[Paraneoplastic sclerodermiform syndrome].
Despite the known association between scleroderma and cancer, the current systemic sclerosis classifications do not clearly identify paraneoplastic sclerodermiform syndrome or sclerodermiform syndrome secondary to cancer treatments. A 56 year old man was hospitalized for severe Raynaud's phenomenon with bilateral digital necrosis and otherwise good health status. X-rays did not show any subcutaneous calcification. Levels of serum antinuclear antibodies were high but anticentromere and anti-topoisomerase 1 antibodies were negative. Chest X-ray and CT-scan identified an irregular opacity in the right upper lobe with enlarged mediastinal lymph nodes. A diagnosis of bronchial adenocarcinoma was made following mediastinoscopy and the patient was treated with neo-adjuvant chemotherapy and lobectomy. After two cycles of treatment, his skin lesions had almost disappeared. The presence of a sclerodermiform syndrome may suggest the existence of an underlying neoplasm. In this case report, the skin lesions disappeared quickly after antineoplastic treatment. We suggest that sclerodermiform syndrome be included in the systemic sclerosis classification.


Reverse shoulder arthroplasty after failed tendon transfer for irreparable posterosuperior rotator cuff tears.
Tendon transfers (TTs) can be successful for the management of selected posterosuperior functionally irreparable rotator cuff tears. However, when these procedures fail to provide adequate pain relief or functional improvement, reverse shoulder arthroplasty (RSA) is commonly considered the next treatment option. The effect of prior TT on RSA remains largely unknown. The purposes of this investigation were to evaluate the outcomes of RSA after previous TT performed for posterosuperior functionally irreparable rotator cuff tears and to determine the effect of various TT types on RSA. A retrospective review of 2 institutional databases identified 33 patients who underwent RSA implantation between 2006 and 2019 with a previous failed tendon transfer (FTT) of the shoulder and at least 2 years of clinical follow-up. FTTs included 21 latissimus dorsi transfers, 6 latissimus dorsi and teres major (LD-TM) transfers, and 6 lower trapezius transfers. RSAs were performed at an average of 5.5 years (range, 0.3-28 years) after FTT, with a mean follow-up period of 4.1 ± 2.0 years. Outcomes evaluated included the visual analog scale pain score, range of motion, absolute Constant-Murley score (CS) and relative CS, American Shoulder and Elbow Surgeons score, Subjective Shoulder Value, complications, and implant survivorship free of reoperation or revision. RSA significantly improved pain and function, with improvements in the visual analog scale pain score (6.2 preoperatively vs. 2.2 at most recent follow-up, P < .001), active elevation (85° vs. 111°, P < .001), American Shoulder and Elbow Surgeons score (51 vs. 74, P = .001), absolute CS (34 vs. 48, P = .003), and relative CS (42% vs. 59%, P = .002), exceeding the minimal clinically important difference threshold. There were 7 complications (21%) across the entire cohort, with dislocation (n = 3, 9.1%) as the most common complication. Comparison across TT groups showed that LD-TM transfer had the highest complication rate (3 shoulders, 50%), followed by lower trapezius transfer (1 shoulder, 16.7%); latissimus dorsi transfer had the lowest rate (3 shoulders, 14.3%; P = .037). Survivorship free of revision or reoperation was estimated to be 90.1% at 1 year, 84.9% at 2 years, and 71.2% at 5 years, with no difference among TT groups (P = .654). RSA can serve as a viable salvage option for FTT procedures. At mid-term follow-up, RSA led to significant improvements in pain, range of motion, and patient-reported outcomes. Patients with prior LD-TM transfers may have a higher complication rate, but no other differences were found between TT groups.


Formation of phosphorus monoxide through the [Formula: see text] reaction.
Phosphorus is a key and vital element for a diverse set of important biological molecules, being indispensable for life as we know. A deeper comprehension of its role in astrochemistry and atmospheric chemistry may aid in finding answers to how this element became available on Earth. The PO molecule is one of the main reservoirs of phosphorus in the interstellar medium (ISM), and a better understanding of the mechanisms and rate coefficients for its formation in the ISM is important for modelling its abundances. In this work, we perform multireference configuration interaction calculations on the formation of PO via the [Formula: see text] reaction, analyzing its potential energy surface and rate coefficients for the global reaction on both doublet and quartet states. We also perform DFT (M06-2X) and CCSD(T) calculations, in order to compare the results. We found that the OPO system possesses a high multiconfigurational character, making DFT and CCSD methodologies not suitable for its potential energy landscape calculation. The rate coefficients have been calculated using the master equation system solver (MESS) package, and the results compared to recent experimental data. It is shown that the quartet state contributes for temperatures higher than 700K. The computed rate coefficient can be described by a modified Arrhenius equation [[Formula: see text]] with [Formula: see text], [Formula: see text] and [Formula: see text] K.


Cerebral biochemical abnormalities in experimental maternal phenylketonuria: gangliosides and sialoglycoproteins.
The present study sought a biochemical explanation for retarded brain development in the heterozygous offspring of the phenylketonuric (PKU) mother. Two rat models of simulated maternal PKU, one induced by p-chlorophenylalanine and phenylalanine and the other by phenylacetate, were employed in this investigation. Maternal PKU had no influence on cerebral concentrations of DNA, protein, and cholesterol, which were normal in the 2 d old pup. However, there was a noticeable disruption of the normal ganglioside pattern and a significant reduction of sialoglycoproteins. Concomitant with a delayed drop in the gangliosides Q1b and D3, was a slower rise in M1 and D1a. At least 66% of sialoglycoproteins located on SDS-PAGE gel chromatograms, by radioactivity incorporated in vivo from radiolabeled N-acetylmannosamine and by (3H) sialic acid released by Neuraminidase from periodate-(3H)borohydride labeled glycoproteins, have mobilities of the cell adhesion molecules N-CAM and D-CAM. Whether the reduction of the sialoglycoproteins induced by maternal PKU is mainly in these cell adhesion molecules requires further investigation. Interference with the function of gangliosides and certain sialoglycoproteins during cerebral development may contribute to the brain dysfunction observed in the offspring of PKU mothers not on diet control during pregnancy.


'Choice' of social media platform or encrypted messaging app to buy and sell illegal drugs.
Social media is increasingly being utilized to facilitate the buying and selling of illegal drugs, particularly by young people. However, the range of social media and messaging platforms means people must make 'choices' around which platforms they will use to conduct drug transactions. Polymedia theory suggests that people use different media to manage their social relationships, 'choosing' appropriate channels or platforms based on platform features and the social context of the relationship. This paper uses polymedia theory to explore how buyers and sellers navigate platform 'choice' for drug trading, and how this bears similarities to the ways in which they move between different platforms in their daily lives. We conducted anonymous online interviews with thirty-three people who buy and/or sell drugs via social media and encrypted messaging apps in New Zealand to explore the factors shaping their selection of platforms for drug transactions. Our findings highlight the importance of the relationship between the buyer and seller in shaping how interviewees weighted the relative importance of platform security and convenience. Though more commercial drug sellers exercised considerable influence in directing buyers of drugs towards a given platform, this pattern was less characteristic of how platform 'choice' was navigated in contexts of drug supply between friends. In social supply contexts, platform 'choices' were often not explicitly made, but rather exchanges were channelled through platforms already in use within the social group. We highlight the tensions that arise between seller preferences for a more secure platform and buyer preferences for greater convenience in contexts of friendship. Our findings highlight the importance of understanding social media drug market engagement as shaped by broader patterns of social media engagement, and the distinctions between different social contexts and personal relationships, consistent with polymedia theory.


Formation of oral and pharyngeal dentition in teleosts depends on differential recruitment of retinoic acid signaling.
One of the goals of evolutionary developmental biology is to link specific adaptations to changes in developmental pathways. The dentition of cypriniform fishes, which in contrast to many other teleost fish species possess pharyngeal teeth but lack oral teeth, provides a suitable model to study the development of feeding adaptations. Here, we have examined the involvement of retinoic acid (RA) in tooth development and show that RA is specifically required to induce the pharyngeal tooth developmental program in zebrafish. Perturbation of RA signaling at this stage abolished tooth induction without affecting the development of tooth-associated ceratobranchial bones. We show that this inductive event is dependent on RA synthesis from aldh1a2 in the ventral posterior pharynx. Fibroblast growth factor (FGF) signaling has been shown to be critical for tooth induction in zebrafish, and its loss has been associated with oral tooth loss in cypriniform fishes. Pharmacological treatments targeting the RA and FGF pathways revealed that both pathways act independently during tooth induction. In contrast, we find that in Mexican tetra and medaka, species that also possess oral teeth, both oral and pharyngeal teeth are induced independently of RA. Our analyses suggest an evolutionary scenario in which the gene network controlling tooth development obtained RA dependency in the lineage leading to the cypriniforms. The loss of pharyngeal teeth in this group was cancelled out through a shift in aldh1a2 expression, while oral teeth might have been lost ultimately due to deficient RA signaling in the oral cavity.


Effect of Atorvastatin Therapy on the Level of CD34+CD133+CD309+ Endothelial Progenitor Cells in Patients with Coronary Heart Disease.
In 58 patients with coronary heart disease, the count of CD34+CD133+CD309+ endothelial progenitor cells in the blood was determined and the dynamics of the content of endothelial progenitor cells, angiogenic growth factors, and lipid parameters over 3 months of atorvastatin therapy was analyzed. Atorvastatin was administered in daily doses of 10 mg (26 patients) and 40 mg (32 patients). Control group comprised 15 healthy volunteers. In patients with coronary heart disease, the count of endothelial progenitor cells was lower by 4 times, the level of VEGF was higher by 52%, and the level of endostatin was lower by 13% than in healthy volunteers. Atorvastatin therapy significantly reduced the levels of VEGF (by 11%), C-reactive protein (by 26%), total cholesterol (by 30%), LDL cholesterol (by 35%), and triglycerides (by 18%); the levels of endostatin, MCP-1, and HDL cholesterol remained unchanged. The count of endothelial progenitor cells increased significantly by 72% irrespectively on the statin dose, but the changes were more pronounced in patients with lower initial endothelial progenitor cell counts and in patients with more drastic decrease in LDL cholesterol.


Arrhythmias in the COVID-19 patient.
Coronavirus disease 2019 (COVID-19) has encompassed the globe since it was first observed just under 2 years ago. Although the disease is predominantly a respiratory illness, there have been observed complications throughout the various organ systems. Namely, cardiovascular complications, and, more specifically, arrhythmic complications have been described throughout the pandemic in patients with COVID-19. Management of atrial arrhythmias, ventricular arrhythmias, and bradyarrhythmias in patients with COVID-19 infection has been largely guided by our prior experience in the management of these arrhythmias in similar patient populations without infection. However, this review aims to highlight the specific considerations as they pertain to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the various arrhythmic manifestations observed with this disease.


Attitudes towards depression of Argentinian, Chilean, and Venezuelan healthcare professionals using the Spanish validated version of the revised depression attitude questionnaire (SR-DAQ).
The beliefs and attitudes of physicians toward depression may predict whether they are supportive or avoidant of patients diagnosed with this condition. Describing the attitudes toward depression of Argentinian, Chilean, and Venezuelan healthcare professionals could be a valuable tool for understanding the Latin American perspective on depression recognition, management, and prevention. A cross-sectional study was conducted among healthcare professionals in Argentina, Chile, and Venezuela using the Spanish validated version of the revised depression attitude questionnaire (R-DAQ). The questionnaire was collected online from August to November 2021, in a quota-based sample of 1759 health professionals (the final analytical sample is 1234). Descriptive data analyses were performed using STATA version 16 statistical software. Depression was considered a disease that anyone could suffer by 90% of the respondents. However, 70% of professionals answered that they feel more comfortable dealing with physical illness than mental illness. Furthermore, the findings show that a quarter of the participants in the study believed that either medical treatment (28.6%) or psychosocial approach (<20%) were ineffective tools for people suffering from depression. Findings also show that depression is seen as a more natural part of life by Argentinian professionals and men. Finally, psychologists and psychiatrists are most likely to treat depression as any other physical disease. Medical providers who routinely perform surgeries are not as likely to know how to treat depression or consider it an actual disease. Healthcare professionals in Argentina, Chile, and Venezuela have varying attitudes toward depression. While they recognize depression as a disease on the same level as other physical diseases, most do not know how to treat it. The findings point to the need for these countries to promote the training of healthcare workers in areas such as depression diagnosis, treatment, and social interventions.


Phage typing set for E1, E2, E3, and E4 salmonellae.
Eighteen common serotypes representative of group E(1), E(2), E(3), and E(4)Salmonella were characterized using a single set of phages.


Neonatal hypertension and thrombosis of the ductus arteriosus.
In a case of neonatal hypertension, radiographic findings showed multiple thromboembolism from the ductus arteriosis diverticulum. Hypertension was well controlled by captopril during the neonatal period. The long-term follow-up of 8 years with normal cardiovascular and renal function indicates a good prognosis for acquired renovascular neonatal hypertension.


Lower plasma total tau in adolescent psychosis: Involvement of the orbitofrontal cortex.
Schizophrenia is thought to be a neurodevelopmental disorder with neuronal migration, differentiation and maturation disturbances. Tau is a microtubule-associated protein with a crucial role in these processes. Lower circulating tau levels have been reported in adults with schizophrenia, but this association has not been investigated in adolescent psychosis. We aimed to test the hypotheses that a) adolescents with early-onset psychosis (EOP; age of onset <18 years) display lower plasma tau concentrations compared to healthy controls, and b) among patients with psychosis, tau levels are linked to structural brain measures associated with the microtubule-associated tau (MAPT) gene and psychosis. We included 37 adolescent patients with EOP (mean age 16.4 years) and 59 adolescent healthy controls (mean age 16.2 years). We investigated putative patient-control differences in plasma total tau concentrations measured by a Single molecule array (Simoa) immunoassay. We explored the correlations between tau and selected structural brain measures based on T1-weighted MRI scans processed in FreeSurfer v6.0. We found significantly lower plasma tau concentrations in patients compared to healthy controls (p = 0.017, partial eta-squared = 0.061). Tau was not associated with antipsychotic use or the antipsychotic dosage. Among patients but not healthy controls, tau levels were positively correlated with the cortical orbitofrontal surface area (p = 0.013, R-squared = 0.24). The results are suggestive of a tau-related neurodevelopmental disturbance in adolescent psychosis.


Assessment of non-financial incentives for volunteer community health workers - the case of Wukro district, Tigray, Ethiopia.
Volunteer community health workers (VCHW) are health care providers who are trained but do not have any professional certification. They are intended to fill the gap for unmet curative, preventative, and health promotion health needs of communities. This study aims to investigate the non-financial incentives for VCHWs and factors affecting their motivation. A cross-sectional quantitative study was performed from February to March 2013. A total of 400 randomly selected female VCHWs were included using the district health office registers. Finally, multivariate logistic regression was used to determine the independent predictors of VCHW motivation. Significant numbers (48%) of study participants have mentioned future training as a major non-financial incentive. Age between 20 and 36 years old (adjusted odds ratio (AOR) = 1.45, 95% CI = 1.18, 2.13), married VCHWs (AOR = 3.84, 95% CI = 1.73, 5.02), presence of children under five years old (AOR = 0.2, 95% CI = 0.09, 0.71), allowing volunteer withdrawal (AOR = 1.35, 95% CI = 1.06, 2.47), and establishment of a local endowment fund for community health workers after they left volunteerism (AOR = 1.11, 95% CI = 1.05, 1.91) are all factors associated with VCHW motivation. Future training was mentioned as the prime non-financial incentive. Age, marital status, presence of children under five, allowing volunteer withdrawal, and establishment of a local endowment fund were identified as the independent predictors of motivation. Therefore, considering a non-financial incentive package, including further training and allowing volunteer withdrawal, would be helpful to sustain volunteerism.


Review article: artificial nutritional support for improved patient care.
Malnutrition is common and undiagnosed in the majority of affected hospital patients; it is associated with impaired organ function, morbidity, and increased length of hospital stay. Artificial nutritional support in malnourished patients leads to improvement in nutritional status and clinical outcome. Nutritional support is required in malnourished patients, patients who are unable to take normal diet and patients with intestinal failure. Gastroenterologists are required to supervise patients with intestinal failure, to insert endoscopic feeding devices, and increasingly to participate in, or lead, nutritional support teams. Major developments in nutrient delivery have included percutaneous endoscopic feeding devices, the recognition that enteral feeding is possible in patients with gastric stasis, and that nutrient needs can be met by peripheral parenteral nutrition. There is much interest in the use of new substrates, or substrates delivered in pharmacological doses such as glutamine and arginine, to manipulate the response to disease. Many hospitals lack an organized approach to artificial nutritional support. Patients continue to suffer from a lack of treatment or the consequences of inappropriate or inadequate treatment. This article reviews the current status of artificial nutritional support and provides guidelines for patient management.


Low psoas muscle index associates with long-term mortality in cirrhosis: construction of a nomogram.
To develop a nomogram incorporating indicator of muscle waste to prognosticate long-term mortality in liver cirrhosis (LC), and identify the prognostic impact of psoas muscle index (PMI). A total of 251 LC patients who underwent computed tomography were included in this study. Multiple Cox regression was performed, and sex-specific nomogram models incorporating PMI were developed. The utility of the proposed models were evaluated by Harrell's concordance index (C-index), calibration curve and decision curve analysis. X-tile was used to determine optimal cutpoint for stratifying subjects with distinct outcomes. Subgroup analysis was implemented in terms of age and MELD score. The correlation between PMI and gait speed was also evaluated. On multiple analysis, independent predictors for 3-year all-cause mortality were age, BMI, PMI and MELD for males, and age, PMI and MELD for females. Both nomogram models gave rise to moderately strong discrimination, with a C-index of 0.792 (95% CI: 0.723-0.861) in males and 0.715 (95% CI: 0.637-0.793) in females, respectively. The calibration curve implied predicted survival corresponding optimally with the actual outcomes. The proposed models were feasible in clinical settings based on decision curve analysis. On subgroup analysis, PMI might confer valid predictive value on LC patients with MELD <15. Moreover, a definitely positive correlation between PMI and gait speed was revealed. Our proposed nomogram embedding PMI rendered an individualized predictive tool for long-term mortality in LC. The diminishing value of PMI is likely indicative of muscle dysfunction.


The structure of the aflatoxin B1-DNA adduct at N7 of guanine. Theoretical intercalation and covalent adduct models.
Two theoretical models are proposed for the conformational structure of both intercalated and covalent adduct complexes of aflatoxin B1, designated AFB1, with N7 of guanine of DNA. The covalent adduct model requires the DNA to kink a minimum of 39 degrees about the covalent site of the C8 and N7 atoms comprising the bond of the covalent complex. The preference of AFB1 for specific G bases within a sequence of GC content followed that of experimental studies with the added feature that for binding to the third G base of a tetramer sequence from the 3'-end, the AFB1 displayed enhanced binding at the 3' site of the targeted guanosine. Binding of AFB1 to the second G base of a tetramer sequence from the 3'-end leads to preference for a 5' site of the targeted guanosine. Inhibition of AFB1's interaction with the targeted DNA in the presence of intercalated ethidium bromide is explained by these proposed models.


Behavioral effects of different contraceptive methods and HIV acquisition: an ancillary study of the ECHO randomized trial.
The ECHO trial randomised 7829 women to depot medroxyprogesterone acetate (DMPA-IM), the copper intrauterine device (IUD) and the levonorgestrel (LNG) implant (1:1:1) and found no clear difference in HIV incidence between these three groups. We have previously hypothesized that oligo-amenorrhoea induced by DMPA-IM may have a protective effect on HIV acquisition. The aim of this ancillary study was to assess the effects of DMPA-IM, the IUD and the LNG implant on menstrual symptoms and sexual behavior and to correlate these with HIV acquisition. At the Effective Care Research Unit (ECRU) in South Africa, of 615 women already randomised to DMPA-IM, the copper IUD and the LNG implant (1:1:1) 552 agreed to participate. Participants completed a 28-day symptom and behavior diary following their one-month ECHO trial visit and returning it at their 3-month follow-up visit. HIV acquisition data were retrieved from ECHO trial records. Of 552 women enrolled on the ancillary study, 390 (70.6%) completed their daily diary; 130, 133, and 127 received DMPA-IM, IUD, and LNG implant, respectively. Thirty-three (5.9%) of these women acquired HIV. Women on the progestin-only contraceptives were more likely to experience amenorrhoea, as expected, and were less likely to have intra-menstrual coitus than IUD users (p < 0.001 for DMPA-IM vs IUD and p = 0.002 for implant vs IUD). Overall coital frequency was highest and condom usage lowest among DMPA-IM users. Intra-menstrual coitus correlated positively, and duration of menstruation correlated negatively, with HIV acquisition, although these effects were not statistically significant (p = 0.09 and p = 0.079, respectively). Findings support the hypothesis that oligo-amenorrhoea and the associated reduced intra-menstrual coitus may mitigate the potential for an increased biological risk of HIV acquisition with DMPA-IM but more evidence is needed. Study registration number PACTR201706001651380.


Results From a Randomized, Open-Label, Crossover Study Evaluating the Effect of the Aldosterone Synthase Inhibitor Baxdrostat on the Pharmacokinetics of Metformin in Healthy Human Subjects.
Due to the high comorbidity of diabetes and hypertension, co-administration of metformin with anti-hypertensive drugs is likely. Baxdrostat is an aldosterone synthase inhibitor in development for the potential treatment of hypertension. In vitro data indicated that baxdrostat inhibits the multidrug and toxin extrusion 1 (MATE1) and MATE2-K renal transporters. Metformin is a MATE substrate, so this study assessed potential effects of baxdrostat on the pharmacokinetics of metformin. Twenty-seven healthy volunteers received 1000 mg metformin alone and 1000 mg metformin in the presence of 10 mg baxdrostat in a randomized, crossover manner. Each treatment was separated by 10 or more days. Blood and urine samples were collected over a 3-day period after each treatment to measure plasma and urine concentrations of metformin. Safety was assessed by adverse events (AEs), physical examinations, electrocardiograms, vital signs, and clinical laboratory evaluations. There were no deaths, serious AEs, discontinuations due to treatment-emergent AEs, or noteworthy increases in AEs with either treatment, indicating that metformin and baxdrostat were well-tolerated when co-administered. Baxdrostat did not significantly affect plasma concentrations or renal clearance of metformin. The results of this study suggest that diabetic patients with hypertension receiving both metformin and baxdrostat are unlikely to require dose adjustment. ClinicalTrials.gov identifier no. NCT05526690.


The regulatory mechanism of neuromedin S on luteinizing hormone in pigs.
Neuromedin S (NMS) has been implicated in the regulation of luteinizing hormone (LH) secretion. However, the regulatory mechanism of NMS on LH in pigs remains unexplored. In the present study, we confirmed the hypothesis that the effect of NMS on LH could be mediated via hypothalamic melanocyte-stimulating hormones (MSH) neurons of ovariectomized pigs. In an immunohistological experiment, NMS receptor NMU2R-positive neurons were found in the paraventricular nucleus of hypothalamus, widely distributed in the anterior pituitary, and sparsely observed in the posterior pituitary. We also found that serum LH level was declined at between 12 and 60 min with the lowest level at 24 min after NMS injection. The decreased LH secretion induced by NMS could be completely abolished by pretreatment with melanocortin receptor-4 antagonist SHU9119, while a signal injection of 1.0 nM SHU9119 per se did not affect the serum LH level. Real time quantitative RT-PCR results showed that the expression of GnRH and LH mRNAs were down-regulated by NMS treatment, but their reduction was restored to normal level by SHU9119 treatments. The expression of NMU2R and PR mRNAs were up-regulated by NMS treatment, but their effects were blocked by SHU9119 treatments. The expression of the estrogen receptor mRNA in the pig hypothalamus and pituitary was unchanged under the NMS and SHU9119+NMS treatments. In summary, all results suggest that the inhibitory effect of NMS on LH is at least in part through its receptor NMU2R and mediated via MSH neurons in hypothalamus-pituitary axis of ovariectomized pigs.


The evolution of practice changes in the use of special observations.
In acute psychiatric settings, it is common practice to increase the intensity of observations of patients who present with self-injurious thoughts, who are at risk of injuring others, or who exhibit behaviors that adversely impact the overall milieu. These intense observations are intrusive and may result in untoward stimulation of the patient. Nurses at an urban academic medical center addressed the problem of intrusive and overstimulating levels of observation by developing two practice changes using intuitive knowledge combined with input from current nursing literature. The first change was designed to move from observation to engagement. The second change was designed to decrease patient agitation related to intense observation. This article discusses the potential adverse consequences associated with the use of intense levels of observation and describes two protocols that have contributed to a reduction in the use of seclusion and restraints, as well as staff members' reported perceptions of feeling safer and experiencing improved job satisfaction.


Evaluation of objective similarity measures for selecting similar images of mammographic lesions.
The purpose of this study was to investigate four objective similarity measures as an image retrieval tool for selecting lesions similar to unknown lesions on mammograms. Measures A and B were based on the Euclidean distance in feature space and the psychophysical similarity measure, respectively. Measure C was the sequential combination of B and A, whereas measure D was the sequential combination of A and B. In this study, we selected 100 lesions each for masses and clustered microcalcifications randomly from our database, and we selected five pairs of lesions from 4,950 pairs based on all combinations of the 100 lesions by use of each measure. In two observer studies for 20 mass pairs and 20 calcification pairs, six radiologists compared all combinations of 20 pairs by using a two-alternative forced-choice method to determine the subjective similarity ranking score which was obtained from the frequency with which a pair was considered as more similar than the other 19 pairs. In both mass and calcification pairs, pairs selected by use of measure D had the highest mean value of the average subjective similarity ranking scores. The difference between measures D and A (P = 0.008 and 0.024), as well as that between measures D and B (P = 0.018 and 0.028) were statistically significant for masses and microcalcifications, respectively. The sequential combination of the objective similarity measure based on the Euclidean distance and the psychophysical similarity measure would be useful in the selection of images similar to those of unknown lesions.


Dairy consumption and patterns of mortality of Australian adults.
Dairy foods contain various nutrients that may affect health. We investigated whether intake of dairy products or related nutrients is associated with mortality due to cardiovascular disease (CVD), cancer and all causes. We carried out a 16-year prospective study among a community-based sample of 1529 adult Australians aged 25-78 years at baseline. Habitual intakes of dairy products (total, high/low-fat dairy, milk, yoghurt and full-fat cheese), calcium and vitamin D were estimated as mean reported intake using validated food frequency questionnaires (FFQs) self-administered in 1992, 1994 and 1996. National Death Index data were used to ascertain mortality and cause of death between 1992 and 2007. Hazard ratios (HRs) were calculated using Cox regression analysis. During an average follow-up time of 14.4 years, 177 participants died, including 61 deaths due to CVD and 58 deaths due to cancer. There was no consistent and significant association between total dairy intake and total or cause-specific mortality. However, compared with those with the lowest intake of full-fat dairy, participants with the highest intake (median intake 339 g/day) had reduced death due to CVD (HR: 0.31; 95% confidence interval (CI): 0.12-0.79; P for trend=0.04) after adjustment for calcium intake and other confounders. Intakes of low-fat dairy, specific dairy foods, calcium and vitamin D showed no consistent associations. Overall intake of dairy products was not associated with mortality. A possible beneficial association between intake of full-fat dairy and cardiovascular mortality needs further assessment and confirmation.


Circulating bacterial signature is linked to metabolic disease and shifts with metabolic alleviation after bariatric surgery.
The microbiome has emerged as an environmental factor contributing to obesity and type 2 diabetes (T2D). Increasing evidence suggests links between circulating bacterial components (i.e., bacterial DNA), cardiometabolic disease, and blunted response to metabolic interventions. In this aspect, thorough next-generation sequencing-based and contaminant-aware approaches are lacking. To address this, we tested whether bacterial DNA could be amplified in the blood of subjects with obesity and high metabolic risk under strict experimental and analytical control and whether a putative bacterial signature is related to metabolic improvement after bariatric surgery. Subjects undergoing bariatric surgery were recruited into sex- and BMI-matched subgroups with (n = 24) or without T2D (n = 24). Bacterial DNA in the blood was quantified and prokaryotic 16S rRNA gene amplicons were sequenced. A contaminant-aware approach was applied to derive a compositional microbial signature from bacterial sequences in all subjects at baseline and at 3 and 12 months after surgery. We modeled associations between bacterial load and composition with host metabolic and anthropometric markers. We further tested whether compositional shifts were related to weight loss response and T2D remission. Lastly, bacteria were visualized in blood samples using catalyzed reporter deposition (CARD)-fluorescence in situ hybridization (FISH). The contaminant-aware blood bacterial signature was associated with metabolic health. Based on bacterial phyla and genera detected in the blood samples, a metabolic syndrome classification index score was derived and shown to robustly classify subjects along their actual clinical group. T2D was characterized by decreased bacterial richness and loss of genera associated with improved metabolic health. Weight loss and metabolic improvement following bariatric surgery were associated with an early and stable increase of these genera in parallel with improvements in key cardiometabolic risk parameters. CARD-FISH allowed the detection of living bacteria in blood samples in obesity. We show that the circulating bacterial signature reflects metabolic disease and its improvement after bariatric surgery. Our work provides contaminant-aware evidence for the presence of living bacteria in the blood and suggests a putative crosstalk between components of the blood and metabolism in metabolic health regulation.


{4-[5-(4-tert-Butyl-phen-yl)-1,3,4-oxa-diazol-2-yl]phen-yl}methanol.
In the title compound, C(19)H(20)N(2)O(2), the 1,3,4-oxadiazole ring is almost coplanar with the two neighboring benzene rings [dihedral angles = 3.76 (4) and 5.49 (4)°]. In the crystal, mol-ecules are connected by strong inter-molecular O-H⋯N hydrogen bonds, forming chains parallel to the c axis.


CT attenuation numbers in the lumbar spine and their utility in diagnosing disc disease.
Normal CT attenuation values for various structures in the lumbar spine were obtained on several CT scanners. The wide range of normal makes using absolute CT numbers unreliable. The utility and pitfalls of using CT attenuation numbers in the lumbar spine are discussed and several examples are illustrated. CT numbers used as absolute values can be misleading, whereas, when used as relative values for comparison with other structures, they can be quite valuable.


Cocaine-induced adaptations in cellular redox balance contributes to enduring behavioral plasticity.
Impaired glutamate homeostasis in the nucleus accumbens has been linked to cocaine relapse in animal models, and results in part from cocaine-induced downregulation of the cystine-glutamate exchanger. In addition to regulating extracellular glutamate, the uptake of cystine by the exchanger is a rate-limiting step in the synthesis of glutathione (GSH). GSH is critical for balancing cellular redox in response to oxidative stress. Cocaine administration induces oxidative stress, and we first determined if downregulated cystine-glutamate exchange alters redox homeostasis in rats withdrawn from daily cocaine injections and then challenged with acute cocaine. Among the daily cocaine-induced changes in redox homeostasis were an increase in protein S-glutathionylation and a decrease in expression of GSH-S-transferase pi (GSTpi). To mimic reduced GSTpi, a genetic mouse model of GSTpi deletion or pharmacological inhibition of GSTpi by administering ketoprofen during daily cocaine administration was used. The capacity of cocaine to induce conditioned place preference or locomotor sensitization was augmented, indicating that reducing GSTpi may contribute to cocaine-induced behavioral neuroplasticity. Conversely, an acute cocaine challenge after withdrawal from daily cocaine elicited a marked increase in accumbens GSTpi, and the expression of behavioral sensitization to a cocaine challenge injection was inhibited by ketoprofen pretreatment; supporting a protective effect by the acute cocaine-induced rise in GSTpi. Together, these data indicate that cocaine-induced oxidative stress induces changes in GSTpi that contribute to cocaine-induced behavioral plasticity.


[Histological and molecular alterations in inflammatory myopathies].
The histological findings in muscle biopsies of inflammatory myopathies have been divided into 2 groups: A) Endomisial infiltrates mainly by T CD8+, CD4+ and macrophages and B) Perivascular infiltrates by CD4+, B cells and macrophages. The first kind of infiltrate suggests an immune reaction against muscle fibers very common in PM and inclusion body myositis, On the other hand the perivascular infiltrate is a hallmark of DM. It has ben shown that autoantigens related with myopathies such as Mi-2, Jo-1, OJ, PL12, Ku, PM/Scl are able to suffer proteolytic cleavage by granzyme B and other stimulus induced by cytotoxic T cells. In this chapter we will review the histological and molecular findings of inflammatory myopathies but we will also discuss a special group of myopathies related to the presence of antibodies against the SRP complex, in particular the SRP72 and SRP54 antibodies, which are associated with a poor prognosis and clinical outcome and present an inadequate response to conventional treatment.


A theoretical study of in vivo lesion repair using a controlled-release device.
A theoretical model of lesion remineralization predicts that in vivo caries repair can be effected in a five-day period by means of a controlled- and sustained-release device containing calcium, phosphate, and fluoride. The calculations detail an 80% repair before the remineralization process stops. However, the fluoridated hydroxyapatite formed is calculated to be about 20% more resistant to future attack than is hydroxyapatite, making effective repair complete. Optimal flux (W) conditions for repair of 100 microns lesions are WCa = 1.0 X 10(-6) kg/m2s, stoichiometric phosphate, and WF = 2.0 X 10(-9) kg/m2s.


Determinant of Covariance Matrix Model Coupled with AdaBoost Classification Algorithm for EEG Seizure Detection.
Experts usually inspect electroencephalogram (EEG) recordings page-by-page in order to identify epileptic seizures, which leads to heavy workloads and is time consuming. However, the efficient extraction and effective selection of informative EEG features is crucial in assisting clinicians to diagnose epilepsy accurately. In this paper, a determinant of covariance matrix (Cov-Det) model is suggested for reducing EEG dimensionality. First, EEG signals are segmented into intervals using a sliding window technique. Then, Cov-Det is applied to each interval. To construct a features vector, a set of statistical features are extracted from each interval. To eliminate redundant features, the Kolmogorov-Smirnov (KST) and Mann-Whitney U (MWUT) tests are integrated, the extracted features ranked based on KST and MWUT metrics, and arithmetic operators are adopted to construe the most pertinent classified features for each pair in the EEG signal group. The selected features are then fed into the proposed AdaBoost Back-Propagation neural network (AB_BP_NN) to effectively classify EEG signals into seizure and free seizure segments. Finally, the AB_BP_NN is compared with several classical machine learning techniques; the results demonstrate that the proposed mode of AB_BP_NN provides insignificant false positive rates, simpler design, and robustness in classifying epileptic signals. Two datasets, the Bern-Barcelona and Bonn datasets, are used for performance evaluation. The proposed technique achieved an average accuracy of 100% and 98.86%, respectively, for the Bern-Barcelona and Bonn datasets, which is considered a noteworthy improvement compared to the current state-of-the-art methods.


COVID-19: Is There a Link between Alcohol Abuse and SARS-CoV-2-Induced Severe Neurological Manifestations?
For the first time, it is shown that severe COVID-19 associated genes (CCR2, DPP9, HSPA1L, TYK2, OAS1, ACE2, and TMPRSS2) were also upregulated in the brain tissue of chronic alcoholics. It is proposed that chronic alcohol abuse should be considered as an important factor in COVID-19-associated neurological complications.


Differential effects of triacylglycerol positional isomers containing n-3 series highly unsaturated fatty acids on lipid metabolism in C57BL/6J mice.
The present study investigated the effects of binding position of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to triacylglycerol (TAG) on lipid metabolism in C57BL/6J mice. Mice were treated with pure TAG positional isomers, including 1,2(2,3)-dipalmitoyl-3(1)-eicosapentaenoyl glycerol, 1,3-dipalmitoyl-2-eicosapentaenoyl glycerol, 1,2(2,3)-dipalmitoyl-3(1)-docosahexaenoyl glycerol, and 1,3-dipalmitoyl-2-docosahexaenoyl glycerol. Compared to DHA bound to the α-position of TAG, DHA bound to the β-position more effectively inhibited fatty acid synthetic enzymes and cholesterol-metabolism enzymes and thus reduced TAG and cholesterol concentrations in the serum and liver. EPA bound to the α-position of TAG, but not EPA bound to the β-position of TAG, significantly decreased hepatic cholesterol concentrations. Additionally, EPA bound to the α-position of TAG increased the ratio of PGI2 to TXA2 to a higher degree than EPA bound to the β-position. These results suggested that the binding position of EPA and DHA to TAG affected TAG and cholesterol metabolism as well as eicosanoid production in C57BL/6J mice.


Index and ring finger ratio--a morphologic sex determinant in South-Indian children.
To investigate the sexual dimorphism of index and ring finger ratio in South Indian children. The index finger length (IFL) and the ring finger length (RFL) were measured in 350 subjects aged between 2 and 12 years using a steel measuring tape. The index and ring finger ratio was computed by dividing index finger length by ring finger length. The data obtained were analyzed statistically using SPSS, version 11.0. Mean RFL was greater than mean IFL in both males and females. The mean ring finger length was longer in males than females and mean index finger length longer in females than males. However, these sex differences observed for index and ring finger length were not significant in both hands. Statistically significant sex differences were observed from the derived index and ring finger ratio. The mean index and ring finger ratio was found to be higher in females than males. Significant correlation was found between age and index and ring finger lengths. Index and ring finger ratio however, did not show any significant correlation with age. This study suggests that among South-Indian children, the index and ring finger ratio of 0.97 and less is indicative of male, and a ratio of more than 0.97 is indicative of female sex. The ratio can be a useful sex indicator irrespective of the age of the individual.


Prenatal retinoic acid treatment upregulates late gestation lung protein 1 in the nitrofen-induced hypoplastic lung in late gestation.
Pulmonary hypoplasia (PH), the leading cause of mortality in congenital diaphragmatic hernia (CDH), is associated with arrested alveolarization. Late gestation lung protein 1 (LGL1) plays a crucial role in the regulation of alveolarization. Inhibition of LGL1 impairs alveolar maturation in fetal rat lungs. LGL1 heterozygotus knockout mice display delayed lung maturation. It is well known that prenatal administration of retinoic acid (RA) stimulates alveologenesis in nitrofen-induced PH. In vitro studies have reported that RA is a key modulator of LGL1 during alveologenesis. We hypothesized, that pulmonary gene expression of LGL1 is downregulated in the late stage of lung development, and that prenatal administration of RA upregulates pulmonary LGL1 expression in the nitrofen CDH model. Pregnant rats were exposed to nitrofen on day 9 (D9) of gestation. RA was given intraperitoneally on D18, D19 and D20. Fetal lungs were dissected on D21 and divided into control, control + RA, CDH and CDH + RA group. Expression levels of LGL1 were determined using RT-PCR and immunohistochemistry. On D21, LGL1 relative mRNA expression levels were significantly downregulated in CDH group compared to controls. After RA treatment, gene expression levels of LGL1 were significantly upregulated in CDH + RA and control + RA compared to CDH group. Immunohistochemical studies confirmed these results. Downregulation of pulmonary LGL1 gene expression in the late stage of lung development may interfere with normal alveologenesis. Upregulation of LGL1 pulmonary gene expression after RA treatment may promote lung growth by stimulating alveologenesis in the nitrofen CDH model.


Calling situated: a survey among medical students supplemented by a qualitative study and a comparison with a surveyed sample of physicians.
Calling within the medical context receives growing academic attention and empirical research has started to demonstrate its beneficial effects. The purpose of this study is to investigate what motivates students to enter medical school and what role calling may play (i), to evaluate if calling influences the way in which they experience their studies (ii), and to compare medical students' experience of calling with those of physicians. A questionnaire survey was distributed among medical students (N = 1048; response rate above 60%) of the University of Lausanne in Switzerland. It was supplemented by a group discussion between bachelor medical students (N = 8) and senior physicians (N = 4), focusing on different facets of calling. An existing data set of a survey among physicians, addressing calling with the same questionnaire, was used to compare students' and physicians' attitudes towards calling. Survey data were analyzed with the habitual statistical procedures for categorical and continuous variables. The group discussion was analyzed with thematic analysis. The survey showed that experiencing calling is a motivational factor for study choice and influences positively choice consistency. Students experiencing calling differed from those who did not: they attributed different definitions to calling, indicated more often prosocial motivational factors for entering medical school and perceived the learning context as less burdensome. The analysis of the group discussion revealed that the concept of calling has a fluid definition. It was conceived as having the characteristics of a double-edged sword and as originating from within or outside or from a dialectic interplay between the inner and outer world. Finally, calling is experienced less often by physicians than by medical students, with a decreasing prevalence as the immersion in the clinical years of the study of medicine progresses. Calling plays an important role in study choice and consistency of medical students. Given its relevance for medical students and its ramifications with the learning context, calling should become a topic of the reflexive parts of the medical curriculum. We critically discuss the role played by calling for medical students and provide some perspectives on how calling could be integrated in the reflection and teaching on physicianhood.


Graphene oxide and its derivatives as potential Ovchinnikov ferromagnets.
Ovchinnikov postulated the possibility of ferromagnetism in organic compounds having a mixed density ofsp3andsp2carbon atoms. Such systems provide an interesting avenue for exploring magnetism in the absence of the quintessentiald- andf-block elements as ingredients. As graphene oxide (GO) and its derivatives naturally possess a mixture ofsp3andsp2carbon atoms, it is pertinent to look at them as potential candidates for Ovchinnikov ferromagnetism. We have looked at the evolution of magnetic property in a series of GO samples with a gradual increase in the degree of oxidation and hence thesp3/sp2fraction. Starting with a GO sample with a highsp3/sp2ratio, we utilize chemical reduction technique to prepare another set of reduced graphene oxide (rGO) samples. Magnetization measurements on these samples further illustrate the importance ofsp3/sp2fraction on magnetic behavior suggesting GO and its derivatives as a potential Ovchinnikov ferromagnet candidate. The evolution of magnetic moment withsp3/sp2carbons can be utilized in carbon based spintronic applications.


Vulvar endometriosis in surgical scar after excision of the Bartholin gland: report of a case.
Endometriosis is a common gynecologic disease characterized by growth of endometrial glands and stroma outside the endometrium. Implants are most commonly found in the pelvis but can occur in many other sites. Vulvar involvement of endometriosis is extremely rare. A case of vulvar endometriosis is presented. Endometriosis was infiltrating the subcutaneous scar tissue of left labia minora after cystectomy of Bartholin gland for abscess that has recurred several times despite office-based treatment.


Metal-organic framework derived hollow CoFe@C composites by the tunable chemical composition for efficient microwave absorption.
Controlling the composition and microstructure of nanomaterials is still a significant challenge in developing high-performance microwave absorption (MA) materials. Herein, metal-organic framework (MOF)-derived hollow CoFe@C nanoboxes are designed and prepared through the facile regulating the mass ratios of ZIF-67/PFC and a thermal annealing treatment. The CoFe@C composite can achieve an excellent MA performance, which have two high reflection loss (RL) values at different thickness. A RL value of -31.0 dB is obtained at 11.84 GHz with a matching thickness of 2.4 mm, and a RL value can reach -44.1 dB (4.08 GHz) at a matching thickness of 5.8 mm, and a correspondingly wide absorbing bandwidth (5.20 GHz, from 9.7 to 14.9 GHz) is simultaneously obtained at a matching thickness of 2.3 mm. The magnetic loss, interfacial polarization and hollow structure are the main reasons for their excellent MA capability. This work provides a research idea for the development of the efficient MOF-based MA materials in practical application.


Insulin and endocannabinoids in the mesolimbic system.
Easy access to palatable food and an abundance of food-related cues exacerbate non-homeostatic feeding. The metabolic and economical sequelae of non-homeostatic feeding outweigh those of homeostatic feeding and contribute significantly to the global obesity pandemic. The mesolimbic dopamine system is the primary central circuit that governs the motivation to consume food. Insulin and endocannabinoids (eCBs) are two major, presumably opposing, players in regulating homeostatic and non-homeostatic feeding centrally and peripherally. Insulin is generally regarded as a postprandial satiety signal, whereas eCBs mainly function as pre-prandial orexinergic signals. In this review, we discuss the effects of insulin and eCB-mediated actions within the mesolimbic pathways. We propose that insulin and eCBs have regional- and time course-dependent roles. We discuss their mechanisms of actions in the ventral tegmental area and nucleus accumbens, as well as how their mechanisms converge to finely tune dopaminergic activity and food intake.


Ribosomal RNA genes of Saccharomyces cerevisiae. I. Physical map of the repeating unit and location of the regions coding for 5 S, 5.8 S, 18 S, and 25 S ribosomal RNAs.
The organization of the ribosomal DNA repeating unit from Saccharomyces cerevisiae has been analyzed. A cloned ribosomal DNA repeating unit has been mapped with the restriction enzymes Xma 1, Kpn 1, HindIII, Xba 1, Bgl I + II, and EcoRI. The locations of the sequences which code for 5 S, 5.8 S, 18 S, and 25 S ribosomal RNAs have been determined by hybridization of the purified RNA species with restriction endonuclease generated fragments of the repeating unit. The position of the 5.8 S ribosomal DNA sequences within the repeat was also established by sequencing the DNA which codes for 83 nucleotides at the 5' end of 5.8 S ribosomal RNA. The polarity of the 35 S ribosomal RNA precursor has been established by a combination of hybridization analysis and DNA sequence determination and is 5'-18 S, 5.8 S, 25 S-3'.


The crystal structure of the signature domain of cartilage oligomeric matrix protein: implications for collagen, glycosaminoglycan and integrin binding.
Cartilage oligomeric matrix protein (COMP), or thrombospondin-5 (TSP-5), is a secreted glycoprotein that is important for growth plate organization and function. Mutations in COMP cause two skeletal dysplasias, pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (EDM1). In this study, we determined the structure of a recombinant protein that contains the last epidermal growth factor repeat, the type 3 repeats and the C-terminal domain (CTD) of COMP to 3.15-A resolution limit by X-ray crystallography. The CTD is a beta-sandwich that is composed of 15 antiparallel beta-strands, and the type 3 repeats are a contiguous series of calcium binding sites that associate with the CTD at multiple points. The crystal packing reveals an exposed potential metal-ion-dependent adhesion site (MIDAS) on one edge of the beta-sandwich that is common to all TSPs and may serve as a binding site for collagens and other ligands. Disease-causing mutations in COMP disrupt calcium binding, disulfide bond formation, intramolecular interactions, or sites for potential ligand binding. The structure presented here and its unique molecular packing in the crystal identify potential interactive sites for glycosaminoglycans, integrins, and collagens, which are key to cartilage structure and function.


Global plant diversity as a reservoir of micronutrients for humanity.
With more than two billion people suffering from malnutrition and diets homogenizing globally, it is vital to identify and conserve nutrient-rich species that may contribute to improving food security and diversifying diets. Of the approximately 390,000 vascular plant species known to science, thousands have been reported to be edible, yet their nutritional content remains poorly characterized. Here we use phylogenetic information to identify plants with the greatest potential to support strategies alleviating B-vitamin deficiencies. We predict the B-vitamin profiles of >6,400 edible plants lacking nutritional data and identify 1,044 species as promising key sources of B vitamins. Several of these source species should become conservation priorities, as 63 (6%) are threatened in the wild and 272 (26%) are absent from seed banks. Moreover, many of these conservation-priority source species overlap with hotspots of malnutrition, highlighting the need for safeguarding strategies to ensure that edible plant diversity remains a reservoir of nutrition for future generations, particularly in countries needing it most. Although by no means a silver bullet to tackling malnutrition, conserving a diverse portfolio of edible plants, unravelling their nutritional potentials, and promoting their sustainable use are essential strategies to enhance global nutritional resilience.


Heterologous expression of HpBHY and CrBKT increases heat tolerance in Physcomitrella patens.
Heat stress can restrict plant growth, development, and crop yield. As essential plant antioxidants, carotenoids play significant roles in plant stress resistance. β-carotene hydroxylase (BHY) and β-carotene ketolase (BKT), which catalyze the conversions of β-carotene to zeaxanthin and β-carotene to canthaxanthin, respectively, are key enzymes in the carotenoid biosynthetic pathway, but little is known about their potential functions in stress resistance. Here, we investigated the roles of β-carotene hydroxylase and β-carotene ketolase during heat stress in Physcomitrella patens through expressing a β-carotene ketolase gene from Chlamydomonas reinhardtii (CrBKT) and a β-carotene hydroxylase gene from Haematococcus pluvialis (HpBHY) in the moss P. patens. In transgenic moss expressing these genes, carotenoids content increased (especially lutein content), and heat stress tolerance increased, with reduced leafy tissue necrosis. To investigate the mechanism of this heat stress resistance, we measured various physiological indicators and found a lower malondialdehyde level, higher peroxidase and superoxide dismutase activities, and higher endogenous abscisic acid and salicylate content in the transgenic plants in response to high-temperature stress. These results demonstrate that CrBKT and HpBHY increase plant heat stress resistance through the antioxidant and damage repair metabolism, which is related to abscisic acid and salicylate signaling.


Generation Pep Study: A population-based survey on diet and physical activity in 12,000 Swedish children and adolescents.
This study presents dietary intake and physical activity in a large nationally representative sample of children and adolescents in Sweden. It also reports the study protocol for the Generation Pep Study that will be used for yearly repeated measurements. A random sample of children and adolescents aged 4-17 years living in Sweden was invited to fill in a Web-based questionnaire on dietary intake and physical activity. For participants aged <12 years, the parents were asked to fill in the questionnaire together with their child. Information on socio-economic background was collected from the parents. A total number of 12,441 children and adolescents participated in the study (participation rate 43%). The results indicate that 13- to 17-year-olds have notably less healthy dietary intake and lower physical activity compared with younger age groups. In general, the dietary intake was most healthy among 4- to 6-year-olds. A socio-economic gradient was seen for many of the studied variables. Participants of a high socio-economic status and younger age generally had healthier dietary intake and higher physical activity. The study provides novel national data as it includes a wide age of children and adolescents (4-17 years).


Prevalence of sleepiness and associations with quality of life in patients with sleep apnea in an online cohort.
Excessive daytime sleepiness (EDS) is a treatment target for many patients with obstructive sleep apnea (OSA). We aimed to understand the prevalence, risk factors, and quality of life associated with EDS in a nonclinical, "real world" sample of patients with OSA. Cross-sectional survey of patients with OSA participating in an online peer support community, assessing demographics, comorbidities, treatment, and quality of life. Differences in those with and without EDS (Epworth Sleepiness Scale > and ≤ 10) were assessed. The sample (n = 422) was 54.2% male, 65.9% were ≥ 55 years, and 43.3% reported sleeping ≤ 6 hours/night. EDS was identified among 31.0% of respondents and 51.7% reported sleepiness as a precipitating factor for seeking initial OSA treatment. EDS was more prevalent in individuals reporting asthma, insomnia symptoms, positive airway pressure (PAP) use less than 6 hours/night on ≥ 5 nights/week, or sleep duration < 6 hours/night. After adjusting for demographics and comorbidities, patients with EDS reported poorer mental and physical health and well-being, lower disease-specific functional status, more activity and work impairment, and more driving impairment (P values < .05). In the subsample (n = 265) with high PAP adherence, 26.0% reported EDS, and similar associations between EDS and outcomes were observed. These "real world" data suggest that patients seeking online OSA support experience a high prevalence of EDS, which was associated with poorer quality of life and worse functional status. Associations persisted among respondents with high self-reported PAP-therapy adherence, potentially driving these individuals to seek online support for sleepiness-related symptoms. Wanberg LJ, Rottapel RE, Reid ML, et al. Prevalence of sleepiness and associations with quality of life in patients with sleep apnea in an online cohort. J Clin Sleep Med. 2021;17(12):2363-2372.


Acetylcholine controls mouse oocyte maturation via downregulation of cAMP.
1. In mice, acetylcholine (ACh) plays an important role in oocyte activation and embryonic development. However, the role of ACh in mouse oocyte maturation has not been investigated. 2. In the present study, the effects of 100 μmol/L and 1 mmol/L ACh on maturation processes of murine germinal vesicle (GV) intact oocytes (GV oocytes) exposed to 10 and 100 μmol/L 3-isobutyl-1-methylxanthine (IBMX), an inhibitor of cyclic nucleotide phosphodiesterase, were evaluated morphologically and immunologically. It has been shown that IBMX inhibits the resumption of meiosis by preventing cAMP breakdown. 3. In the present study, at the start of in vitro culture 100% of oocytes were at the GV stage. After 18 h culture, 95 ± 3, 0 and 85.8 ± 10.2% of oocytes had passed the GV stage in the control, IBMX and IBMX + ACh groups, respectively. The IBMX-induced inhibition of the maturation process was significantly attenuated by approximately 90% by ACh in groups treated with 10 μmol/L IBMX + 100 μmol/L ACh and 100 μmol/L IBMX + 1 mmol/L ACh. Although cAMP levels were high in oocytes treated with 100 μmol/L IBMX, levels were reduced in groups treated simultaneously with 100 μmol/L ACh. Furthermore, compared with mature oocytes, ACh-treated GV oocytes exhibited significantly lower (by approximately 2.3-fold) or absent Ca(2+) peaks. 4. The results of the present study indicate that maturation of GV oocytes, arrested by IBMX treatment, is resumed following ACh treatment and that this effect is due to downregulation of cAMP rather than changes in intracellular Ca(2+) levels.


Community-based cross-sectional survey of latent tuberculosis infection in Afar pastoralists, Ethiopia, using QuantiFERON-TB Gold In-Tube and tuberculin skin test.
There is little information concerning community-based prevalence of latent tuberculosis infection (LTBI) using T-cell based interferon-γ (IFN-γ) release assays (IGRAs), particularly in TB endemic settings. In this study, the prevalence of LTBI in the Afar pastoral community was assessed using QuantiFERON-TB Gold In-Tube (QFTGIT) and tuberculin skin tests (TST). A community-based cross-sectional survey of LTBI involving 652 apparently healthy adult pastoralists was undertaken in the pastoral community of Amibara District of the Afar Region between April and June 2010. The prevalence of LTBI was estimated as 63.7% (363/570) using QFTGIT at the cut-off point recommended by the manufacturer (≥0.35 IU/ml IFN-γ), while it was 74.9% (427/570) using a cut-off point≥0.1 IU/ml IFN-γ. The QFTGIT-based prevalence of LTBI was not significantly associated with the gender or age of the study participants. However, the prevalence of LTBI was 31.2% (183/587) using TST at a cut-off point≥10 mm of skin indurations, and it was higher in males than females (36.8% vs. 23.5%, X2=11.76; p<0.001). There was poor agreement between the results of the tests (k=0.098, 95% CI, 0.08-0.13). However, there was a positive trend between QFTGIT and TST positivity (X2=96.76, P<0.001). Furthermore, individuals with skin indurations≥10 mm were 13.6 times more likely to have positive results using QFTGIT than individuals with skin indurations of 0 mm (adjusted OR=13.6; 95%CI, 7.5 to 24.7, p<0.001). There is currently no agreed gold standard for diagnosis of LTBI. However, the higher prevalence of LTBI detected using QFTGIT rather than TST suggests that QFTGIT could be used for epidemiological studies concerning LTBI at the community level, even in a population unreactive to TST. Further studies of adults and children will be required to assess the effects of factors such as malnutrition, non-tuberculosis mycobacterial infections, HIV and parasitic infections on the performance of QFTGIT.


A novel DOK7 mutation causing congenital myasthenic syndrome with limb-girdle weakness: case series of three family members.
Congenital myasthenia syndrome (CMS) is a group of heterogeneous diseases affecting the neuromuscular endplate. CMS has a considerably different phenotypic presentations, with the onset time ranging from early infancy to late adulthood. Here, we report a case of a CMS due to a new DOK7 mutation in a 28-year-old man and two of his sisters, who have a pure limb-girdle weakness. DOK7 CMS has a varying presentation. Typically, the onset occurs in childhood with ptosis, bulbar symptoms, difficulty walking, weakness, and gait abnormality. This case sheds light on a novel DOK7 gene mutation with a unique presentation of CMS and provides insight into its unique phenotypic presentation.


Nanomedicine: perspective and promises with ligand-directed molecular imaging.
Molecular imaging and targeted drug delivery play an important role toward personalized medicine, which is the future of patient management. Of late, nanoparticle-based molecular imaging has emerged as an interdisciplinary area, which shows promises to understand the components, processes, dynamics and therapies of a disease at a molecular level. The unprecedented potential of nanoplatforms for early detection, diagnosis and personalized treatment of diseases, have found application in every biomedical imaging modality. Biological and biophysical barriers are overcome by the integration of targeting ligands, imaging agents and therapeutics into the nanoplatform which allow for theranostic applications. In this article, we have discussed the opportunities and potential of targeted molecular imaging with various modalities putting a particular emphasis on perfluorocarbon nanoemulsion-based platform technology.


Improvement of toughness by stereocomplex crystal formation in optically pure polylactides of high molecular weight.
A solution casting method followed by thermal homogenization was performed for the preparation of 1:1 blends and non-blended films from poly(d-lactide) (PDLA) and poly(l-lactide) (PLLA) of three different molecular weights, and their thermal and mechanical properties were determined via differential scanning calorimetry (DSC) and tensile tests. According to the literature, when Mw is below 1.0×10(5)g/mol only stereocomplex crystallization takes place, and when it is higher, both homocrystallites and stereocomplex crystallites co-exist. In order to promote crystallization as a homocrystal in neat polylactides and to promote the stereoselective crystallization as stereocomplex in the case of non-blended films, and in turn, to achieve different degrees of crystallinity, several thermal treatments of annealing were carried out in this work. Highly stereocomplexed blends were found by the stereospecific thermal treatments. As a consequence, the toughness of 1:1 blends was found significantly enhanced over those of non-blended films, irrespective of molecular weight. For instance, in B2-5050 stereocomplexed blend having poly(l-lactide) and poly(d-lactide) of Mw=1.2×10(5)g/mol, tensile strength increased from 44.0±2.1MPa to 65.1±6.1MPa, and the elongation at break from 10.8±2.5% to 33.1±8.1% with respect to its non-blended poly(l-lactide) counterpart crystallized as homocrystal. This improvement in mechanical properties in stereocomplexed blends is not attributed to the inherent properties of the type of crystal polymorph but to the presence of a higher density of intercrystalline connections through a mobile amorphous phase, i.e. tie chains in the stereocomplexed supramolecular spherulitic entities that provide in the stereocomplexed samples enhanced strength and elongation at break at the same time.


Colorimetric detection of food freshness based on amine-responsive dopamine polymerization on gold nanoparticles.
Biogenic amines (BAs) are not only well-known indicators for food freshness but can cause serious harm to the body after excessive consumption, which makes the determination of its content in food of great significance. In this work, a simple and convenient method for colorimetric detection of BAs was developed based on the sensitivity of the polymerization of dopamine to the presence of BAs on the surface of gold nanoparticles (AuNPs). Taking histamine as a representative, the system exhibited a distinct color change from wine red to black among the amine concentration of 1-100 μg/mL with the detection limit of 2.8 μg/mL. The detection system also exhibited sensitivity to other common kinds of BAs, such as putrescine, cadaverine, spermine, spermidine, tyramine, and tryptamine. Moreover, the proposed method showed encouraging performance in visual detection of the freshness of real samples, which provided a new approach for food quality and freshness evaluation.


Intercostal pleuroperitoneal hernia.
The patient described in this report had the initial symptoms and signs of a fractured right ninth rib followed soon by severe signs of trauma to the local chest wall. In the ensuing 5 months sequella suggesting an intercostal hernia gradually developed. Further studies indicated that this hernia consisted of a posterior pleural and anterior peritoneal component. At operation the diaphragm was found to have torn away from its costal attachments. In addition to repairing the intercostal pleural hernia, we recommend that a strip of Marlex mesh be fixed to the inner costal surfaces to form a continuous and durable new attachment for the diaphragmatic margin prior to the repair of the peritoneal component. Determining a probable explanation for the mechanism of the injury was helpful in understanding the reconstruction procedure.


Enhancement of the peroxidase-mediated oxidation of butylated hydroxytoluene to a quinone methide by phenolic and amine compounds.
We have recently demonstrated that butylated hydroxyanisole (BHA) markedly stimulates the peroxidase-dependent oxidation of butylated hydroxytoluene (BHT) to the potentially toxic BHT-quinone methide. Using both horseradish peroxidase and prostaglandin H synthase we now report the ability of a wide variety of compounds to stimulate peroxidase-dependent activation of BHT. These compounds include several phenolic compounds commonly present in pharmacologic preparations or occurring naturally in foods. The ability of a given compound to stimulate BHT oxidation was found to depend on the type of radical it forms upon peroxidase oxidation. Compounds which have been shown to form phenoxy radicals or nitrogen-centered cation radicals were observed to enhance BHT oxidation. Conversely, compounds which are known to form peroxy radicals or semiquinone radicals either inhibited or had no effect on BHT oxidation. Compounds which enhanced BHT oxidation (monitored by covalent binding of [14C]BHT to protein) were also observed to stimulate the formation of BHT-quinone methide and stilbenequinone. This suggested a common mechanism of interaction of these compounds with BHT. The stimulation of BHT covalent binding by BHA was also seen in various human and animal tissues using either arachidonic acid or hydrogen peroxide as substrate. The possible toxicologic implications of the enhancement of peroxidase-catalyzed BHT oxidation to BHT-quinone methide are discussed.


Differential phytate utilization in Candida species.
The present study was undertaken to evaluate and characterize the phytase activity in different Candida species. A total of 113 Candida isolates representing eight species were examined for phytase activity by an agar plate assay using the calcium salt of phytic acid as the sole phosphorus source. A phytase-positive phenotype was identified by the formation of a clear halo around a fungal colony. Cell-bound differential phytase activity was observed in Candida isolates at inter- and intra-species levels. Although phytase activity was not affected by the supplementation of external phosphate in C. albicans, C. dubliniensis, C. glabrata, and C. kefyr, elevated phytase activity was evident in C. guilliermondii, C. krusei, C. parapsilosis, and C. tropicalis in phosphate-free medium. Further characterization showed that, in general, relatively higher phytase activity was observed at more acidic pHs, and the phytase activity increased with incubation temperature, reaching a maximum at 55 or 65°C. Taken together, the findings demonstrated, for the first time, differential phytase activities in different Candida species. Phytase activity may be a contributing factor to fungal survival and proliferation within the human gastrointestinal tract, where nutrients are usually scarce.


Properties of the extra-positional signal in hippocampal place cell discharge derived from the overdispersion in location-specific firing.
There is a good deal of evidence that in the rodent, an internal model of the external world is encoded by hippocampal pyramidal cells, called 'place cells'. During free exploration, the activity of place cells is higher within a small part of the space, called the firing field, and virtually silent elsewhere. We have previously shown that the spiking activity during passes through the firing field is characterized not only by the high firing rate, but also by its very high variability ('overdispersion'). This overdispersion indicates that place cells carry information in addition to position. Here we demonstrate by simulations of an integrate-and-fire neuronal model that while a rat is foraging in an open space this additional information may arise from a process that alternatingly modulates the inputs to place cells by about 10% with a mean period of about 1 s. We propose that the overdispersion reflects switches of the rats attention between different spatial reference frames of the environment. This predicts that the overdispersion will not be observed in rats that use only room-based cues for navigation. We show that while place cell firing is overdispersed in rats during foraging in an open arena, the firing is less overdispersed during the same behavior in the same environment, when the rats have been trained to use only room-based and not arena-based cues to navigate.


Rapid and sensitive detection of methyl parathion in rice based on carbon quantum dots nano-fluorescence probe and inner filter effect.
A highly sensitive fluorescent sensing system of novel carbon quantum dots nano-fluorescent probe based on corn stalks was established for the determination of methyl parathion by alkaline catalytic hydrolysis and inner filter effect mechanism. The carbon quantum dots nano-fluorescent probe was prepared from corn stalks using an optimized one-step hydrothermal method. The detection mechanism of methyl parathion was revealed. The reaction conditions were optimized. The linear range, sensitivity and selectivity of the method were evaluated. Under the optimal conditions, the carbon quantum dots nano-fluorescent probe exhibited high selectivity and sensitivity to methyl parathion, achieving a linear range of 0.005-14 µg/mL. The fluorescence sensing platform was applied to the detection of methyl parathion in rice samples, and the results showed that the recoveries range from 91.64 to 104.28 %, and the relative standard deviations were less than 4.17 %. The detection limit for methyl parathion in rice samples was 1.22 µg/kg, and the limit of quantitation (LOQ) was 4.07 µg/kg, which was very satisfactory.


Long non-coding RNA H19 and MALAT1 gene variants in patients with ischemic stroke in a northern Chinese Han population.
Objectives Long non-coding RNAs (lncRNAs) have been identified as key regulators in the development of atherosclerosis, which is a major cause of ischemic stroke. However, to date, there are no reports on the association between lncRNA gene variation and the risk of ischemic stroke. Therefore, we assessed the association between H19 and MALAT1 gene polymorphisms and susceptibility to ischemic stroke in a northern Chinese Han population. Methods In our study, we genotyped four genetic variations in lncRNA-H19 and -MALAT1 (rs217727, rs2251375, rs619586, and rs3200401) in a case-control study of 567 ischemic stroke patients and 552 control subjects. Results We found that the TT genotype of the rs217727 polymorphism within H19 was significantly associated with increased risk of ischemic stroke in our northern Chinese Han population (odds ration (OR) = 1.519, 95% confidence interval (CI) = 1.072-2.152, p = 0.018). Stratified analysis based on stroke subtype revealed that the increased risk was more evident in small vessel ischemic stroke (OR = 1.941, 95% CI = 1.260-2.992, p = 0.02). Individuals with the TT genotype had a 1.941 times higher risk of small vessel ischemic stroke when compared with the subjects of CC + CT. These correlations remained after adjusting for confounding risk factors of stroke (OR = 1.913, 95% CI = 1.221-2.998, p = 0.005). However, there was no significant association between H19 rs2251375 or MALAT1 rs3200401 and ischemic stroke in either total population analysis or subgroup analysis. Conclusion In conclusion, our findings suggest that the H19 rs217727 gene polymorphism contributes to small vessel ischemic stroke susceptibility in the Chinese Han population and may serve as a potential indicator for ischemic stroke susceptibility.


Glycyrrhiza glabra (Linn.) and Lavandula officinalis (L.) cell suspension cultures-based biotransformation of β-artemether.
The biotransformation of β-artemether (1) by cell suspension cultures of Glycyrrhiza glabra and Lavandula officinalis is reported here for the first time. The major biotransformed product appeared as a grayish-blue color spot on thin-layer chromatography (TLC) with transparent crystal-like texture. Based on its infrared (IR) and (1)H nuclear magnetic resonance (NMR) spectra, the product was characterized as a tetrahydrofuran (THF)-acetate derivative (2). The highest conversion efficiencies of 57 and 60% were obtained when 8-9-day-old cell suspensions of G. glabra and L. officinalis were respectively fed with 4-7 mg of compound 1 in 40 ml of medium per culture and the cells were harvested after 2-5 days of incubation. The addition of compound 1 at the beginning of the culture cycle caused severe growth depression in a dose-dependent manner, resulting in poor bioconversion efficiency of ~25% at 2-5 mg/culture dose only.


Biogenesis of plasmalemmal glycoproteins. Intracellular site of synthesis of mouse liver plasmalemmal 5'-nucleotidase as determined by the sub-cellular location of messenger RNA coding for 5'-nucleotidase.
1. Free and membrane-bound mouse liver polyribosomes were separated by prolonged density-gradient centrifugation of the post-mitochondrial supernatant. RNA was extracted from free and membrane-bound polyribosomes and mRNA purified by oligo(dT)-cellulose column chromatography. 2. Antisera against purified mouse liver plasma membrane 5'-nucleotidase and moust albumin were prepared and characterized. 3. Microinjection of equivalent amounts of mRNA from free and membrane-bound liver polyribosomes into Xenopus laevis oocytes indicated by immuno precipitation and sodium dodecylsulphate gel electrophoresis a higher proportion of mRNA coding for 5'-nucleotidase and serum albumin in membrane-bound polyribosomes than free polyribosomes. 4. Although small, significant amounts of serum albumin and 5'-nucleotidase were also coded for by mRNA purified from free polyribosomes. The results suggest that in vivo, mRNA in mouse liver membrane-bound polyribosomes codes for the synthesis of 17 times more 5'-nucleotidase than does the mRNA in free polyribosomes.


Functional heterogeneity of GEF-free initiation factor 2 purified from suckling and adult rat brain.
The functional behavior of initiation factor 2 was studied in purified preparations from the brains of suckling (4-12-day-old) and adult (60-day-old) rats. Adult eIF2 has lower GDP and GTP affinity than suckling eIF2, even in the presence of a large excess of GTP, whereas suckling eIF2 has a lower capacity to bind GTP. Since these two factors are free of guanine nucleotide exchange factor (GEF), and ribosomal fractions show an age-dependent difference in GEF activity, the observed functional heterogeneity may be due to a different ratio in eIF2 species (eIF2-GDP, eIF2(alpha P)).


[A case of delayed post-anoxic encephalopathy after acute carbon monoxide poisoning].
The authors report the case of a young 18 year-old man presenting delayed encephalopathy after severe intoxication with carbon monoxide, and transient cerebral swelling. This condition is characterized by diffuse demyelinating lesions of both cerebral hemispheres, the mechanism of which is unknown.


Neurotoxicological profile of the hallucinogenic compound 25I-NBOMe.
4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25I-NBOMe) is a new psychoactive substance with strong hallucinogenic properties. Our previous data reported increased release of dopamine, serotonin, and glutamate after acute injections and a tolerance development in the neurotransmitters release and rats' behavior after chronic treatment with 25I-NBOMe. The recreational use of 25I-NBOMe is associated with severe intoxication and deaths in humans. There is no data about 25I-NBOMe in vivo toxicity towards the brain tissue. In this article 25I-NBOMe-crossing through the blood-brain barrier (BBB), the impact on DNA damage, apoptosis induction, and changes in the number of cortical and hippocampal cells were studied. The presence of 25I-NBOMe in several brain regions shortly after the drug administration and its accumulation after multiple injections was found. The DNA damage was detected 72 h after the chronic treatment. On the contrary, at the same time point apoptotic signal was not identified. A decrease in the number of glial but not in neural cells in the frontal (FC) and medial prefrontal cortex (mPFC) was observed. The obtained data indicate that 25I-NBOMe passes easily across the BBB and accumulates in the brain tissue. Observed oxidative DNA damage may lead to the glial cells' death.


Role of aquaporin-1 in trabecular meshwork cell homeostasis during mechanical strain.
Aquaporin-1 (AQP1) channels are expressed by trabecular meshwork (TM) and Schlemm's canal cells of the conventional outflow pathway where fluid movement is predominantly paracellular, suggesting a non-canonical role for AQP1. We hypothesized that AQP1 functions to protect TM cells during periods of mechanical strain. To test this idea, primary cultures of confluent human TM cells on Bioflex membranes were exposed to static and cyclic stretch for 8 and 24h using the Flexcell system. AQP1 expression in TM cells was assessed by SDS-PAGE and Western blot using anti-AQP1 IgGs. AQP1 protein bands were analyzed using densitometry and normalized to beta-actin expression. Cell damage was monitored by measuring lactate dehydrogenase (LDH) and histone deacetylase appearance in conditioned media. Recombinant expression of AQP1 in TM cell cultures was facilitated by transduction with adenovirus. Results show that AQP1 expression significantly increased 2-fold with 10% static stretch and 3.5-fold with 20% static stretch at 8h (n=4, p<0.05) and 24h (n=6, p<0.05). While histone deacetylase levels were unaffected by treatments, release of LDH from TM cells was the most profound at the 20% static stretch level (n=4, p<0.05). Significantly, cells were refractory to the 20% static stretch level when AQP1 expression was increased to near tissue levels. Analysis of LDH release with respect to AQP1 expression revealed an inverse linear relationship (r(2)=0.7780). Taken together, AQP1 in human TM appears to serve a protective role by facilitating improved cell viability during conditions of mechanical strain.


Focused Information Criterion and Model Averaging with Generalized Rank Regression.
Generalized rank regression, which is a class of weighted rank regression with weights based on factor space, provides a powerful tool for conducting robust estimation. In this article, we first establish the asymptotic properties of generalized rank regression under local model misspecification. We then apply the generalized rank regression to the focus information criterion and frequentist model averaging and establish their properties.


Predictive factors of tumor response after neoadjuvant chemoradiation for locally advanced rectal cancer.
Neoadjuvant chemoradiation followed by surgery is the standard of care for locally advanced rectal cancer. The aim of this study was to correlate tumor response to survival and to identify predictive factors for tumor response after chemoradiation. From 1998 to 2008, 168 patients with histologically proven locally advanced adenocarcinoma treated by preoperative chemoradiation before total mesorectal excision were retrospectively studied. They received a radiation dose of 45 Gy with a concomitant 5-fluorouracil (5-FU)-based chemotherapy. Analysis of tumor response was based on lowering of the T stage between pretreatment endorectal ultrasound and pathologic specimens. Overall and progression-free survival rates were correlated with tumor response. Tumor response was analyzed with predictive factors. The median follow-up was 34 months. Five-year disease-free survival and overall survival rates were, of 44.4% and 74.5% in the whole population, 83.4% and 83.4%, respectively, in patients with pathological complete response, 38.6% and 71.9%, respectively, in patients with tumor downstaging, and 29.1 and 58.9% respectively, in patients with absence of response. A pretreatment carcinoembryonic antigen (CEA) level of <5 ng/ml was significantly independently associated with pathologic complete tumor response (p = 0.019). Pretreatment small tumor size (p = 0.04), pretreatment CEA level of <5 ng/ml (p = 0.008), and chemotherapy with capecitabine (vs. 5-FU) (p = 0.04) were significantly associated with tumor downstaging. Downstaging and complete response after CRT improved progression-free survival and overall survival of locally advanced rectal adenocarcinoma. In multivariate analysis, a pretreatment CEA level of <5 ng/ml was associated with complete tumor response. Thus, small tumor size, a pretreatment CEA level of < 5 ng/ml, and use of capecitabine were associated with tumor downstaging.


Genistein-based reactive oxygen species-responsive nanomaterial site-specifically relieves the intestinal toxicity of endocrine-disrupting chemicals.
Endocrine-disrupting chemicals (EDCs) can disrupt the gastrointestinal endocrine system and induce oxidative stress, which eventually leads to intestinal toxicity. Genistein (Gen) has a beneficial effect on the physiological functions of the gastrointestinal tract and can alleviate EDCs damage. As an estrogen-like substance, Gen may also synergize the deleterious influence of EDCs. Therefore, the targeting and concentration of Gen must be controlled during its application. In this study, a novel reactive oxygen species (ROS)-responsive nanomaterial (Gen-NM-2) containing Tempol conjugated β-cyclodextrin and Gen was prepared. The nano-polymer exhibits a uniform rod-like morphology with an average diameter of 833 ± 12 nm and a negative zeta-potential of -20.3 ± 3.7 mV. Gen-NM-2 protected Gen from rapid metabolism in gastrointestinal tract and displayed a strong ROS scavenging ability. In response to high ROS levels, this material can effectively locate the target site and release Gen, which then exerted its effect by reducing the ROS content and regulating the ERβ signaling pathway. Owing to its high bioavailability, Gen-NM-2 at relatively low doses can reduce the intestinal cytotoxicity of EDCs, thus providing a basis for the development of EDCs detoxification therapy.


Decreased abundance of Akkermansia after adrenocorticotropic hormone therapy in patients with West syndrome.
Infants suffer from a severe epileptic encephalopathy known as West syndrome (WS). Treatment with adrenocorticotropic hormone (ACTH) indicates the involvement of the gut-brain axis in WS. Several pieces of evidence show the communication of the gut microbiota (GM) with the brain via the hypothalamic-pituitary-adrenal axis (HPA axis) and blood cytokines. This study aimed at (1) determining the GM diversity in infants having WS and (2) comparing the results of infants having WS with those of the healthy infants and also in the patients with WS before and after the ACTH therapy. In this study, 29 infants with WS and 29 healthy infants aged 3-13 months were recruited. Fecal samples were collected, and DNA was extracted and sequenced on the Illumina MiSeq platform. Kruskal-Wallis rank-sum test was used to analyze the between-group differences in the Chao1 index, Shannon index, and the abundances of GM at different taxonomy levels. R software was used to plot the graphs. The top five dominant GM genera between patients with WS and healthy infants showed no significant differences. However, the relative abundance of genus Akkermansia was observed to be significantly (P = 0.011) higher in the BT group than in the HC group and AT group. After 2 weeks of ACTH therapy, the relative abundance of Akkermansia significantly (P = 0.003) decreased. The relative abundance of Akkermansia was observed to be significantly higher in patients with WS than that in healthy infants. However, the relationship between Akkermansia and WS pathogenesis needs to be clarified in further studies.


Identification of histidyl and thiol groups at the active site of rabbit renal dipeptide transporter.
Active transport of dipeptides in rabbit renal brush-border membrane vesicles is energized by an inward-directed H+ gradient rather than a Na+ gradient. We examined the effects of treatment of membrane vesicles with diethylpyrocarbonate (DEP), a reagent specific for histidyl groups, on this H+ gradient-dependent dipeptide uptake. DEP inhibited the uptake of all three dipeptides studied, Gly-sarcosine, Gly-Gly, and Gly-Pro (Ki = 0.6-0.9 mM), and the inhibition was noncompetitive. The dipeptide transporter could be protected from DEP inhibition by the presence of dipeptide substrates during the treatment of the vesicles with the inhibitor, whereas leucine plus Na+ failed to offer the protection. Na+-dependent leucine uptake was also inhibited by DEP (Ki = 2.5 mM) and the amino acid transporter could be protected from the inhibition by leucine plus Na+, but not by dipeptides. Treatment of membrane vesicles with the thiol group-specific reagents, 7-chloro-4-nitrobenz-2-oxa-1,3-diazole,3-bromopyruvate, p-chloromercuribenzenesulfonic acid, and N-ethylmaleimide, also inhibited the H+ gradient-dependent dipeptide uptake. The potency of their inhibition was in the order: 7-chloro-4-nitrobenz-2-oxa-1,3-diazol greater than p-chloromercuribenzenesulfonic acid greater than 3-bromopyruvate greater than N-ethylmaleimide. The inhibition could be reversed in some cases by treatment of the membrane vesicles with reducing agents such as 2,3-dimercaptopropanol following incubation with the inhibitors. Dipeptide substrates could protect the dipeptide transporter from the inhibition. We conclude that histidyl and thiol groups are present at or near the substrate-binding site of the rabbit renal dipeptide transporter.


[Studies on the antitumor activity of traditional Chinese medicines. (II). The antitumor mechanism of traditional Chinese medicines].
Either i.p. or p.o. administration of Zhu-Ling-Tang, Xiao-Chai-Hu-Tang, Shi-Quan-Da-Bu-Tang and Ren-Shen-Tang enhanced the function of the reticuloendothelial system (RES) in mice. The relative organ weights of thymus, spleen and liver were increased as compared with the control. Furthermore, binding of C3 cleavage product (C3b) to peritoneal macrophages after p.o. administration of Xiao-Chai-Hu-Tang was enhanced as shown by fluorescent antibody technique. In conclusion, it was considered that one of the mechanisms of the antitumor activities of theses drugs was the stimulation of a host-mediated factor such as the phagocytic function of the RES and C3 cleavage producibility.


Age-related macular degeneration.
Age-related macular degeneration is an increasingly important public health issue due to ageing populations and increased longevity. Age-related macular degeneration affects individuals older than 55 years and threatens high-acuity central vision required for important tasks such as reading, driving, and recognising faces. Advances in retinal imaging have identified biomarkers of progression to late age-related macular degeneration. New treatments for neovascular age-related macular degeneration offer potentially longer-lasting effects, and progress is being made towards a treatment for atrophic late age-related macular degeneration. An effective intervention to slow progression in the earlier stages of disease, or to prevent late age-related macular degeneration development remains elusive, and our understanding of underlying mechanistic pathways continues to evolve.


Documentation of Microtubule Collisions with Myosin VIII ATM1 Containing Membrane-Associated Structures.
Collisions of microtubules with membrane-associated structures containing myosin VIII were recently described, and these data suggested that such collisions can happen between microtubules and other membrane-associated proteins. Such collisions may contribute to a coordinated organization between microtubules and membrane-associated proteins especially in cases of low lateral diffusion rates of the protein. Coordinated organization of cortical cytoskeleton and membrane structures can have consequences on membrane compartmentalization and downstream signaling. Here we describe a way to analyze collisions of cortical microtubules and membrane-associated proteins by confocal microscopy. In addition, we describe a tool to measure and quantify these collisions.


From 3D Back to 2D Monolayer Stomach Organoids-on-a-Chip.
2D monolayer gastric organoids (2DMGOs)-on-a-chip have consistent structures and can live for more than a year in culture. This state-of-the-art cell physiological system in a microfluidic device provides a way to investigate biomedically relevant, stimuli-dependent cellular responses in a variety of differentiated 2DMGOs.


Pregnancy outcomes in women with inflammatory bowel disease--a population-based cohort study.
Our purpose was to assess the frequency of adverse pregnancy outcomes in women with inflammatory bowel disease compared with the general population. Of all 239,773 pregnant women with single births in Sweden from 1991 to 1992, 756 women with inflammatory bowel disease could be analyzed for late fetal and infant death, preterm birth, low birth weight, small for gestational age, and cesarean section. Logistic regression analyses was used to estimate the odds ratios. Pregnancies in women with inflammatory bowel disease were associated with an increased risk of preterm birth at < 33 weeks (odds ratio 1.81, 95% confidence interval 1.06 to 3.07) and at 33 to 36 weeks (odds ratio 1.48, 95% confidence interval 1.10 to 1.99); low birth weight < 1500 gm (odds ratio 2.15, 95% confidence interval 1.11 to 4.15) or 1500 to 2499 gm (odds ratio 1.57, 95% confidence interval 1.12 to 2.22); small for gestational age (odds ratio 1.40, 95% confidence interval 0.97 to 2.02); and cesarean section (odds ratio 1.51, 95% confidence interval 1.27 to 1.89). Inflammatory bowel disease in pregnant women is associated with an increased frequency of adverse pregnancy outcomes.


The DiGeorge sequence. II. Immunologic findings in partial and complete forms of the disorder.
We present immunological in vitro data on a group of 16 patients with the DiGeorge sequence (DGS). Detailed tests gave evidence that the decrease in number and function of mature T-cells is closely correlated with phenotypic expression and represents a wide immunological spectrum ranging from normal function to severe combined immunodeficiency with B-cells. Careful immunological testing in DGS may help to plan therapeutic procedures (i.e. thymic factor therapy or bone marrow transplantation), may also have prognostic significance and help to gain insight into mechanisms operative in disturbances of T-cell regulation.