regret. For each CIQOL domain, patients without decisional regret obtained post-CI outcome scores closer to pre-CI expectations compared with patients with decisional regret ( d = 0.34 to 0.91); similar results were observed with higher CI user satisfaction ( d = 0.17-0.83). Notably, the degree of pre- to post-CI improvement in CNC or AzBio scores did not differ between patients with and without decisional regret or with lower and higher satisfaction. Finally, greater pre-/postimprovement in CIQOL-35 Profile domain scores demonstrated far stronger associations with lower decisional regret and higher satisfaction than changes in speech recognition scores. Patients with better alignment of their pre-CI expectations and post-CI outcomes and greater pre-/post-CIQOL improvement had lower decisional regret and higher satisfaction. This emphasizes the importance of evidence-based pre-CI counseling regarding real-world CI benefits and caution against assuming that improvements in speech recognition are related to patient satisfaction.


Metabolic clearance and blood production rates of estradiol in hyperthyroidism.
The metabolic clearance rate of 17beta-estradiol (MCR2), the plasma levels of 17beta-estradiol (E2)1, sex-steroid binding globulin (SSBG), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured in 10 hyperthyroid subjects (7 men and 3 women). The blood production rate of 17beta-estradiol (PB2) was calculated for all subjects. Nine of the 10 hyperthyroid subjects had a decreased MCR2 which returned towards normal in 5 of the 6 subjects restudied following therapy. In all 10 subjects the levels of SSBG were increased when they were hyperthyroid and returned toward normal with therapy. It is concluded that the decrease in MCR2 is largely due to the increased binding of 17beta-estradiol to SSBG. In 7 of the 10 hyperthyroid the plasma E2 concentrations were normal whereas 3 had slightly elevated levels. In 8 of the 10 hyperthyroid the PB2 was within the normal range. Only 2 hyperthyroid subjects had slightly elevated PB2. In the 6 subjects who were restudied after therapy, there was no consistent change in PB2 which remained in the normal range in all cases. It is concluded that the MCR2 is decreased in most subjects with hyperthyroidism in association with an increase of SSBG. Despite this change in MCR2 there is no significant change in PB2. The increase in SSBG levels in hyperthyroidism appears to be a direct effect of the elevation of thyroid hormone activity and is not mediated through estrogen.


Adverse events in cardiac surgery, a mixed methods retrospective study in an Italian teaching hospital.
Adverse events (AEs) are a major concern in surgery, but the evidence in cardiac surgery is limited, especially on the contributory factors. According to the data of the National Outcomes Program, a unit was selected to conduct a mixed methods investigation into the incidence, type, and cause of AE, given its mortality rate that was double the national average on coronary artery bypass grafting, valve reparation, and replacement. A retrospective investigation on the performance of a cardiac surgery, combining the routinely collected data on process and outcome measures with a 2-stage structured review of 280 medical records performed by 3 expert clinicians, with the support of a methodologist. At least one risk had been verified in 137 of 280 cases (48.9%, 95% CI, 43.1-54.8). The total number of AE was 42, with an incidence of 15% (95% CI, 10.8-20.2) and a preventability of 80.9% (95% CI, 69.1-92.8). In 11.9% of AE, the consequence is death, disability in 40.5%, and extended hospital stay in 69% of the cases. Adverse events are associated with problems in care management at the ward (89/137, 64.9%, 95% CI, 56.9-72.9), followed by surgical complications (46/137, 33.6%, 95% CI, 25.7-41.5) and infection/sepsis (32/137, 23.4%, 95% CI, 16.3-30.4). An active error was made by the health care workers in 31 of 42 cases with AE, either during the decision making or during the execution of an action. A total of 36 AEs were due to deficiencies attributed to organizational factors and 31 were linked to poor teamwork. The mixed methods approach demonstrated how a deep understanding of AE and poor performance may emerge thanks to the combination of routinely available data and experts' evaluations. The main limitation of this study is its focus on the cardiac surgery rather than on the entire process of care. The evaluation could have been integrated with on-site observations and the analysis of reported incidents.


Glucose variability in diabetic pregnancy.
Fetal overgrowth is the most important complication of gestational (GDM) and pregestational diabetes mellitus. We correlated maternal glucose profiles, as detected by continuous glucose monitoring (CGM), with fetal growth parameters for 80 pregnant women (32 with type 1 diabetes, 31 with GDM, and 17 healthy controls). Glucose profiles were monitored in the first, second, and third trimesters of pregnancy for type 1 diabetes women and in the second and third trimesters for GDM women and controls. To analyze glycemic variability, we considered the mean amplitude of glycemic excursion, mean glycemia, the continuous overlapping net glycemic action (CONGA), the SD, the High Blood Glucose Index (HBGI), the Low Blood Glucose Index, and the interquartile range (IQR). Mean age was the same for the three groups. Prepregnancy body mass index was higher for the women with diabetes (GDM and type 1) than for controls. The newborn's mean birth weight and ponderal index were higher, although not significantly so, for the women with diabetes than for controls. For the type 1 diabetes patients, ponderal index correlated with the HBGI in the first trimester, CONGA1 and IQR in the second, and mean glycemia and SD in the third. For GDM patients, ponderal index correlated with mean glycemia and the HBGI in the second trimester. Fetal exposure to glycemic variability and hyperglycemia seems to be important in determining fetal overgrowth in pregnant women with diabetes. Optimal glucose control and less glucose variability are needed as early as possible in both type 1 diabetes and GDM patients to ensure normal fetal growth.


Differences in history-taking skills between male and female chiropractic student interns.
The purpose of this study was to determine if there was a difference in history-taking skills between male and female chiropractic student interns. This study included 2040 patient histories collected by student interns over a 3-year period. Students were assessed by chiropractic college clinicians on reasoning (ability to derive clinically relevant information using a mnemonic for taking a history), communication, and professionalism using a modified Dreyfus model scoring system on a 1-4 scale (1 = novice, 4 = proficient). Ordinal dependent variables were scores for reasoning, communication, and professionalism. The categorical independent variable was sex of the student intern (male or female). A Mann-Whitney U test was used to compare for differences in nonparametric dependent variables by the sex of the students. The Mann-Whitney U test revealed that communication scores were greater for female chiropractic interns compared with male chiropractic interns (p < .001, with a small effect size (r = -.08). There was no statistically significant effect for sex on reasoning (p = .263) or professionalism (p = .098). Female chiropractic student interns scored higher than male interns on communication skills during a history-taking patient encounter. This supports the trend seen among female medical school students and physicians that women score higher than men on communication-related assessments.


Anomalous electrochemical dissolution and passivation of iron growth catalysts in carbon nanotubes.
Catalytically synthesized carbon nanotubes (CNTs) such as those prepared via chemical vapor deposition (CVD) contain metallic impurities including Fe, Ni, Co, and Mo. Transition metal contaminants such as Fe can participate in redox cycling reactions that catalyze the generation of reactive oxygen species and other products. Through the nature of the CVD growth process, metallic nanoparticles become encased within the CNT graphene lattice and may still be chemically accessible and participate in redox chemistry, especially when these materials are utilized as electrodes in electrochemical applications. We demonstrate that metallic impurities can be selectively dissolved and/or passivated during electrochemical potential cycling. Anomalous Fe dissolution and passivation behavior is observed in neutral (pH=6.40+/-0.03) aqueous solutions when using multiwalled CNTs prepared from CVD. Fe particles contained within these CNTs display intriguing, potential-dependent Fe redox activity that varies with supporting electrolyte composition. In neutral solutions containing dibasic sodium phosphate, sodium acetate, and sodium citrate, FeII dissolution and surface confined FeII/III redox activity are significant despite Fe being encapsulated within CNT graphene layers. However, no apparent Fe dissolution is observed in 1 M potassium nitrate solutions, suggesting that the electrolyte composition plays an important role in observing FeII dissolution, passivation, and surface confined FeII/III redox activity. Between potentials of 0 and -1.1 V versus Hg/Hg2SO4, the primary redox-active Fe species are surface FeII/III oxides/oxyhydroxides. This FeII/III surface oxide redox chemistry can be completely suppressed by passivating Fe through repeated cycling of the CNTs in supporting electrolyte. By increasing the potential to more negative values (>-1.3 V), FeII dissolution may be induced in electrolyte solutions containing acetate and phosphate and inhibited by addition of sodium benzoate, which adsorbs on exposed Fe particles, effectively passivating them. Finally, we observe that the FeII/III redox chemistry or subsequent passivation does not affect the onset of oxygen reduction at nitrogen-doped CNTs, suggesting that the surface-bound FeII species is not the primary catalytically active site for oxygen reduction in these materials.


Surface induced in vitro angiogenesis: surface property is a determinant of angiogenesis.
The control of cellular responses on substrate surfaces is essential for logical surface design aiming at endothelialized, vital implant devices. In this paper, the surface property that alters cell adhesion, spreading, migration, and proliferation processes is shown to be a determinant of endothelial cell assembly or angiogenesis in vitro. This was clearly demonstrated on slightly hydrophobic cellulosic surfaces, which induced organized three-dimensional cellular assemblies of bovine thoracic endothelial cells. The results indicated that this was driven by enhanced migratory response and/or retraction or involution of two-dimensional adherent cells, in which cell-cell interaction was enforced in a time dependent fashion. The present study strongly suggests that the mechanism leading to in vitro angiogenesis is primarily due to a weak cell-substrate interaction relative to cell-cell interaction.


Tissue-Dependent Adaptations and Functions of Innate Lymphoid Cells.
Tissue-resident immune cells reside in distinct niches across organs, where they contribute to tissue homeostasis and rapidly respond to perturbations in the local microenvironment. Innate lymphoid cells (ILCs) are a family of innate immune cells that regulate immune and tissue homeostasis. Across anatomical locations throughout the body, ILCs adopt tissue-specific fates, differing from circulating ILC populations. Adaptations of ILCs to microenvironmental changes have been documented in several inflammatory contexts, including obesity, asthma, and inflammatory bowel disease. While our understanding of ILC functions within tissues have predominantly been based on mouse studies, development of advanced single cell platforms to study tissue-resident ILCs in humans and emerging patient-based data is providing new insights into this lymphocyte family. Within this review, we discuss current concepts of ILC fate and function, exploring tissue-specific functions of ILCs and their contribution to health and disease across organ systems.


Challenges and opportunities for gender-affirming healthcare for transgender women in prison.
Purpose The purpose of this paper is to briefly address three interrelated areas of concerns - victimization, housing placement and healthcare provision - related to the health and welfare of transgender women in jails, prisons and other types of detention facilities. Design/methodology/approach Drawing on a growing body of research on health risks for transgender women who are detained in facilities in California and elsewhere, the authors provide recommendations for policy and practice that constitutes gender-affirming healthcare for transgender women behind bars. Findings Policymakers, correctional leaders, and prison-based clinicians have a number of opportunities to address the welfare of transgender women in jails, prisons and other types of detention facilities. Originality/value This policy brief offers concrete steps government officials can take to better meet their professional and constitutional obligations, provide higher quality care for transgender women involved in the criminal justice system, and effectuate positive changes in transgender women's health and welfare both inside and outside of carceral environments.


Toward an integration of interpersonal and biological processes: evolutionary psychiatry as an empirically testable framework for psychiatric research.
Phenomenological, biological, and interpersonal aspects of psychiatric disorders lack an integrative empirical framework. In this paper evolutionary psychiatry is proposed as a meta-theory to integrate biological and interpersonal aspects of psychopathology. Pathological cognition, emotions, and behaviors may be examined according to specific biosocial goals originally pursued to increase the individual's inclusive fitness, similar to the ways that "normal" processes have been analyzed by evolutionary psychology. Sex-specific differences in prevalence rates and symptomatology of psychiatric disorders may also be better understood if divergent problems of adaptation for men and women in human evolutionary history are taken into account. Instead of mistaking the evolutionary approach for being deterministic and empirically untestable, it may rather be appropriate to provide a functional classification which adds to the contemporary psychiatric nosology through analysis according to specific conflicts of adaptation (at the ultimate level), the pursuit of biosocial goals, and proximate specifiers such as genetic, developmental, and interpersonal causes of disorders.


The association of micronucleus frequency with obesity, diabetes and cardiovascular disease.
Obesity and metabolic syndrome (MetS) are serious and growing health care problems worldwide, leading an increased risk for type 2 diabetes (T2D) and cardiovascular disease (CVD). Over the past decade, emerging evidence has shown that an increased chromosomal damage, as determined by the cytokinesis-block micronucleus (CBMN) assay, is correlated to the pathogenesis of metabolic and CVD. An increased micronuclei (MN) frequency has been demonstrated in peripheral blood lymphocytes of patients with polycystic ovary syndrome, a common condition in reproductive-aged women associated with impaired glucose tolerance, T2D mellitus and the MetS. High levels of MN have been detected to be significantly correlated with T2D as well as with the occurrence and the severity of coronary artery disease (CAD). Long-term follow-up studies have shown that an increased MN frequency is a predictive biomarker of cardiovascular mortality within a population of healthy subjects as well as of major adverse cardiovascular events in patients with known CAD. Overall, these findings support the hypothesis that CBMN assay may provide an useful tool for screening of the MetS and its progression to diabetes and CVD in adults as well in children. Large population-based cohorts are needed in order to compare the MN frequencies as well as to better define whether MN is a biomarker or a mediator of cardiometabolic diseases.


Fluorescence optical imaging and 3T-MRI for detection of synovitis in patients with rheumatoid arthritis in comparison to a composite standard of reference.
To address whether Indocyanine Green (ICG) enhanced fluorescence optical imaging (FOI) is more sensitive than magnetic resonance imaging (MRI) in the detection of synovitis of the wrist and finger joints in rheumatoid arthritis and to analyze the performance of FOI depending on the grade of synovitis. Twenty patients with highly active rheumatoid arthritis (mean DAS28-ESR 5.25±1.0) and thirteen healthy volunteers underwent clinical examination, FOI and contrast-enhanced 3T-MRI. Joints were rated by three independent readers semiquantitatively (grade 0-3: no, low, moderate and high grade synovitis) and compared to a semiquantitative composite standard of reference (cSOR, grade 0-3) that incorporated clinical parameters, FOI and MRI results. 2.868 evaluations in 956 joints were performed. FOI had an overall sensitivity of 57.3% and a specificity of 92.1%, whereas MRI had a sensitivity of 89.2% and a specificity of 92.6%. The sensitivity of FOI increased with the degree of synovitis to 65.0% for moderate and severe synovitis (specificity 88.1%) and 76,3% for severe synovitis (specificity 80.5%). The performance of FOI decreased with the degree of synovitis with false negative results predominantly for mild (156/343, 45.5%) and moderate (160/343, 46.6%) synovitis and false positive FOI evaluations predominantly based on weak (grade 1) signals (133/163, 81,6%). FOI has a lower sensitivity than 3T-MRI in the detection of synovitis of the hand and finger joints. The diagnostic performance of FOI decreases with the degree of synovitis and with the strength of FOI signals.


Brassinosteroid Mediated Cell Wall Remodeling in Grasses under Abiotic Stress.
Unlike animals, plants, being sessile, cannot escape from exposure to severe abiotic stresses such as extreme temperature and water deficit. The dynamic structure of plant cell wall enables them to undergo compensatory changes, as well as maintain physical strength, with changing environments. Plant hormones known as brassinosteroids (BRs) play a key role in determining cell wall expansion during stress responses. Cell wall deposition differs between grasses (Poaceae) and dicots. Grass species include many important food, fiber, and biofuel crops. In this article, we focus on recent advances in BR-regulated cell wall biosynthesis and remodeling in response to stresses, comparing our understanding of the mechanisms in grass species with those in the more studied dicots. A more comprehensive understanding of BR-mediated changes in cell wall integrity in grass species will benefit the development of genetic tools to improve crop productivity, fiber quality and plant biomass recalcitrance.


Family matters: How MYC family oncogenes impact small cell lung cancer.
Small cell lung cancer (SCLC) is one of the most deadly cancers and currently lacks effective targeted treatment options. Recent advances in the molecular characterization of SCLC has provided novel insight into the biology of this disease and raises hope for a paradigm shift in the treatment of SCLC. We and others have identified activation of MYC as a driver of susceptibility to Aurora kinase inhibition in SCLC cells and tumors that translates into a therapeutic option for the targeted treatment of MYC-driven SCLC. While MYC shares major features with its paralogs MYCN and MYCL, the sensitivity to Aurora kinase inhibitors is unique for MYC-driven SCLC. In this review, we will compare the distinct molecular features of the 3 MYC family members and address the potential implications for targeted therapy of SCLC.


Substance misuse prevention and economic analysis: challenges and opportunities regarding international utility.
Economic analyses of substance misuse prevention assess the intervention cost necessary to achieve a particular outcome, and thereby provide an additional dimension for evaluating prevention programming. This article reviews several types of economic analysis, considers how they can be applied to substance misuse prevention, and discusses challenges to enhancing their international relevance, particularly their usefulness for informing policy decisions. Important first steps taken to address these challenges are presented, including the disease burden concept and the development of generalized cost-effectiveness, advances that facilitate international policy discussions by providing a common framework for evaluating health care needs and program effects.


[A comparison of corneal sensitivity between healthy cats and cats with corneal sequestra].
In order to establish reference values for corneal sensitivity in ophthalmologically healthy persians (n = 40) and domestic short hair cats (n = 60) a prospective study was conducted. Furthermore corneal sensitivity in 48 cats with a corneal sequestrum was measured. Corneal sensitivity was recorded with the help of the aesthesiometer according to Cochet and Bonnet in five different corneal locations (central, nasal, dorsal, temporal, and ventral). The sensitivity for the central corneal region was recorded as amounting to 3.58 +/- 0.56 cm in ophthalmologically healthy domestic short hair cats and to 2.97 +/- 0.58 cm in healthy persian cats. The sensitivity of the central corneal area of a cat with a corneal sequester only amounts to 2.03 +/- 0.53 cm. Between the diseased and the healthy eyes no statistical difference could be demonstrated for any of the measured corneal locations. The sensitivity of the peripheral corneal locations is significantly lower than that of the central corneal region in all three groups examined.


Probing local effects in silica sol-gel media by fluorescence spectroscopy of p-DASPMI.
Stillbazolium salts present remarkable potential for application in several scientific areas. Their versatile behavior is explained by invoking the "twisted intramolecular charge-transfer" (TICT) mechanism, a model that describes the multiple fluorescence of DASPMI (4-(4-(dimethylamino)styryl)- N-methylpyridiniumiodine). One feature of their behavior is the sensitivity of the fluorescence lifetime to viscosity, thus identifying them as suitable probes for microheterogeneous systems, such as cells and sol-gel derived media. Because of their optical transparency, sol-gel matrices are light addressable and therefore appropriate for performing spectroscopic studies. The sol-gel process has been successfully used to produce hosts to biomolecules like proteins, for biosensor applications; however, these systems have to be optimized. Therefore, in this study modification of the matrices was performed through the incorporation of either silanes or polymers. (Aminopropyl)triethoxysilane, trimethoxypropylsilane, or (glycidyloxypropyl)triethoxysilane were added. The modification was also extended to the incorporation of the polymers poly(ethylene glycol) (molecular weight 300 and 20000) and Gelrite. The effect of these modifiers upon the gelation and aging processes was examined via the study of the photophysics of p-DASPMI by using both steady-state and time-resolved fluorescence. It was possible to discriminate the dominant dye-host interactions in each of the main steps of the preparation of modified sol-gel matrices.


Chemotherapy education for patients with cancer: a literature review.
A literature review was conducted to determine the best way to provide chemotherapy education to patients. Sixteen articles that employed various teaching methods (e.g., video recordings, in-person class) were identified. Some educational methods have been proven to decrease anxiety, which allows patients to retain more information. Many ways can be used to provide chemotherapy education, and no method has been proven to be significantly more effective than another. Maximum retention is largely based on patient preference.


An Intriguing Endoscopic Case of Asymptomatic Crohn's Disease.
We present the case of a 64-year old male with Crohn's disease, who has intriguing endoscopic findings. Upon initial diagnosis at age 20, he received steroid therapy, but has not required any further medical intervention. He has remained relatively asymptomatic and keeps a healthy lifestyle. At routine colonoscopy, we identified pseudopolyps as well as tissue bridges within the colon, giving an unusual "swiss cheese" appearance. This case exemplifies the heterogeneity of Crohn's disease, emphasizing the possibility of finding evidence of ongoing disease despite lack of symptoms.


Cadmium-Associated Differential Methylation throughout the Placental Genome: Epigenome-Wide Association Study of Two U.S. Birth Cohorts.
Cadmium (Cd) is a ubiquitous environmental toxicant that can accumulate in the placenta during pregnancy, where it may impair placental function and affect fetal development. We aimed to investigate Cd-associated variations in placental DNA methylation (DNAM) and associations with gene expression; we also aimed to identify novel pathways involved in Cd-associated reproductive toxicity. Using placental DNAM and Cd concentrations in the New Hampshire Birth Cohort Study (NHBCS, n=343) and the Rhode Island Child Health Study (RICHS, n=141), we performed an epigenome-wide association study (EWAS) between Cd and DNAM, adjusting for tissue heterogeneity using a reference-free method. Cohort-specific results were aggregated via inverse variance weighted fixed effects meta-analysis, and variably methylated CpGs were associated with gene expression. We then performed functional enrichment analysis and tests for associations between gene expression and birth size metrics. We identified 17 Cd-associated differentially methylated CpG sites with meta-analysis p-values<1×10−5, two of which were within a 5% false discovery rate (FDR). DNAM levels at 9 of the 17 loci were associated with increased expression of 6 genes (5% FDR): TNFAIP2, EXOC3L4, GAS7, SREBF1, ACOT7, and RORA. Higher placental expression of TNFAIP2 and ACOT7 and lower expression of RORA were associated with lower birth weight z-scores (p-values<0.05). Cd-associated differential DNAM and corresponding DNAM-expression associations were observed at loci involved in inflammatory signaling and cell growth. The expression levels of genes involved in inflammatory signaling (TNFAIP2, ACOT7, and RORA) were also associated with birth weight, suggesting a role for inflammatory processes in Cd-associated reproductive toxicity. https://doi.org/10.1289/EHP2192.


Protein arginine methyltransferase 5 regulates multiple signaling pathways to promote lung cancer cell proliferation.
Protein arginine methyltransferase 5 (PRMT5) catalyzes the formation of symmetrical dimethylation of arginine residues in proteins. WD repeat domain 77 (WDR77), also known as p44, MEP50, or WD45, forms a stoichiometric complex with PRMT5. The PRMT5/p44 complex is required for cellular proliferation of lung and prostate epithelial cells during earlier stages of development and is re-activated during prostate and lung tumorigenesis. The molecular mechanisms by which PRMT5 and p44 promote cellular proliferation are unknown. Expression of PRMT5 and p44 in lung and prostate cancer cells was silenced and their target genes were identified. The regulation of target genes was validated in various cancer cells during lung development and tumorigenesis. Altered expression of target genes was achieved by ectopic cDNA expression and shRNA-mediated silencing. PRMT5 and p44 regulate expression of a specific set of genes encoding growth and anti-growth factors, including receptor tyrosine kinases and antiproliferative proteins. Genes whose expression was suppressed by PRMT5 and p44 encoded anti-growth factors and inhibited cell growth when ectopically expressed. In contrast, genes whose expression was enhanced by PRMT5 and p44 encoded growth factors and increased cell growth when expressed. Altered expression of target genes is associated with re-activation of PRMT5 and p44 during lung tumorigenesis. Our data provide the molecular basis by which PRMT5 and p44 regulate cell growth and lay a foundation for further investigation of their role in lung tumor initiation.


Close link between CD4+ and CD8+ T cell proliferation defects in patients with human immunodeficiency virus disease and relationship to extended periods of CD4+ lymphopenia.
T cell proliferation failure is commonly associated with human immunodeficiency virus (HIV) infection. By examining T cell function on a single-cell basis, we found that CD4(+) T cell proliferation failure was often accompanied by CD8(+) T cell proliferation defects in patients with HIV disease. The defects are characterized by a proportional failure and reduced efficiency of precursor T cell proliferation after stimulation. In this study, patients who historically had low levels of circulating CD4(+) T cells were most likely to demonstrate cellular proliferation failure, regardless of current CD4(+) T cell counts. In contrast, neither historical nor current plasma HIV RNA levels were predictive of proliferation failure. These results suggest that mechanisms of T cell proliferation failure are more complex than can be explained by the direct effects of HIV replication and that therapeutic intervention to avoid prolonged periods of CD4(+) lymphopenia may be desirable for the preservation of immune function in patients with HIV disease.


Machine learning on thyroid disease: a review.
This study reviews the recent progress of machine learning for the early diagnosis of thyroid disease. Based on the results of this review, different machine learning methods would be appropriate for different types of data for the early diagnosis of thyroid disease: (1) the random forest and gradient boosting in the case of numeric data; (2) the random forest in the case of genomic data; (3) the random forest and the ensemble in the case of radiomic data; and (4) the random forest in the case of ultrasound data. Their performance measures varied within 64.3-99.5 for accuracy, 66.8-90.1 for sensitivity, 61.8-85.5 for specificity, and 64.0-96.9 for the area under the receiver operating characteristic curve. According to the findings of this review, indeed, the following attributes would be important variables for the early diagnosis of thyroid disease: clinical stage, marital status, histological type, age, nerve injury symptom, economic income, surgery type [the quality of life 3 months after thyroid cancer surgery]; tumor diameter, symptoms, extrathyroidal extension [the local recurrence of differentiated thyroid carcinoma]; RNA feasures including ADD3-AS1 (downregulation), MIR100HG (downregulation), FAM95C (downregulation), MORC2-AS1 (downregulation), LINC00506 (downregulation), ST7-AS1 (downregulation), LOC339059 (downregulation), MIR181A2HG (upregulation), FAM181A-AS1 (downregulation), LBX2-AS1 (upregulation), BLACAT1 (upregulation), hsa-miR-9-5p (downregulation), hsa-miR-146b-3p (upregulation), hsa-miR-199b-5p (downregulation), hsa-miR-4709-3p (upregulation), hsa-miR-34a-5p (upregulation), hsa-miR-214-3p (downregulation) [papillary thyroid carcinoma]; gut microbiota RNA features such as veillonella, paraprevotella, neisseria, rheinheimera [hypothyroidism]; and ultrasound features, i.e., wreath-shaped feature, micro-calcification, strain ratio [the malignancy of thyroid nodules].


Case Report: SATB2-Associated Syndrome Overlapping With Clinical Mitochondrial Disease Presentation: Report of Two Cases.
SATB2-associated syndrome (SAS) is an autosomal dominant neurogenetic multisystemic disorder. We describe two individuals with global developmental delay and hypotonia who underwent an extensive evaluation to rule out an underlying mitochondrial disorder before their eventual diagnosis of SAS. Although the strict application of the clinical mitochondrial disease score only led to the designation of "possible" mitochondrial disorder for these two individuals, other documented abnormalities included nonspecific neuroimaging findings on magnetic resonance imaging and magnetic resonance spectroscopy, decreased complex I activity on muscle biopsy for patient 2, and variation in the size and relative proportion of types of muscle fibers in the muscle biopsies that were aligned with mitochondrial diseases. SAS should be in the differential diagnoses of mitochondrial disorders, and broad-spectrum diagnostic tests such as exome sequencing need to be considered early in the evaluation process of undiagnosed neurodevelopmental disorders.