High-risk early-stage lung adenocarcinoma patients are identified by an immune-related circadian clock gene signature.
Twenty-four-hour oscillations of circadian rhythms control comprehensive biological processes in the human body. In lung adenocarcinoma (LUAD), chronic circadian rhythm disruption is positively associated with tumorigenesis. However, few studies focus on circadian clock gene signatures (CGSs) for prognosis evaluation of patients with early-stage LUAD. In this study, we aimed to construct a robust prognostic circadian rhythm-related biomarker from multiple public databases, including the Gene Expression Omnibus database and The Cancer Genome Atlas database. The least absolute shrinkage and selection operator (LASSO)-penalized Cox regression model was performed to select optimal circadian clock gene pairs. Bioinformatic analyses were performed to estimate the abundance of different immune cells and immunohistochemical analyses were conducted to validate the differential proportion of tumor-infiltrating lymphocytes in different groups. Results demonstrated that the CGS could accurately identify patients with early-stage LUAD at a high risk in the training dataset [hazard ratio (HR) =3.06; 95% confidence interval (CI): 2.47-3.78; P<0.001], testing dataset (HR =2.44; 95% CI: 1.74-3.43; P<0.001), and validation dataset (HR =2.09, 95% CI: 1.09-4.00; P=0.023). Bioinformatic and immunohistochemical analyses demonstrated that the abundance of tumor-infiltrating CD4+ T cells was higher in the low-CGS groups. Integration of the CGS and clinical characteristics improved the accuracy of the CGS in predicting overall survival (OS) of patients with early-stage LUAD. In conclusion, the CGS was an independent immune-related circadian biomarker that could identify early-stage LUAD patients with different OS.


Screening girls with Turner syndrome: the National Cooperative Growth Study experience.
The National Cooperative Growth Study (NCGS) database was examined to determine whether the availability of expert guidelines affected the clinical management of 955 patients with Turner syndrome (TS). Although cardiac and renal evaluations increased in frequency after guideline publication, hearing screenings declined. Although girls with TS show significant cardiac, renal, and hearing problems, screening for these disorders remains inadequate.


Gold Catalyzed Synthesis of Substituted Furan by Intermolecular Cascade Reaction of Propargyl Alcohol and Alkyne.
Using a combination of triazole-gold (TA-Au) and copper catalysts, the substituted furan was achieved in one pot through a three-step reaction cascade. The reaction tolerates a large substrate scope with simple starting materials. The desired di-, tri-, and tetrasubstituted furans were prepared in good to excellent yields.


mFOLFOXIRI versus mFOLFOX6 as neoadjuvant chemotherapy in locally advanced rectal cancer: A Propensity Score Matching Analysis.
Preoperative chemoradiotherapy (CRT) is the standard treatment for locally advanced rectal cancer (LARC). However, CRT failed to impact metastatic recurrence and the risk of side effects on bowel and genitourinary remained a concern. Neoadjuvant chemotherapy alone with mFOLFOX6 or FOLFOXIRI had been investigated in LARC. Here, we tried to compare the efficacy of mFOLFOXIRI with mFOLFOX6 as neoadjuvant chemotherapy in LARC. Between January 2014 and December 2019, patients with LARC receiving neoadjuvant chemotherapy with mFOLFOXIRI or mFOLFOX6 were retrospective analyzed, including data from a prospective trial (NCT02217020). All patients underwent total mesorectal excision (TME). The propensity-score matching was preformed to adjust baseline potential confounders and to estimate differences in outcomes between patients receiving mFOLFOXIRI and mFOLFOX6. Survival analysis was done using Kaplan-Meier analysis and Cox proportional regression analysis. The median follow-up time was 31.1 months. After propensity score matching, 156 patients were available for comparison in each group. The pathological complete response (pCR) rate was 17.9% vs. 5.1% (P< .001), the incidence rate of anastomotic fistula was 3.2% vs. 9% (P = .03), the 3 year disease-free survival (DFS) rate was 75% vs. 66.7% (P = .047) and the distant metastasis rate was 16.4% versus 26.6% (P = .013) for mFOLFOXIRI and mFOLFOX6 group, respectively. Patients receiving mFOLFOXIRI had higher incidence of grade III and/or IV nausea and/or vomiting (7.6% vs. 2.5%, P = .04). Neoadjuvant mFOLFOXIRI regimens improved pCR rate and survival outcome, reduced the rate of distant metastasis and anastomotic fistula when comparing with propensity-score matched controls of mFOLFOX6 neoadjuvant chemotherapy. This trial assessed the short-term and long-term effects of neoadjuvant chemotherapy with mFOLFOXIRI and mFOLFOX6 in patients with locally advanced rectal cancer. Comparing with propensity-score matched historical control of chemoradiotherapy, neoadjuvant mFOLFOXIRI chemotherapy was well tolerated and led to higher rates of 3 year disease-free survival in patients with locally advanced rectal cancer.


Study protocol of the ESUB-MG cluster randomized trial: a pragmatic trial assessing the implementation of urine drug screening in general practice for buprenorphine maintained patients.
In addiction care, urine drug screening tests are recommended to assess psychoactive substances use. While intrinsic diagnostic value of these tests is demonstrated, the consequences of carrying out these tests on opiate maintenance treatment (OMT) have not been established. The main objective will be to assess the impact of on-site urine drug screening tests (OS-UDS) in general practice compared to routine medical care on OMT retention at 6 months in opioid-dependent patients initiating buprenorphine. The ESUB-MG study uses a pragmatic, cluster randomized controlled trial design. General Practitioners (GPs) regularly managing patients treated with buprenorphine and consenting for participating will be invited to participate. GPs will be randomly assigned to one of two groups for 6 to 24 months: (a) control group (usual care: standard medical strategy for assessing drug use); (b) interventional group (including 1/ a training session on practice and interpretation of OS-UDS; 2/ the supply of OS-UDS at GPs' medical offices; 3/ performing an OS-UDS before the first prescription of buprénorphine). GPs will have to include 1 to 10 patients aged 18 years-old or more, consulting for starting treatment by buprenorphine, not opposed to participate. The primary outcome will be OMT retention at 6 months. This randomized interventional trial should bring sufficient level of evidence to assess effectiveness of performing OS-UDS in general practice for patients treated by buprenorphine. Training GPs to drug tests and supplying them in their office should lead to an improvement of opioid-addicted patients' care through helping decision. NCT02345655 (first registration May 14, 2014).


What is the relevance of quality of life assessment for patients with attention impairment?
Attention disturbances are frequently observed in multiple sclerosis (MS) patients. The aim of this study was to provide new evidence regarding the suitability of using self-reported QoL information in this impaired population by exploring the construct validity, reliability, and external validity of a MS-specific quality of life (QoL) instrument. cross-sectional study. MS patients of any disease subtype. sociodemographic (age, gender, marital status, education level, and occupational activity) and clinical data (Expanded Disability Status Scale, disease duration); QoL (MusiQoL and SF36); and attention performance (Wechsler Memory Scale and PASAT). According to the French norms, non-impaired and impaired populations were defined. For each population, suitability indices were provided to quantify how the structures matched with the initial structure of the reference population assessed in the validation study. One hundred and twenty-four consecutive patients were enrolled. The factor analysis performed in the impaired populations showed that the questionnaire structure adequately matched the initial structure of the MusiQoL. The unidimensionality of the dimensions was preserved, and the internal/external validity indices were close to those of the reference population. Our study suggests that attention impairment dysfunction did not compromise the reliability and validity of the self-reported QoL questionnaires.


Ultrasound-activated nanosonosensitizer for oxygen/sulfate dual-radical nanotherapy.
An all-in-one therapy for cooperatively fighting cancer, infection and boosting wound repair is exceedingly demanded for patients with advanced superficial cancers or after surgical intervention to avoid multiple drug abuse and resultant adverse effects. Here, the ultrasound-activated nanosonosensitizer PHMP that integrated peroxymonosulfate (PMS) into the Pd-catalyzed hydrogenated mesoporous titanium dioxide (PHM) was dexterously designed for combined therapy of cancer and infected wound based on oxygen/sulfate dual-radical nanotherapy. Firstly, the PHM with single crystal structure and abundant oxygen deficiencies exhibited excellent ultrasound-excited reactive oxygen species (ROS) production for enhanced sonodynamic therapy (SDT) under the support of Pd nanozyme-mediated O2 supply. Simultaneously, the physically targeted ultrasound irradiation effectively transformed PMS loaded in the hollow cavities into distinct sulfate radical (•SO4-) with longer half-life and stronger oxidation, which remarkably enhanced the therapeutic efficacy of PHM-mediated SDT for cancer and bacteria. In addition, by embedding PHMP into the hydrogel, the enrichment of PHMP in the focal site was guaranteed, and meanwhile a moist and ventilated environment was created to speed up wound repair. The study broadens the potential of •SO4- in the therapeutic fields and contributes a simple and appealing tactic for the comprehensive treatment of cancer, infection and wound repair.


Explaining educational-related inequalities in health: Mediation and moderator models.
This paper studies how education and certain lifestyle factors affect people's self-reported health. In addition to the assessment of the effects of education and lifestyle, the study contrasts two models of explaining educational-related health inequalities: the mediation model and the moderator model. The mediation model posits that well-educated people's better health, as compared to the poorly educated, is caused by their more 'healthy' lifestyles. The moderator model suggests, by contrast, that the effects of the lifestyle variables on health are dependent upon educational level. Several analyses are carried out on two large data sets comprising of middle-aged men and women in two Norwegian counties, Rogaland and Nordland. Two main findings are presented: (1) Both education and lifestyle factors have the expected effects on health. (2) The results do not permit a clear-cut conclusion as to which of the two models of educational-related health inequalities should be preferred: whereas the results support the mediation model in the data from Rogaland, the moderator model is partially supported in the Nordland data.


Role of Nerve Conduction Studies in Hansen's Disease.
To report the role of nerve conduction study (NCS) in diagnosis, monitoring, and prognosis of Hansen's disease (HD). In a hospital-based prospecive observational study, the patients with HD as per World Health Organization (WHO) criteria were included; muscle wasting power, reflexes, and sensations were recorded. Motor NCS of median, ulnar, and peroneal nerves and sensory NCS of ulnar, median, and sural nerves were recorded. Disability was graded using WHO grading scale. The outcome was assessed after 6 months using modified Rankin scale. In the present study, 38 patients with a median age of 40 (15-80) years and five females were included. The diagnosis was tuberculoid in seven, borderline tuberculoid in 23, borderline lepromatous in two, and borderline in six patients. The disability was grade 1 and 2 in 19 patients each. Out of 480 nerves studied, NCS was normal in 139 sensory (57.4%) and 160 (67.2%) motor nerves. NCSs were axonal in seven sensory and eight motor nerves, demyelinating in three nerves, and mixed in one in seven patients who had lepra reaction. NCS findings did not correlate with disability (p = 1.0) or outcome (0.304) and provided additional information in 11 nerves (seven patients). Peripheral nerves were enlarged in 79. NCSs were normal in 32 (29.90%) in thickened nerves. In HD, NCS abnormalities correlated with respective sensory or motor abnormality but related with neither disability nor the outcome.


Interfrontal sinus septal cell: a cause of obstructing inflammation and mucoceles.
Recent interest in the origin and complications associated with frontal intersinus septal cells prompted us to review our material looking for cases of the uncommon occurrence of a mucocele developing within such a cell. The purpose of this article was to present the imaging findings on 4 cases of mucoceles arising within surgically proven frontal intersinus septal cells. A retrospective review of the case material in our department of otolaryngology since 2000 was made looking for cases of patients with surgically proven frontal intersinus septal cell mucoceles. Institutional review board approval for the review was obtained. Four cases were identified that also had CT and/or MR imaging studies. Examples of 4 additional classic frontal sinus mucoceles and 3 anterior ethmoid mucoceles were also identified for comparison. All 4 of the cases of frontal intersinus septal cell mucoceles had an expanded midline frontal sinus cell, which thinned the posterior and/or anterior frontal sinus tables. The classic frontal sinus mucoceles were either to the left or right side, and any table thinning was off midline. The ethmoid mucoceles were clearly centered below the frontal sinuses. The rare occurrence of a frontal intersinus septal mucocele can be diagnosed on CT and MR imaging studies, because its appearance in the midline is clearly distinct from the more common classic frontal sinus mucoceles that develop within the left or right frontal sinus proper. Distinction is also routinely made from large anterior ethmoid mucoceles.


Age estimation on the female sternum by quantification theory I and stepwise regression analysis.
One hundred and nine sternums from Chinese females aged 18-50 years were examined in this study. Six morphological characteristics and their changing degree in the female sternum were observed and scored. The data were statistically processed by quantification theory I and stepwise regression analysis on a computer and the following regression equation for age estimation of the female sternum was calculated: y = 19.28 + 1.83x1 + 1.66x2 + 3.02x3 + 1.57x4 + 3.02x5 + 7.75x6 + 1.25x7 + 3.45x8 + 4.88x9 + 0.82x10 + 2.76x11 + 2.48x12 + 7.84x13 + 1.26x14 + 3.80x15 (the correlation coefficient R = 0.9774, the standard deviation S = 2.20, F > 0.01). For convenience, the changing degree of the morphological characters and the equation were also converted into two tables. This method of age estimation on the female sternum is simple and accurate and is of importance to forensic medicine and anthropology.


Preparation and in vitro bioactivity of novel merwinite ceramic.
The ceramic of merwinite (Ca3MgSi2O8) was prepared by sintering sol-gel-derived merwinite powder compacts. The mechanical properties and the coefficient of thermal expansion (CTE) of the merwinite ceramic were determined. In vitro bioactivity of the merwinite ceramics was evaluated. Our results showed that the sintered body was single-phase merwinite ceramic, and that its bending strength, fracture toughness and Young's modulus were approximately 151 MPa, 1.72 MPa m(1/2) and 31 GPa, respectively. The CTE of the ceramic was 9.87 x 10(-6) degrees C(-1) and close to that for the Ti-6Al-4V alloy (9.80 x 10(-6) degrees C(-1)). Immersion of the sintered body in simulated body fluid induced surface precipitation of Ca-P rich layers. Cell culture experiment results confirmed that soluble ionic products from merwinite dissolution significantly stimulated osteoblast proliferation, and osteoblasts adhered and spread well on merwinite ceramic surfaces.


Children in Immigrant Families: Advocacy Within and Beyond the Pediatric Emergency Department.
In the United States, 1 in 4 children lives in an immigrant family. State and national policies have historically precluded equitable access to health care among children in immigrant families. More recently, increasingly restrictive policies, political rhetoric, and xenophobic stances have made immigrant families less able to access health care and less comfortable in attempting to do so, thus increasing the likelihood that patients will present to the emergency department. Once in the emergency department, language, cultural, and health literacy barriers make providing high-quality care potentially challenging for some families. Emergency care professionals can therefore glean critical insight regarding inequities from clinical work to inform advocacy and policy changes at institutional, community, regional, and national levels.


Risk factors and outcome variables of cardiorenal syndrome type 1 from the nephrologist's perspective.
In cardiorenal syndrome (CRS) type 1, acute cardiac failure or acute decompensation of chronic heart failure causes acute kidney injury (AKI). Every individual AKI episode increases the risk for chronic kidney disease (CKD) in the long term. In this study, we aimed to evaluate epidemiological characteristics and outcome variables of CRS type 1 individuals from the nephrologist's perspective. The study was performed in a retrospective, observational manner. All AKI patients treated at the Brandenburg Hospital of the Medical School of Brandenburg between January and December 2019 were screened for diagnostic criteria of CRS type 1. Endpoints were in-hospital death, need for dialysis, and renal recovery. During the screening, 198 out of 1189 (16.6%) AKI subjects were assigned to the diagnosis CRS type 1. The overall in-hospital mortality was 19.2%; 9.6% of the patients required dialysis due to AKI. Complete recovery of kidney function was observed in 86 individuals (43.4%); incomplete recovery occurred in 55 patients (27.8%). Mortality-predictive variables were AKIN stage 2, longer ICU treatment, and insulin-dependent diabetes. Regarding dialysis, AKIN stage 3 and higher potassium at the time of diagnosis were predictive. Subjects with longer in-hospital stay recovered more often from CRS type 1. The incidence of CRS type 1 is high (∼16% of all in-hospital AKI subjects) and the mortality is higher than the average mortality of AKI in general. At the same time, complete recovery of kidney function occurs less frequent. The kidney-related follow-up management of CRS type 1 needs to be significantly optimized to improve the long-term outcome of affected patients.


A prospective study on non-surgical correction of protruding ears: the importance of early treatment.
Splinting is an elegant method to correct ear deformities in the newborn. However evidence is lacking on the relation between age and efficacy and duration of the treatment. We prospectively studied these questions on protruding ears in 132 babies. A splint in the scaphal hollow was used in combination with tape (Earbuddies(®)). Treatment continued until the desired shape persisted. Results were judged from photographs and mastoid-helical distance was measured. In 132 babies 209 ears were treated. Twenty-four patients had no follow-up, 27 stopped therapy for skin irritation and fixation problems. In the remaining patients results were good in 28%, fair in 36%, poor in 36%. Efficacy deteriorates with age; with fair or good results in 66.7% if therapy started before the sixth week. Older children needed to be splinted longer. The anti-helical fold was easier corrected than a deep concha (correction in 69.8% versus 26.8%). Considering splinting therapy for protruding ears, a reasonable chance of success can only be offered to parents of children up to six weeks of age. It is favorable if the deformity is mainly due to a flat antihelix.


Advances in the understanding and treatment of biliary atresia.
The purpose of this study is to review both the basic science and clinical advancements in the last 12 months that have furthered our understanding of biliary atresia. Early diagnosis and further understanding of the disease process may be the next major step in advancement. Stool color cards have been shown to be an accurate screening tool. Basic science developments have focused on defects in morphogenesis, immunologic dysregulation, and viral infection as the major theories of causes. There have been initial reports of minimally invasive approaches to hepatic portoenterostomy but there has been little comparative study. Postoperative corticosteroid therapy remains an area of debate without definitive data. Early postoperative testing of serum bilirubin levels and hepatobiliary scintigraphy are showing strong correlation with long-term outcomes. The comparison of regions with decentralization policies compared with those with central referral policies is providing a good forum to monitor real-time outcome data. Biliary atresia continues to represent a major challenge with many unanswered questions. The establishment of multicentered collaboration in both basic science and clinical research interests has been an important step in improving outcomes for this disease.


Identification of novel benzimidazole series of potent and selective ORL1 antagonists.
Structure-activity studies on benzimidazole lead 1 obtained from library screening led to the discovery of potent and selective ORL1 antagonist 28, 5-chloro-2-[(1-ethyl-1-methylpropyl)thio]-6-[4-(2-hydroxyethyl)piperazin-1-yl]-1H-benzimidazole, which is structurally distinct from conventional non-peptide antagonists known to date.


[The importance of the choice of materials and their design for the efficacy of orthodontic appliances].
The aim of this study is to stress the importance of correct selection of materials for orthodontic appliances, and thereby emphasize the functional relationship between choice and use of material. The outlined state of the art is the result of carefully-conducted research, the development of which has been briefly mentioned; however, the type of problem resulted from critical observations by orthodontic practitioners who apply the research results for the benefit of their patients.


The gnotobiotic piglet as a model for the pathogenesis of Campylobacter jejuni infection.
The pathogenesis of enteric changes was studied in gnotobiotic piglets which, after hysterectomy had been infected orally with Campylobacter jejuni on the first day of their life. The involvement of the entire large intestine became clinically manifest by scouring on days post infection (DPI) 4 to DPI 5, and pathomorphologically, by simultaneous inflammation and severe edema of the intestinal wall. Histology and SEM revealed inflammatory edema with abundant neutrophils, microulcerations, focal propagation and activation of goblet cells, and a presence of mucin-positive material within the intestinal lumen. TEM examination revealed disconnected interdigitating folds and wide dilated intercellular spaces between enterocytes. The endothelial cells of small blood vessels in the lamina propria showed hypertrophy with increase in the thickness of their basal lamina. Ultrastructural lesions of the large intestinal microcirculation also support the hypothesis that disturbances in the vascular system are responsible for edema in the cecum and colon. Gnotobiotic piglets may be used as a suitable animal model to study colitis induced by C. jejuni.


CRY2 is associated with rapid cycling in bipolar disorder patients.
Bipolar disorder patients often display abnormalities in circadian rhythm, and they are sensitive to irregular diurnal rhythms. CRY2 participates in the core clock that generates circadian rhythms. CRY2 mRNA expression in blood mononuclear cells was recently shown to display a marked diurnal variation and to respond to total sleep deprivation in healthy human volunteers. It was also shown that bipolar patients in a depressive state had lower CRY2 mRNA levels, nonresponsive to total sleep deprivation, compared to healthy controls, and that CRY2 gene variation was associated with winter depression in both Swedish and Finnish cohorts. Four CRY2 SNPs spanning from intron 2 to downstream 3'UTR were analyzed for association to bipolar disorder type 1 (n = 497), bipolar disorder type 2 (n = 60) and bipolar disorder with the feature rapid cycling (n = 155) versus blood donors (n = 1044) in Sweden. Also, the rapid cycling cases were compared with bipolar disorder cases without rapid cycling (n = 422). The haplotype GGAC was underrepresented among rapid cycling cases versus controls and versus bipolar disorder cases without rapid cycling (OR = 0.7, P = 0.006-0.02), whereas overrepresentation among rapid cycling cases was seen for AAAC (OR = 1.3-1.4, P = 0.03-0.04) and AGGA (OR = 1.5, P = 0.05). The risk and protective CRY2 haplotypes and their effect sizes were similar to those recently suggested to be associated with winter depression in Swedes. We propose that the circadian gene CRY2 is associated with rapid cycling in bipolar disorder. This is the first time a clock gene is implicated in rapid cycling, and one of few findings showing a molecular discrimination between rapid cycling and other forms of bipolar disorder.


The protein-creatinine ratio in spot morning urine samples and 24-h urinary protein excretion in patients with systemic lupus erythematosus.
A 24-h urinary protein is a standard way to diagnose lupus nephritis. Assessment of protein-creatinine (Pr-Cr) ratio in morning spot urine is a valuable method in diabetic patients but not use in systemic lupus erythematous (SLE) patients routinely. In this study Pr-Cr ratio in spot urine was compare with 24-h urine protein; if they have valuable correlation we can use this test instead of 24-h urinary protein. The aim of this study was to evaluate the correlation of spot urine Pr-Cr ratio for prediction of significant proteinuria (>or=300 mg/24 h) in patients with SLE. A cross-section study was conducted in 74 hospitalized women with SLE. The correlation between Pr-Cr in first morning urine specimens and urinary protein excretion in 24-h collections were analyzed. Correlation between Pr-Cr ratio in spot morning urine specimens and urinary protein excretion in 24-h collections was significant (P < 0.0001, r = 0.83). A high correlation and precision of agreement were demonstrated between the two methods of assessment proteinuria in lupus patients. The difference between the two methods was less than the biological variability in the protein excretion and its measurement, enabling the methods to be used interchangeably creatinine ratio in spot morning urine samples is a precise indicator of proteinuria in patients with lupus nephritis and represents a simple and inexpensive procedure in establishing severity of proteinuria in patients with SLE.


Ultraviolet flow dichroism of brain microtubule.
Ultraviolet flow dichroism of brain microtubule was measured. Large positive dichroisms were observed at 255 nm, 285 nm and 292 nm. The dichroism at about 255 nm is due to bound GDP or GTP. The dichroism at 285 nm is due to tyrosine and tryptophan residues, and that at 292 nm is due to the tryptophan residues of the protein. These results show that the electronic transition moments of nucleotides and aromatic groups are both nearly parallel to the polymer axis.


Determinants of functional independence and quality of life in children with spina bifida.
To investigate determinants of functional independence and study which functional abilities were determinants for 'health-related quality of life' in children with myelomeningocele. Cross-sectional study by means of clinical assessment, 'disability' measurement and questionnaires. Uni- and multivariate logistic regression models were used to investigate factors that were determinants for these outcomes. Results were expressed as odds ratios (OR) and 95% confidence intervals (95% CI). Outpatient spina bifida clinic at a university hospital. One hundred and twenty-two children with myelomeningocele. Mean age 7.9; range 1-18 years. Functional independence as measured by the Pediatric Evaluation of Disability Inventory (PEDI), and quality of life as measured by the Spina Bifida Health Related Quality of Life Questionnaire. Lesion level below L3 (OR 0.4, 95% CI 0.1-1.0), mental status of IQ > or =80 (OR 4.2, 95% CI 1.2-14.9), having no contractures in lower extremities (OR 3.4, 95% CI 1.3-8.8), and having normal strength of knee extensor muscles (OR 4.1, 95% CI 1.4-11.5) were most strongly associated with independence in self-care. Mental status (OR 16.1, 95% CI 2.8-93.9), having no contractures in lower extremities (OR 1.5, 95% CI 1.4-5.3), and normal strength in knee extensors (OR 11.0, 95% CI 1.3-97.0) were the most important determinants for independence in mobility. Concerning functional abilities, being independent with regard to mobility was the most important determinant for 'health-related quality of life' (OR 5.3, 95% CI 1.6-17.4). In children with myelomeningocele, good muscle strength, mental ability and being independent in mobility appeared to be much more important for daily life function and quality of life than other medical indicators of the disorder.


A waves in electroneurography: differential diagnosis with other late responses.
Neurographic studies are an extension of clinical examination and are performed for the functional assessment of peripheral nerves. The study of motor and sensory conduction velocity and the presence, amplitude, morphology and symmetry of the response to electrical stimulation are crucial for the diagnosis and management of peripheral neuromuscular disorders. Neurography also plays an important role in the search for so-called late responses comprising the F wave, H reflex, axonal response and A wave. By analysing the parameters of each late wave, this paper addresses the pathophysiological features and the most common conditions impairing the physiology of late responses, with a special focus on A waves.


A 3-year follow-up study of uncut Roux-en-Y reconstruction: clinical results and outcomes.
The goal of this study was to identify the clinical outcomes of uncut Roux-en-Y reconstruction in patients who underwent totally laparoscopic distal gastrectomy (TLDG) over 3-year follow-up. From January 2016 to December 2017, 269 patients who underwent TLDG were enrolled in the study and analyzed retrospectively. They were classified into two groups according to the reconstruction method: uncut Roux-en-Y reconstruction (uncut RY) (n = 154) and Billroth II with Braun anastomosis (B-II/Braun) (n = 115). Postoperative endoscopic findings (residual food, bile reflux, gastritis, and esophagitis) and nutritional status (body weight, serum hemoglobin, total protein, and albumin levels) were assessed every 6 months for 3 years. Residual food was less frequent in the uncut RY group in the 6th month after TLDG (p = 0.022), but there were no differences between the two groups for the rest of the study period. The incidence of bile reflux and gastritis was low in the uncut RY group during all postoperative periods (all p < 0.001). In the B-II/Braun group, the frequency of reflux esophagitis was high in the 30th and 36th months after TLDG (both p < 0.001), and there were no differences between the two groups during the preceding periods. No significant differences were found with respect to nutritional status, such as body weight, serum hemoglobin, total protein, and albumin levels during all postoperative periods. Three-year follow-up outcomes showed that uncut RY can effectively reduce the incidence of bile reflux and gastritis in the remnant stomach compared to B-II/Braun after TLDG.


[Microbiological contamination of disinfectants used in hospitals for the disinfection of medical instruments. Part II: The estimation of sensitivity of isolated strains of bacteria in disinfectants].
The sensitivity, on basic disinfectants, of 30 strains of bacteria isolated from disinfecting fluid used in hospitals were estimated. The sensitivity of isolated strains were compared with that of laboratory test strains.


Replication of chromosomal loci involved in Parkinson's disease: A quantitative synthesis of GWAS.
Parkinson's disease is a neurodegenerative disorder with a complex etiology coming from interactions between genetic and environmental factors. Research on Parkinson's disease genetics has been an effortful struggle, while new technologies and novel study designs served as indispensable boosters. Until now, 90 loci and 20 disease-causing gene mutations have been identified. In this study we describe a novel non-parametric approach to GWAS meta-analysis and its application in PD genetics. A literature search was conducted to identify Genome-Wide Association Studies (GWAS) regarding Parkinson's disease. We applied predefined inclusion criteria and extracted the reported SNPs and their respective position and statistical significance. We divided all chromosomes in approximately equal genetic distance segments called bins and recorded the most significant SNP from each bin and each study and ranked them in terms of their p-value. Ranks from each bin were summed, averaged and added in a heterogeneity-based analysis using the METRADISC-XL software. Weighted and unweighted analysis was performed. Five-hundred and forty-three SNPs and their respective p-values from 15 studies were matched in their corresponding bins. The METRADISC-XL analysis resulted in 7 bins with a significant p-value. A bin on chromosome 4 where the SNCA gene is located found with genome-wide significant association with Parkinson's Disease. This is the first time a non-parametric method is applied in GWAS meta-analysis. The results add some insight on the overall understanding of Parkinson's disease genetics and serve as a first step of further convergent analysis with Genome-wide linkage studies.


Radiotherapy of the rhabdomyosarcoma R1H of the rat: kinetics of cellular inactivation by fractionated irradiation.
The kinetics of cellular inactivation by fractionated irradiation in the R1H rhabdomyosarcoma of the rat was studied in the dose range of 1.07 to 12.50 Gy per fraction. Regimens of 1, 3, 5, 7, and 10 fractions per week for several weeks were compared. The number of clonogenic tumor cells per tumor in the course of the different treatment schedules was determined using an in vitro colony assay. The results show that the proliferation of clonogenic tumor cells is decelerated in the course of a fractionated radiotherapy. The deceleration persists for several days after end of treatment, until accelerated repopulation is initiated. The fraction of tumor cells inactivated per week was only dependent on the total dose per week, that is the cellular response was the same whether the weekly dose was applied in 1,3,5,7, or 10 fractions. Thus, the fractionation regimens were considerably more effective than expected from calculations based on single-dose in situ survival curves.


Intrinsic stimuli-responsive nanocarriers for smart drug delivery of antibacterial agents-An in-depth review of the last two decades.
Antibiotic resistance due to suboptimal targeting and inconsistent antibiotic release at bacterial infection sites has driven the formulation of stimuli-responsive nanocarriers for antibacterial therapy. Unlike conventional nanocarriers, stimuli-responsive nanocarriers have the ability to specifically enhance targeting and drug release profiles. There has been a significant escalation in the design and development of novel nanomaterials worldwide; in particular, intrinsic stimuli-responsive antibiotic nanocarriers, due to their enhanced activity, improved targeted delivery, and superior potential for bacterial penetration and eradication. Herein, we provide an extensive and critical review of pH-, enzyme-, redox-, and ionic microenvironment-responsive nanocarriers that have been reported in literature to date, with an emphasis on the mechanisms of drug release, the nanomaterials used, the nanosystems constructed and the antibacterial efficacy of the nanocarriers. The review also highlights further avenues of research for optimizing their potential and commercialization. This review confirms the potential of intrinsic stimuli-responsive nanocarriers for enhanced drug delivery and antibacterial killing. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.


The Association of Inflammatory Bowel Disease with Coeliac Disease and Coeliac Autoimmunity in Children and Adults: A Nationwide Study from the epi-IIRN.
Given the paucity of population-based data on the association between inflammatory bowel diseases [IBD], coeliac disease [CeD], and coeliac autoimmunity [CeA] we aimed to study the associations in a nationwide study. Using health administrative data for all four health maintenance organisations in Israel, covering 98% of the population, we explored the prevalence of CeD in children and adults with IBD versus non-IBD matched controls. CeD was defined by three ICD-9 codes and CeA by positivity for tissue transglutaminase antibodies. In total, 34 375 IBD patients (56% Crohn's disease [CD] and 44% ulcerative colitis [UC]) were compared with 93 603 non-IBD controls. Among IBD patients, 319 [0.93%] had CeD versus 294 [0.31%] non-IBD controls (odds ratio [OR] = 2.97, 95% confidence interval [CI] 2.54-3.48; p <0.001). CeA was identified in 575 [1.67%] IBD patients vs 158 [0.17%] controls [OR = 10.06, 95% CI 8.43-12; p <0.001]. The prevalence of CeD was higher in paediatric-onset IBD (87/5243 [1.66%]) than adult-onset IBD (232/29 132 [0.79%]; p <0.001). CD patients had a higher prevalence of CeD (229/19 264 [1.19%]) than UC patients (90/15 111 [0.56%]; OR = 2.01, 95% CI 1.57-2.56; p <0.001). The diagnosis of CeD preceded the diagnosis of IBD in 241/319 cases [76%]. The time to treatment escalation was shorter in patients with both IBD and CeD than in patients with IBD without CeD [p = 0.017]. CeD and CeA are more prevalent in IBD patients, especially in paediatric-onset IBD and in CD. The diagnosis of CeD usually precedes that of IBD. Having CeD is associated with more intensified treatment for IBD.


Determination of mini-short tandem repeat (miniSTR) loci by using the combination of polymerase chain reaction (PCR) and microchip electrophoresis.
In this work, a simple and convenient method for the detection of mini-short tandem repeat (miniSTR) loci has been developed by the combination of polymerase chain reaction (PCR) and microchip electrophoresis (MCE). Degraded or inhibitor DNA greatly limited STR loci analysis. Therefore, The proper primers was designed as close as possible to the STRs region to produce smaller size STRs, and made the assay suitable for the destroyed samples. Two annealing temperatures were applied in one PCR procedure and the corresponding cycle numbers were studied to improve the sensitivity of PCR reaction. Under optimal conditions, 0.001 ng DNA templates were enough to generate miniSTRs. The relative standard deviations (n=3) of the size fifteen miniSTRs from DNA9947A ranged from 0.49% to 4.41%. The RSDs of concentrations were between 0.94% and 4.95%. Fifteen miniSTRs were also well produced from human hair, indicating that the method has great potential application in criminal identification and paternity testing.


[Cloverleaf skull and bilateral facial clefts].
Cloverleaf skull syndrome, or Kleeblattschädel syndrome, is a rare malformation in which the skull has a cloverleaf appearance. It is caused by the premature closure of several sutures, being evident before birth. To present our experience in a case of cloverleaf skull syndrome, and update the information from the literature. A female infant of 5 months of age, diagnosed at birth with cleft lip and palate and hydrocephaly. A peritoneal ventricle valve was implanted at 30 days of life, and an ocular enucleation was performed due to an infectious process. The patient was followed-up in Genetics, where it confirmed a macrocephaly and craniosynostosis type cloverleaf skull. The 46XX cytogenetic study and echocardiography were normal. The brain CT scan showed multiple anomalies associated with hydrocephaly and non-specific malformations. Cloverleaf skull may be present in isolated form or associated with other congenital abnormalities, leading to various craniosynostosis syndromes, such as Crouzon, Pfeiffer or Carpenter. It may also be a component of the amniotic rupture sequence or to different dysplasias, such as campomelic dysplasia, thanatophoric dysplasia type 2, or the asphyxiating thoracic dystrophy of Jeune. The case presented does not fulfil all the characteristics needed to be included within a specific syndrome, and on not having a family history that suggests a hereditary pattern or chromosome abnormalities, it is concluded that it is a case of a congenital anomaly of sporadic presentation.


Impact of lower pole anatomy on stone clearance after shock wave lithotripsy.
This study retrospectively analyzed patients treated with shock wave ithotripsy (SWL) for lower calyceal stones, to determine the influence of the lower pole anatomy and stone size in predicting the clearance of fragments. Between June 2000 and March 2002, we reviewed excretory urography (IVU) of 59 patients with isolated lower pole stones treated with SWL. A total of 44 men and 15 women, with an age ranging between 23 and 78 years (mean, 55 years), were included in the study. The patients were divided into two groups, either a stone-free group or residual-stone group. After SWL, overall stone rate was 57.6%, and clearance for stones less than 10 mm in diameter was 64.5%, whereas clearance was 50% for stones between 10 and 20 mm in diameter. Intrarenal anatomy on IVU, such as infundibular width and infundibulopelvi-ureteric angle showed no significant difference between the stone-free and residual-stone groups. Our analysis showed that three significant variables were relevant to stone clearance: infundibular length, stone size and stone burden. We conclude that SWL is the best treatment for lower pole kidney stones 10 mm or less in diameter, showing lower complication and acceptable stone-free rates.


Effect of dietary selenium and omega-3 fatty acids on muscle composition and quality in broilers.
Human health may be improved if dietary intakes of selenium and omega-3 fatty acids are increased. Consumption of broiler meat is increasing, and the meat content of selenium and omega-3 fatty acids are affected by the composition of broiler feed. A two-way analyses of variance was used to study the effect of feed containing omega-3 rich plant oils and selenium enriched yeast on broiler meat composition, antioxidation- and sensory parameters. Four different wheat-based dietary treatments supplemented with 5% rapeseed oil or 4% rapeseed oil plus 1% linseed oil, and either 0.50 mg selenium or 0.84 mg selenium (organic form) per kg diet was fed to newly hatched broilers for 22 days. The different dietary treatments gave distinct different concentrations of selenium and fatty acids in thigh muscle; one percent linseed oil in the diet increased the concentration of the omega-3 fatty acids 18:3, 20:5 and 22:5, and 0.84 mg selenium per kg diet gave muscle selenium concentration at the same level as is in fish muscle (0.39 mg/kg muscle). The high selenium intake also resulted in increased concentration of the long-chain omega-3 fatty acids EPA (20:5), DPA (22:5) and DHA (22:6), thus it may be speculated if high dietary selenium might have a role in increasing the concentration of EPA, DPA and DHA in tissues after intake of plant oils contning omega-3 fatty acids. Moderate modifications of broiler feed may give a healthier broiler meat, having increased content of selenium and omega-3 fatty acids. High intakes of selenium (organic form) may increase the concentration of very long-chain omega-3 fatty acids in muscle.


On the mechanism of an increase of muscle performance and of vasodilation during emotional stress in man.
The mechanism of the increase of muscle performance and of vasodilation during emotional stress was studied. The "emotional" increment of voluntary performance does not depend on the level of blood supply to the working muscles, and the effect is maintained under conditions of cessation of arterial inflow. Augmentation of muscle performance is also observed during emotional stress when isometric contraction is evoked by electrical tetanic stimulation of the nerve, when the number of muscle fibres participating in the evoked response does not increase during emotional stress. The "emotional" vasodilation is greatly reduced in patients suffering from McArdle's syndrome, in whom the normal course of glycolysis in muscles is disrupted. It is suggested that acetylcholine liberated from sympathetic fibres causes the activation of glycolysis in muscles, which in its turn induces vasodilation in resting skeletal muscles and increase of muscle performance during emotional stress.


Effects of Tai Chi on glucose homeostasis and insulin sensitivity in older adults with type 2 diabetes: a randomised double-blind sham-exercise-controlled trial.
a large proportion of adults with type 2 diabetes remain sedentary despite evidence of benefits from exercise for type 2 diabetes. Simplified Yang Tai Chi has been shown in one study to have no effect on insulin sensitivity in older adults. However, a modified Tai Chi form, Tai Chi for Diabetes (TCD) has recently been composed, claiming to improve diabetes control. subjects were randomised to Tai Chi or sham exercise, twice a week for 16 weeks. Primary outcomes were insulin resistance 72 h post-exercise (HOMA2-IR), and long-term glucose control (HbA(1c)). thirty-eight subjects (65 +/- 7.8 years, 79% women) were enrolled. Baseline BMI was 32.2 +/- 6.3 kg/m(2), 84% had osteoarthritis, 76% hypertension, and 34% cardiac disease. There was one dropout, no adverse events, and median compliance was 100 (0-100)%. There were no effects of time or group assignment on insulin resistance or HbA(1c) ( -0.07 +/- 0.4% Tai Chi versus 0.12 +/- 0.3% Sham; P = 0.13) at 16 weeks. Improvement in HbA(1c) was related to decreased body fat (r = 0.484, P = 0.004) and improvement in insulin resistance was related to decreased body fat (r = 0.37, P = 0.03) and central adiposity (r = 0.38, P = 0.02), as well as increased fat-free mass (r = -0.46, P = 0.005). TCD did not improve glucose homeostasis or insulin sensitivity measured 72 h after the last bout of exercise. More intense forms of Tai Chi may be required to produce the body composition changes associated with metabolic benefits in type 2 diabetes.


The effect of eccentricity and colour on negativity in pattern onset visual evoked potentials.
The effects of stimulus size, eccentricity and colour on the amplitudes of N100 and N130 were investigated in pattern onset VEPs. For black-and-white pattern stimulation, the first set of stimuli was derived from a full dartboard pattern. Central stimulation of various extents was produced by patterns with reduced number of outer rings and for eccentric stimuli a number of central rings were removed from the full pattern. It was found that amplitude of N100 was maximal in VEPs to central stimuli and that it was greatly reduced when eccentric stimulation was applied. The amplitude of N130 showed no significant change in relation to the type of stimulus. When checkerboard stimuli of identical configuration were used for black-and-white pattern stimulation instead of dartboards, systematic changes in peak latencies of N100 were observed in relation to check size. In VEPs to centrally presented small checks the emergence of an early negative peak preceding N100 was recorded at 75 msec. In VEPs to coarse checkerboards presented centrally N100 was often observed with a delayed peak latency of 110 msec. Changes in N130 were not regular when checkerboards with different check sizes were presented centrally. For eccentric checkerboard stimulation, both negative peaks N100 and N130 were revealed. Their peak latencies were similar to those observed in the case of dartboard paracentral stimulation. In VEPs to patterns projected through red or blue filters, regular changes were observed in both negative peaks. Introduction of the red filter led to enhancement of the N100 amplitude in VEPs to dartboard and to checkerboards with fine checks, but it caused no effect on N100 in the VEPs to coarse checkerboards. Introduction of the blue filter led to a decrease in the N100 amplitude in VEPs to dartboard and fine checkerboards and to a slight increase of N100 in VEPs to coarse checkerboards. Changes in N130 were observed only when the blue filter was introduced and they corresponded to those which take place when the level of illumination changes from photopic to mesopic.


Rubella epidemic caused by genotype 1E rubella viruses in Beijing, China, in 2007-2011.
A series of different rubella vaccination strategies were implemented to control rubella and prevent congenital rubella virus infection in Beijing, China. The rubella vaccine was available in 1995 in Beijing, and was introduced into the Beijing immunization program (vaccine recipients at their own expense vaccination) in 2000, and was introduced into the National Expanded Program on Immunization (vaccine recipients free vaccination) in 2006. Rubella virological surveillance started in Beijing in 2007. The reported rubella incidence rate has decreased dramatically due to the introduction of the vaccine in Beijing since 1995. However, rubella epidemics occurred regardless in 2001 and 2007. The incidence rate among the floating population has gradually increased since 2002, reaching 2 or more times that in the permanent resident population. The peak age of rubella cases gradually changed from <15 years of age to adults after 2005. Phylogenetic analysis was performed and a phylogenetic tree was constructed based on the World Health Organization standard sequence window for rubella virus isolates. All Beijing rubella virus isolates belong to genotype 1E/cluster1 and were clustered interspersed with viruses from other provinces in China. The effective number of infections indicated by a Bayesian skyline plot remained constant from 2007 to 2011. The proportion of rubella cases among the floating population has increased significantly in Beijing since 2002, and the disease burden gradually shifted to the older age group (15- to 39-year olds), which has become a major group with rubella infection since 2006. Genotype 1E rubella virus continuously caused a rubella epidemic in Beijing in 2007-2011 and was the predominant virus, and all Beijing genotype 1E viruses belong to cluster 1, which is also widely circulated throughout the country.


Comprehensive study of algal blooms variation in Jiaozhou Bay based on google earth engine and deep learning.
The Jiaozhou Bay ecosystem, a crucial marine ecosystem in China, has been plagued by frequent harmful algal blooms as due to deteriorating water quality and eutrophication. This study analyzed the temporal and spatial changes of harmful algal blooms in Jiaozhou Bay from 2000 to 2022 using the Floating Algae Index (FAI) calculated from MODIS (2000-2022) and Sentinel-2 (2015-2022) satellite image datasets. The calculation results of the image datasets were compared. The frequency of planktonic algal outbreaks was low and constant until 2017, but has increased annually since then. Algae blooms are most common in the summer and primarily concentrated along the bay's coast, middle, and mouth, with obvious seasonal and spatial distribution characteristics. Several factors influencing algal outbreaks were identified, including sea surface temperature, wind speed, air pressure, dissolved oxygen, nitrogen and phosphorus ratios, chemical oxygen demand, and petroleum pollutants. Algal bloom outbreaks in Jiaozhou Bay are expected to remain high in 2023. The findings provide crucial information for water quality management and future algal outbreak prediction and prevention in Jiaozhou Bay.


Central and peripheral release of oxytocin following chronic homotypic stress in rats.
Accumulation of continuous life stress (chronic stress) often causes gastric symptoms. Centrally released oxytocin has anxiolytic and anti-stress effects. We have recently shown that impaired gastric and colonic motility observed in acute restraint stress was restored following repeated restraint stress for 5 consecutive days (chronic homotypic stress) in mice and rats. Chronic homotypic stress upregulates oxytocin mRNA expression and downregulates corticotrophin-releasing factor (CRF) mRNA expression at the hypothalamus. However, it still remains unclear whether stress responses induced by chronic homotypic stress are accompanied by the central or peripheral release of oxytocin. Adult male SD rats were chronically implanted with microdialysis probes at the hypothalamic paraventricular nucleus (PVN) and jugular vein catheters. Microdialysis and blood sampling were performed following 1st, 3rd and 5th of chronic homotypic stress. Oxytocin levels in the dialysates and plasma were measured by radioimmunoassay (RIA). On day 1 of chronic homotypic stress, oxytocin release was slightly, but not significantly, increased in the PVN and plasma. Oxytocin release was significantly increased in the PVN on day 3 (12.7 ± 1.3 pg/sample, n=5, P<0.05) and day 5 (28.2 ± 2.4 pg/sample, n=5, P<0.05) from basal (6.9 ± 1.8 pg/sample, n=5). In contrast, there were no significant changes observed in the plasma on day 3 and day 5. This suggests that central, but not peripheral, release of oxytocin plays an important role in response to chronic homotypic stress in rats.


Causal model of health literacy in dietary supplement use and sufficient health behavior among working-age adults.
Sufficient health behavior (SHB) and health literacy in dietary supplement use (HL-DSU) are the key determinants of health status. However, the link between HL-DSU and SHB is not fully understood. Therefore, the objective of this research was to investigate the model and identify the size of its effect on HL-DSU and SHB among adults of working age. The study employed a cross-sectional survey design, with cluster random sampling used for the selection of 696 working-age adults ranging from 20-59 years. Data on their SHB, HL-DSU, awareness of dietary supplement advertising (DSA), and social support were collected from August to October 2021 through questionnaires employing a 5-point rating scale. Content validity was determined using item-objective congruence (IOC) values ranging from 0.6 to 1.0 obtained for each item on the questionnaire. The Cronbach's alpha values ranging from 0.93 to 0.96 indicated reliability, while the independent t-test, descriptive analysis, and structural equation modeling (SEM) were performed. SHB is defined as the health-beneficial behaviors based on a balanced lifestyle, utilizing conceptual approaches resulting in positive health outcomes relating to fundamental goals in the use of dietary supplements and other contexts emphasizing sufficiency. The causal model was found to fit the empirical data with an acceptable goodness-of-fit value. The findings indicate that social support, awareness of DSA, and HL-DSU directly affect SHB (Beta of 0.33, 0.20, and 0.13, respectively, p < .05) and could predict 34% of SHB overall. HL-DSU is shown to be significantly and directly impacted by social support and awareness of DSA, with influence coefficients of 0.36 and 0.57, respectively. The variance of HL-DSU can be predicted by these two factors as 67%. The establishment of campaign activities to promote awareness regarding the advantage and disadvantages, as well as media literacy of supplementary food products in health centers and communities, should be the focus of healthcare providers.


Acute muscle and joint mechanical responses following a high-intensity stretching protocol.
A previous study observed a joint passive torque increase above baseline ~30 min after a high-intensity stretching. This study examined the effect of a high-intensity stretching on ankle dorsiflexion passive torque, medial gastrocnemius (MG) shear modulus, and plantar flexors maximal voluntary isometric force (MVIC). Participants (n = 11, age 27.2 ± 6.5 years, height 172.0 ± 10.0 cm, weight 69.5 ± 10.4 kg) underwent two stretching sessions with plantar flexors isometric contractions performed: (1) 5 min before, 1 min after, and every 10 min after stretching (MVC session); (2) 5 min before, and 60 min after the stretching (no-MVC session). In both sessions, no changes were observed for MG shear modulus (p > 0.109). In the no-MVC session, passive torque decreased 1 min after stretching (-7.5 ± 8.4 %, p = 0.015), but increased above baseline 30 min after stretching (+6.3 ± 9.3 %, p = 0.049). In the MVC session, passive torque decreased at 1 min (-10.1 ± 6.3 %, p < 0.001), 10 min (-6.3 ± 8.2 %, p = 0.03), 20 min (-8.0 ± 9.2 %, p = 0.017), and 60 min (-9.2 ± 12.4 %, p = 0.034) after the stretching, whereas the MVIC decreased at 1 min (-5.0 ± 9.3 %, p = 0.04) and 10 min (-6.7 ± 8.7 %, p = 0.02) after stretching. The ankle passive torque increase 30 min following the stretch was not due to the MG shear modulus response; consequently, response may be due to changes in surrounding connective tissue mechanical properties.


Variable VOCs in plastic culture flasks and their potential impact on cell volatile biomarkers.
In order to find out cancer markers in human breath, in vitro cell culture is often used to study the characteristic volatile organic compounds (VOCs). In the cell culture process, disposable vessels are frequently adopted. However, these vessels are normally made of plastic, and they have the possibility to release some VOCs, which may interfere with the cell-specific volatiles and even can result in an incorrect conclusion. In this study, by using glass cell culture flasks as control, the headspace solid-phase microextraction gas chromatography mass spectrometry (HS-SPME-GC-MS) analyses of the VOCs in plastic cell culture flasks were systematically carried out for the first time. A total of 35 VOCs were detected in five brands of flasks. In each flask, there were between 13 and 25 volatile compounds. Furthermore, the components and packaging bag of each flask were also sampled and analyzed by HS-SPME-GC-MS. The results show that the flask cap, septum, flask body, and packaging bag exhibit respectively different volatile behaviors. The former two parts release the most volatiles which have obvious contributions to the headspace gases in the flasks, while the flask body mainly liberates styrene. For different flasks packed within the same bag, the headspace analyses show that their residual VOCs are inconsistent with each other. Moreover, the residual VOCs in the same flask are variable in three consecutive days. These results indicate that the multiple flasks in parallel cell culture experiments, or the same flask with different cell culture durations, will produce an indelible disturbance to the cell-specific VOCs. In addition, among the 35 VOCs detectable in five brands of empty plastic flasks, 15 VOCs were previously reported as characteristic VOCs from lung cancer, melanoma, cervical cancer cells, or normal cells. This is an alert that, when using plastic flasks, it must be careful to treat the possible interference from the background VOCs in the flasks. This study demonstrates that the cell culture tool needs to be standardized, and the clean glass or metal vessels are strongly recommended for usage when studying cell volatile biomarkers. Graphical abstract.


Mobilization without immune depletion fails to restore immunological tolerance or preserve beta cell function in recent onset type 1 diabetes.
Granulocyte colony-stimulating factor (G-CSF) has been used to restore immune competence following chemoablative cancer therapy and to promote immunological tolerance in certain settings of autoimmunity. Therefore, we tested the potential of G-CSF to impact type 1 diabetes (T1D) progression in patients with recent-onset disease [n = 14; n = 7 (placebo)] and assessed safety, efficacy and mechanistic effects on the immune system. We hypothesized that pegylated G-CSF (6 mg administered subcutaneously every 2 weeks for 12 weeks) would promote regulatory T cell (Treg) mobilization to a degree capable of restoring immunological tolerance, thus preventing further decline in C-peptide production. Although treatment was well tolerated, G-CSF monotherapy did not affect C-peptide production, glycated haemoglobin (HbA1c) or insulin dose. Mechanistically, G-CSF treatment increased circulating neutrophils during the 12-week course of therapy (P < 0·01) but did not alter Treg frequencies. No effects were observed for CD4(+) : CD8(+) T cell ratio or the ratio of naive : memory (CD45RA(+)/CD45RO(+)) CD4(+) T cells. As expected, manageable bone pain was common in subjects receiving G-CSF, but notably, no severe adverse events such as splenomegaly occurred. This study supports the continued exploration of G-CSF and other mobilizing agents in subjects with T1D, but only when combined with immunodepleting agents where synergistic mechanisms of action have previously demonstrated efficacy towards the preservation of C-peptide.


Tetracycline-regulated intratumoral expression of interleukin-3 enhances the efficacy of radiation therapy for murine prostate cancer.
The aim of this study was to investigate means of increasing the efficiency with which cancer cell death following local radiation therapy (RT) is translated into the generation of tumor immunity since, if this were to be achieved, it would be expected to enhance the rates of disease-free recurrence and survival. Our investigations centered around the use of interleukin-3 (IL-3), expressed intratumorally using an inducible adenoviral vector, to alter the immunogenicity of established murine TRAMP-C1 prostate cancer receiving a course of fractionated local RT (7 Gy per fraction per day for 5 days). Because high systemic levels of IL-3 can be associated with toxicity, a tetracycline-regulated gene delivery system was employed. The results show that while intratumoral IL-3 expression or RT alone caused a modest delay in TRAMP-C1 tumor growth, the combination was synergistic with 50% of mice being cured and developing a long-term, tumor-specific state of immunity. Immunological analyses performed on splenic lymphocytes demonstrated that, compared to RT or IL-3 alone, combined treatment significantly increased the number of tumor-specific IFN-gamma-secreting and cytotoxic T cells. The study demonstrates that tetracycline-regulated IL-3 gene expression within tumors can enhance the immune response to prostate cancer and this can augment the efficacy of a course of RT without additional side effects.


In vivo transcription from deletion mutations introduced near Escherichia coli ribosomal RNA promoter P2.
In order to characterize the tandem rrnB promoters transcribing one of the ribosomal RNA operons in E. coli we subcloned the basic promoter unit. This 185 bp fragment extends from -64 to +121 counted from the transcription start site of upstream promoter P1. The start site of downstream promoter P2 is also included in the promoter cartridge. S1 mapping experiments show that both promoters on this fragment are active in vivo. BAL-31 deletion mutations generated at the start site for promoter P2 were also tested by S1 mapping. Transcription from P2 remained active in all cases with the exception of one construction which lacks the -10 region. This demonstrates that the sequences downstream from the -10 region of P2 are not essential for basic promoter function.


Fractures in a tertiary Neonatal Intensive Care Unit in Wales.
To explore associations with fractures reported in a tertiary neonatal intensive care unit (NICU). Babies admitted to NICU from 1998 to 2007 in Cardiff, UK, with fractures during admission were identified. Clinical information was extracted from inpatient records. Results were reported as median (ranges). Seventy-one fractures were recorded in 27 (boys = 16) infants with a gestational age of 28 (23.6-40.4) weeks and birthweight of 920 g (485-4875). Fractures were recognized at 57 (1-128) days of age. Neonates with fractures without clear aetiologies (n = 17) were more preterm (p < 0.001), were born lighter (p < 0.001), required multiple medical interventions, were more commonly osteopenic (p < 0.001), had fractures detected later (p < 0.001) and had more posterior rib fractures (p = 0.009). Rib fractures were detected later than other sites (p = 0.002). Associations with rib fractures included osteopenia (p = 0.04), longer oxygen therapy (p = 0.018), length on total parental nutrition (p = 0.03), later achievement of full enteral feeds (p = 0.038), sepsis (p = 0.038) and surgical procedures (p = 0.004). Posterior rib fractures were more common in babies born more preterm (25.1 vs. 29.4 weeks, p = 0.003) and requiring diuretics (p = 0.027). Fractures in premature infants are associated with a variety of predisposing factors. Clinicians evaluating the cause of rib and multiple fractures in preterm neonates shortly after discharge need to take these factors into consideration.


Exploratory study of humoral and cellular immunity to 17DD Yellow Fever vaccination in children and adults residents of areas without circulation of Yellow Fever Virus.
The present investigation comprised two independent observational arms to evaluate the influence of pre-existing flavivirus humoral immunity and the age-impact on 17DD-YF vaccination immunity. Flavivirus (YFV; DENV; ZIKV) serology and YF-specific cellular immunity was evaluated in 288 children/9Mths-4Yrs and 288 adults/18-49Yrs residents of areas without YFV circulation. Data demonstrated that flavivirus seropositivity at baseline was higher in Adults as compared to Children (26%;87%;67% vs 6%;13%;15%, respectively). The heterologous flavivirus seropositivity (DENV; ZIKV) did not impact the YF-specific cellular immune response at baseline. However, higher levels of NCD4, EMCD8, IFN-MCD8, NCD19 and nCMCD19 were observed in subjects with pre-existing YFV seropositivity. Primary vaccination of YFV-seronegative volunteers led to higher levels of YF-neutralizing antibodies in Adults as compared to Younger Children (9Mths-2Yrs). Although similar seropositivity rates observed amongst Children and Adults at D30-45, lower rates were observed in Younger Children (9Mths-2Yrs) at D365 (94%;95%;100% vs 87%;96%;99%, respectively). A progressive decline in antibody levels were reported at D365, being more expressive in Children as compared to Adults. All age-subgroups exhibited at D30-45 increased levels of eEfCD4, EMCD4, IFN-MCD8 and nCMCD19 together with a decrease of eEfCD8 and CMCD8. While an increase of EMCD8 were observed in all subgroups at D30-45, a declined duration at D365 was reported only in Younger Children (9Mths-2Yrs). Biomarker signatures further support that only Younger Children (9Mths-2Yrs) presented a progressive decline of EMCD8 at D365. Together, these findings demonstrated that regardless the similarities observed in YF-neutralizing antibodies, the age impacts the duration of cellular immune response to primary 17DD-YF vaccination.


Clustering of Cardiac Transcriptome Profiles Reveals Unique: Subgroups of Dilated Cardiomyopathy Patients.
Dilated cardiomyopathy is a heterogeneous disease characterized by multiple genetic and environmental etiologies. The majority of patients are treated the same despite these differences. The cardiac transcriptome provides information on the patient's pathophysiology, which allows targeted therapy. Using clustering techniques on data from the genotype, phenotype, and cardiac transcriptome of patients with early- and end-stage dilated cardiomyopathy, more homogeneous patient subgroups are identified based on shared underlying pathophysiology. Distinct patient subgroups are identified based on differences in protein quality control, cardiac metabolism, cardiomyocyte function, and inflammatory pathways. The identified pathways have the potential to guide future treatment and individualize patient care.


Existence of endogenous inhibitors of platelet-activating factor (PAF) with PAF in rat uterus.
Two kinds of phospholipids in normal rat uterus were found to inhibit the aggregation of washed rabbit platelets induced by 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (alkylacetyl-GPC) and were named Inhibitor I and Inhibitor II and identified by mass spectrometry. Inhibitor I was a mixture of 1-acyl (16:0, 18:0, 18:1, 18:2, and 20:4)-2-lyso-sn-glycero-3-phosphocholine (acyllyso-GPC) and 1-alkyl (16:0, 18:0, and 18:1)-2-lyso-sn-glycero-3-phosphocholine (alkyllyso-GPC). 16:0 acyllyso-GPC was the most inhibitory, followed by 18:1, 18:2, 20:4, and 18:0 acyllyso-GPCs and 16:0 alkyllyso-GPC. Their IC50 values were in the range of 1-4 X 10(-5) M against the platelet aggregation induced by 1 X 10(-10) M 16:0 alkylacetyl-GPC, indicating that they were about 100 times weaker inhibitors than CV-3988. Inhibitor II was a mixture of N-acyl sphing-4-enyl phosphocholine (18:1/18:0, 18:1/20:0, 18:1/24:0, and 18:1/24:2). The most inhibitory of these components were 18:1/20:0 and 18:1/24:0, followed by 18:1/24:2 and 18:1/18:0, and their IC50 values were in the range of 4-5 X 10(-5) M against platelet aggregation induced by the alkylacetyl-GPC. Quantitatively, about 10(5) times higher concentrations of these inhibitors should be necessary to inhibit platelet aggregation induced by 1 X 10(-10) M 16:0 alkylacetyl-GPC. In fact, the contents of Inhibitors I and II, respectively, were approximately 10(5) times (4.7 X 10(-2) and 7.1 X 10(-2) mol/mol lipid-phosphorus of the original uterine phospholipids) than that of 16:0 alkylacetyl-GPC (1.4 X 10(-6) mol/mol lipid-phosphorus). The role of alkylacetyl-GPC in normal rat uterus is uncertain, but it coexists in situ with two kinds of endogenous inhibitors, choline containing lysoglycerophospholipids and sphingophospholipids.


Differences in adrenoreception in the microcirculatory bed of the pia mater in normotensive and spontaneously hypertensive rats.
Adrenoceptors in pial vascular bed of normotensive Wistar-Kyoto rats are distributed unevenly during stimulation of the superior cervical ganglion, their density was maximum in the 5th-generation arteries. In spontaneously hypertensive rats (SHR) the density of adrenoceptor is lower than in normotensive rats and their number is maximum in the 1st-generation arteries.


Pygopus activates Wingless target gene transcription through the mediator complex subunits Med12 and Med13.
Wnt target gene transcription is mediated by nuclear translocation of stabilized beta-catenin, which binds to TCF and recruits Pygopus, a cofactor with an unknown mechanism of action. The mediator complex is essential for the transcription of RNA polymerase II-dependent genes; it associates with an accessory subcomplex consisting of the Med12, Med13, Cdk8, and Cyclin C subunits. We show here that the Med12 and Med13 subunits of the Drosophila mediator complex, encoded by kohtalo and skuld, are essential for the transcription of Wingless target genes. kohtalo and skuld act downstream of beta-catenin stabilization both in vivo and in cell culture. They are required for transcriptional activation by the N-terminal domain of Pygopus, and their physical interaction with Pygopus depends on this domain. We propose that Pygopus promotes Wnt target gene transcription by recruiting the mediator complex through interactions with Med12 and Med13.


Impact of medical scribes on dermatology trainee and attending experience.
Medical scribe integration into academic dermatology practices results in decreased attending documentation time, improved physician efficiency, and positive patient satisfaction. However, scribes' impact on dermatology education has not been explored. We conducted a cross-sectional survey at the Brigham and Women's Hospital Dermatology Department and its associated residency program assessing trainee and attending perceptions of scribe impact on documentation time, teaching time, and quality of teaching. Thirty-nine surveys (67% of eligible population) were analyzed. The majority of faculty and trainees perceived that scribes decreased documentation time (92% attendings, 88% trainees), increased attendings' direct teaching time (57% attendings, 76% trainees), increased attending availability to answer questions (57% attendings, 68% trainees), and improved overall education (57% attendings, 80% trainees). Trainees generally perceived educational benefits of scribes more strongly than attendings. Trainees and attendings had discordant views regarding number of patients that the trainee sees (29% attendings, 72% trainees, P<0.05) and the amount of supervision provided for procedures (43% attendings, 56% trainees). The positive impact of scribes on dermatology education is consistent with results in other disciplines. Although hospitals typically invest in scribes to increase physician efficiency, this study suggests that scribes can also improve the educational experience.


Clinical and oncologic outcomes of totally robotic total mesorectal excision for rectal cancer: initial results in a center for minimally invasive surgery.
A robotic system was mainly designed to allow precise dissection in deep and narrow spaces. We report the clinical and oncologic outcomes of totally robotic total mesorectal excision for rectal cancer. Between July 2009 and January 2012, 60 consecutive patients undergoing robotic surgery for rectal cancer at the Eulji University Hospital were included. The mean total operation time, docking time, and surgeon console time were 466.8 ± 115.6, 7.5 ± 6.7, and 261 ± 87.5 min, respectively. Oral intake of diet was started at 3.3 ± 0.9 days and the mean hospital stay was 8.6 ± 2.4 days. All 60 procedures were technically successful without the need for conversion to open or laparoscopic surgery. Complications included anastomotic leakage, anastomotic stricture, postoperative bleeding, ileus, and perineal wound infection in 3 (5 %), 1 (1.7 %), 2 (3.3 %), 2 (3.3 %), and 1 (1.7 %) patient, respectively. The mean distal resection margin and total number of lymph nodes harvested was 3.1 ± 1.7 cm and 20.1 ± 11.5, respectively. During the mean follow-up period of 48.5 months (range, 7-75), the 4-year overall and disease-free survival rates were 87.7 and 72.8 %, respectively. A totally robotic approach for rectal cancer operations was a time-consuming procedure, although we already had a lot experience in laparoscopic colorectal surgery. However, the dexterity of the robotic surgery could enable the surgeon to expand the choice of surgical methods according to the condition of the rectal cancer without the need for conversion.


Resolution of Penicillium roqueforti toxin and eremofortins A, B, and C by high-performance liquid chromatography.
A method for the quantitative analysis of Penicillium roqueforti toxin using a high-performance liquid chromatography system is proposed.


Added value of Joint ENT-Rheumatology clinic in the management of ANCA-associated vasculitis: One year's experience.
ANCA-associated vasculitides (AAV) represent a group of diagnoses, including granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA) and microscopic polyangiitis (MPA). Most commonly, they present initially with ENT-associated symptomatology, and therefore they often pose a diagnostic challenge. We aim to present our one-year experience in the joint management of AAV in a multi-disciplinary setting. We performed a retrospective analysis based on the records of 39 patients who were seen in the joint clinic, during a period of one year. After clinical assessment, 13 patients had changes made to their ENT treatment, 2 had some changes in their immunosuppression, while 11 had changes in both ENT and Rheumatology treatment. Six patients did not require any alterations to their therapeutic scheme. On average three separate appointments were reduced to a single appointment in the joint clinic where definitive treatment decisions were made. This led to significant cost reductions. Cost-effectiveness, patient satisfaction, rapid multi-disciplinary evaluation, avoidance of unnecessary immunosuppression, patient education and medical training are only a few of the many advantages of this proposed joint service.


Regulation of the cellular content of the organic osmolyte taurine in mammalian cells.
Change in the intracellular concentration of osmolytes or the extracellular tonicity results in a rapid transmembrane water flow in mammalian cells until intracellular and extracellular tonicities are equilibrated. Most cells respond to the osmotic cell swelling by activation of volume-sensitive flux pathways for ions and organic osmolytes to restore their original cell volume. Taurine is an important organic osmolyte in mammalian cells, and taurine release via a volume-sensitive taurine efflux pathway is increased and the active taurine uptake via the taurine specific taurine transporter TauT decreased following osmotic cell swelling. The cellular signaling cascades, the second messengers profile, the activation of specific transporters, and the subsequent time course for the readjustment of the cellular content of osmolytes and volume vary from cell type to cell type. Using Ehrlich ascites tumor cells, NIH3T3 mouse fibroblasts and HeLa cells as biological systems, it is revealed that phospholipase A2-mediated mobilization of arachidonic acid from phospholipids and subsequent oxidation of the fatty acid via lipoxygenase systems to potent eicosanoids are essential elements in the signaling cascade that is activated by cell swelling and leads to release of osmolytes. The cellular signaling cascade and the activity of the volume-sensitive taurine efflux pathway are modulated by elements of the cytoskeleton, protein tyrosine kinases/phosphatases, GTP-binding proteins, Ca2+/calmodulin, and reactive oxygen species and nucleotides. Serine/threonine phosphorylation of the active taurine uptake system TauT or a putative regulator, as well as change in the membrane potential, are important elements in the regulation of TauT activity. A model describing the cellular sequence, which is activated by cell swelling and leads to activation of the volume-sensitive efflux pathway, is presented at the end of the review.


Cytogenetic effects of vaginally administered gossypol in murine bone marrow cells.
The cytogenetic effects of gossypol were evaluated by determining the frequency of sister chromatid exchanges (SCEs), percentage of pulverized metaphases, mitotic indices and micronuclei in bone marrow cells of mice treated per vaginam. A dose-dependent increase in the frequency of SCEs was observed when gossypol suspended in corn oil was administered at dosages of 10, 20 or 40 micrograms/g. In comparison with controls, incidences of SCEs were significantly higher in mice given 20 and 40 micrograms/g gossypol, whereas the mitotic indices, percentages of pulverized metaphases and the frequency of interphase micronuclei in treated animals were not different from their control counterparts. The SCE data suggest that gossypol has a DNA-damaging potency in murine bone marrow cells.


[Comparison of the predictive value of Padua and the IMPEDE assessment scores for venous thromboembolism in patients with newly diagnosed multiple myeloma: A single institution experience].
Objective: To compare the predictive efficacy of the two thrombosis risk assessment scores (Padua and IMPEDE scores) in venous thromboembolism (VTE) within 6 months in patients with newly diagnosed multiple myeloma (NDMM) in China. Methods: This study reviewed the clinical data of 421 patients with NDMM hospitalized in Beijing Jishuitan Hospital from April 2014 to February 2022. The sensitivity, specificity, accuracy, and Youden index of the two scores were calculated to quantify the thrombus risk assessment of VTE by the Padua and IMPEDE scores. The receiver operating characteristics curves of the two evaluation scores were drawn. Results: The incidence of VTE was 14.73%. The sensitivity, specificity, accuracy, and Youden index of the Padua score were 100%, 0%, 14.7%, and 0% and that of the IMPEDE score was 79%, 44%, 49.2%, and 23%, respectively. The areas under the curve of Padua and IMPEDE risk assessment scores were 0.591 and 0.722, respectively. Conclusion: IMPEDE score is suitable for predicting VTE within 6 months in patients with NDMM.


Effect of mutation K85R on GSK-3beta: Molecular dynamics simulation.
As a serine-threonine protein kinase, glycogen synthase kinase-3 (GSK-3) regulates the synthesis of glycogen and plays important roles in several signaling pathways. It is a key therapeutic target for a number of diseases, such as diabetes, cancer, Alzheimer's disease and chronic inflammation. The conserved Lys85 is important to GSK-3beta activity and in this paper we illustrate the significant role of Lys85 using dynamic simulation. We find that when Lys85 is mutated to Arg, one of the two conserved hydrogen bonds between Lys85 and ATP disappears, the salt bridge between Lys85 and Glu97 cannot form, and conformational changes of Phe93, Arg96 and Glu211 occur. These will cause conformational changes of the substrate binding groove that would inhibit the activity of GSK-3beta. MM-GBSA calculations reveal that the K85R mutation could lead to a less energy-favorable complex, which is consistent with the structural analysis.


Aquaporin-4 IgG neuromyelitis optica spectrum disorder onset after Covid-19 vaccination: Systematic review.
Neuromyelitis optica spectrum disorder (NMOSD) is rarely reported following Coronavirus disease 2019 (COVID-19) vaccination. We identified 16 cases of new onset NMOSD with positive aquaporin-4 IgG (AQP4-IgG) following COVID-19 vaccination. Transverse myelitis was the most common clinical presentation (75%). Most patients received high dose steroids for acute treatment and maintenance therapy was started in 12 patients (75%). Twelve patients (75%) had improvement of their symptoms at the time of discharge or follow-up. The included cases share similar epidemiology and natural course to non-vaccine related cases. Clinicians should be aware of possible post-vaccination NMOSD to help with earlier diagnosis and treatment.


A method for studying the depolarization-induced calcium ion release from fragmented sarcoplasmic reticulum.
An optical method of studying the 'depolarizatoin'-induced Ca2+ release from isolated sarcoplasmic reticulum was presented. The method, which involves the use of metallochromic indicators, has the advantage of being able to perform the rapid kinetic measurement of the release. It was suggested that the velocity of the 'depolarization'-induced Ca2+ release was rapid enough to account for the velocity of muscle contraction if the phenomenon is involved in the contraction mechanism. The change of membrane potential was also measured optically using a potential-sensitive dye. The possibility that this type of release is caused by osmotic effects is discussed.


Isolation and phenotypic characterization of Tetrahymena thermophila size mutants: the relationship between cell size and regulation of DNA content.
Temperature-sensitive size mutants of the ciliate Tetrahymena thermophila were selected following chemical mutagenesis. Phenotypical characteristics are given for seven cell lines, which have a range of average cell volumes from 8000 microns 3 to more than 100 000 microns 3. wild-type Tetrahymena cells have an average cell volume of 15 000 microns 3. Two of the mutagenized cell lines have comparatively small cells at 29 degrees C but normal cells at 37 degrees C; whereas the other five lines are normal at 29 degrees C but large at 37 degrees C. While the small cells are poor growers, the large cells grow excellently at 37 degrees C. Measurements of DNA, RNA and protein contents indicate a significant correlation between all parameters and cell size. However, since the cells tolerate considerably different concentrations of each class of macromolecules, the amount of any of these macromolecules cannot be tightly controlled by cell size.


The lived experience and meaning of stress in acute mental health nurses.
While studies into stress in mental health nursing are small, studies specifically looking at acute mental health nurses are even fewer. Acute mental health nurses work in environments that are challenging and unpredictable, and care for some of the most seriously ill patients. This area, therefore, needs staff that are physically and psychologically fit for purpose. However, little is known about this cohort of nurses. In an attempt to address this imbalance, this study aims to ascertain the stressors--the lived experience and meaning--for acute qualified mental health staff. Using a hermeneutical phenomenological tradition, eight qualified staff from a London mental health Trust were interviewed. Heavy workloads and violent and aggressive behaviours were among the stressors giving rise to staff experiencing difficulties with switching off from work, poor support from management and fear of blame. These experiences culminated in feeling professionally compromised, less valued and struggling for recognition of the therapeutics of nursing interventions. There is an urgent need to implement stress reduction strategies in this nursing specialty.


Subtypes of aggression in patients with schizophrenia: the role of personality disorders.
Research has repeatedly demonstrated that schizophrenia has a small but significant association with violence. It is further recognised that a subgroup of people with such links also have personality disorders, but the extent to which type of violence or aggression varies according to subgroup is less clear. This study aimed to investigate, among co-morbid cases, if the number or type of personality disorders predicts type of aggression. In a cross-sectional study, 108 patients with schizophrenia were assessed for personality disorder, Axis-I diagnosis, verbal IQ, social functioning and type of aggression. Logistic regression revealed that the more personality disorders identified (Cluster B personality disorders compared with Clusters A and C) and anti-social personality disorder compared with other Cluster B disorders significantly predicted premeditated aggression. These findings suggest that detailed personality assessment should be a routine part of comprehensive assessment of patients with schizophrenia. Improved knowledge of the presence and type of personality disorders may help detect and manage the risk of some types of aggression.


Alzheimer's disease: The next frontier-Special Report 2017.
In the history of medicine, one means to progress is when we make the decision that our assumptions and definitions of disease are no longer consistent with the scientific evidence, and no longer serve our health care needs. The arc of scientific progress is now requiring a change in how we diagnose Alzheimer's disease. Both the National Institute on Aging-Alzheimer's Association (NIA-AA) 2011 workgroup and the International Work Group (IWG) have proposed guidelines that use detectable measures of biological changes in the brain, commonly known as biological markers, or biomarkers, as part of the diagnosis. This Special Report examines how the development and validation of Alzheimer's disease biomarkers-including those detectable in the blood or cerebral spinal fluid, or through neuroimaging-is a top research priority. This has the potential to markedly change how we diagnose Alzheimer's disease and, as a result, how we count the number of people with this disease. As research advances a biomarker-based method for diagnosis and treatment at the earliest stages of Alzheimer's disease, we envision a future in which Alzheimer's disease is placed in the same category as other chronic diseases, such as cardiovascular disease or diabetes, which can be readily identified with biomarkers and treated before irrevocable disability occurs.


A novel ferritin L (FerL) in hybrid crucian carp could participate in host defense against Aeromonas hydrophila infection and diminish inflammatory signals.
FerL, a multifunctional iron-storage polypeptide, not only exhibited a regulatory role in iron metabolism, but also participated in the regulation of fish immunity. In this study, ORF sequence of WR-FerL was 522 bp, encoding 173 amino acid residues. Tissue-specific analysis revealed that the highest expression of WR-FerL was detected in spleen. A. hydrophila challenge and LPS stimulation could sharply enhance WR-FerL mRNA expression in tissues and fish cells, respectively. Purified WR-FerL fusion peptide exhibited in vitro binding activity to A. hydrophila and endotoxin, limited bacterial dissemination to tissues as well as attenuated A. hydrophila-induced production of pro-inflammatory cytokines. Moreover, WR-FerL overexpression could abrogate NF-κB and TNFα promoter activity in fish cells. These results indicated that WR-FerL could play an important role in host defense against A. hydrophila infection.


Six-month survival of critically ill patients with HIV-related disease and tuberculosis: a retrospective study.
Tuberculosis is one of the leading causes of death from infectious diseases worldwide, mainly after the human immunodeficiency virus (HIV) epidemics. Patient with HIV-related illness are more likely to present with severe TB due to immunosuppression. Very few studies have explored HIV/TB co-infection in critically ill patients. The goal of this study was to analyze factors associated with long-term mortality in critically ill patient with HIV-related disease coinfected with TB. We conducted a retrospective study in an infectious disease reference center in Brazil that included all patient with HIV-related illness admitted to the ICU with laboratory-confirmed tuberculosis from March 2007 until June 2012. Clinical and laboratory variables were analyzed based on six-month survival. Forty-four patients with HIV-related illness with a confirmed diagnosis of tuberculosis were analyzed. The six-month mortality was 52 % (23 patients). The main causes of admission were respiratory failure (41 %), severe sepsis/septic shock (32 %) and coma/torpor (14 %). The median time between HIV diagnosis and ICU admission was 5 (1-60) months, and 41 % of patients received their HIV infection diagnosis ≤ 30 days before admission. The median CD4 count was 72 (IQR: 23-136) cells/mm(3). The clinical presentation was pulmonary tuberculosis in 22 patients (50 %) and disseminated TB in 20 patients (45.5 %). No aspect of TB diagnosis or treatment was different between survivors and nonsurvivors. Neurological dysfunction was more prevalent among nonsurvivors (43 % vs. 14 %, p = 0.04). The nadir CD4 cell count lower than 50 cells/mm(3) was independently associated with Six-month mortality (hazard ratio 4.58 [1.64-12.74], p < 0.01), while HIV diagnosis less than three months after positive serology was protective (hazard ratio 0.27, CI 95 % [0.10-0.72], p = 0.01). The Six-month mortality of HIV critically ill patients with TB coinfection is high and strongly associated with the nadir CD4 cell count less than 50 cels/mm(3).


A Sustainable Nanocomposite Au(Salen)@CC for Catalytic Degradation of Eosin Y and Chromotrope 2R Dyes.
Up to now, a very few catalysts have been developed approaching the heterogeneous catalytic degradation of Eosin Y and Chromotrope 2R dyes (Acid Red 29). The present study provides a complete perspective of recyclable nanocomposite Au(Salen)@CC for catalytic degradation of hazardous water pollutant dyes viz., Eosin Y & Chromotrope 2R using mild reaction conditions. New gold Salen complex doped carbon nanocomposite Au(Salen)@CC was developed by easy methodology using nano carbon cage (CC) prepared from low-priced Pyrolysis fuel oil (PFO) residue based Pitch. The UV-Vis adsorption spectroscopy results of Eosin Y and Chromotrope 2R dyes indicated complete degradation into acidic compounds which can be further mineralized to CO2 and H2O under mild reaction conditions. The heterogeneous catalyst recycled and reused successfully for four repeated experiments without loss in its adequate performance. This new sustainable and eco-friendly catalyst delivered significant degradation activity compared to existing reports and it can be further utilized for new multifunctional applications such as, radiopharmaceutical activities, heterogeneous catalysis and chiral resolution.


Clinical practices in neonatal oxygenation: where have we failed? What can we do?
Oxygen is among the most frequently used therapies in neonates worldwide. Nevertheless, many times it is used unnecessarily. Neonatal practices have changed over the last several years; treatments originally believed to be beneficial have been discarded. Oxygen utilized 'just in case' or 'prophylactically' can lead to great damage previously ignored and/or unseen by healthcare providers. It is imperative to improve education on neonatal oxygenation and saturation monitoring. It is also important not to depend on old assumptions, which were not based on evidences. The potential for unseen damage at the cellular and tissue levels cannot be ignored. Therapies that prove to be outdated or even dangerous must be eliminated while further research and confirmation of the best practices are determined. Freedom to choose can come at a price.


Differential detection of Newcastle disease virus strains by degenerate primers based RT-PCR.
Degenerate primers based RT-PCR (previously described by [Avian Dis 26 (1997) 837]) has been used for the detection and differentiation of Newcastle disease (ND) viruses. Two sets of primers (A+B and A+C), with common forward primer and distinct reverse degenerate primers, designed from fusion protein gene encoding for cleavage site, could differentiate virulent and avirulent Newcastle disease viruses (NDV). Both sets of primers amplified "F" gene sequence of virulent (velogenic and mesogenic) viruses, whereas in avirulent strains, amplification was only with primer set A+C. Total 10 NDV isolates and two clinical samples including both known and unknown pathotypes, were checked. Based on amplification results 5 viruses were found to be virulent type and 6 as avirulent with one of the two clinical samples, earlier positive by RT-PCR using non-degenerate "F" gene specific primers was found negative in this study. The technique has been found to be a simple and quick for the detection and differentiation of virulent and avirulent NDV, which is important for control of the disease in the events of the outbreaks.


Segmental pedicle screw fixation in the treatment of thoracic idiopathic scoliosis.
This retrospective clinical study compared the results of correction of idiopathic thoracic scoliosis using Cotrel-Dubousset segmental pedicle screw fixation with those of hooks and screws inserted in a hook pattern. The study's objective was to evaluate the efficacy and safety of segmental pedicle screw fixation in the management of idiopathic thoracic scoliosis. Seventy-eight idiopathic thoracic scoliosis patients were treated with Cotrel-Dubousset instrumentation from 1987 to 1991. Thirty-one were treated with hooks; 23 were treated with pedicle screws inserted in a hook pattern; and 24 were treated with segmental pedicle screws. After a minimum follow-up of 2 years (range, 25-52 months), the results of frontal, sagittal, and rotational correction of each group were compared and statistically analyzed using analysis of variance. Major curve correction was 55% with hooks, 66% with hook pattern screws, and 72% with segmental screws, with loss of correction of 6%, 2%, and 1%, respectively. Compensatory curve correction was 57% with hooks, 67% with hook pattern screws, and 70% with segmental pedicle screws. In patients with hypokyphosis, all showed significant improvement with best restoration in segmental screws. Rotational correction of the apical vertebra measured by the Perdriolle method was 19% with hooks, 26% with hook pattern screws, and 59% with segmental screws. Thirteen screws (3%) were malpositioned, but they did not cause neurologic impairment or adversely affect the results of treatment. Segmental pedicle screw fixation is a safe and effective method for correcting the triplanar deformity of the idiopathic thoracic scoliosis.


Temporal and spatial variation in palatability of soybean and cotton leaves following wounding.
Leaves of soybean (Glycine max (L.) Merr.) and cotton (Gossypium hirsutum L.) were mechanically damaged with a single hole and offered to Spodoptera littoralis Boisd (Lep., Noctuidae) larvae in laboratory bioassays at intervals of between 0 and 7 days from damage. The subsequent within-leaf grazing patterns of damaged and undamaged areas were compared using an image-analysing computer, and estimations were made by eye of percentage, areas grazed at three spatial scales. Reduction in palatability of damaged areas of both plant species was detected, at time intervals ranging from 0 to 7 days after damage. This effect was strongest for the longer time intervals and the effect became weaker with increasing distance from the site of damage. These results are discussed in relation to possible defensive roles of wound-induced changes.