Fine-scale sampling uncovers the complexity of migrations in 5th-6th century Pannonia.
As the collapse of the Western Roman Empire accelerated during the 4th and 5th centuries, arriving "barbarian" groups began to establish new communities in the border provinces of the declining (and eventually former) empire. This was a time of significant cultural and political change throughout not only these border regions but Europe as a whole.1,2 To better understand post-Roman community formation in one of these key frontier zones after the collapse of the Hunnic movement, we generated new paleogenomic data for a set of 38 burials from a time series of three 5th century cemeteries3,4,5 at Lake Balaton, Hungary. We utilized a comprehensive sampling approach to characterize these cemeteries along with data from 38 additional burials from a previously published mid-6th century site6 and analyzed them alongside data from over 550 penecontemporaneous individuals.7,8,9,10,11,12,13,14,15,16,17,18,19 The range of genetic diversity in all four of these local burial communities is extensive and wider ranging than penecontemporaneous Europeans sequenced to date. Despite many commonalities in burial customs and demography, we find that there were substantial differences in genetic ancestry between the sites. We detect evidence of northern European gene flow into the Lake Balaton region. Additionally, we observe a statistically significant association between dress artifacts and genetic ancestry among 5th century genetically female burials. Our analysis shows that the formation of early Medieval communities was a multifarious process even at a local level, consisting of genetically heterogeneous groups.


Successful management of prolonged venovenous extracorporeal membrane oxygenation in an octogenarian.
Venovenous extracorporeal membrane oxygenation is now an established treatment for acute respiratory distress syndrome. However, this treatment remains rare in octogenarians and is associated with poor outcomes. An 81-year-old man with a history of chronic obstructive pulmonary disease and heavy smoking underwent mitral and tricuspid valve repair and the Maze procedure for mitral and tricuspid regurgitation and paroxysmal atrial fibrillation. Although he was extubated the following day, his postoperative course was complicated with pneumonia followed by acute respiratory distress syndrome. He was reintubated on day 7. Ratio of partial pressure of arterial oxygen to fraction of inspired oxygen continuously dropped to less than 100 mmHg, and venovenous extracorporeal membrane oxygenation support was induced on day 18. His lung condition showed slow and steady recovery, and he was successfully weaned from mechanical support on day 44 (total support, 27 days). Bleeding complication from tracheotomy (day 31) due to disseminated intravascular coagulation was successfully managed using recombinant human soluble thrombomodulin. He was ambulatory and discharged to a nursing facility without tracheotomy on day 172. Proper extracorporeal membrane oxygenation management, while challenging to keep the elderly patient away from further complications, saved an 81-year-old patient.


Experimental concurrent infection of sheep with Oestrus ovis and Trichostrongylus colubriformis: negative interactions between parasite populations and related changes in the cellular responses of nasal and digestive mucosae.
Concurrent infections of sheep with Oestrus ovis and trichostrongyles of the digestive tract are common in the field. In order to examine the possible occurrence of interactions between these two parasites and the consequences on parasite biology and the associated pathophysiological changes, an experimental study was conducted on four groups of naïve sheep. Group O was infected repeatedly with O. ovis larvae from D0 to D42 of experiment; group T received a single infection of Trichostrongylus colubriformis on D49; sheep from group OT received both infections, and animals from group C remained uninfected as controls. Parasitological and pathophysiological parameters were measured regularly. At necropsy (D94), the mucosal cellular responses in the nasal cavities and digestive tract from all animals were analysed from histological sections. Infection of the digestive tract with nematodes did not modify the biology of Oestrus populations. In contrast, the presence of O. ovis was related to significant reductions in nematode egg excretion, worm fecundity and worm burdens. These changes were associated with significant modifications in tissular populations of mast cells, globule leucocytes and eosinophils in the respiratory and digestive tracts. These results indicate that parasitic infection in one particular anatomical site induces "at distance" inflammatory reactions of the whole mucosal system. The relationships between the cellular response and the changes in worm biology are discussed.


Three-phase study of phlebitis in patients receiving peripheral intravenous hyperalimentation.
We found clinical phlebitis in 57 of 88 patients with peripheral hyperalimentation (65%). To determine if this was a problem common to all intravenous fluid therapy at our hospital, we performed a point-prevalence study. The prevalence of phlebitis in nonhyperalimentation intravenous patients was 18% (84 of 456 patients). We then performed a randomized, prospective, double-blind trial of sham versus standard in-line filters to determine if bacteria or filterable particulate matter was responsible for phlebitis in the peripheral hyperalimentation group. The standard-filter group had a phlebitis rate of 74% compared with 64% in the sham-filter group. We then eliminated in-line filters and replaced the standard glucose-based solution with a glycerol-based peripheral hyperalimentation solution. The phlebitis rate decreased from 68% to 27% (p less than 0.001). In conclusion, phlebitis in peripheral hyperalimentation patients was probably due to chemical properties of the peripheral hyperalimentation solution rather than bacteria or particulates.


Physical exercise reverses glutamate uptake and oxidative stress effects of chronic homocysteine administration in the rat.
The influence of physical exercise on the effects elicited by homocysteine on glutamate uptake and some parameters of oxidative stress, namely thiobarbituric acid-reactive substances, 2',7'-dichlorofluorescein (H(2)DCF) oxidation, as well as enzymatic antioxidant activities, superoxide dismutase, catalase and glutathione peroxidase in rat cerebral cortex were investigated. Wistar rats received subcutaneous administration of homocysteine or saline (control) from the 6th to 29th day of life. The physical exercise was performed from the 30th to 60th day of life; 12 h after the last exercise session animals were sacrificed and the cerebral cortex was dissected out. It is shown that homocysteine reduces glutamate uptake increases thiobarbituric acid-reactive substances and disrupts enzymatic antioxidant defenses in cerebral cortex. Physical activity reversed the homocysteine effects on glutamate uptake and on antioxidant enzymes activities; although the increase in thiobarbituric acid-reactive substances was only partially reversed by exercise. These findings allow us to suggest that physical exercise may have a protective role against homocysteine-induced oxidative imbalance and brain damage to the glutamatergic system.


Risk Assessment of Lead and Cadmium in Drinking Water for School use in Nakhon Si Thammarat Province, Thailand.
This research aimed to evaluate children's health risk based on the concentration of lead (Pb) and cadmium (Cd) in the drinking water used by 44 primary schools. Samples were collected from bottled water, tap water, filtered tap water and raw water, for a total of 146 samples, between 1 September 2018 and 31 January 2019. The concentrations of Pb and Cd in drinking water samples were determined by graphite furnace atomic absorption spectrometry. The results showed that the concentration of Pb and Cd in bottled water samples were in the range of non-detected (ND)-0.0180 mg/L and ND-0.0013 mg/L, respectively. The concentration of Pb and Cd in tap water samples ranged from ND-0.0250 mg/L and ND-0.0042 mg/L, respectively, from ND-0.005 mg/L and ND- 0.0021 mg/L, respectively, in filtered tap water samples and from ND-0.0400 mg/L and ND-0.0049 mg/L, respectively, in raw water samples. The summation of the total hazardous index (HI)-values of bottled water samples, tap water samples, filtered tap water, and raw water samples were less than 1, was considered health-protective. The results will provide the direct evidence needed by school managers to warn learners about the health risk of ingestion exposure among children.


Treated wastewater irrigation effect on soil, crop and environment: wastewater recycling in the loess area of China.
A study was carried out at the Loess Plateau in Dongzhi, China, to test the feasibility of using secondary treatment sewage effluent and to determine whether the water quality would then meet the recommended irrigation norm. Seven crops, including celery, wheat, maize, millet, apples, rapeseed and yellow beans, were tested in the study. Physical and chemical properties of the soil, crop yield and quality and leachate at different soil depths were measured. In most cases, the quality of the crops that made use of treated sewage was not distinctively different from those that did not use treated sewage. However, yields for the former were much higher than they were for the latter. Leachates at different soil depths were analyzed and the results did not show alarming levels of constituents. For a period of approximately 14 months, the treated sewage irrigation had no significant effect on the loess soil and no cases of illness resulting from contact with the treated sewage were reported. With treated sewage irrigation, a slight increase in the organic content of the soil was observed.


The relationship between asthma and obesity in urban minority children and adolescents.
To investigate the relationship between asthma and obesity in children and adolescents. Medical record review. Urban community health center. One hundred seventy-one children aged 4 to 16 years, 85 with asthma and 86 nonasthmatic controls. Diagnosis of asthma, age, and sex-adjusted body mass index (weight in kilograms divided by the square of the height in meters). Seventy-eight percent of the sample was Hispanic, 17% was African American, 2% were white, and 3% were other minorities. There were significantly more children with asthma (30.6%) who were very obese (> or =95th body mass index percentile) compared with controls (11.6%) (P=.004). Children with asthma were also significantly more overweight than controls (mean+/-SD, 22.5%+/-28.3% vs 12.0%+/-19.6% overweight; P=.004). The difference in obesity between children with asthma and controls was significant for both sexes and across the 4.5 to 10.9 years and 11 to 16 years age groups. Asthma severity was not related to obesity. Asthma is a risk factor for obesity in children and adolescents.


Validation of the Return To Work Self-Efficacy questionnaire in a population of employees undergoing treatment for cancer.
Several Return To Work Self-Efficacy (RTWSE) questionnaires have been developed and found relevant to understanding the return to work (RTW) process of employees with various health problems, including employees with cancer. The aim of the present study was to examine the reliability and validity of the Danish 19-item RTWSE questionnaire (RTWSE-19DK ) in a sample of employees with cancer. Employees undergoing treatment for cancer completed the RTWSE-19DK at baseline (n = 68) and at 1 week (n = 49). Additional questionnaires measured work ability, cancer-related self-efficacy and psychological distress. Internal consistency, test-retest reliability and construct validity were examined. The total and the three subscales of the RTWSE-19DK showed good internal consistencies with Cronbach's alphas between 0.90 and 0.97 and high test-retest reliability with Intraclass Correlation Coefficients between 0.84 and 0.90. Examining construct validity, the RTWSE-19DK showed medium and large correlations with cancer-related self-efficacy (r = 0.54), mental work ability (r = 0.51), and general work ability (r = 0.35), small correlations with physical work ability (r = 0.26) and anxiety (r = -0.10), and no correlations with depression (r = -0.08) and test date (r = 0.03). The RTWSE-19DK showed good reliability and adequate validity in employees undergoing cancer treatment. In clinical practice, the RTWSE-19 questionnaire may help practitioners identify areas of concern in the RTW process of cancer patients.


Inhibitory effect of microplastics on soil extracellular enzymatic activities by changing soil properties and direct adsorption: An investigation at the aggregate-fraction level.
Microplastics (MPs), as a new type of environmental pollutant, pose a serious threat to soil ecosystems. The activities of soil extracellular enzymes produced by microorganisms are the potential sensitive indicators of soil quality. However, little is known about the response mechanism of enzyme activities toward MPs on a long-term scale. Moreover, information on differences in enzyme activities across different soil aggregates is lacking. In this study, 150 days of incubation experiments and soil aggregate fractionation were combined to investigate the influence of MPs on extracellular enzyme activities in soil. 28% concentration of polyethylene with size 100 μm was adopted in the treatments added with MPs. The results show that MPs inhibited enzyme activities through changing soil nutritional substrates and physicochemical properties or through adsorption. Moreover, MPs competed with soil microorganisms for physicochemical niches to reduce microbial activity and eventually, extracellular enzyme activity. Enzyme activities in different aggregate-size fractions responded differently to the MPs exposure. The catalase in the coarse particulate fraction and phenol oxidase and β-glucosidase in the micro-aggregate fraction exerted the greatest response. With comparison, urease, manganese peroxidase, and laccase activities showed the greatest responses in the non-aggregated silt and clay fraction. These observations are believed to stem from differences in the key factors determining the enzyme activities in different aggregate-size fractions. The inhibitory pathway of microplastics on activities of extracellular enzymes in soil varies significantly across different aggregate fractions.


Changes in physical activity level of adolescents and its relationship with mental health during regular COVID-19 prevention and control.
This study aimed to analyze the impact of regular prevention and control of COVID-19 on the physical activity level (PAL) of adolescents and the relationship between PAL and mental health. Using the convenience sampling method, two stages of the on-site cross-sectional investigation were conducted in 11 middle schools in Guiyang City in China. There were 1132 participants who completed the Physical Activity Questionnaire for old children (PAQ-C) in October 2020, and 1503 participants who completed the PAQ-C and Mental Health Inventory of Middle-school students (MMHI-60) in October 2021. All participants reported their demographic data. Descriptive, quantitative statistics were used for data analysis. One-way ANOVA was used to explore associations between PAL and mental health. The results of statistical analysis showed a gradual yearly increase in the PAL of teenagers, and the PAL of male junior middle school students has a significant increase (p < .05); while that of adolescents in Grade 10 significantly decreased (p < .001). There is a statistically significant correlation between adolescents' mental health (except for anxiety) and PAL (p < .05). The overall abnormal rate of mental health was 27.9%; The PAL and the total mean score of mental health had a negative correlation (p < .001). There was a significant difference between mental health scores and corresponding PAL (p < .001). Furthermore, there are statistically significant differences in scores of mental health factors corresponding to varying PAL among junior high school students and male students (p < .05). The regular epidemic prevention and control measures had significant adverse effects on the PAL of girls and high school adolescents, especially Grade 10 adolescents. Improving adolescents' PAL can promote their mental health. Interventions based on PAL slightly lower than the level recommended in the physical activity guidelines can bring significant mental health effects.


CRISPR-assisted detection of RNA-protein interactions in living cells.
We have developed CRISPR-assisted RNA-protein interaction detection method (CARPID), which leverages CRISPR-CasRx-based RNA targeting and proximity labeling to identify binding proteins of specific long non-coding RNAs (lncRNAs) in the native cellular context. We applied CARPID to the nuclear lncRNA XIST, and it captured a list of known interacting proteins and multiple previously uncharacterized binding proteins. We generalized CARPID to explore binders of the lncRNAs DANCR and MALAT1, revealing the method's wide applicability in identifying RNA-binding proteins.


Effect of hypoxia on neural induction in colonies of human parthenogenetic stem cells.
We studied neural induction and generation of neuroectoderm in the colonies of human parthenogenetic SC cultured in the presence of 5 and 19±2% oxygen. We found that neuroectoderm was more actively generated at high oxygen content. At the same time, the transcription of stem cell pluripotency genes was not completely suppressed during neural induction at low oxygen content, while the expression of endoderm and mesodermal marker genes attested to the absence of specific differentiation. These findings demonstrate more efficient neuroectoderm generation induced in the colonies of pluripotent stem cells under conditions of normoxia.


School-based Psychosocial interventions on mental health among Chinese rural children with traumatic experiences: a protocol using cluster randomized controlled trial.
The first aim of this study is to test the effectiveness of school-based psychosocial interventions for improving mental health in rural Chinese children with traumatic experiences. The second aim is to examine which individual, family and school related factors could explain the effectiveness of school-based psychosocial interventions. Third, we will investigate whether individual, family, and school related conditions play a moderator role on the effectiveness of school-based psychosocial interventions. This study will conduct a cluster randomized controlled trial (RCT) in a large sample of Chinese rural children. Four rural counties in Shandong (Central China), Henan (Central China), Inner Mongolia (Northern China), and Xinjiang (Western China) will be selected as study settings from which schools will be sampled. Each sampled school will be randomly allocated either the intervention groups or a control group. Randomization will be performed by the research member who is not involved in the intervention stage. In each school students in grade 5 or higher will be recruited to ensure that approximately 50 children aged 10 to 18 years will be included. In each county, one high school, one middle school, and one primary school will be randomly chosen as the intervention group, and the other three similar schools will be chosen as control (waiting list) groups. A standardized and uniform research protocol will be applied in all intervention schools. All school social workers and psychological teachers would receive one week of in-person training following procedures. School-based psychosocial interventions included 14 group sessions for 14 consecutive weeks. This study would develop school-based mental health promotion policy recommendations to improve Chinese rural children's mental health. This study can provide solid evidence for the promotion of school-based intervention in general. ChiCTR2300069405, Registered on 15 March 2023.


Federated healthcare record server--the Synapses paradigm.
The delivery of healthcare relies on the sharing of patient information between those who are providing for the care of the patient and this information is increasingly being expressed in terms of a 'record'. Further, it is desirable that these records are available in electronic form as Electronic HealthCare Records. As it is likely that patient records or parts of records will be stored in many different information systems and in the form of disparate record architectures, uniform access to patient records would be problematic. This paper presents an overview of the Synapses computing environment in which a Federated Healthcare Record Server provides uniform access to patient information stored in connected heterogeneous autonomous information systems and other Synapses servers. The Synapses record architecture is based on the architecture proposed by the Technical Committee 251 of the European Committee for Standardisation and the interfaces to the Synapses server are specified in the ISO standard Interface Definition Language. Synapses is a pan-European project involving a number of hospitals, software companies, universities and research institutes and is partly funded by the EU Health Telematics Programme. The overview is described in terms of the Open Distributed Processing Reference Model.


Prevalence and impact of upper and lower gastrointestinal symptoms in the Greek urban general population.
To study the prevalence of gastrointestinal symptoms in the Greek urban general population, their associations with patient characteristics, and their effect on patients' daily activities. The study included 700 adults from the Athens-Piraeus area selected by a 2-stage scheme based on the official maps of the Hellenic Statistic Service. Structured questionnaires were completed through personal interviews. Dyspepsia, gastroesophageal reflux disease (GERD), and irritable bowel syndrome (IBS) were diagnosed according to widely accepted definitions. Of the 700 individuals, 53% reported > or = 1 gastrointestinal symptom during the past week and 55% during the past 6 months (dyspepsia: 48%, GERD: 38%, IBS: 21%). Only one disorder was diagnosed in 25% (dyspepsia: 18%, GERD: 7%), and > or = 2 disorders in 75% of symptomatic individuals. Dyspepsia or GERD was predominant in 7% and 16% and IBS in 28% and 19% of the patients with relevant symptoms during the past week and the past 6 months, respectively (p = 0.017). Substantial symptoms during the past 6 months were reported by 60% of the symptomatic individuals. Affected daily activities were reported by 22% of symptomatic and 5% of asymptomatic individuals (p < 0.001). Gastrointestinal symptoms are highly prevalent in the Greek urban general population and are substantial in the majority of symptomatic individuals. Dyspepsia and GERD are reported much more frequently than IBS symptoms, but there is a significant overlap between symptomatic diagnoses, while the predominant diagnosis may change over time. Gastrointestinal symptoms have a significant impact on patients' daily activities.


Upper respiratory infections.
Upper respiratory infections (URIs) are infections of the mouth, nose, throat, larynx (voice box), and trachea (windpipe). This article outlines the epidemiology, etiology, diagnosis, and management of URIs, including nasopharyngitis (common cold), sinusitis, pharyngitis, laryngitis, and laryngotracheitis.


A systematic review and meta-analysis of the association between periodontitis and oral high-risk human papillomavirus infection.
The incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is increasing globally. Common oral conditions such as periodontitis may contribute. We undertook a meta-analysis to quantify the association between periodontitis, oral HPV and OPSCCs. Multiple electronic databases were searched until 12 February 2020. Studies conducted in males and/or females aged ≥ 18 years that examined periodontitis, periodontal procedures, oral HPV infection, and where possible, oral cancers, were eligible. Meta-analyses were conducted and the GRADE approach was used to examine the quality of evidence. Of 2709 studies identified, 13 met the eligibility criteria. Five studies could be included in the meta-analyses. There was no significant increase in the odds of high-risk oral HPV infection among individuals with confirmed periodontitis (odds ratio 4.71, 95% confidence interval 0.57-38.97). Individuals with periodontitis had a 3.65 times higher odds of having any type of oral HPV infection compared with those without periodontitis (95% confidence interval 1.67-8.01). The overall body of evidence was rated as low to very-low certainty. Meta-analysis confirms there is a positive association between periodontitis and oral HPV infection, although the overall quality of this evidence is low. Evidence for an association between periodontitis and high-risk oral HPV infection is inconclusive.


Combined cytotoxicity of ZnO nanoparticles and chlorpyrifos in the rainbow trout, Oncorhynchus mikyss, gonadal cell line RTG-2.
The toxicity of ZnO nanoparticles (ZnO NPs) in aquatic organisms has been extensively studied, but little information is available on the effects associated with their interaction with other contaminants. In this context, the in vitro effects of co-exposure of chlorpyrifos (CPF) and ZnO NPs on fish-derived cells were investigated. A selection of concentrations was tested in single and binary exposures: CPF (0.312 - 75 mg/L) and ZnO NPs (10 - 100 mg/L). Cytotoxicity was measured using commonly used cellular endpoints: Alamar Blue/CFDA-AM for viability and plasma membrane integrity, NRU for lysosomal disruption and MTT for mitochondrial function. In addition, specific mechanisms of toxicity for CPF and ZnO NPs were tested: acetylcholinesterase (AChE) activity and ROS generation, respectively. AChE was by far the most sensitive assay for single exposure to CPF. There was no concentration-response relationship for ROS after single exposure to ZnO NPs, but 10 mg/L produced significant effects only for this cellular endpoint. Co-exposure of CPF with 10 m/L of ZnO NPs produced significant effects in almost all endpoints tested, which were enhanced by co-exposure with 100 mg/L of ZnO NPs. AChE testing of additional co-exposures with bulk ZnO, together with the application of the Independent Action (IA) prediction model, which allowed us to draw more in-depth conclusions on the toxicological behavior of the mixture. Synergism was observed at 0.625 mg/L CPF concentration and antagonism at 5 mg/L CPF in mixtures containing 100 mg/L of both ZnO NPs and bulk ZnO. However, more cases of synergism between CPF and ZnO NPs occurred at intermediate CPF concentrations, demonstrating that nano-sized particles have a more toxic interaction with CPF than bulk ZnO. Therefore it can be argued that in vitro assays allow the identification of interaction profiles of NP-containing mixtures by achieving multiple endpoints with a large number of concentration combinations.


Functional Characterization of Human ProNGF and NGF Mutants: Identification of NGF P61SR100E as a "Painless" Lead Investigational Candidate for Therapeutic Applications.
Nerve Growth Factor (NGF) holds a great therapeutic promise for Alzheimer's disease, diabetic neuropathies, ophthalmic diseases, dermatological ulcers. However, the necessity for systemic delivery has hampered the clinical applications of NGF due to its potent pro-nociceptive action. A "painless" human NGF (hNGF R100E) mutant has been engineered. It has equal neurotrophic potency to hNGF but a lower nociceptive activity. We previously described and characterized the neurotrophic and nociceptive properties also of the hNGF P61S and P61SR100E mutants, selectively detectable against wild type hNGF. However, the reduced pain-sensitizing potency of the "painless" hNGF mutants has not been quantified. Aiming at the therapeutic application of the "painless" hNGF mutants, we report on the comparative functional characterization of the precursor and mature forms of the mutants hNGF R100E and hNGF P61SR100E as therapeutic candidates, also in comparison to wild type hNGF and to hNGF P61S. The mutants were assessed by a number of biochemical, biophysical methods and assayed by cellular assays. Moreover, a highly sensitive ELISA for the detection of the P61S-tagged mutants in biological samples has been developed. Finally, we explored the pro-nociceptive effects elicited by hNGF mutants in vivo, demonstrating an expanded therapeutic window with a ten-fold increase in potency. This structure-activity relationship study has led to validate the concept of developing painless NGF as a therapeutic, targeting the NGF receptor system and supporting the choice of hNGF P61S R100E as the best candidate to advance in clinical development. Moreover, this study contributes to the identification of the molecular determinants modulating the properties of the hNGF "painless" mutants.


Diarrhea associated with lopinavir/ritonavir-based therapy: results of a meta-analysis of 1469 HIV-1-infected participants.
Antiretroviral therapy is associated with adverse events (AEs). The most frequently reported AE associated with lopinavir/ritonavir (LPV/r) containing regimens is diarrhea. The objective of this meta-analysis is to describe the incidence, prevalence, and duration of diarrhea in individuals taking LPV/r. This is a meta-analysis of Abbott-conducted clinical trials. Inclusion criteria included prospective randomized clinical trials with the LPV/r tablet formulation and had AE data (moderate/severe diarrhea) available through 48 weeks of treatment. Three trials (total 1469 participants) met the inclusion criteria. In all, 11.2% of participants reported moderate/severe diarrhea by week 8, with median time to resolution of 7.4 weeks. The overall 48-week incidence of moderate/severe diarrhea was 15.5%. The discontinuation rate due to moderate/severe diarrhea was 1.3%. Moderate/severe diarrhea occurred in less than 1 in 6 participants taking LPV/r, typically started in the first 8 weeks of treatment and infrequently resulted in premature discontinuation.


Effects of pH during liquid storage of goat semen on sperm viability and fertilizing potential.
A specific problem in goat semen preservation is the detrimental effect of seminal plasma on sperm viability in extenders containing yolk or milk. Thus, the use of chemically defined extenders will have obvious advantages. Although previous studies indicate that the initial pH of an extender is crucial to sustain high sperm motility, changes in extender pH during long-term semen storage have not been observed. Monitoring extender pH at different times of semen storage and modeling its variation according to nonlinear models is thus important for protocol optimization for long-term liquid semen preservation. The present results showed that during long-term liquid storage of goat semen, both sperm motility and semen pH decreased gradually, and a strong correlation was observed between the two. Whereas increasing the initial extender pH from 6.04 to 6.25 or storage with stabilized pH improved, storage with artificially lowered pH impaired sperm motility. Extender renewal improved sperm motility by maintaining a stable pH. Sperm coating with chicken (Gallus gallus) egg yolk improved motility by increasing tolerance to pH decline. A new extender (n-mZAP) with a higher buffering capacity was formulated, and n-mZAP maintained higher sperm motility, membrane integrity and acrosome intactness than the currently used mZAP extender did. Goat semen liquid-stored for 12 d in n-mZAP produced pregnancy and kidding rates similar to those obtained with freshly collected semen following artificial insemination. In conclusion, maintenance of a stable pH during liquid semen storage dramatically improved sperm viability and fertilizing potential.


Cross-talk between 4-1BB and TLR1-TLR2 Signaling in CD8+ T Cells Regulates TLR2's Costimulatory Effects.
The activation of TLR-MyD88 (Toll-like receptor-myeloid differentiation factor 88) signaling within T cells functions as a potent costimulatory signal that boosts antitumor and antiviral responses. However, the molecular mechanisms underlying the costimulatory processes are poorly understood. We compared microarray gene analysis data between TLR1-TLR2-stimulated and unstimulated T-cell receptor transgenic "pmel" and MyD88(-/-) pmel CD8(+) T cells and identified changes in the expression of several TNF family members. In particular, TLR stimulation increased 4-1BB levels in pmel but not in MyD88(-/-)pmel T cells. A link between 4-1BB and TLR1-TLR2 signaling in CD8(+) T cells was highlighted by the suboptimal responses of 4-1BB(-/-) T cells to TLR1-TLR2 agonist, but their normal response to CD28 or OX40 costimulation. Blocking 4-1BB signaling with antibodies also hindered the costimulatory effects of the TLR1-TLR2 agonist. The elevated levels of 4-1BB transcripts in TLR1-TLR2-stimulated cells were not due to increased mRNA stability nor increased histone activation, but instead were associated with increased binding of p65 and c-Jun to two distinct 4-1BB promoter sites. Combining TLR1-TLR2 ligand with an agonistic antibody to 4-1BB enhanced the antitumor activity in mice with established melanoma tumors. These studies reveal that the costimulatory effects of TLR1-TLR2 signaling in CD8(+) T cells are in part mediated by 4-1BB and are important for mounting an effective antitumor immune response. Cancer Immunol Res; 4(8); 708-16. ©2016 AACR.


Spatial distribution and molecular characterization of Anopheles nivipes and Anopheles philippinensis (Diptera: Culicidae) in north-east India.
Anopheles philippinensis-nivipes species of mosquitoes are considered secondary malaria vectors in the north-east India. However, difficulty in separating An. philippinensis and An. nivipes accurately on the basis of morphological identification, due to the overlapping female wing characters, has led to the paucity of information on their spatial distribution and vectorial importance, essential for understanding malaria disease epidemiology in areas under their influence. In view of this a study was undertaken to generate authentic information on distribution of An. philippinensis and An. nivipes in the north-east India using molecular tools. Between the two, An. nivipes was recorded as the dominant species in Assam, and Nagaland states whereas An. philippinensis was found predominant in the state of Mizoram and Arunachal Pradesh. Species differentiation based on female wing characters proved wrong in about 74% specimens of An. philippinensis but found accurate in case of An. nivipes. No intra-specific variation in second internal transcribed spacer (ITS2) region of ribosomal DNA(r-DNA) in either An. nivipes or An. philippinensis from different geographical areas of north-east India was noted.


Middle cerebral artery occlusion in the rabbit using selective angiography: application for assessment of thrombolysis.
An animal model of selective middle cerebral artery (MCA) occlusion is needed for evaluation of intra-arterial (IA) delivery of thrombolytic agents. We describe a technique for MCA thrombo-occlusion in the rabbit with real-time angiographic documentation of occlusion and thrombolytic recanalization. After femoral artery cutdown, a microcatheter was advanced from the internal carotid artery to the MCA. MCA occlusion was achieved by IA thrombin and reperfusion by IA plasmin. The terminal internal carotid artery was successfully catheterized in 12 of 13 animals. Stable (2-hour) MCA occlusion was induced and verified angiographically in all 12 animals; 2 animals also had distal internal carotid artery thrombus. Recanalization was achieved rapidly after IA plasmin in 3 of 3 animals. We describe a new animal model of selective MCA occlusion documented by real-time angiography and used to demonstrate recanalization with IA plasmin.


Loss of USP28 and SPINT2 expression promotes cancer cell survival after whole genome doubling.
Whole genome doubling is a frequent event during cancer evolution and shapes the cancer genome due to the occurrence of chromosomal instability. Yet, erroneously arising human tetraploid cells usually do not proliferate due to p53 activation that leads to CDKN1A expression, cell cycle arrest, senescence and/or apoptosis. To uncover the barriers that block the proliferation of tetraploids, we performed a RNAi mediated genome-wide screen in a human colorectal cancer cell line (HCT116). We identified 140 genes whose depletion improved the survival of tetraploid cells and characterized in depth two of them: SPINT2 and USP28. We found that SPINT2 is a general regulator of CDKN1A transcription via histone acetylation. Using mass spectrometry and immunoprecipitation, we found that USP28 interacts with NuMA1 and affects centrosome clustering. Tetraploid cells accumulate DNA damage and loss of USP28 reduces checkpoint activation, thus facilitating their proliferation. Our results indicate three aspects that contribute to the survival of tetraploid cells: (i) increased mitogenic signaling and reduced expression of cell cycle inhibitors, (ii) the ability to establish functional bipolar spindles and (iii) reduced DNA damage signaling.


Contribution of non-point source pollution that migrated with underground runoff process based on the SWAT model and a digital filter algorithm.
Non-point source (NPS) pollution has always been the focus of research worldwide, and understanding the migration process is the basis for effective control of NPS pollution. In this study, the SWAT model and digital filtering algorithm were combined to explore the contribution of NPS pollution that migrated with underground runoff (UR) process to the Xiangxi River watershed. The results showed that the surface runoff (SR) was the main migration process of NPS pollution, while the contribution of NPS pollution that migrated with the UR process only accounted for 30.9%. With the decrease in annual precipitation among the three selected hydrological years, the proportion of NPS pollution that migrated with the UR process for TN decreased, whereas the proportion for TP increased. The contribution of NPS pollution migrated with UR process varied remarkably during different months. Although the maximum total load and the load of NPS pollution that migrated with the UR process for TN and TP all appeared in the wet season, due to the hysteresis effect, the load of NPS pollution that migrated with the UR process for TP appeared 1 month later than the total load of NPS pollution. With an increase in precipitation from the dry season to the wet season, the proportion of NPS pollution that migrated with the UR process for TN and TP decreased gradually, and the degree of decrease in NPS pollution that migrated with the UR process for TP was more evident than that for TN. Besides, being affected by topography, land use, and other factors, the proportion of NPS pollution that migrated with the UR process for TN decreased from 80% in upstream areas to 9% in downstream areas, while that for TP reached a maximum of 20% in downstream areas. Based on the research results, the contribution of soil and groundwater cumulative nitrogen and phosphorus should be considered, and different managements and control measures for different migration routes should be adopted in controlling pollution.


Large abdominal wall endometrioma following laparoscopic hysterectomy.
Endometriosis is a common condition in women that affects up to 45% of patients in the reproductive age group by causing pelvic pain. It is characterized by the presence of endometrial tissue outside the uterine cavity and is rarely found subcutaneously or in abdominal incisions, causing it to be overlooked in patients with abdominal pain. A 45-year-old woman presented with lower abdominal pain 2 years following a laparoscopic supracervical hysterectomy. She was found to have incidental cholelithiasis and a large abdominal mass suggestive of a significant ventral hernia on CT scan. Due to the peculiar presentation, surgical intervention took place that revealed a large 9cm×7.6cm×6.2cm abdominal wall endometrioma. Although extrapelvic endometriosis is rare, it should be entertained in the differential diagnosis for the female patient who presents with an abdominal mass and pain and has a previous surgical history.


Locoregional failure in early-stage breast cancer patients treated with radical mastectomy and adjuvant systemic therapy: which patients benefit from postmastectomy irradiation?
To assess the locoregional failure in patients with Stage I-II breast cancer treated with radical mastectomy and to evaluate whether a subset of these patients might be at sufficiently high risk of locoregional recurrence (LRR) to benefit from postmastectomy irradiation (PMRT). Stage I-II breast cancer patients (n = 150) treated with radical mastectomy without adjuvant irradiation between 1999 and 2005 were analyzed. The pattern of LRR was reported. Kaplan-Meier analysis was used to calculate rates of LRR, and Cox proportional hazards methods were used to evaluate potential risk factors. Median follow-up was 75 months. Mean patient age was 56 years. One-hundred forty-three (95%) patients received adjuvant systemic therapy: 85 (57%) hormonal therapy alone, 14 (9%) chemotherapy alone, and 44 (29%) both chemotherapy and hormonal therapy. Statistically significant factors associated with increased risk of LRR were premenopausal status (p = 0.004), estrogen receptor negative cancer (p = 0.02), pathologic grade 3 (p = 0.02), and lymphovascular invasion (p = 0.001). T and N stage were not associated with increased risk of regional recurrence. The 5-year LRR rate for patients with zero or one, two, three, and four risk factors was 1%, 10.3%, 24.2%, and 75%, respectively. A subset of patients with early-stage breast cancer is at high risk of LRR, and therefore PMRT might be beneficial.


Identification of epithelial cells and fibroblasts in hypophysis intermediate lobe cultures by scanning electron microscopy.
Cell cultures of the rat pituitary intermediate lobe grown for eight days were studied in the scanning electron microscope. The epithelial cells and fibroblasts could be differentiated by the characteristic structures of the cell surface and the cell association features, The epithelial cells were characterized by blebs and rugae, microvilli, and occasionally by some cilia. The surface of the fibroblasts was smooth or bore microvilli. Scanning electron microscopy may provide special information for the characterization of endocrine cell cultures.


The response of thermoluminescence dosemeters to fast (14-7 MeV) and thermal neutrons.
The response of common TLD materials has been measured in a 14-7 MeV neutron field with a small and well known gamma component. Values for the thermal neutron response of some TLD materials with low thermal neutron sensitivity have been determined in the NPL standard thermal flux facility.


DNA-arrays with electrical detection: a label-free low cost technology for routine use in life sciences and diagnostics.
Fast and highly parallel DNA analysis are essential for improved biomedical research and development. Currently fluorescence-based methods are state of the art in DNA microarray analysis. The necessity to modify the target DNA with labels is costly, laborious and requires skilled personnel. Moreover, false positive calls from unspecific adsorption are possible and it is difficult to discriminate perfect matching target sequences from those with a single mismatch. In this paper a new and simple electrochemical approach for hybridisation detection without the need of labelling the target DNA is described. The EDDA (Electrically Detected Displacement Assay) method uses a solution of short redox-labelled signalling oligonucleotides (oligonucleotides carrying a covalently attached redox active compound like ferrocene) to characterize the hybridisation state of label-free capture probe DNA immobilised on gold electrodes. The number of capture probes associated with signalling oligonucleotides is determined by chronocoulometry. This technique allows to separate the electrochemical response of capture probe associated signal probes from the response of freely diffusing signalling probes. In the absence of the complementary target sequences the redox-labelled signalling probes at the surface give rise to an instantaneous increase of the detection signal, while freely diffusing signalling probes show a significantly delayed response. Hybridisation with targets complementary to the capture probe displace the loosely associated signalling probes thereby decreasing the instantaneous signal. Besides an introduction to the EDDA technology, data validating the method for biological material will be presented and an outlook to the detection of single nucleotide polymorphisms (SNPs) is given.


Water quality and health risk assessment of heavy metals in groundwater of Ranbir Singh Pura tehsil of Jammu and Kashmir, India.
Groundwater is one of the important sources available for drinking, agricultural, domestic, and various other purposes in the study area. Study area is having agricultural importance and is famous for Basmati rice production in the world. In order to assess water suitability for irrigation and drinking purposes, 25 sampling sites were selected and water samples were collected from handpumps, borewells and motors from May 2022 to June 2022. Fifteen physico-chemical parameters and water quality index (WQI) was calculated to assess the drinking water suitability. The results obtained then compared with the BIS (2012) and WHO drinking water guidelines. For irrigation water suitability, irrigation water quality index (IWQI) and other indices were calculated. Heavy metal health risk assessment was also evaluated using target hazard quotient (THQ), carcinogenic risks (CR), non-carcinogenic risks, heavy metal pollution index (HPI), etc. Study found 60% of water samples under poor category of WQI. All water samples were found suitable for irrigation purposes according to different indices except for permeability index for which only 32% samples were found suitable. IWQI classifies 52%, 32%, and 12% of water samples under moderate, low, and no restriction category respectively. Groundwater of the study area found to be contaminated with copper (Cu), iron (Fe), lead (Pb), and chromium (Cr) while low contamination of zinc (Zn) and arsenic (As) was found according to heavy metal evaluation index (HEI). High contamination of chromium (HPI= 9740.8) and lead (HPI=188) was recorded as per HPI. HQ value for men, women, and children in case of zinc were found safe while HQ values for copper and lead in all population groups were found at risk. Overall, the study area was found highly contaminated with the lead, copper, and chromium concentrations. Thus, study recommends regular monitoring of the groundwater of study area as well as treatment before using this water for drinking purposes.


Synthesis of new curcumin derivatives as influential antidiabetic α-glucosidase and α-amylase inhibitors with anti-oxidant activity.
In this study, a new class of curcumin derivatives was synthesized using a multicomponent reaction containing curcumin, aldehydes, and malononitrile. This new protocol afforded a novel class of 4H-pyran heterocycles incorporating curcumin moiety. The products were obtained in the presence of p-toluenesulfonic acid (PTSA) as a catalyst in ethanol solvent in good to excellent yields. The synthetic compounds indicated a notable inhibitory activity against α-glucosidase (α-Gls) and revealed a weak inhibitory property against α-amylase (α-Amy). Also, these synthetic compounds indicated significant antioxidant activity. The new curcumin derivatives were also discovered to display no significant effect against the growth of two bacterial microflora in the human intestine. A molecular docking study was done to realize the binding interaction of the synthetic curcumin derivatives with the α-Gls enzyme. The results of our study introduced new synthetic curcumin derivatives as potential antidiabetic drugs.


RNA-Sequencing of Heterorhabditis nematodes to identify factors involved in symbiosis with Photorhabdus bacteria.
Nematodes are a major group of soil inhabiting organisms. Heterorhabditis nematodes are insect-pathogenic nematodes and live in a close symbiotic association with Photorhabdus bacteria. Heterorhabditis-Photorhabdus pair offers a powerful and genetically tractable model to study animal-microbe symbiosis. It is possible to generate symbiont bacteria free (axenic) stages in Heterorhabditis. Here, we compared the transcriptome of symbiotic early-adult stage Heterorhabditis nematodes with axenic early-adult nematodes to determine the nematode genes and pathways involved in symbiosis with Photorhabdus bacteria. A de-novo reference transcriptome assembly of 95.7 Mb was created for H. bacteriophora by using all the reads. The assembly contained 46,599 transcripts with N50 value of 2,681 bp and the average transcript length was 2,054 bp. The differentially expressed transcripts were identified by mapping reads from symbiotic and axenic nematodes to the reference assembly. A total of 754 differentially expressed transcripts were identified in symbiotic nematodes as compared to the axenic nematodes. The ribosomal pathway was identified as the most affected among the differentially expressed transcripts. Additionally, 12,151 transcripts were unique to symbiotic nematodes. Endocytosis, cAMP signalling and focal adhesion were the top three enriched pathways in symbiotic nematodes, while a large number of transcripts coding for various responses against bacteria, such as bacterial recognition, canonical immune signalling pathways, and antimicrobial effectors could also be identified. The symbiotic Heterorhabditis nematodes respond to the presence of symbiotic bacteria by expressing various transcripts involved in a multi-layered immune response which might represent non-systemic and evolved localized responses to maintain mutualistic bacteria at non-threatening levels. Subject to further functional validation of the identified transcripts, our findings suggest that Heterorhabditis nematode immune system plays a critical role in maintenance of symbiosis with Photorhabdus bacteria.


Heroin snorters versus injectors: comparison on drug use and treatment outcome in age-matched samples.
Drug use histories and treatment outcomes were compared for age, race and gender-matched samples of intravenous (IV; n = 28) versus intranasal (IN; n = 28) opiate abusers entering a 3-day inpatient detoxification unit. Data were derived from the Addiction Severity Index (ASI) interview. Both groups reported daily heroin use prior to detoxification, but IV users reported more days of alcohol and multiple drug use during the past 30 days. Despite age matching, IV users also started using alcohol at an earlier age and accumulated more lifetime months of regular alcohol, cocaine and multidrug use. IV users were more likely to enter treatment following the detox, but no significant outcome differences were noted at 1 and 3 months post-detoxification. The results show that intravenous, as compared to intranasal, opiate users have both a more severe pattern and a more extensive history of the use of non-opiate drugs.


Fibroblast levels are increased in chronic rhinosinusitis with nasal polyps and are associated with worse subjective disease severity.
Fibroblasts are implicated in tissue remodeling and recruitment of inflammatory cells in chronic rhinosinusitis (CRS). Populations of fibroblasts remain unquantified in CRS subtypes. The objectives of this study were to measure fibroblast populations in subtypes of CRS, and to investigate the association between fibroblasts and disease severity. Patients undergoing endoscopic sinus surgery (ESS) for CRS were prospectively enrolled from January 2011 to December 2014. Control subjects included patients undergoing endoscopic surgery for non-inflammatory conditions such as cerebrospinal fluid leak repair or non-hormone-secreting pituitary tumors. Patients completed 22-item Sino-Nasal Outcome Test (SNOT-22) questionnaires prior to surgery. Blood and tissue biopsies were taken during surgery. Percent of sinonasal fibroblasts was determined via flow cytometry by selecting fibroblast-specific protein (FSP)-positive and Mucin 1 (MUC1)-negative cells. A total of 69 patients were enrolled: control (n = 24), CRS without nasal polyps (CRSsNP) (n = 13), CRS with nasal polyps (CRSwNP) (n = 22), and allergic fungal rhinosinusitis (AFRS) (n = 10). Patients with CRSwNP had significantly more fibroblasts than both control (p < 0.001) and CRSsNP (p < 0.01). Patients with AFRS had the most fibroblasts when compared to control (p < 0.0001), CRSsNP (p < 0.0001), and CRSwNP (p < 0.05). Atopy and asthma were not associated with increased fibroblasts in CRSwNP (p = 0.21, p = 0.26, respectively). Increased fibroblasts correlated with subjective disease severity as measured by SNOT-22 for CRSwNP (p = 0.003) and AFRS (p = 0.048). Sinonasal fibroblasts are increased in CRSwNP and AFRS compared to control and CRSsNP. Increased fibroblasts correlated with worse quality of life in CRSwNP and AFRS.


Retrospectively analyze and compare the efficacy and safety of thoracoscopic-assisted Nuss repair of pectus excavatum under intubation anesthesia and non-intubation anesthesia.
Thoracoscopic-assisted Nuss repair is a commonly used method for treating pectus excavatum, which has always been performed under tracheal intubation and general anesthesia. However, general anesthesia with endotracheal intubation can produce intubation and anesthetic drug related complications. In non-intubation anesthesia, laryngeal mask is used instead of tracheal intubation without muscle relaxants and small doses of sedative and analgesic drugs. Therefore, non-intubation anesthesia can reduce complications and speed up postoperative recovery. This study retrospectively analyzed the clinical impact of these two anesthesia methods on thoracoscopic-assisted Nuss repair for the treatment of pectus excavatum. A total of 115 pectus excavatum patients who underwent thoracoscopic-assisted Nuss procedure repair in the Department of Thoracic Surgery of Yunnan First People's Hospital from January 2017 to January 2022 were included. All subjects in this study underwent thoracoscopic assisted Nuss repair in the same thoracic surgical team. According to different anesthesia methods, they were divided into non-intubation anesthesia group (n=62) and intubation anesthesia group (n=53). The intubation time, intraoperative mean heart rate, postoperative complications, postoperative first oral food intake, water intake, ambulation, defecation time, postoperative blood drawing results, postoperative hospital stay and total hospitalization cost were compared between the two groups. There were no significant differences in clinical characteristics and preoperative examination indexes between the two groups, which were comparable. Compared with the intubation anesthesia group, the non-intubation anesthesia group had less anesthesia intubation time, lower intraoperative mean heart rate, less postoperative complications, such as pneumothorax, pleural effusion, and lung infection. In the non-intubation anesthesia group, the first time to eat, drink, get out of bed, and defecate were all earlier. Routine blood results 24 h after surgery indicated that the non-intubation anesthesia group had lower white blood cell, neutrophil and lymphocyte, an earlier postoperative discharge time, and lower total hospitalization expenses. Non-intubation anesthesia in thoracoscopic-assisted Nuss procedure for the repair of pectus excavatum can make the postoperative recovery of patients faster and has better safety and efficacy.


Comparable graft survival is achievable with the usage of donation after circulatory death liver grafts from donors at or above 70 years of age: A long-term UK national analysis.
The aim of the study was to assess the UK donation after circulatory death (DCD) liver transplant experience from donors ≥70 years. Nationwide UK DCD retrospective analysis was conducted between 2001 and 2015 (n = 1163). Recipients were divided into group 1 vs. group 2 (donors 70≥ vs. <70 years, respectively). group 1 (n = 69, 5.9%) recipients were older (median 59 vs. 55 years, p = .001) and had longer waitlist time (128 vs. 84 days; p = .039). 94.2% of group 1 clustered in London and Birmingham, where the two busiest centers are located. group 1 allografts had higher UKDRI and UK DCD Risk Scores but similar WIT and CIT and were more likely to have been imported. Both groups had similar 1-, 3-, and 5-year graft survival (group 1, 90%, 81.4%, and 74% vs. group 2, 88.6%, 81.4%, and 78.6%, respectively; p = .54). Both groups had similar ICU stay length (p = .22), 3-month hepatic artery thrombosis rates (4.4% vs 4.0%; p = .9), and 12-month readmission rates for all biliary complications (20.3% vs 25.7%; p = .32). This study demonstrates that acceptable outcomes are achievable using older grafts in a highly selected cohort at experienced centers. Advanced age should not be an absolute contraindication to utilizing a DCD graft from donors aged ≥70 years.


Canadian radiology workforce demographics: Results from a national survey.
Demographic data collected about Canadian radiologists and trainees has been limited primarily to binary gender and geographic location. The purpose of this study was to investigate: (1) demographic characteristics of Canadian radiologists and trainees; (2) types of diversity important to radiologists; (3) relationship of radiologist demographics to practice characteristics; and (4) relationship of radiologist demographics to years in practice, (YIP). French and English surveys were distributed via email through radiology associations and social media. Frequency counts of demographic variables were calculated, and chi-square and Fisher's Exact tests were performed to explore the relationships between demographic characteristics and role. 611 individuals responded to the survey. 573 respondents were included in the analysis. 454 (78.8%) were practicing radiologists and 119 (20.7%) were residents/fellows. Half identified as women (50.4%). English was the primary language for most respondents. There was an association between role and sexual orientation (p = 0.02), visible minority (χ2 = 4.79, p < 0.05), religion (χ2 = 4.11, p < 0.05), and having children (χ2 = 136.65, p < 0.05). For radiologists, being a visible minority (χ2 = 11.59, p < 0.05) and age (χ2 = 56.3, p < 0.05) were associated with academic rank while gender (χ2 = 3.83, p < 0.05) and age (χ2 = 13.74, p < 0.05) were related to part-/full-time status. Less women, visible minorities, and women with children had been in practice for long. This study represents a comprehensive analysis of Canadian radiology demographics. Results suggest there is increasing diversity among trainees; however, significant demographic underrepresentation compared to the diversity of Canada exists.


RNA interference to reveal roles of β-N-acetylglucosaminidase gene during molting process in Locusta migratoria.
β-N-acetylglucosaminidases are crucial enzymes involved in chitin degradation in insects. We identified a β-N-acetylglucosaminidase gene (LmNAG1) from Locusta migratoria. The full-length complementary DNA (cDNA) of LmNAG1 consists of 2 667 nucleotides, including an open reading frame (ORF) of 1 845 nucleotides encoding 614 amino acid residues, and 233- and 589-nucleotide non-coding regions at the 5'- and 3'-ends, respectively. Phylogenetic analysis grouped the cDNA-deduced LmNAG1 protein with the enzymatically characterized β-N-acetylglucosaminidases in group I. Analyses of stage- and tissue-dependent expression patterns of LmNAG1 were carried out by real-time quantitative polymerase chain reaction. Our results showed that LmNAG1 transcript level in the integument was significantly high in the last 2 days of the fourth and fifth instar nymphs. LmNAG1 was highly expressed in foregut and hindgut. RNA interference of LmNAG1 resulted in an effective silence of the gene and a significantly reduced total LmNAG enzyme activity at 48 and 72 h after the injection of LmNAG1 double-stranded RNA (dsRNA). As compared with the control nymphs injected with GFP dsRNA, 50% of the dsLmNAG1-injected nymphs were not able to molt successfully and eventually died. Our results suggest that LmNAG1 plays an essential role in molting process of L. migratoria.


The Impact of Chemotherapy on Toxic Effects and Cosmetic Outcome in Patients Receiving Whole Breast Irradiation: An Analysis Within a Statewide Quality Consortium.
We investigated whether the use of chemotherapy before whole breast irradiation (WBI) using either conventional fractionation (CWBI) or hypofractionation (HWBI) is associated with increased toxic effects or worse cosmetic outcome compared with WBI alone. We identified 6754 patients who received WBI alone (without a third field covering the superior axillary and supraclavicular nodal regions) with data prospectively collected in a statewide consortium. We reported rates of 4 toxic effects: physician-reported acute moist desquamation, patient-reported acute moderate/severe breast pain, a composite acute toxic effect measure (including moist desquamation and either patient- or physician-reported moderate/significant breast pain), and physician-reported impaired cosmetic outcome at 1 year after WBI. Successive multivariable models were constructed to estimate the effect of chemotherapy on these outcomes. Rates of moist desquamation, patient-reported pain, composite acute toxic effects, and impaired cosmetic outcome were 23%, 34%, 42%, and 10% for 2859 patients receiving CWBI and 13%, 28%, 31%, and 11% for 3895 patients receiving HWBI. Receipt of chemotherapy before CWBI was not associated with higher rates of patient-reported pain, composite acute toxic effects, or impaired cosmetic outcome compared with CWBI without chemotherapy but was associated with more moist desquamation (odds ratio, 1.32 [1.07-1.63]; P = .01). Receipt of chemotherapy before HWBI was not associated with higher rates of any of the 4 toxic effects compared with HWBI alone. In this cohort, use of chemotherapy before WBI was generally well tolerated. CWBI with chemotherapy but not HWBI with chemotherapy was associated with higher rates of moist desquamation. Rates of acute breast pain and impaired cosmetic outcome at 1 year were comparable in patients receiving chemotherapy before either CWBI or HWBI. These data support the use of HWBI after chemotherapy.


Cost-effectiveness of new oral anticoagulants in the prevention of stroke in patients with atrial fibrillation.
Atrial fibrillation (AF) is a common arrhythmia and the leading cause of stroke, an event with high human and economic burden. Novel oral anticoagulants have been approved in many markets as alternatives to warfarin for stroke prevention in patients with AF - dabigatran etexilate, apixaban and rivaroxaban. Given the high burden of AF, and given that new treatments can more effectively prevent stroke than warfarin, but at higher drug cost, there has been a need for systematic evaluation of the costs and benefits of these new treatments. In this study, we summarize the findings of a systematic literature review on the cost-effectiveness of the new oral anticoagulants. We find that there is substantial heterogeneity between the studies and their numerical findings, despite using a common set of four trials for their clinical inputs. However, there is broad consensus among them that each of the novel oral anticoagulants is cost-effective versus warfarin or aspirin.


HIV Incidence, Recent HIV Infection, and Associated Factors, Kenya, 2007-2018.
Nationally representative surveys provide an opportunity to assess trends in recent human immunodeficiency virus (HIV) infection based on assays for recent HIV infection. We assessed HIV incidence in Kenya in 2018 and trends in recent HIV infection among adolescents and adults in Kenya using nationally representative household surveys conducted in 2007, 2012, and 2018. To assess trends, we defined a recent HIV infection testing algorithm (RITA) that classified as recently infected (<12 months) those HIV-positive participants that were recent on the HIV-1 limiting antigen (LAg)-avidity assay without evidence of antiretroviral use. We assessed factors associated with recent and long-term (≥12 months) HIV infection versus no infection using a multinomial logit model while accounting for complex survey design. Of 1,523 HIV-positive participants in 2018, 11 were classified as recent. Annual HIV incidence was 0.14% in 2018 [95% confidence interval (CI) 0.057-0.23], representing 35,900 (95% CI 16,300-55,600) new infections per year in Kenya among persons aged 15-64 years. The percentage of HIV infections that were determined to be recent was similar in 2007 and 2012 but fell significantly from 2012 to 2018 [adjusted odds ratio (aOR) = 0.31, p < .001]. Compared to no HIV infection, being aged 25-34 versus 35-64 years (aOR = 4.2, 95% CI 1.4-13), having more lifetime sex partners (aOR = 5.2, 95% CI 1.6-17 for 2-3 partners and aOR = 8.6, 95% CI 2.8-26 for ≥4 partners vs. 0-1 partners), and never having tested for HIV (aOR = 4.1, 95% CI 1.5-11) were independently associated with recent HIV infection. Although HIV remains a public health priority in Kenya, HIV incidence estimates and trends in recent HIV infection support a significant decrease in new HIV infections from 2012 to 2018, a period of rapid expansion in HIV diagnosis, prevention, and treatment.


Tissue-resident Eomes+ NK cells are the major innate lymphoid cell population in human infant intestine.
Innate lymphoid cells (ILC), including natural killer (NK) cells, are implicated in host-defense and tissue-growth. However, the composition and kinetics of NK cells in the intestine during the first year of life, when infants are first broadly exposed to exogenous antigens, are still unclear. Here we show that CD103+ NK cells are the major ILC population in the small intestines of infants. When compared to adult intestinal NK cells, infant intestinal NK cells exhibit a robust effector phenotype, characterized by Eomes, perforin and granzyme B expression, and superior degranulation capacity. Absolute intestinal NK cell numbers decrease gradually during the first year of life, coinciding with an influx of intestinal Eomes+ T cells; by contrast, epithelial NKp44+CD69+ NK cells with less cytotoxic capacity persist in adults. In conclusion, NK cells are abundant in infant intestines, where they can provide effector functions while Eomes+ T cell responses mature.


Testicular dislocation: an uncommon and easily overlooked complication of blunt abdominal trauma.
We report testicular dislocation as an unusual complication of blunt abdominal trauma. The computer data bank of Chang Gung Memorial Hospital was searched for the period from 1987 to 2002, and 1,967 male patients with blunt abdominal trauma were admitted to the emergency department. Among these patients, records of 9 patients associated with testicular dislocation were collected. A retrospective review of the clinical records, abdominal computed tomography (CT) results, and subsequent scrotal sonograms was jointly performed by 2 radiologists, an emergency physician, and a trauma surgeon. Of these 9 patients (age range 6 to 53 years; mean 23 years), 7 patients were in motorcycle crashes, 1 patient had explosive injury, and 1 patient had seat belt injury. Associated testicular dislocation was initially missed in all patients. CT for evaluating blunt abdominal trauma revealed liver lacerations in 2 patients and pancreatic fracture, pancreatitis, bowel perforation, pubic bone fracture, and contralateral inguinal hernia in 1 each. Typical CT findings of testicular dislocation (empty scrotum and displaced testis) were retrospectively seen in 7 patients, but prompt CT diagnosis of testicular dislocation was achieved only in 3 patients, who were subsequently treated with closed manual reduction, obviating surgery. In the remaining 2 patients, CT examination did not include the scrotum and testicular dislocation, which was diagnosed by subsequent sonography. Delayed diagnosis occurred in 6 patients (duration 3 to 60 days; mean 19 days). Five of the patients underwent orchiopexy, and 1 underwent orchiectomy. In blunt abdominal trauma patients, associated testicular dislocation is easily overlooked. A complete physical examination in the trauma patient, including palpation of both testes, is strongly recommended.


Seek and Ye Shall Find: Subclonal Anaplastic Lymphoma Kinase Mutations.
Bellini and colleagues demonstrate the importance of next-generation sequencing to uncover subclonal anaplastic lymphoma kinase (ALK) mutations in neuroblastoma. Although the significance of these subclonal aberrations is not yet understood, deep sequencing could identify patients whose tumors may respond to ALK inhibitors.


The role of lysosome in cell death regulation.
Lysosome is a highly membrane-bound organelle which possesses a sequence of biological functions including protein degradation, cell signal transduction, plasma membrane repairment, homoeostasis, and autophagy. The lysosome contains more than 50 soluble acid hydrolases, and the acidification of lysosome is the most important biological characteristic. The integrity of lysosome is of vital importance. During the past few years, it was reported that the destabilization of lysosomal membrane can result in the release of lysosomal contents into cytosol and trigger cell death in a caspase-dependent or caspase-independent pathway. Lysosome functions at the late stage of autophagy and degrades cellular components delivered by autophagosome, which is a complicated process. The present article will summarize the current knowledge on the role of lysosome in cell death regulation and the underlying mechanisms.


Quality assurance and cardiopulmonary exercise testing in clinical trials.
Peak oxygen uptake (VO2) measured during cardiopulmonary exercise testing (CPX) is often used as an outcome measure in clinical trials. The purposes of this study are (a) to report the outcomes of a quality assurance (QA) procedure instituted in multisite clinical trials by a CPX data core laboratory and (b) to report a normative VO2 reference dataset for future use. The CPX laboratory at each site participating in a multisite clinical trial in which Henry Ford Hospital served as the CPX data core laboratory was required to pass a standardized QA procedure before site activation and regularly thereafter. Data were compared with a VO2 reference dataset (pilot data) and assessed for test-retest reproducibility. VO2 data that represented a normal physiologic response were used to develop a final normative VO2 reference dataset. Between 2003 and 2006, 81 laboratories submitted 144 baseline QA tests. Of these, 34% did not initially meet the passing criteria, largely because of poor test-retest reproducibility. Among all QA tests submitted to the core laboratory, 159 unique volunteers had exercise data that met the criteria to be entered into the final normative VO2 reference dataset. Within this dataset, the mean coefficient of variation for VO2 between the test and retest was 5.1%. A standardized QA procedure can be used to identify aberrant data and minimize the variability of VO2 measured in a clinical trial or the routine evaluation of patients.


Mitogen activated protein kinase (MAPK) mediates non-genomic pathway of estrogen on T cell cytokine production following trauma-hemorrhage.
Although studies have shown 17beta-estradiol (E2) administration following trauma-hemorrhage (T-H) attenuates alterations in T cell cytokine production, it remains unknown whether such effects of E2 are mediated via genomic or non-genomic pathways. In this study, we determined the non-genomic effects of E2 on splenic T cell cytokine production and the role of MAPK following T-H. Male Sprague-Dawley rats underwent T-H (mean BP 40 mmHg for 90 min, then resuscitation). E2, E2 conjugated with BSA (E2-BSA, 1 mg/kg E2) with or without an estrogen receptor antagonist (ICI 182 780), or vehicle was administered during resuscitation. Two hours thereafter, T cell production of IL-2 and IFN-gamma and activation of MAPK (p38, ERK-1/2 and JNK) were determined. The effect of selective MAPK inhibitors on cytokine production was also examined in vitro. IL-2 and IFN-gamma production capacity and MAPK activation decreased in T cells following T-H. However, E2 administration normalized these parameters. Although E2-BSA administration also attenuated suppression in cytokine production, the values were lower compared to sham. In contrast, E2-BSA prevented T-H-induced suppression in MAPK activation to the same extent as E2. Co-administration of ICI 182 780 abolished E2-BSA effects. These findings suggest E2 effects on T cell cytokine production following T-H are mediated at least in part via non-genomic pathway and these non-genomic effects are likely mediated via MAPK pathways.


Conversion to open laparotomy during laparoscopic distal pancreatectomy: lessons from a single-center experience in 70 consecutive patients.
The purpose of this study was to determine the factors influencing conversion from laparoscopic distal pancreatectomy (LDP) to open surgery, and the effect of such conversion on the outcome. This retrospective single-center study included 70 consecutive patients undergoing LDP. The primary endpoint was the rate of conversion to open surgery during LDP. The secondary endpoints were determining the reasons for conversion to open surgery, with detailed analyses of these cases and a comparison of the surgical outcome with and without conversion. Seven patients (10%) required conversion to open surgery during LDP. Pancreatic ductal adenocarcinoma (PDAC) was identified as a risk factor for conversion (p = 0.010). The reasons for conversion included technical difficulty (two bleeding, one severe adhesion) and pancreatic stump-related issues (two margin-positive, two stapling failures). Although the overall morbidity rate (29 vs. 11%, p = 0.48) and the rate of clinically relevant postoperative pancreatic fistula (14 vs. 5%, p = 0.82) were no different for the patients with or without open conversion, the postoperative hospital stay was significantly longer in the former (median 15 vs. 10 days, p = 0.03). Careful preoperative assessment is required when planning LDP for PDAC. Although conversion to open surgery does not result in failure of LDP, efforts to reduce the duration of postoperative hospital stay and the occurrence of complications are desirable to improve the outcome of LDP.


Far-ultraviolet laser ablation of the cornea: photoacoustic studies.
Wide bandwidth piezoelectric transducers made of thin (9 microns) polyvinylidene fluoride film have been used to make time-resolved measurements of the stress-wave generated by far-ultraviolet (193 nm) laser ablation in corneal tissue in vitro. At high fluence (approximately 250 mJ/cm2), ablation commences within 10 ns (+/- 5 ns) of the laser pulse and generates short acoustic impulses (approximately 30 ns). The time profile of the ablation, when coupled to the energy requirements for ablation from earlier work, allows the estimation of a temperature and a half-life for the thermal decomposition of the collagen in cornea. These values do not support a photothermal mechanism for the ablation under the experimental conditions.


[Study of the cervix of normal pregnancy and threatened preterm delivery using transvaginal sonography].
To observe the changes of cervix in women between 16 and 35 weeks of gestation using transvaginal ultrasound and to determine the value of the cervix length in predicting preterm delivery among the women with threatened preterm labor. Transvaginal sonography were performed in 154 normal single nulliparous pregnant women between 16 and 35 weeks of gestation and 58 women with threatened preterm labor but without premature rupture of membrane. (1) There is no definitely change in either cervical length or internal diameter of cervix among the pregnant women over the studied period. There was also no funneling to be observed. The mean cervical length is (36 +/- 5) mm, and the mean cervical internal diameter is (4 +/- 1) mm. (2) Eleven preterm deliveries occurred among the 58 pregnancy women with threatened preterm labor. The cervical length by sonography of 11 preterm deliveries was (18 +/- 6) mm, and was significant shorter than the women without preterm deliveries whose mean cervical length was (32 +/- 6) mm (P < 0.001). The cervical length of women who delivered pretermly was totally <or= 26 mm. (3) A cervical length of 26 mm (x-2 s) as the cutoff to predict the preterm delivery among women with the threatened preterm labor has a 100% of sensitivity, 81% of specificity, 55% positive predictive value and a 100% of negative predictive value. Cervical length by transvaginal sonography can be used to predict preterm delivery among the women with threatened preterm labor. Among women treated for preterm delivery, a cervical length of less than 26 mm indicated a high risk of preterm delivery, and intensive management is required.


Simple method for comparing reliability of two serum tumour markers in breast carcinoma.
To compare the two breast tumour markers, CA15-3 and mucinous-like carcinoma associated antigen (MCA), using Receiver Operating Characteristic (ROC) curve analysis. One hundred and ninety six patients "presenting" with breast carcinoma had serum CA15-3 and MCA concentrations measured. Using these markers as indicators of stage IV disease at the recommended laboratory level, true positive rates (TPR) and false positive rates (FPR) were obtained as follows: CA15-3 TPR = 75%, FPR = 7.4%, MCA TPR = 80%, FPR = 59.1%. By increasing the CA15-3 cutoff level to 45 U/ml, a TPR and FPR of 75% and 0.6%, respectively were obtained. By increasing the MCA cutoff level to 23 U/ml, a TPR and FPR of 65% and 2.3%, respectively, were obtained. Using ROC curve analysis shows that CA15-3 is a superior indicator of metastatic breast disease than MCA at recommended laboratory levels, and by altering the cutoff points, the specificity and sensitivity for both these markers can be improved.


Dose distribution throughout the body from radiotherapy for Hodgkin's disease in childhood.
The individual dosimetry performed for a multicentre European cohort study of second malignant neoplasm following radiotherapy for a solid cancer in childhood demonstrated a large variation in the radiation doses estimated to any site. From this study we have extracted the present work, i.e. estimation of doses for patients who underwent radiotherapy for Hodgkin's disease in their childhood. These patients were treated using high energy X-rays from linear accelerators (MV group), gamma-radiation from Cobalt machines (Cobalt group), soft X-rays from orthovoltage machines (kV group) and electron beams from accelerators (MeV group) at six French and UK centres. All patients started their radiotherapy between 1955 and 1985 and about 12% of them received more than one beam quality. Most of the patients were irradiated with large mantle AP/PA or partial mantle fields. Patients with transdiaphragmatic extension were also irradiated using inverted-Y paraaortic fields. The absorbed doses at the 91 skeleton points are used to calculate the mean dose to the active bone marrow. Estimates of the median and mean doses, standard deviations and ranges to 13 specific sites of the body and to the active bone marrow are reported. Depending upon the size and sex of patients, target volume and position and radiotherapy techniques, the estimated doses are highly spread, attaining 0.19-106.07% of the target dose. This study underscores the need for individual dosimetry in epidemiological studies. Comparison with the available measured and calculated doses to the ovary and testis shows good agreement. This study underscores the need for individual dosimetry in epidemiological studies.


Biophysical properties of tear film lipid layer II. Polymorphism of FAHFA.
Fatty acid esters of hydroxy fatty acids (FAHFAs) are a newly discovered class of endogenous lipids that consist of two acyl chains connected through a single ester bond. Being a unique species of FAHFAs, (O-acyl)-ω-hydroxy fatty acids (OAHFAs) differ from other FAHFAs in that their hydroxy fatty acid backbones are ultralong and their hydroxy esterification is believed to be solely at the terminal (ω-) position. Only in recent years with technological advances in lipidomics have OAHFAs been identified as an important component of the tear film lipid layer (TFLL). It was found that OAHFAs account for approximately 4 mol% of the total lipids and 20 mol% of the polar lipids in the TFLL. However, their biophysical function and contribution to the TFLL is still poorly understood. Here we studied the molecular biophysical mechanisms of OAHFAs using palmitic-acid-9-hydroxy-stearic-acid (PAHSA) as a model. PAHSA and OAHFAs share key structural similarities that could result in comparable biophysical properties and molecular mechanisms. With combined biophysical experiments, atomic force microscopy observations, and all-atom molecular dynamics simulations, we found that the biophysical properties of a dynamic PAHSA monolayer under physiologically relevant conditions depend on a balance between kinetics and thermal relaxation. PAHSA molecules at the air-water surface demonstrate unique polymorphic behaviors, which can be explained by configurational transitions of the molecules under various lateral pressures. These findings could have novel implications in understanding biophysical functions that FAHFAs, in general, or OAHFAs, specifically, play in the TFLL.


Hepatoprotective effect of ethanolic extract of Phyllanthus amarus Schum. et Thonn. on aflatoxin B1-induced liver damage in mice.
Phyllanthus amarus Schum. et Thonn. (Bhuia amla; Euphorbiacae) is a herb common to central and southern India. It is an ayurvedic herb and has a wide range of traditional uses in different diseases. The aim of this work was to evaluate the hepatoprotective effect of ethanolic extract of Phyllanthus amarus (Phyllanthus amarus) on aflatoxin B(1)-induced liver damage in mice using different biochemical parameters and histopathological studies. Aflatoxin was administered orally (66.6 microg kg(-1)BW 0.2 ml(-1)day(-1)) to the mice of each group except control to which normal saline and ascorbic acid (0.1g kg(-1)BW 0.2 ml(-1)day(-1)) were given, respectively. Ethanolic extract of Phyllanthus amarus (0.3g kg(-1)BW 0.2 ml(-1)day(-1)) was given to all groups except control groups (gp. I and gp. V) after 30 min of aflatoxin administration. The entire study was carried out for 3 months and animals were sacrificed after an interval of 30 days till the completion of study. Phyllanthus amarus extract was found to show hepatoprotective effect by lowering down the content of thiobarbituric acid reactive substances (TBARS) and enhancing the reduced glutathione level and the activities of antioxidant enzymes, glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT). Histopathological analyses of liver samples also confirmed the hepatoprotective value and antioxidant activity of the ethanolic extract of the herb, which was comparable to the standard antioxidant, ascorbic acid. The overall data indicated that Phyllanthus amarus possesses a potent protective effect against aflatoxin B(1)-induced hepatic damage, and the main mechanism involved in the protection could be associated with its strong capability to reduce the intracellular level of reactive oxygen species by enhancing the level of both enzymatic and non-enzymatic antioxidants.


Studies of carbohydrate and lipid metabolism in women using the progesterone-T intrauterine device for six months: blood glucose, insulin, cholesterol, and triglyceride levels.
A prospective, detailed study of both lipid and carbohydrate metabolism was carried out in 35 women who used a progesterone-T type intrauterine device (IUD). A 3-hour oral glucose tolerance test was performed in each woman before the IUD was inserted and again after 6 months of use. There was no change in the patients' weight or in the fasting glucose, cholesterol, or triglyceride levels. There were significant increases in the 3-hour glucose and the fasting, 0.5-, and 3-hour plasma insulin values in the 6-month tests. These values were less than those found after 6 months of systemic progestogen use, but do suggest some systemic effect of the released progesterone.


Mutation of the uracil DNA glycosylase gene detected in glioblastoma.
Despite extensive characterization of genetic changes in gliomas, the underlying etiology of these tumors remains largely unknown. Spontaneous DNA damage due to hydrolysis, methylation, and oxidation is a frequent event in the brain. Failure of DNA repair following this damage may contribute to tumorigenesis of gliomas. Uracil DNA glycosylase (UDG), an enzyme which excises uracil from DNA, is an important component of the base excision repair pathway. The sequence of a human homologue of uracil DNA glycosylase gene (UNG) has been recently identified. We performed PCR-based SSCP mutational analysis of UNG in 11 sporadic gliomas (six glioblastomas, two anaplastic astrocytomas, and three oligodendrogliomas) and eight glioblastoma cell lines. One out of six sporadic glioblastomas had a point mutation in exon 3, which resulted in a missense mutation in codon 143. None of the eight glioblastoma cell lines or the five non-glioblastoma sporadic gliomas showed a mutation. Genetic alterations of UNG may play a role in the development of a subset of primary glioblastomas.


An enzymatic colorimetric assay of calcium-dependent phospholipases A.
In this paper we describe a new method for the assay of calcium-dependent phospholipases A. In this method released fatty acids are quantitated by an enzymatic colorimetric reagent kit which is commercially available. We have tested the applicability of this assay with enzymes from porcine pancreas (phospholipase A2), snake venom (phospholipase A2), and Rhizopus arrhizus (a lipase with phospholipase A1-like activity) as well as with a phospholipase A2 activity of bovine seminal vesicle fluid. We conclude that the kit procedure is a convenient, rapid and sensitive endpoint assay for calcium-dependent phospholipases A.


The Role of Sarcopenia and Myosteatosis in Short- and Long-Term Outcomes Following Curative-Intent Surgery for Hepatocellular Carcinoma in a European Cohort.
Alterations of body composition, especially decreased muscle mass (sarcopenia) and impaired muscle quality (myosteatosis), are associated with inferior outcomes in various clinical conditions. The data of 100 consecutive patients who underwent partial hepatectomy for hepatocellular carcinoma (HCC) at a German university medical centre were retrospectively analysed (May 2008-December 2019). Myosteatosis and sarcopenia were evaluated using preoperative computed-tomography-based segmentation. We investigated the predictive role of alterations in body composition on perioperative morbidity, mortality and long-term oncological outcome. Myosteatotic patients were significantly inferior in terms of major postoperative complications (Clavien-Dindo ≥ 3b; 25% vs. 5%, p = 0.007), and myosteatosis could be confirmed as an independent risk factor for perioperative morbidity in multivariate analysis (odds ratio: 6.184, confidence interval: 1.184-32.305, p = 0.031). Both sarcopenic and myosteatotic patients received more intraoperative blood transfusions (1.6 ± 22 vs. 0.3 ± 1 units, p = 0.000; 1.4 ± 2.1 vs. 0.3 ± 0.8 units, respectively, p = 0.002). In terms of long-term overall and recurrence-free survival, no statistically significant differences could be found between the groups, although survival was tendentially worse in patients with reduced muscle density (median survival: 41 vs. 60 months, p = 0.223). This study confirms the prognostic role of myosteatosis in patients suffering from HCC with a particularly strong value in the perioperative phase and supports the role of muscle quality over quantity in this setting. Further studies are warranted to validate these findings.


Fourier transform IR imaging of primary tumors predicts lymph node metastasis of bladder carcinoma.
The process of metastasis is complex and often impossible to be recognized in conventional clinical diagnosis. Lymph node metastasis (LNM) of bladder carcinoma (BC) is often associated with muscle-invasive tumors. To prevent and recognize LNM, the standard treatment includes radical cystectomy with lymph node dissection and histological examination. Here, we propose infrared (IR) microscopy as a tool for the prediction of LNM. For this purpose, IR images of bladder biopsies from patients with diagnosed non-metastatic early (E BC) and advanced (A BC), as well as metastatic advanced (M BC) bladder cancer were first collected. Furthermore, this dataset was complemented with images of the secondary tumors from the lymph nodes (M LN) of the M BC patients. Unsupervised clustering was used to extract tissue structures from IR images to create a data set comprising 382 IR spectra of non-metastatic bladder tumors and 241 metastatic ones. Based on that, we next established discrimination models using PLS-DA with repeated random sampling double cross-validation, and permutation test to perform the classification. The accuracy of BC metastasis prediction from IR bladder biopsies was 83 % and 78 % for early and advanced BC, respectively, herein demonstrating a proof-of-concept IR detection of BC metastasis. The analysis of spectral profiles additionally showed molecular composition similarity between metastatic bladder and lymph node tumors. We also determined spectral biomarkers of LNM that are associated with sugar metabolism, remodeling of extracellular matrix, and morphological features of cancer cells. Our approach can improve clinical decision-making in urological oncology.


Management of Mandible Fracture by Plating and Wiring: An Otolaryngologist Perspective at Teritiary Care Center.
The facial area is one of the most frequently injured parts of the body (Abiose in Br J Oral Maxillofac Surg 24(1):319, 1986; Adi et al. in Br J Oral Maxillofac Surg 28(3):1949, 1990; Allan and Daly in Int J Oral Maxillofac Surg 19(5):26871, 1990), and the mandible is one of the most commonly fractured maxillofacial bones (1990; Azevedo et al. in J Trauma 45(6):10847, 1998; Bremerich et al. in Acta Stomatol Belg 93:511, 1996). Mandible is the only mobile bone of the skeleton, and hence vulnerable to fracture. This is a retrospective study of 50 mandibular fracture cases managed at the Department of ENT, Govt. Medical College Bhavnagar during the 2 years period from 2014 to 2016. Maximum subjects were in age group 21-30 years with a male preponderance. Road traffic accident is the main cause followed by falls and assault. Symphysis is the most common site of Mandibular fracture. Mandible fracture is a common entity in Road traffic accidents. Multiple fractures are seen in 40% of mandibular fracture cases. The results were equally good in patients requiring only MMF (Maxillo Mandibular Fixation) and inpatients requiring MMF and Plating, during the follow up up to 8 weeks. Physiotherapy was advised for all the post op patients after 2 months.


Rheumatoid-nodule-like cutaneous granuloma associated with recombinase activating gene 1-deficient severe combined immunodeficiency: A rare case.
Cutaneous granulomas without detectable infectious etiology rarely occur in children and adults with primary immunodeficiency disorders. These cutaneous granulomas are primarily seen in combined variable immunodeficiency, ataxia-telangiectasia, and severe combined immunodeficiency (SCID) and can emulate the reaction patterns seen in sarcoidosis and granuloma annulare. To date, the literature has described only six cases of non-infectious cutaneous granulomas in SCID. We report an unusual case of cutaneous granuloma, mimicking a sarcoma, in a 40-year old male with recombinase activating gene 1-deficient SCID, who presented with a slow-growing globus mass over the lateral aspect of the right elbow. There was heterogeneous enhancement on MRI, which was concerning for neoplasm but no malignancy was found on frozen or permanent sections. GMS, PAS with diastase, and AFB stains, as well as microbiology cultures, were negative. An AE1/AE3 stain was negative and a CD163 stain highlighted histiocytes. No infectious etiology was identified and histopathology revealed palisaded granulomatous dermatitis, most closely resembling a rheumatoid nodule. Although cutaneous manifestations have been reported in nearly half of primary immunodeficiency disorder cases, non-infectious cutaneous granulomas are exceedingly rare in SCID. To our knowledge, this is the first case report of cutaneous palisaded granulomatous dermatitis mimicking a rheumatoid nodule in a major joint.


Concurrent measurement of substance P and serotonin in spinal superfusates: failure of capsaicin and p-chloroamphetamine to co-release.
This study examined the efflux of endogenous serotonin and substance P-like immunoreactive material into in vivo superfusates of the rat spinal cord under quiescent conditions and during the addition of either capsaicin or p-chloroamphetamine to the superfusate. Using a method which permitted concurrent measurement of serotonin and substance P-like immunoreactive material in the same sample of superfusate, it was found that capsaicin increased the efflux of substance P-like immunoreactive material from the spinal cord but did not alter the efflux of serotonin. Conversely, the addition of p-chloroamphetamine caused the efflux of serotonin from the spinal cord to increase, but did not affect the efflux of substance P-like immunoreactive material.


The 15-year national trends of endocrine cancers incidence among Iranian men and women; 2005-2020.
Cancer is one of the important health problems in Iran, which is considered as the third cause of death. Endocrine cancers are rare but mostly curable. Thyroid cancer, the most common endocrine tumors, includes about one percent of malignant cancer. In this study, we examined the 15-year national trend of endocrine cancer incidence in Iranian men and women. The data in each province were evaluated based on age, gender, and cancer type according to International Classification of Disease Codes version 10 (ICD-10) from 2005 to 2020 in Iran. All data were obtained from the reports of the Statistics Center of Iran (SCI), 6 phases of the step-by-step approach to monitoring the risk factors of chronic diseases over 18 years old (STEPs), and 3 periods of the CASPIAN study (survey of non-communicable diseases in childhood and adolescence). Statistical analyzes and graph generation were done using R statistical software. Poisson regression with mixed effects was used for data modeling and incidence rate estimation. The incidence of thyroid gland malignancy is higher in women than in men. On the other hand, the incidence of adrenal gland cancer is slightly higher in men than in women. The same pattern is observed for other endocrine neoplasms and related structures. The incidence rate of these types of cancers has generally increased from 2005 to 2020 in Iran. This increase is more in women than in men. In addition, in the middle of the country, there is a strong region in terms of the occurrence of these types of cancers. The incidence rate in these provinces is relatively higher for both sexes and all studied periods. We conducted a study to observe the changing trends for various types of endocrine cancers over 15 years in men and women. Considering the increasing trend of thyroid cancers in Iran, therefore, creating essential policies for the management of these types of cancers for prevention, rapid diagnosis, and, timely treatment is particularly important.


Magnetofection™ of NMDA Receptor Subunits GluN1 and GluN2A Expression Vectors in Non-Neuronal Host Cells.
The functional study of reconstituted NMDA receptors (NMDARs) in host cells requires that the corresponding vectors for the expression of the NMDAR subunits are co-transfected with high efficiency. Magnetofection™ is a technology used to deliver nucleic acids to cells. It is driven and site-specifically guided by the attractive forces of magnetic fields acting on magnetic nanoparticles that are associated with nucleic acid vectors. In magnetofection™, cationic lipids form self-assembled complexes with the nucleic acid vectors of interest. Those complexes are then associated with magnetic nanoparticles that are concentrated at the surface of cultured cells by applying a permanent magnetic field. Magnetofection™ is a simple method to transfect cultured cells with high transfection rates. Satisfactory expression levels are obtained with very low amounts of nucleic acid vector. Moreover, incubation time with host cells is less than 1 h, as compared with the several hours needed with standard transfection assays.


Antibody titres to lamb rotavirus in colostrum and milk of vaccinated ewes.
Ewes were vaccinated two to three weeks prior to mating with a formalin-treated preparation of lamb rotavirus. The colostrum and milk produced by vaccinated ewes after the subsequent pregnancy were shown to contain significantly higher titres of antibody to the virus than did mammary secretions from non-vaccinates. The virus neutralising antibody activity was associated with IgG in both colostrum and milk. However, IgG concentrations in the mammary secretions of vaccinates and non-vaccinates did not differ. It is suggested that vaccination of the dam may be of value in protecting the suckled neonatal lamb against rotavirus infection.