Chromosome translocation and its consequence in the genome of Burkholderia cenocepacia AU-1054.
Most bacterial genomes have one single chromosome. The species Burkholderia cenocepacia, a Gram-negative β-proteobacterium, is one of the exceptions. Genomes of four strains of the species have been sequenced and each has three circular chromosomes. In the genus Burkholderia, there are another seven sequenced strains that have three chromosomes. In this paper, the numbers of essential genes and tRNA genes among the 11 strains of the genus Burkholderia are compared. Interestingly, it is found that the shortest chromosome of B. cenocepacia AU-1054 has much (over three times) more essential genes and tRNA genes than the corresponding chromosomes in the other 10 strains. However, no significant difference has been found on the two longer chromosomes among the 11 strains. Non-homologous chromosomal translocation between chromosomes I and III in the species B. cenocepacia is found to be responsible for the unusual distribution of essential genes. The present work may contribute to the understanding of how the secondary chromosomes of multipartite bacterial genomes originate and evolve. The computer program, DEG_match, for comparatively identifying essential genes in any annotated bacterial genomes is freely available at http://cobi.uestc.edu.cn/resource/AU1054/.


The modulatory effect of plant polysaccharides on gut flora and the implication for neurodegenerative diseases from the perspective of the microbiota-gut-brain axis.
The microbiota-gut-brain axis includes a two-way communication pattern between the microorganisms that live in our gut and our brain function and behavior. Intestinal flora disorders not only induce related metabolic diseases, but also have an important relationship with neurodegenerative diseases. The present studies have shown that natural polysaccharides are important for maintaining the steady status of intestinal flora. This review aims to summarize the two-way relationship between the gut microbiota and the brain, and the modulatory effect of plant polysaccharides on gut flora, which provides new ideas for the prevention and treatment of the neurodegenerative diseases.


Machine learning in protein structure prediction.
Prediction of protein structure from sequence has been intensely studied for many decades, owing to the problem's importance and its uniquely well-defined physical and computational bases. While progress has historically ebbed and flowed, the past two years saw dramatic advances driven by the increasing "neuralization" of structure prediction pipelines, whereby computations previously based on energy models and sampling procedures are replaced by neural networks. The extraction of physical contacts from the evolutionary record; the distillation of sequence-structure patterns from known structures; the incorporation of templates from homologs in the Protein Databank; and the refinement of coarsely predicted structures into finely resolved ones have all been reformulated using neural networks. Cumulatively, this transformation has resulted in algorithms that can now predict single protein domains with a median accuracy of 2.1 Å, setting the stage for a foundational reconfiguration of the role of biomolecular modeling within the life sciences.


Effect of culturally tailored diabetes education in ethnic minorities with type 2 diabetes: a meta-analysis.
Diabetes is a major cause of cardiovascular morbidity and mortality. Ethnic minorities experience a disproportionate burden of diabetes; however, few studies have critically analyzed the effectiveness of a culturally tailored diabetes intervention for these minorities. The aim of this study was to evaluate the effectiveness of a culturally tailored diabetes educational intervention (CTDEI) on glycemic control in ethnic minorities with type 2 diabetes. We searched databases within PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Education Resources Information Center (ERIC), PsycINFO, and ProQuest for randomized controlled trials (RCTs). We performed a meta-analysis for the effect of diabetes educational intervention on glycemic control using glycosylated hemoglobin (HbA(1c)) value in ethnic minority groups with type 2 diabetes. We calculated the effect size (ES) with HbA(1c) change from baseline to follow-up between control and treatment groups. The 12 studies yielded 1495 participants with a mean age of 63.6 years and a mean of 68% female participants. Most studies (84%) used either group education sessions or a combination of group sessions and individual patient counseling. The duration of interventions ranged from 1 session to 12 months. The pooled ES of glycemic control in RCTs with CTDEI was -0.29 (95% confidence interval, -0.46 to -0.13) at last follow-up, indicating that ethnic minorities benefit more from CTDEI when compared with the usual care. The effect of intervention was greatest and significant when HbA(1c) level was measured at 6 months (ES, -0.41; 95% confidence interval, -0.61 to -0.21). The ES also differed by each participant's baseline HbA1c level, with lower baseline levels associated with higher ESs. Based on this meta-analysis, CTDEI is effective for improving glycemic control among ethnic minorities. The magnitude of effect varies based on the settings of intervention, baseline HbA1c level, and time of HbA1c measurement. More rigorous RCTs that examine tailored diabetes education, ethnically matched educators, and more diverse ethnic minority groups are needed to reduce health disparities in diabetes care.


Rare Diseases of the Nose, the Paranasal Sinuses, and the Anterior Skull Base.
Due to their low incidence and thus resulting limited diagnostic criteria as well as therapeutic options, rare diseases of the nose, the paranasal sinuses, and the anterior skull base are a significant challenge. The value as of which a disease has to be considered as rare amounts to a maximum of 5 patients per 10 000 people. Within these diseases, however, there are extreme differences. Some rare or orphan diseases like for example the inverted papilloma belong to regularly diagnosed and treated diseases of larger departments of oto-rhino-laryngology whereas other rare diseases and malformations have only been described in less than 100 case reports worldwide. This fact emphasizes the necessity of bundling the available experience of diagnostics and therapy. The present article gives an overview about rare diseases of the nose, the paranasal sinuses, and the anterior skull base from the field of diseases/syndromes of the olfactory system, malformations of the nose and paranasal sinuses, ventilation and functional disorders as well as benign and malignant tumors. The classification and data on diagnostic and therapeutic options were established based on the current literature.


Basic behavioral management techniques in pediatric dentistry: A systematic review and meta-analysis.
To systematically retrieve and assess studies regarding the effectiveness of basic behavioral management techniques (BMTs) in pediatric patients. Electronic and hand searches were conducted to locate Randomized Controlled Trials (RCTs) reporting on objective and subjective evaluation of anxiety and behavior of children up to 12 years of age. Data extraction and risk of bias evaluation, using the Cochrane risk of bias tool (RoB 2.0 Tool), were performed independently and in duplicate for all included studies. Mean differences and standard deviations were used to summarize the data from each study and meta-analyses were conducted with studies of limited heterogeneity. A total of 708 papers were identified and screened, 122 retrieved for full text appraisal and 62 finally included. Results suggested that all basic BMTs have acceptable effectiveness on pediatric patients' anxiety, fear and behavior during dental treatment. Meta-analysis showed a statistically significant difference in favor of distraction for subjective anxiety using Facial scale (Mean diff.: 2.78; 95% CI: -3.08, -0.53; p = 0.005) and Modified Child Dental Anxiety Scale (Mean diff.: 12.76; 95% CI: -6.09, -4.47; p = 0.001) and a non-significant difference for heart rate (Mean diff.: 1.70; 95% CI: -6.54, 0.46; p = 0.09). Music significantly reduced heart rate when compared to a control comparator, underlining the superiority of the BMT (Mean diff.: 2.71; 95% CI: -3.70, -0.59; p = 0.007). Limited evidence about efficacy of one technique over another raises important issues on the topic for future research regarding the management of the child patient in the dental setting of the 21st century. Behavioral management comprises a challenge for clinicians, who need to be familiar with a range of techniques to meet patients' needs at individual level and be flexible in their implementation. Appropriate technique should incorporate patients' personality and parents' active involvement, within the contents of the changes in modern societies.


Factors influencing survival in metastatic castration-resistant prostate cancer therapy.
The number of patients with metastatic castration-resistant prostate cancer (mCRPC) is expected to increase due to the long life expectancy of those with advanced disease who are also more commonly diagnosed today because of stage migration. Several compounds are available for treating these patients. We reviewed currently available treatments for mCRPC, their mechanism of action and resistance, and we explored possible predictors of treatment success useful to predict survival in mCRPC patients. A combination of molecular, clinical, pathological, and imaging features is necessary to correctly estimate patients' risk of death. The combination of these biomarkers may allow clinicians to tailor treatments based on cancer history and patients' features. The search of predictive biomarkers remains an unmet medical need for most patients with mCRPC.


Aaprb1, a subtilsin-like protease, required for autophagy and virulence of the tangerine pathotype of Alternaria alternata.
Subtilisin-like serine protease secreted by pathogenic fungi can facilitate the infection and acquisition of nutrients. Functions of subtilisin-like serine proteases in the phytopathogenic fungus Alternaria alternata remains unknown. In the current study, 15 subtilisin-like serine proteases were individually deleted in the citrus fungal pathogen A. alternata. Only one, designated AaPrb1, was found to be required for A. alternata pathogenesis. The AaPrb1 deficiency strain (ΔAaprb1) reduced growth, conidiation, the formation of aerial hyphae, protease production, and virulence on citrus leaves. However, biochemical analyses and bioassays revealed that ΔAaprb1 plays no role in the production of ACT toxin. Through Y2H assays, Aaprb1 was found to interact with Aapep4, a vacuole-localized proteinase A in A. alternata. Furthermore, silencing AaPep4 in A. alternata resulted in phenotypes similar with those of ΔAaprb1. Expression of AaPrb1 was found to be regulated by AaPep4. TEM showed that AaPrb1and AaPep4 were involved in the suppression of the degradation of autophagosomes. Deletion of the autophagy gene AaAtg8 in A. alternata decreased conidiation, the formation of aerial hyphae and pathogenicity similar to ΔAaprb1, implying that some phenotypes of ΔAaprb1 were due to the impairment of autophagy. Overall, this study expands our understanding of how A. alternata utilizes the subtilisin-like serine protease to achieve successful infection in the plant host.


Response map properties of units in the dorsal cochlear nucleus of barbiturate-anesthetized gerbil (Meriones unguiculatus).
The response map scheme introduced by Evans and Nelson (1973) and modified by others, including Davis et al. (1996) for use with gerbils, has been used primarily for classifying units recorded in the cochlear nucleus of unanesthetized decerebrate preparations. Units lacking spontaneous activity (SpAc) have been classified as either type I/III or type II units based on the relative strength of their responses to broad-band noise compared to their responses to best-frequency (BF) tones. The relative noise index (rho), a ratio of these responses after SpAc is subtracted out, provides a convenient measure of this relative strength. In this paper, responses of 320 units recorded in the dorsal cochlear nucleus (DCN) of barbiturate-anesthetized gerbils to short-duration BF tones and broad-band noise were recorded. Since 87.5% of these units lacked SpAc, their response maps resembled those of type II and type I/III units. Units were characterized by rho and the normalized slope (m) of a best line fit to the BF rate versus level plot starting from the sound level corresponding to the first inflection point of the rate curve (typically its maximum value or the start of its sloping saturation). The distributions of rho and m values do not form distinct clusters as they do for units in the decerebrate preparation. Thus, the criteria developed for classifying DCN units in the decerebrate preparation do not appear appropriate for units in the barbiturate-anesthetized preparation. Deposits of horseradish peroxidase were used to locate 52 units. Most of the low SpAc units, 56% with poor noise responses (5/9) and nearly 70% with strong noise responses (25/36), and nearly all of the high SpAc units (6/7), were located either within or below the fusiform cell layer.


[Research funding for rare diseases in Germany].
There is high need for more research in the field of rare diseases. Not only must the causes and mechanisms of the numerous and often heterogeneous diseases be delineated, but criteria must also be defined for optimal stratification of patients for individualized therapies. In this context, research and innovative diagnostics are linked together more closely than in other fields of medicine. The early stages of disease-oriented research can be performed in individual institutions but, due to low numbers of patients, late translation and transfer into clinics requires multicentric and international collaboration. In Germany research on rare diseases takes place mostly in faculties of medicine at universities. Since the institutional financial support is very low, research grants have substantial significance. The German Research Foundation (DFG) and the Federal Ministry of Education and Research (BMBF) are the main grant agencies for national projects, but foundations and patient advocacy groups also finance research to a certain extent. The ERA-Net "E-Rare" and the programs of the EU target primarily international cross-border projects and patient trials. All of these programs need to be adapted more efficiently to the particular needs of rare disease research. For national and international research projects on rare diseases, sufficient funds are needed but also sustainable interdisciplinary platforms and centers must be established in order to share expert knowledge and to implement complex programs such as proof-of-concept studies in humans.


Central obesity and survival in subjects with coronary artery disease: a systematic review of the literature and collaborative analysis with individual subject data.
The aim of this study was to examine the association of central (waist circumference [WC] and waist-hip ratio [WHR]) and total obesity (body mass index [BMI]) measures with mortality in coronary artery disease (CAD) patients. The question of which measure of obesity better predicts survival in patients with CAD is controversial. We searched OVID/Medline, EMBASE, CENTRAL, and Web of Science from 1980 to 2008 and asked experts in the field for unpublished data meeting inclusion criteria, in which all subjects had: 1) CAD at baseline; 2) measures of WC or WHR; 3) mortality data; and 4) a minimum follow-up of 6 months. From 2,188 studies found, 6 met inclusion criteria. We obtained individual subject data from 4, adding unpublished data from a cardiac rehabilitation cohort. A variable called "central obesity" was created on the basis of tertiles of WHR or WC. Cox-proportional hazards were adjusted for age, sex, and confounders. The final sample consisted of 15,923 subjects. There were 5,696 deaths after a median follow-up of 2.3 (interquartile range 0.5 to 7.4) years. Central obesity was associated with mortality (hazard ratio [HR]: 1.70, 95% confidence interval [CI]: 1.58 to 1.83), whereas BMI was inversely associated with mortality (HR: 0.64, 95% CI: 0.59 to 0.69). Central obesity was also associated with higher mortality in the subset of subjects with normal BMI (HR: 1.70, 95% CI: 1.52 to 1.89) and BMI ≥30 kg/m(2) (HR: 1.93, 95% CI: 1.61 to 2.32). In subjects with CAD, including those with normal and high BMI, central obesity but not BMI is directly associated with mortality.


Reconstruction of circumferential pharyngeal defects after tumour resection: reference or preference.
Reconstruction of circumferential hypopharyngeal defects is often challenging. The aim of the study is to examine the result of our experience and to formulate improved management guidelines. Between 1980 and 2009, all patients who have circumferential pharyngectomy were recruited. Data were recorded prospectively for analysis. A total of 202 patients were recruited. Majority had primary tumour in the hypopharynx (n=165), and the remaining patients had recurrent laryngeal carcinoma. Radiotherapy was given preoperatively in 72 patients and postoperatively in 108 patients. A pectoralis major (PM) flap was used in 92 (45.5%) patients, a free anterolateral thigh (ALT) flap in 24 (11.9%) patients and a free jejunal flap in 86 (42.6%) patients. Early fistula rate was 23.9% in the PM flap group, 12.5% in the ALT group and 4.6% in the jejunum group. Late anastomotic stricture rate was 27.2% in the PM flap group, 12.5% in the free ALT group and 2.3% in the jejunum group. Early fistula formation significantly increased the risk of subsequent anastomotic stricture (p=0.023). In patients with no stricture, 61.9% of them in the jejunal group were able to resume solid diet, compared with 35.8% and 38.1% in the PM and ALT groups. After PM flap harvesting, 34.8% of the chest wall defects could not be closed primarily, which were best repaired using the lateral thoracic flap. The donor-site morbidity of ALT and jejunal flap was low. In suitable patients, free jejunal flap reconstruction of circumferential pharyngectomy defects achieves the best functional outcome with minimal donor-site morbidity.


Genomic Medicine and Advances in Vaccine Technology and Development in the Developing and Developed World.
Vaccinations are one of the most effective public health measures available at present [...].


[Preventive health measures in accordance with the health insurance law].
The recently introduced (1.1.96) new health legislation in Switzerland provides in article 26 the coverage of preventive measures. The present article discusses the actual list of preventive measures admitted to the basic health insurance package.


Serial circulating tumor DNA monitoring of CDK4/6 inhibitors response in metastatic breast cancer.
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) significantly improve progression-free survival and have become the standard therapy for estrogen receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer patients. Treatment surveillance by radiological imaging has some limitations in detection and repeated biopsy genomic profiling is not clinically feasible. Serial circulating tumor DNA (ctDNA) analysis may provide insights into treatment response. Here we performed serial ctDNA analysis (n = 178) on 33 patients. Serial ctDNA analysis identified disease progression with sensitivity of 75% and specificity of 92%. In eight of 12 patients (61%) responding to CDK4/6i who eventually developed progressive disease, serial sampling every 3 or 6 months captured the initial rise of ctDNA with an average lead time of 3 months. In three of eight patients that did not respond to CDK4/6i (progressive disease at first radiological assessment, 3 months), biweekly sequencing within the first cycle of CDK4/6i treatment (1 month) detected sustained ctDNA levels (≥0.2% variant allele frequency), with lead time of 2 months. Serial ctDNA analysis tracked RECIST response, including clinically challenging scenarios (bone metastases or small-sized target lesions), as well as detecting acquired genetic alterations linked to CDK4/6i resistance in the G1 to S transition phase. Circulating tumor DNA analysis was more sensitive than carcinoembryonic antigen or cancer antigen 15-3 serum tumor markers at monitoring tumor response to CDK4/6i treatment. Our findings indicated the possible clinical utility of serial ctDNA analysis for earlier progressive disease detection and real-time monitoring of CDK4/6i response.


Whither the challenge hypothesis?
Almost fifty years ago the advent of assay methods to measure circulating levels of hormones revolutionized endocrinology in relation to investigations of free-living and captive animals. This new field "environmental endocrinology" revealed that endocrine profiles in animals in their natural habitat were not only different from captive animals, but often deviated from predictions. It quickly became apparent that the organization and analysis of data from the field should be sorted by life history stages such as for reproductive processes, migration, molt etc. and spaced in time according to natural duration of those processes. Presentation of data by calendar date alone gives much simpler, even misleading, patterns. Stage-organized analyses revealed species-specific patterns of hormone secretion and dramatic inter-individual differences. The "Challenge Hypothesis" sparked exploration of these results, which diverged from expectations of hormone-behavior interactions. The hypothesis led to specific predictions about how the hypothalamo-pituitary-gonad axis, and particularly circulating patterns of testosterone, might respond to social challenges such as simulated territorial intrusions. Initially, a group of studies on free-living and captive birds played a key role in the formulation of the hypothesis. Over the decades since, the effects of social challenge and environmental context on hormonal responses have been tested in all vertebrate taxa, including humans, as well as in insects. Although it is now clear that the Challenge Hypothesis in its original form is simplistic, field and laboratory tests of the hypothesis have led to other concepts that have become seminal to the development of environmental endocrinology as a field. In this special issue these developments are addressed and examples from many different taxa enrich the emerging concepts, paving the way for investigations using recent technologies for genetic and transcriptome analyses.


Safety and efficacy of low-dose and long-course tirofiban in large hemispheric infarction.
The clinical efficacy and safety of tirofiban in the treatment of large hemispheric infarction (LHI) remain controversial. This study prospectively enrolled patients with acute LHI who were admitted to Putuo Hospital affiliated with Shanghai University of Traditional Chinese Medicine from June 2021 to December 2021. The patients were randomly assigned to the tirofiban group [3-4 μg/(kg·h)] or control group (clopidogrel 75 mg/d). A total of 71 patients with acute LHI were selected: 36 in the tirofiban group and 35 in the control group. The reduction of the NIHSS score in the tirofiban group was 2.92 ± 9.31 at discharge, and that of the control group was -3.23 ± 12.06 (p = 0.021, OR, 0.006; 95% CI, 0.004-0.008). Six patients (16.7%) in tirofiban group and 14 patients (40%) in control group died during hospitalization (p = 0.029, OR, 0.300; 95% CI, 0.099-0.908). There was significant difference in Modified Rankin Scale (mRS) 5-6 scores at 90 days between the two groups (p = 0.023, OR, 0.327; 95% CI, 0.124-0.867). However, there was no significant difference in mRS 0-1 (p = 0.321, OR, 0.972; 95% CI, 0.920-1.027), mRS 2 (p = 0.572, OR, 2.00; 95% CI, 0.173-23.109), mRS 3 (p = 0.225, OR, 2.214; 95% CI, 0.601-8.161), or mRS 4(p = 0.284, OR, 1.859; 95% CI, 0.593-5.825) scores between the two groups. There was no difference in symptomatic intracranial hemorrhage (p = 0.29, OR, 0.305; 95% CI, 0.030-3.081), asymptomatic intracranial hemorrhage (p = 0.123, OR, 0.284; 95% CI, 0.053-1.518). There was a significant difference in systemic bleeding events during hospitalization (p = 0.044, OR, 0.309; 95% CI, 0.096-1.000). Low-dose and long-course tirofiban treatment may significantly improve the early neurological function and reduce the in-hospital mortality in LHI patients. Meanwhile, tirofiban does not increase the risk of any type of bleeding events.


Epidemiological investigations of abortions due to Neospora caninum on Swiss dairy farms.
Abortions apparently due to Neospora caninum in two Swiss dairy herds were investigated by means of a PCR and ELISA, and other potential causes were eliminated. In addition, a case-control study of 24 case herds and 24 control herds indicated that N caninum-associated abortions were more likely to occur in herds with antibodies to Coxiella burnetii (with an odds ratio [OR] of 3.38 with a 95 per cent confidence interval [CI] of 1.82 to 6.22), whereas the likelihood was less in herds with antibodies to Leptospira species (OR 0.34,95 per cent CI 0.13 to 0.75), or in herds with antibodies to bovine viral diarrhoea (BVD) virus (OR 0.75,95 per cent CI 0.56 to 1.00), or Chlamydia psittaci (OR 0.18,95 per cent CI 0.09 to 0.35), or in herds in which BVD virus had been isolated from an aborted fetus (OR 0.11,95 per cent CI 0.02 to 0-58).


Strong antioxidant phenolics from Acacia nilotica: profiling by ESI-MS and qualitative-quantitative determination by LC-ESI-MS.
Acacia nilotica (L.) Del. syn is a species rich in polyphenolic constituents, in which catechins are hypothesized to possess antioxidant properties and to play a role in the anti-inflammatory activity of several plants. Due to the complexity of catechin derivatives, the investigation of this class of natural compounds has been limited by difficulties in their separation. In this paper, rationalization of the phenolics occurring in the 80% EtOH extract of Acacia nilotica pods, on the basis of ESI-MS and ESI-MS/MS profiles, has been proposed. Additionally, an LC-ESI-MS qualitative study has been performed by using a C18 polar endcapped stationary phase. The fragmentation pattern obtained evidenced the presence in A. nilotica pods of galloylated catechin- and gallocatechin derivatives along with galloylated glucose derivatives. The structures were confirmed by NMR, after isolation of the pure compounds. In addition, the radical scavenging activities of extracts and pure compounds were investigated, by using the TEAC assay. Furthermore quantitative analyses were performed by LC-ESI-MS/MS, confirming the interest of this species as a rich source of very strong antioxidant principles.


[Discovery of the luminescence of water during irradiation of radiation at a lower energy than the Cherenkov light threshold].
This is a review article on luminescence in water published by JSRT and JSMP (https://www.jsmp.org/en).abe.


Correction: Aberrant DNA Damage Response Pathways May Predict the Outcome of Platinum Chemotherapy in Ovarian Cancer.
[This corrects the article DOI: 10.1371/journal.pone.0117654.].


Genome-wide survival analysis of age at onset of alcohol dependence in extended high-risk COGA families.
The age at onset of alcohol dependence (AD) is a critical moderator of genetic associations for alcohol dependence. The present study evaluated whether single nucleotide polymorphisms (SNPs) can influence the age at onset of AD in large high-risk families from the Collaborative Study on the Genetics of Alcoholism (COGA). Genomewide SNP genotyping was performed in 1788 regular drinkers from 118 large European American families densely affected with alcoholism. We used a genome-wide Cox proportional hazards regression model to test for association between age at onset of AD and SNPs. This family-based analysis identified an intergenic SNP, rs2168784 on chromosome 3 that showed strong evidence of association (P=5×10(-9)) with age at onset of AD among regular drinkers. Carriers of the minor allele of rs2168784 had 1.5 times the hazard of AD onset as compared with those homozygous for the major allele. By the age of 20 years, nearly 30% of subjects homozygous for the minor allele were alcohol dependent while only 19% of those homozygous for the major allele were. We also identified intronic SNPs in the ADP-ribosylation factor like 15 (ARL15) gene on chromosome 5 (P=1.11×10(-8)) and the UTP20 small subunit (UTP20) gene on chromosome 12 (P=4.32×10(-8)) that were associated with age at onset of AD. This extended family based genome-wide cox-proportional hazards analysis identified several loci that might be associated with age at onset of AD.


Short-Term Responses of the Natural Planktonic Bacterial Community to the Changing Water Properties in an Estuarine Environment: Ectoenzymatic Activity, Glucose Incorporation, and BiomassProduction.
The possibility that two principal bacterial communities expressing different levels of heterotrophic activity might coexist in an estuarine ecosystem (Ria de Aveiro, Portugal) and could quickly respond to tidal fluctuations of environmental factors was experimentally tested in diffusion chambers by swapping the dissolved components of the natural water between the two communities and comparing their reactivity against the unaltered controls. The results for ectoenzymatic activity (Leu-aminopeptidase and b-glucosidase), glucose incorporation and biomass production after transference of the marine bacterial community to brackish water showed maxima in the range of 241-384% of the control values. The opposite transference of the brackish-water bacterial community to marine water produced maximal decreases to 0.14-0.58% of the control values. In a reverse experiment, designed as the return to the initial conditions after 2 hours of the first exposure, the marine community rapidly re-acquired the characteristic low profile of activity. Contrastingly, the negative effects of 2 hours of exposure to marine water on the activity of the brackish water bacteria persisted, at least for 4 hours, after return to their own water. The apparent short-term irreversibility of the decline in activity of the brackish water bacteria when exposed to marine water, in parallel with the quick and reversible positive response of the marine water bacteria to the brackish water, suggests the development of two distinct bacterioplankton communities adapted to the environmental conditions prevailing at distinct sections of the estuary. The reactivity to environmental changes demonstrated by the two communities allows the prediction of estuarine profiles of bacterial activity steeper than those expected from the conservative transport of bacterial cells associated with tidal currents.


Trastuzumab in combination with 5-fluorouracil, leucovorin, oxaliplatin and docetaxel as perioperative treatment for patients with human epidermal growth factor receptor 2-positive locally advanced esophagogastric adenocarcinoma: A phase II trial of the Arbeitsgemeinschaft Internistische Onkologie Gastric Cancer Study Group.
Perioperative chemotherapy with 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) is a mainstay in the treatment of esophagogastric adenocarcinomas (EGA). Trastuzumab improved survival when added to chemotherapy in patients with HER-2-positive metastatic EGA. We investigated the combination of trastuzumab and FLOT as perioperative treatment in patients with locally advanced EGA. A multicenter phase II study evaluated the efficacy and toxicity of perioperative FLOT (24-hours 5-FU 2600 mg/m2 , leucovorin 200 mg/m2 , oxaliplatin 85 mg/mg2 , docetaxel 50 mg/m2 , trastuzumab 6 mg/kg then 4 mg/kg d1, repeated d15 for four cycles preoperatively and postoperatively followed by 9 cycles of trastuzumab monotherapy) in patients with HER-2 positive EGA. Patients had ≥cT2, any N, M0 EGA. The primary endpoint was the rate of centrally assessed pathological complete response (pCR). Secondary endpoints comprised disease-free (DFS) and overall survival (OS), R0 resection rate, toxicity and surgical morbidity. Fifty-six evaluable patients (median age 62 years) were included; n = 40 had tumors originating from the esophagogastric junction; T stage was (cT2/3/4/unknown): 4/42/8/2; n = 50 patients had cN+ disease. Main adverse events grades 3-4: leukopenia (17.9%), neutropenia (46.6%) and diarrhea (17.0%). All patients underwent tumor resections. R0 resection rate was 92.9%. Eight patients had anastomotic leakage. One postoperative death occurred. pCR was found in 12 patients (21.4%) and a further n = 14 patients (25.0%) had near complete response. Median DFS was 42.5 months and the 3-year OS rate was 82.1%. The primary endpoint of achieving a pCR >20% was reached. No unexpected safety issues were observed. Survival data are promising.


Testosterone dependent effects of methylphenidate on social investigatory behavior of the rat.
Previous work suggested a sex difference in social investigatory behavior of a novel conspecific during acute exposure to methylphenidate. In contrast to caffeine, which has been observed to increase social investigatory behavior only in males, methylphenidate decreased social investigatory behavior only in females. Testosterone-treated females were comparable to males and were unaffected by methylphenidate. Castrated males were comparable to females in their sensitivity to methylphenidate. Like caffeine, methylphenidate increased locomotor activity in both males and females, suggesting that drug effects on social investigation cannot be attributed to a nonspecific stimulant effect. The combined results reveal a sex-related interaction of circulating testosterone with acute methylphendiate exposure. Interpretations are discussed including the behavioral contrast following exposure to methylphenidate or to caffeine.


Genetic relationships among four minorities in Guangxi revealed by analysis of 15 STRs.
The aim of this study is to investigate the genetic diversity in 15 STRs (short tandem repeats) loci of four minorities in Guangxi Province and to probe into the genetic variation and relationships among these ethnic groups. Allele frequencies of 15 STR loci were collected from 766 unrelated Mulao, Maonan, Miao, and Yao ethnic individuals by PCR-STR and sequencing, and their allele-frequency distribution were compared with each other. The genetic parameters and genetic distances were calculated, and the phylogenetic tree was constructed. Based on the results from this study, 135, 134, 148, and 145 alleles and 424, 432, 445, and 436 genotypes for 15 STR loci were observed in the Mulao, Maonan, Miao, and Yao minorities, respectively. The average heterozygosity of all ethnic groups analyzed was above 0.7; the cumulative power of discrimination (DP), the probabilities of paternity exclusion (EPP), and the polymorphic information content (PIC) were greater than 0.99999. Comparison of the allele-frequency distribution indicated that there were significant differences at most loci between Maonan vs. Miao, Yao vs. other groups, but no distinct differences between Mulao vs. Maonan, and Mulao vs. Miao minorities. The NJ tree based on the genetic distance showed that the four minorities were separated into two groups. Mulao and Maonan were clustered into one group, whereas Miao and Yao into the other. Our results revealed that 15 STR loci of the four minorities possessed high genetic diversities. Therefore, the combination of these 15 STRs is a powerful tool for forensic individual identification and paternity investigation, as well as anthropologic and genetic researches. The genetic variation and relationships among the 4 populations revealed by 15 STRs are basically consistent with their linguistic culture and ethical history.


What Are We Missing From Asymmetric Relationship Between the Retinal Nerve Fiber Layer Thickness Profiles and Sphenoid Sinus Volume?
Detailed analysis of retinal structure such as the retinal nerve fiber layer can be performed by spectral-domain optical coherence tomography (OCT). There are no published studies concerning a relationship between retinal nerve fiber layer and human sphenoid sinus volumes. We investigated this relationship. Spectral-domain OCT. The peripapillary retinal nerve fiber layer (RNFL) thickness and sphenoid sinus volume estimation of both sides of sex-matched patients were retrospectively analyzed. The mean RNFL thicknesses at the left side (91.8 μm) were significantly smaller than the right side (94.5 μm) (P = 0.040). However, the mean left sinus volume (44.5 cm) is larger than the right side, (34.5 mm) (P < 0.005). Left and right differences of both parameters are statistically significant (P < 0.05). There is a negative correlation between mean RNFL thicknesses and mean sinus volumes. To our knowledge, this article is the first report demonstrating the asymmetry relationship between RNFL and sphenoid sinus volumes.


hzAnalyzer: detection, quantification, and visualization of contiguous homozygosity in high-density genotyping datasets.
The analysis of contiguous homozygosity (runs of homozygous loci) in human genotyping datasets is critical in the search for causal disease variants in monogenic disorders, studies of population history and the identification of targets of natural selection. Here, we report methods for extracting homozygous segments from high-density genotyping datasets, quantifying their local genomic structure, identifying outstanding regions within the genome and visualizing results for comparative analysis between population samples.


Prevalence and related influencing factors of depression symptoms among empty-nest older adults in China.
The phenomenon of empty-nest older adults has raised growing concerns in contemporary Chinese society. In this study, we examined the prevalence and related influencing factors of depression symptoms among empty-nest older adults in China at a national level. The database of the 2015 China Health and Retirement Longitudinal Study (N = 8549, aged ≥ 60) was used. The 10-item version of the Centre for Epidemiologic Studies Depression Scale was employed to measure depression symptoms. The prevalence of depression symptoms was 34.7 % for empty-nest respondents, 32.2 % for respondents living with a spouse only and 43.4 % for those living alone. Multivariable logistic regression indicated that, compared with the non-empty-nest respondents, older adults living alone were more susceptible to depression symptoms (OR 1.194, 95 %CI 1.016-1.405) whereas older adults living with a spouse only were not exposed to an elevated probability of being depressed (OR 0.945, 95 %CI 0.847-1.055). Multivariable logistic regression also suggested that empty nesters who were female, lived in rural areas, had a lower frequency of children's visits, had lower socioeconomic status and had worse physical health conditions were more vulnerable to depression symptoms. The association between empty-nest status and later-life depression is mixed. More concerns should be raised about the mental health of empty nesters living alone. Increased attention should also be paid to empty nesters who are female, rural residents and have low contact frequency with their children, disadvantaged socioeconomic status and poor physical health conditions.


A systematic review of the psychometric properties of the Jebsen-Taylor Hand Function Test (JTHFT).
This systematic review of the literature aimed to identify studies examining the psychometric properties of the Jebsen-Taylor Hand Function Test (JTHFT) in various international populations on. The search was conducted in MEDLINE, SCOPUS, CINAHL and Web Of Science, with no restrictions on publication period, the country in which the study was conducted, or the age of the patients. Eligible studies were selected on the basis of inclusion criteria and data were extracted. Study quality and the risk of bias were assessed using the COnsensus-based Standards to select the health Measurement Instruments (COSMIN) checklist. 805 articles were identified; after removing duplicates, there were 361 single studies. 338 articles did not concern the psychometric properties of JTHFT. The remaining 23 studies were selected for full text review, and all were included. They comprised 8 languages and 9 pathologies. These findings suggest the JTHFT is a useful test of manual dexterity in activities of daily living. This study provides specific information on the instrument's psychometric properties in different populations and supports clinicians in making informed decisions when choosing instruments for upper-limb evaluations.


Air quality impact of particulate matter (PM10) releases from an industrial source.
This study is the initial air quality modeling application to investigate the atmospheric dispersion of particulate matter (PM10) released from an industrial plant in a mid-sized city in the northwestern region of Turkey. The study aims to determine how an industrial application might affect air pollution levels in the urban area of that city. Different types of PM10 emission sources at the plant were analyzed to determine their contribution to the overall PM10 level. The main concern of the study was to define whether the PM10 emission from the plant produced any air quality effects on the nearby hospital and downtown area. According to the modeling result, the maximum daily PM10 concentration was observed mostly in the southern part of the plant. The highest daily downwind PM10 was estimated to be 286.3 μg m-3, while the annual mean of downwind PM10 concentration was estimated to be 72.6 μg m-3. It was found that the highest PM10 was emitted from the line source (282.2 μg m-3)-located at the south and southwest of the plant-that has been continuously used for hauling raw materials to the cement plant. In this study, the hauling roads (as a line source) were the hot-spot at the plant and needed serious maintenance for the reduction of PM10 emissions from the plant. In the study area, a sensitive community state facility was subject to be considered an environmental concern since the central hospital complex was located nearby the PM10 source. For this purpose, the American Meteorological Society/Environmental Protection Agency Regulatory Model (AERMOD) was followed to determine whether the plant caused any severe PM10 effect on the central hospital. The results indicate that the maximum hourly PM10 concentrations were predicted as 20 μg m-3 for the central hospital area. Overall, the modeled PM10 concentrations from the source at different time scales and locations did not exceed the national air quality limits in the area.


Correlation between lactoferrin and beneficial microbiota in breast milk and infant's feces.
Lactoferrin (LF) is a natural component of human milk with antimicrobial, immunostimulatory and immunomodulatory properties. Several in vitro studies suggest that LF could promote an environment in the gut of neonates that favors colonization with beneficial bacteria. However, clinical studies on the correlation between the concentration of LF in breast milk and feces of infants and the gut microbiota in infants are lacking. In our study we analyzed the content of LF and the microbiota of breast milk and feces of infants of 48 mother-infant pairs (34 full-term and 14 pre-term infants) at birth and 30 days after delivery. In the term group, a significant decrease of mean LF concentration between colostrum (7.0 ± 5.1 mg/ml) and mature milk (2.3 ± 0.4 mg/ml) was observed. In pre-term group, breast milk LF levels were similar to those observed in full-term group. Fecal LF concentration of healthy infants was extremely high both in term and pre-term infants, higher than the amount reported in healthy children and adults. In term infants mean fecal LF levels significantly increased from birth (994 ± 1,828 μg/ml) to 1 month of age (3,052 ± 4,323 μg/ml). The amount of LF in the feces of 30 day-old term infants was significantly associated with maternal mature milk LF concentration (p = 0.030) confirming that breast milk represents the main source of LF found in the gut of infants. A linear positive correlation between colostrum and mature milk LF concentration was observed (p = 0.008) indicating that milk LF levels reflect individual characteristics. In pre-term infants higher mean concentrations of fecal LF at birth (1,631 ± 2,206 μg/ml) and 30 days after delivery (7,633 ± 9,960 μg/ml) were observed in comparison to full-term infants. The amount of fecal bifidobacteria and lactobacilli resulted associated with the concentration of fecal LF 3 days after delivery (p = 0.017 and p = 0.026, respectively). These results suggest that high levels of fecal LF in neonates, particularly in the first days of life, could represent an important factor in the initiation, development and/or composition of the neonatal gut microbiota. Since early host-microbe interaction is a crucial component of healthy immune and metabolic programming, high levels of fecal LF in neonates may beneficially contribute to the immunologic maturation and well-being of the newborn, especially in pre-term infants.


A simulation of human heart function.
A simulation of the function of the human heart and heart muscle has been developed in the form of a digital computer code. For a given set of values for the input variables, realistic values of the cardiac output variables are predicted. A detailed discussion of the simulation and some results obtained from its application are presented. This simulation represents a unique combination of what was known in muscle mechanics, muscle thermodynamics, and of the structure, size, and shape of the heart, into an engineering model to improve the understanding of human heart muscle function. The left ventricle (LV) is treated as a thick-walled sphere whose wall is composed entirely of muscle fibers. Force-length velocity relationships are used to determine the tension in each fiber. The pressure in the LV is computed from fiber tension and fiber structure in the LV. A lumped-parameter simulation of the arterial tree provides a load impedance for the LV. Results are presented for simulation of normal human LV performance.


Achieving R0 resection in the colorectum using endoscopic submucosal dissection.
Endoscopic mucosal resection is established for the removal of non-invasive colorectal tumours smaller than 20 mm but is unsatisfactory for larger lesions. Endoscopic submucosal dissection (ESD) enables en bloc resection of lesions larger than 20 mm. A UK-based prospective feasibility study of ESD for colorectal tumours was undertaken; primary endpoints were R0 resection, safety and recurrence. Patients with Paris 0-II adenomas or laterally spreading tumours (LSTs) greater than 20 mm in diameter were enrolled between November 2004 and August 2006. Lesions were assessed by chromoscopy and high-frequency ultrasonography. Dysplasia, resection status, 30-day complication rates and recurrence after ESD were recorded. ESD was performed in 42 of 56 identified patients; en bloc resection was possible in 33. Fourteen Paris 0-II lesions and 28 LSTs were identified; 40 were dysplastic adenomas and two adenocarcinomas. R0 resection was achieved in 31 patients (74 per cent). The 30-day mortality rate was 0 per cent. Perforation occurred in one patient and uncomplicated bleeding in five. The 6-month cure rate was 81 per cent (34 of 42 patients). High cure rates are achievable using ESD for Paris 0-II adenomas and LSTs greater than 20 mm in diameter, with R0 resection possible in most patients. ESD is feasible throughout the colorectum with no increase in complication rates. It should be considered for selected Tim/T1 N0 colorectal lesions.


Atypical keloids after dermabrasion of patients taking isotretinoin.
Six patients underwent dermabrasion while on or having recently completed isotretinoin (Accutane) therapy. All patients developed keloids in atypical locations; the keloids eventually responded to topical or intralesional steroid therapy. Retinoids have a modulatory effect on connective tissue metabolism, including suppression of collagenase, which may enhance keloid formation. Dermabrasion should be delayed in those patients taking or recently on isotretinoin therapy.


Partial transection of the external ear caused by a mask worn for COVID-19 protection.
During the COVID-19 pandemic surgical mask-wearing was widely adopted as a means of preventing infections, but there have been several reports of mask-induced skin problems. In this report, we describe a case in which surgery was required for a mask-induced ear injury. An otherwise healthy 63-year-old male presented to the plastic surgery department with an auricle injury. He had been using a mask that was too small for his face for more than 1 month; the tight ear loops caused the upper part of his left auricle to begin to dissect, resulting in a large tear. More than a third of the left upper auricle was torn, and the wound surface was epithelialized. The patient had no history of skin disease or psychiatric disorder but was engaged in a job that required wearing a helmet constantly. Surgery was performed to refresh the epithelialized wound surface and suture it, and the patient healed without complication. While mask-wearing mandates and recommendations have considerably eased since the height of the pandemic, the current authors' experience has brought to light problems related to mask usage. Thus, efforts should be made to investigate the causes of these problems and provide appropriate advice.


Altered temporal variability in brain functional connectivity identified by fuzzy entropy underlines schizophrenia deficits.
Investigation of the temporal variability of resting-state brain networks informs our understanding of how neural connectivity aggregates and disassociates over time, further shedding light on the aberrant neural interactions that underlie symptomatology and psychosis development. In the current work, an electroencephalogram-based sliding window analysis was utilized for the first time to measure the nonlinear complexity of dynamic resting-state brain networks of schizophrenia (SZ) patients by applying fuzzy entropy. The results of this study demonstrated the attenuated temporal variability among multiple electrodes that were distributed in the frontal and right parietal lobes for SZ patients when compared with healthy controls (HCs). Meanwhile, a concomitant strengthening of the posterior and peripheral flexible connections that may be attributed to the excessive alertness or sensitivity of SZ patients to the external environment was also revealed. These temporal fluctuation distortions combined reflect an abnormality in the coordination of functional network switching in SZ, which is further the source of worse task performance (i.e., P300 amplitude) and the negative relationship between individual complexity metrics and P300 amplitude. Notably, when using the network metrics as features, multiple linear regressions of P300 amplitudes were also exactly achieved for both the SZ and HC groups. These findings shed light on the pathophysiological mechanisms of SZ from a temporal variability perspective and provide potential biomarkers for quantifying SZ's progressive neurophysiological deterioration.


Murine thymocytes mediate a natural killer-like activity against herpes virus-infected target cells but not YAC-1 target cells.
In this report, we demonstrated a natural killer (NK)-like activity against HSV-1 infected cells mediated by CD-1 mouse thymocytes. This cytolytic activity is specific for HSV-1-infected MCN cells, since both uninfected MCN and YAC-1 target cells are not susceptible to thymocyte lysis. Antibody plus complement depletion experiments indicate that a portion of the activity is associated with the Lyt 2-/L3T4- thymocyte subpopulation. This NK-like activity cannot be enhanced by addition of interleukin 2 in vitro.


Non-obstructive müllerian anomalies.
The nonobstructive group of anatomic variants involving the reproductive tract includes vaginal agenesis as well as the congenital anomalies of the vagina and uterus, occurring without pain during the pubertal years. The objective is to discuss the non-obstructive morphologic variations in anatomy of the uterus and vagina. Systematic review using the GRADE system. These congenital anomalies are not associated with abnormalities of the external genitalia and therefore may be missed on routine physical examination. When these anomalies do cause symptoms they may be as minor as difficulty with menstrual hygiene or more significant such as primary amenorrhea, dyspareunia, recurrent pregnancy loss, and reproductive complications. Women with non-obstructive reproductive tract anomalies present at various ages due to the asymptomatic nature or late symptom onset of certain conditions. An MRI is the gold standard in evaluation of such conditions to aid in confirming the müllerian variant. Each condition requires careful counseling because obstetric and gynecologic risks and consequences may differ. Treatment is individualized in cases of uterovaginal agenesis with both nonsurgical and surgical options available for neovagina creation. In cases of uterine or vaginal septae, the treatment timing may vary depending on patient history. Finally, in cases of non-obstructive communicating uterine horns, the risk of ectopic pregnancy is high in the remnant horn. Should a pregnancy occur in this small underdeveloped horn, therefore, excision is recommended.


Why do veterinarians ask for antimicrobial susceptibility testing? A qualitative study exploring determinants and evaluating the impact of antibiotic reduction policy.
For public health reasons, increasing attention has focused on more rational use of antimicrobials in farm animals. Guidance concerning the prescription of antibiotics and antimicrobial susceptibility testing (antibiograms in this case) are beneficial tools to help control the development of antimicrobial resistance. Nevertheless, even though there are already several qualitative studies analysing the determinants of antimicrobial prescription and use in veterinary medicine, little is known about decision-making concerning the use of antibiograms. The aim of this study was to provide a better understanding of veterinarians' motivations and role-players' influence concerning the choice of whether to ask for an antibiogram in the bovine, porcine, poultry and equine sectors in France. We concurrently evaluated the impact of a new French decree (2016) requiring an antibiogram before certain critically important antimicrobial agents can be used in veterinary medicine. Semi-structured interviews with veterinarians were conducted in France. Thematic analysis was used to analyse transcripts. In all, we surveyed 66 veterinarians. Use of antibiograms in veterinary medicine was multifactorial - 46 factors grouped into 11 categories were identified - and differed between animal sectors: use was almost systematic in poultry, frequent in pigs and rare in both the bovine and equine sectors. The decree has not increased the use of antibiograms but has induced a change in prescriptions due to field constraints and the time needed to obtain the results of antibiograms. Respondents see the decree as an aid in promoting responsible and rational use of antibiotics, fostering the use of alternatives. Our findings provide the basis of veterinarians' position regarding antibiogram use and antimicrobial resistance, pointing out levers to facilitate the use of antibiograms in veterinary medicine (for example communication on the benefits of this test and external financial support). Furthermore, the evaluation of the impact of the decree aimed at reducing the use of critically important antibiotic highlights key factors for a successful change in regulations, such as advance planning, precise and adapted communication, and demonstration of the measure's legitimacy. These results will be useful in guiding representative veterinary bodies and regulatory authorities during their decision-making, communication, and policy and regulation choices to combat antimicrobial resistance.


Metagenomic insights into the effects of submerged plants on functional potential of microbial communities in wetland sediments.
Submerged plants in wetlands play important roles as ecosystem engineers to improve self-purification and promote elemental cycling. However, their effects on the functional capacity of microbial communities in wetland sediments remain poorly understood. Here, we provide detailed metagenomic insights into the biogeochemical potential of microbial communities in wetland sediments with and without submerged plants (i.e., Vallisneria natans). A large number of functional genes involved in carbon (C), nitrogen (N) and sulfur (S) cycling were detected in the wetland sediments. However, most functional genes showed higher abundance in sediments with submerged plants than in those without plants. Based on the comparison of annotated functional genes in the N and S cycling databases (i.e., NCycDB and SCycDB), we found that genes involved in nitrogen fixation (e.g., nifD/H/K/W), assimilatory nitrate reduction (e.g., nasA and nirA), denitrification (e.g., nirK/S and nosZ), assimilatory sulfate reduction (e.g., cysD/H/J/N/Q and sir), and sulfur oxidation (e.g., glpE, soeA, sqr and sseA) were significantly higher (corrected p < 0.05) in vegetated vs. unvegetated sediments. This could be mainly driven by environmental factors including total phosphorus, total nitrogen, and C:N ratio. The binning of metagenomes further revealed that some archaeal taxa could have the potential of methane metabolism including hydrogenotrophic, acetoclastic, and methylotrophic methanogenesis, which are crucial to the wetland methane budget and carbon cycling. This study opens a new avenue for linking submerged plants with microbial functions, and has further implications for understanding global carbon, nitrogen and sulfur cycling in wetland ecosystems. The online version contains supplementary material available at 10.1007/s42995-021-00100-3.


Expert consensus-based clinical recommendation for an integrative anthroposophic treatment of acute bronchitis in children: A Delphi survey.
Acute bronchitis is one of the most common pediatric diseases. In addition to conventional therapies, a frequent use of complementary and alternative medicine (CAM) has been stated. Anthroposophic medicine (AM) is one of the most practiced complementary and integrative medicine (CIM) approaches in Central Europe but hitherto no consensus-based clinical recommendations or guidelines are available. Therefore, a consensus-based recommendation leading to an informed and reasonable use of AM in the treatment of acute bronchitis in pediatrics was developed. A total of 61 physicians in Germany with expertise in the field of anthroposophic pediatrics was invited to complete an online multistep Delphi process. Two independent reviewers quantitatively and qualitatively evaluated the results. The survey was completed when >75 % consensus was achieved. The clinical recommendation comprises 15 subitems related to treatment as well as clinical and psychosocial aspects. All items reached strong consensus (>90 %; N = 9) or consensus (75-90 %; N = 6). The comprehensive clinical recommendation creates a scientific base for the anthroposophic integrative treatment of acute bronchitis in children in Germany. It will make the anthroposophic approach more applicable, understandable and comparable to a wider public of physicians and other health professionals in Germany.


Thoracic neoplasms in children.
This article presents an overview of the benign and malignant neoplasms that affect the chest in children and their imaging characteristics. The relative roles of plain film, fluoroscopy, ultrasound, CT, MR imaging, and nuclear imaging in assessing these lesions are reviewed. Areas covered include the mediastinum, heart, lungs, airway, pleura, and chest wall.


Achyranthes polysaccharide based dual-responsive nano-delivery system for treatment of rheumatoid arthritis.
Achyranthes plays the role of dredging the meridians and clearing the joints with a certain anti-inflammatory effect, peripheral analgesic activity and central analgesic activity. A novel self-assembled nanoparticles containing Celastrol (Cel) with matrix metalloproteinase (MMP)-sensitive chemotherapy-sonodynamic therapy was fabricated targeting macrophages at the inflammatory site of rheumatoid arthritis. Dextran sulfate (DS) with highly expressed SR-A receptor on the surface of macrophages is used to specifically target the site of inflammation; by introducing PVGLIG enzyme-sensitive polypeptides and ROS-responsive bonds, it can achieve the desired effect on MMP-2/9 and reactive oxygen species at the joint site. The preparation forms DS-PVGLIG-Cel&Abps-thioketal-Cur@Cel nanomicelles, referred to as D&A@Cel. The resulting micelles had an average size of 204.8 nm and the zeta potential -16.46 mV. The results show that activated macrophages can effectively capture Cel in in vivo experiments, indicating that Cel delivered by nanoparticles can significantly improve bioavailability.


Illness Severity Moderated Association Between Trait Anxiety and Amygdala-Based Functional Connectivity in Generalized Anxiety Disorder.
Trait anxiety is considered a vulnerability factor for the development of generalized anxiety disorder (GAD). The amygdala is related to both trait anxiety and GAD. Thus, we investigated amygdala-based functional connectivity (FC) in drug-naive non-comorbid GAD patients and explored its associations with personality, symptoms, and illness severity. FC analyses using the bilateral amygdala as seeds were performed with resting-state functional MRI data from 38 GAD patients and 20 matched healthy controls (HCs). Clinical characteristics were correlated with FC Z-scores from regions showing significant group differences. Furthermore, moderation analyses were used to explore the conditional effect of illness severity measured by the Clinical Global Impression-Severity (CGI-S) scale on the relationship between FC and trait anxiety. Relative to HCs, GAD patients showed hypoconnectivity between the amygdala and the rostral anterior cingulate cortex (rACC), inferior frontal gyrus (IFG), parahippocampal gyrus, and cerebellum and hyperconnectivity between the amygdala and the superior temporal gyrus (STG), insula, and postcentral gyrus. In GAD patients, amygdala-rACC connectivity was negatively associated with symptom severity and trait anxiety, and amygdala-IFG connectivity was positively associated with symptom severity. Moreover, CGI-S scores moderated the negative correlation between trait anxiety and amygdala-rACC FC. We demonstrate that there is extensive amygdala-based network dysfunction in patients with GAD. More importantly, amygdala-rACC connectivity plays a key role in the neural pathology of trait anxiety. Finally, the more severe the illness, the stronger the negative association between trait anxiety and amygdala-rACC FC. Our results emphasize the importance of personalized intervention in GAD.


[The effect of cystamine on the level of postradiation peroxidation products in the lymph of dogs].
The experiments on irradiated dogs with a drained pectoral lymph duct revealed an early accumulation of radiotoxins (diene conjugates and malonic dialdehyde) in the lymph and blood plasmas and; simultaneously, a lowering of water-soluble antioxidants. The prophylactic application of cystamine improved the drain-detoxifying function of the lymphatic system, lowered the level of radiotoxins, and aided in the antioxidant properties of lymph and blood plasmas.


Anticipated support from children and later-life health in the United States and China.
Past research has shown that anticipated support, the belief that someone will provide support if needed, benefits health. Few studies considered whether the relationship between anticipated support and health depends on the source of such support. This project addresses this gap and examines how anticipated support from children is related to older parents' health and whether such support can be replaced by anticipated support from other relatives and friends. Ordered logit and negative binomial regression models with lagged health outcomes were estimated using nationally representative data from the 2010 and 2012 Health and Retirement Study and the 2011 and 2013 China Health and Retirement Longitudinal Study. Results suggest that anticipated support from children is related to older parents' better self-rated health and fewer depressive symptoms in both countries. In the U.S. where filial norms are relatively weak, anticipated support from others is no less important for health than anticipated support from children. However, in China where filial norms are relatively strong, parents anticipating support only from others are no different in health from those anticipating support from no one.


Seasonal dynamics survey and association analysis of microbiota communities, antibiotic resistance genes distribution, and biotoxicities characterization in landfill-leachate.
To reflect the potential and intrinsic association among microbiota structure, antibiotic resistance genes distribution and biological toxicity of landfill-leachate according to seasonal change, and accurately assess the potential threat of leachate to the surrounding environment. On the basis of the leachate water quality monitoring data from January to December 2020, principal component analysis (PCA) was used to identify the main pollutants in the leachate; Vibrio fischeri luminescence inhibition test was used to detect the comprehensive biotoxicity of the leachate; 16S rDNA amplicon sequencing was used for leachate microbiota. q-PCR was used to detect the class 1 integron (intI1), and eight antibiotic resistance genes (sul1, sul2, tetA, tetB, tetM, tetQ, mefA, and mexF); Canonical correspondence (CCA) analysis was carried out for the association analysis. The biotoxicity of leachate in the second quarter was the highest. The dominant phylum of leachate microbiota from 1st quarters to 4th quarters was Proteobacteria (94.97 %, 85.43 %, 88.20 %, and 84.11 %), and the dominant genera were Thiomonas (60.41 %, 26.83 %, 25.66 %, and 30.51 %), Pseudomonas (5.89 %, 1.86 %, 0.68 %, and 4.72 %), Desulfurella (8.52 %, 0.57 %, 3.81 %, and 8.25 %), and Acidithiobacillus (4.71 %, 0.69 %, 0.87 %, and 5.91 %); Nitrospirillum was negatively correlated with chemical oxygen demand (COD) (R=-0.561, P = 0.008) and five-day biochemical oxygen demand (BOD5) (R=-0.591, P = 0.005); Limnohabitans was positively correlated with pH (R=0.444, P = 0.044). Four AR genes (sul1, sul2,tetM, and tetQ) were detected in all the samples, while the second quarter had the highest concentration of sul1(6.31 ± 0.49 lg copies/ng DNA), tetM (3.01 ± 1.38 lg copies/ng DNA) and tetQ (3.64 ± 0.90 lg copies/ng DNA). As the mature landfill, the quality of this leachate met the pollution control standards for domestic waste landfills. Thiomycetes, Pseudomonas, Desulfurization, and Thiopterus acidophyllum constitute the dominant microbiota. However, leachate in the second quarter had more serious contamination, the higher biotoxicity, higher concentration of AR genes, together with higher microbiota richness and diversity, which deserved more attention for the potential threat to the surrounding environment.


Supraclavicular subclavian technique of intra-aortic balloon insertion.
Insertion of the intra-aortic balloon through the subclavian artery is described. This antegrade method of insertion is useful in patients in whom the retrograde transfemoral approach is not possible.


Computationally Optimized SARS-CoV-2 MHC Class I and II Vaccine Formulations Predicted to Target Human Haplotype Distributions.
We present a combinatorial machine learning method to evaluate and optimize peptide vaccine formulations for SARS-CoV-2. Our approach optimizes the presentation likelihood of a diverse set of vaccine peptides conditioned on a target human-population HLA haplotype distribution and expected epitope drift. Our proposed SARS-CoV-2 MHC class I vaccine formulations provide 93.21% predicted population coverage with at least five vaccine peptide-HLA average hits per person (≥ 1 peptide: 99.91%) with all vaccine peptides perfectly conserved across 4,690 geographically sampled SARS-CoV-2 genomes. Our proposed MHC class II vaccine formulations provide 97.21% predicted coverage with at least five vaccine peptide-HLA average hits per person with all peptides having an observed mutation probability of ≤ 0.001. We provide an open-source implementation of our design methods (OptiVax), vaccine evaluation tool (EvalVax), as well as the data used in our design efforts here: https://github.com/gifford-lab/optivax.


Microwave ablation of hepatic cyst: A case report.
Hepatic cystadenoma is an urgent problem due to the high risk of malignant transformation. There are both radical and minimally invasive methods of treatment. We present a clinical case describing the successful use of microwave ablation (MWA) in a 72-year-old woman with hepatic cystadenoma. The patient was admitted to the clinic with abdominal discomfort, dull pain in the right hypochondrium, and weight loss of 10 kg during the previous year. The patient had a past medical history of liver cyst in segment VII. Ultrasound scanning, computed tomography (CT) of abdominal organs detected an increase in the size of the cyst, heterogeneity of its structure; the contrast enhancement was noted in the cyst wall. We suspected hepatic cystadenoma in segment VII and performed cyst puncture under ultrasound control - the obtained fluid revealed the presence of cylindrical epithelial cells, mucin, and macrophages in large quantities, high telomerase activity, CA 19-9 levels were greater than 1000 U/mL. Surgery was accomplished using the MWA catheter. Biological and cytological examination of the fluid confirmed the presence of signs of liver cystadenoma with a high malignancy risk. On the 2nd day after surgery ultrasound imaging of the abdomen revealed the residual cavity of 2 × 1 cm in segment VII. The patient was discharged with recommendations to conduct ultrasound examinations every six months. The control CT scan in 2020 showed no focal or cystic formations in the liver. In what way, MWA under control of ultrasound is a promising method of biliary cystadenoma treatment with high malignancy risk.


The Role of Neuregulin and Stem Cells as Therapy Post-Myocardial Infarction.
Coronary artery disease, including myocardial infarction (MI), is a leading cause of morbidity and mortality in the United States. Due to the limited self-renewal capacity of cardiac tissue, MIs can lead to progressive heart disease with a lasting impact on health and quality of life. The recent discovery of cardiac stem cells has incited research into their potential therapeutic applications for patients suffering from cardiovascular disease. Studies have demonstrated the ability of stem cells to both generate cardiac tissues in vitro and aid in the recovery of cardiovascular function in vivo in animal models. However, the long-term efficacy of stem cells as regenerative therapy is still unknown. Exploration of alternative therapies is underway, including the use of cardiac growth factor neuregulin-1 (NRG-1). Research has demonstrated that NRG-1 not only has direct effects on cardiomyocytes (CM) but also acts within the tissues supporting the CM. Transplantation of NRG-1 into ischemic cardiac tissue mitigates the progression of heart failure and can reverse cardiac remodeling. Recent publications have sought to study the combined use of these agents, and while the results are promising, they do warrant further research. This review aims to consider these therapies separately as well as in combination.


Correction to: High throughput transcriptome analysis of coffee reveals prehaustorial resistance in response to Hemileia vastatrix infection.
All the transcriptome sequencing data mentioned in the original article is publicly available at the National Center of Biotechnology Information (NCBI).


Sugar kelp (Saccharina latissima) inhibits hepatic inflammation and fibrosis in a mouse model of diet-induced nonalcoholic steatohepatitis.
Nonalcoholic steatohepatitis (NASH), closely associated with obesity, is a health concern worldwide. We investigated whether the consumption of U.S.-grown sugar kelp (Saccharina latissima), an edible brown alga, can prevent obesity-associated metabolic disturbances and NASH in a mouse model of diet-induced NASH. Male C57BL/6J mice were fed a low-fat diet, a high-fat/high-sucrose/high-cholesterol diet (HF), or a HF diet containing sugar kelp (HF-Kelp) for 14 weeks. HF-Kelp group showed lower body weight with increased O2 consumption, CO2 production, physical activity, and energy expenditure compared with the HF. In the liver, there were significant decreases in weight, triglycerides, total cholesterol, and steatosis with HF-Kelp. The HF-Kelp group decreased hepatic expression of a macrophage marker adhesion G protein-coupled receptor E1 (Adgre1) and an M1 macrophage marker integrin alpha x (Itgax). HF-Kelp group also exhibited decreased liver fibrosis, as evidenced by less expression of fibrogenic genes and collagen accumulation than those of HF group. In epididymal white adipose tissue (eWAT), HF-Kelp group exhibited decreases in eWAT weight and adipocyte size compared with those of the HF. HF-Kelp group showed decreased expression of collagen type VI alpha 1 chain, Adgre1, Itgax, and tumor necrosis factor α in eWAT. We demonstrated, for the first time, that the consumption of U.S-grown sugar kelp prevented the development of obesity and its associated metabolic disturbances, steatosis, inflammation, and fibrosis in the liver and eWAT of a diet-induced NASH mouse model.


Crystal structures of the apo form of β-fructofuranosidase from Bifidobacterium longum and its complex with fructose.
We solved the 1.8 Å crystal structure of β-fructofuranosidase from Bifidobacterium longum KN29.1 - a unique enzyme that allows these probiotic bacteria to function in the human digestive system. The sequence of β-fructofuranosidase classifies it as belonging to the glycoside hydrolase family 32 (GH32). GH32 enzymes show a wide range of substrate specificity and different functions in various organisms. All enzymes from this family share a similar fold, containing two domains: an N-terminal five-bladed β-propeller and a C-terminal β-sandwich module. The active site is located in the centre of the β-propeller domain, in the bottom of a 'funnel'. The binding site, -1, responsible for tight fructose binding, is highly conserved among the GH32 enzymes. Bifidobacterium longum KN29.1 β-fructofuranosidase has a 35-residue elongation of the N-terminus containing a five-turn α-helix, which distinguishes it from the other known members of the GH32 family. This new structural element could be one of the functional modifications of the enzyme that allows the bacteria to act in a human digestive system. We also solved the 1.8 Å crystal structure of the β-fructofuranosidase complex with β-D-fructose, a hydrolysis product obtained by soaking apo crystal in raffinose.


Immunomodulatory effect of intracellular polysaccharide from mycelia of Agaricus bitorquis (QuéL.) Sacc. Chaidam by TLR4-mediated MyD88 dependent signaling pathway.
Agaricus bitorquis (QuéL.) Sacc. Chaidam is a valuable edible fungus in Qinghai-Tibet plateau and ABSP is a novel intracellular polysaccharide from its mycelia. GC and NMR analysis determined ABSP is galactoglucomannan-like polysaccharide that may have immunomodulatory effect. This study used RAW264.7 as model cell to determine immunomodulatory effect of ABSP. After ABSP treatment, viability and phagocytic ability promoted, and NO, ROS, TNF-α levels also raised which proved ABSP had immune regulation to RAW264.7. WB and qRT-PCR determined the key proteins and genes expression of TLR4, MyD88, TRAF-6 and NF-κB significantly increased while protein and gene expression of TRAM had no significant increase. Also, TNF-α level extremely decreased by adding inhibitors of TLR4 and MyD88 which confirmed ABSP could immunologically regulate RAW264.7 byTLR4-MyD88 dependent pathway. This study would provide theoretical basis for further study on ABSP and be helpful for development of beneficial functionally foods and exploitation of this resource.


A cranial nail for fetal shunting.
A small number of human fetal hydrocephalics have been treated by ventriculoamniotic shunts of silastic tubing. The Colorado device appears to be the one most commonly used. The original experimental device tested on a primate model resembled a hollow shingle nail. This was designed by Michedja and Hodgen, contained a spring valve, measured approximately 32 X 4 mm and was placed by hysterotomy. An attractive feature of this design was its fixation by impaction in the skull, preventing displacement by fetal activity, a reported disadvantage with the silastic devices. To our knowledge, no one has used this nail-like design and tailored it to transuterine percutaneous placement in a human case.


Derivatives of side-chain hydroxylated nitrosamines direct acting mutagens in Salmonella typhimurium.
Methyl-(beta-tosyloxyethyl)nitrosamine and 3-methyl-4,5-dihydro-1,2,3-oxadiazolium tosylate are potent direct acting mutagens in the Ames assay, as is N-nitrosoprolinyl tosylate. These compounds are derived from beta-hydroxylated nitrosamines. The closely related methyl-(gamma-tosyloxypropyl)nitrosamine is not mutagenic without activation. These data are consistent with the chemical behavior of these substances, which suggest that suitable derivatives of beta-hydroxylated nitrosamines, such as O-sulfates, may be direct-acting biological alkylating agents.


Enhancement of in vitro chemotherapeutic activity by dimethylsulfoxide.
The effects of the differentiation-inducing polar solvent dimethylsulfoxide (DMSO) on the in vitro response of murine hepatocarcinoma cells to cisplatinum, BCNU, and melphalan were investigated using the sister chromatid exchange (SCE) and cell survival assays. Growth of cells in medium containing 2 per cent DMSO enhanced drug-induced SCEs and cell kill. In order for the enhancement to occur, cells had to be exposed to DMSO for at least 48 h prior to drug treatment. The presence of DMSO during drug treatment did not affect cell response to the three chemotherapeutic agents. The enhancement of chemosensitivity was eliminated within 24 h of DMSO removal. These data suggest that the differentiation-inducing polar solvents may provide antineoplastic benefits when administered in combination with standard chemotherapeutic agents.


Hepatitis B infection in hospital personnel during an eight-year period; policies for screening and pregnancy in high risk areas.
From 1972 through 1979, acute hepatitis, type B, or asymptomatic hepatitis B surface (HBs) antigenemia developed in 34 employees at Yale-New Haven Hospital. The average yearly incidence of the infection was 1.2 cases per 1,000 employees. The incidence was highest in those administering venipunctures followed, respectively, by those in the emergency room, hemodialysis unit, housestaff, laboratory, general nursing, and support service personnel. Three cases were detected during eight years of routine screening of personnel; in 1972, one of these, a pregnant nurse working in the hemodialysis unit, was moved from that unit. Subsequently, seven personnel in the unit have been transferred during pregnancy. However, staphylococcal pneumonia was acquired by one of them on a medical floor, and another nurse, seeking work in oncology, was not hired while pregnant. Both cases resulted in administrative complaints. Currently, we screen personnel in the hemodialysis and venipuncture units quarterly for hepatitis B surface antigen (HBsAg) and antibody (anti-HBs) (participation is optional for those in the emergency room and oncology) and strongly urge seronegative pregnant women to transfer from these areas.


The effect of interaction between human urokinase and its competitive inhibitor, N alpha-benzoyl-L-arginine amide, on reduction of a specific SS bond related to enzymatic activity.
The 55- (H-UK) and 36-kDa forms (L-UK) of human urinary urokinase lost most of esterase activity toward acetyl-glycyl-L-lysine methyl ester upon reductive cleavage of 3 SS bonds with dithiothreitol in the presence of the competitive inhibitor, N alpha-benzoyl-L-arginine amide (BAA), bound to polyacrylyl azide with C16N3-arm (PAA) at 0.3 M guanidine, a threshold point of the native state where a protein-denaturating transition began. One of the 3 SS bonds was protected from reduction, with an unaltered activity, under the similar conditions except for replacement of BAA-PAA conjugate by glycine-PAA conjugate. This "specific" SS bond was reduced and, after the other SH groups produced were blocked with iodoacetamide (IAM), selectively reoxidized, which resulted in complete reactivation. The intact B-chain isolated from H-UK was completely inactivated when its specific SS bond was reduced and selectively alkylated with IAM after the other SH groups were reversibly blocked with 5, 5'-dithiobis (2-nitrobenzoic acid), which was finally removed. The results indicate that a single specific SS bond is essential for retaining a conformation necessary to activity exhibition.


Saturated and aromatic aldehydes originating from skin and cutaneous bacteria activate the Nrf2-keap1 pathway in human keratinocytes.
Skin homeostasis is constantly challenged by environmental factors, affecting its delicate redox balance. The skin is also home to a wide variety of bacterial species, including Staphylococci. The cutaneous redox state is governed by the Nrf2-keap1 pathway, which is responsible for the induction of phase II cytoprotective enzymes, thus sustaining a healthy oxidative state. As part of normal metabolism, both bacteria and cutaneous tissue emit copious amounts of volatile organic compounds (VOCs), one subgroup of which are aldehydes. α,β-unsaturated aldehydes are known activators of Nrf2-keap1 pathway by direct oxidation of the keap1 protein. However, we did not encounter reports of Nrf2 activation by saturated or aromatic aldehydes, neither bacteria nor skin-derived. We hypothesized that non-α,β-unsaturated aldehydes derived from skin or cutaneous bacteria may act as Nrf2-keap1 pathway activators and therefore afford protection against environmental insults. The saturated aldehydes nonanal and decanal (known skin metabolites) and the aromatic aldehyde benzaldehyde (known skin and Staphylococcus epidermidis metabolite) were shown to induce the Nrf2-keap1 pathway in human keratinocytes. We also identified a newly described aromatic aldehyde, 3-furaldehyde (3-FA), emitted from S. aureus and S. epidermidis cultures, which also activated the pathway. Moreover, Nrf2-keap1 induction led to a significant protection against UVB-induced apoptosis. The mechanism involved in this activation has been partially elucidated. This work emphasizes the importance of cutaneous bacteria, as well as healthy skin lipid peroxidation processes in the maintenance and regulation of the cellular antioxidant response, namely with regard to coping with environmental stressors.


Promoting exercise for patients with multiple myeloma: attitudes and practices of clinical haematologists.
To explore the attitudes and practices of clinical haematologists towards promoting physical activity (PA) and exercise for patients with multiple myeloma (MM). Using a quantitative cross-sectional survey, clinical haematologists reported on the perceived benefits and acceptability of PA and exercise and frequency, confidence and barriers to providing exercise advice. Clinical haematologists (n=34; 68% response rate), who cumulatively treated ~340 patients with MM each week, completed the survey. Almost all (97%) agreed that PA was important, with benefits for quality of life, activities of daily living, mental health and fatigue. Whilst 88% discussed PA at least occasionally with their patients, approximately two-thirds were not confident advising specific exercises (68%) or identifying PA resources (62%). Despite this, 44% never referred patients to exercise professionals, with 18% only doing so if the patient asked. Over half did not recommend exercise when patients had spine fractures or were physically unwell. No differences were observed in individual factors (age, gender, practice type and own PA participation) and promotion of PA. Clinical haematologists perceive PA as important, but lack confidence on what exercise/s to recommend and if exercise is appropriate for specific disease complications. They tend to not refer patients to exercise professionals. Patients with MM often suffer from symptoms and toxicities that may be alleviated through PA. However, PA participation rates are low. Support for clinical haematologists for when and how to discuss exercise, and clearer referral pathways to exercise professionals may improve PA uptake and hence ensure access to optimal care, thereby improving patient outcomes.


GEEP Method: An Optimized Electroporation-Mediated Gene Editing Approach for Establishment of Knockout Pig Lines.
Pigs are excellent large animal models owing to their several physiological and anatomical similarities to humans. Somatic cell nuclear transfer using gene-modified cells is the mainstream approach for generating genetically modified pigs. Recent advances in improving gene editors such as the CRISPR/Cas9 system have enabled direct gene modification in zygotes/embryos. Here, we describe the gene editing by electroporation of Cas9 protein (GEEP) method, an optimized electroporation-mediated method for the introduction of CRISPR/Cas9 into porcine zygotes/embryos. The simplicity and micromanipulation-free procedures are the major advantages of this method.


An efficient compression scheme for 4-D medical images using hierarchical vector quantization and motion compensation.
This paper proposes an efficient compression scheme for compressing time-varying medical volumetric data. The scheme uses 3-D motion estimation to create a homogenous preprocessed data to be compressed by a 3-D image compression algorithm using hierarchical vector quantization. A new block distortion measure, called variance of residual (VOR), and three 3-D fast block matching algorithms are used to improve the motion estimation process in term of speed and data fidelity. The 3-D image compression process involves the application of two different encoding techniques based on the homogeneity of input data. Our method can achieve a higher fidelity and faster decompression time compared to other lossy compression methods producing similar compression ratios. The combination of 3-D motion estimation using VOR and hierarchical vector quantization contributes to the good performance.


Toxigenic mycoflora, aflatoxin and fumonisin contamination of poultry feeds in Ghana.
The study was undertaken to identify the major mycotoxigenic fungi, aflatoxin and fumonisin levels in prepared poultry feeds in Ghana. Three hundred and fifty (350) prepared feed samples were randomly collected from 133 commercial poultry farms, 76 feed processors and eight (8) feed vendors in three major poultry producing regions of Ghana over two seasons. Fungi were isolated using the serial dilution method on potato dextrose agar and identified using standard methods of identification. Total aflatoxin and fumonisin levels were quantified using AgraStrip® Total Aflatoxin and Fumonisin Quantitative test Watex® from RomerLab, USA. Eight (8) different fungi were isolated from the feed samples with isolation frequency as follows: Aspergillus flavus (47%), A. niger (24%), A. fumigatus (17%), A. oryzae (3%), A. tamarii (2%), Penicillium sp. (3%), Colletotrichum sp. (4%) and Rhizopus sp. (0.1%). Feed samples collected during the rainy season recorded higher mean colony counts (3.39 ± 0.29) than that of the dry season (1.10 ± 0.18). Total aflatoxin and fumonisin levels ranged from 0 to 118 ppb with a mean of 57.25 ± 2.55 ppb, and 0.28-15 ppm with a mean of 1.54 ± 0.12 ppm, respectively. The study revealed co-occurrence of aflatoxin and fumonisin in all the feed samples. Significant correlations (r = 0.298, r = 0.694) (p < 0.05) were observed among the aflatoxin and fumonisin levels and the fungi isolated. Seventy-four percent (74%) of all the feed samples exceeded the 15 ppb Ghana Standards Authority threshold, the EU regulatory limit of 20 ppb and the FAO/WHO recommended maximum permissible limit of 30 ppb for poultry feeds. Although fumonisin levels were less than the EU guidance values of 20 ppm for poultry feeds, 20% of the samples were higher than the FAO/WHO maximum tolerable daily intake limit of 2 ppm. Proper handling of prepared feeds and ingredients could prevent or minimize toxigenic fungi contamination and lower the likelihood of mycotoxin development in poultry feeds.


Inosine attenuates spontaneous activity in the rat neurogenic bladder through an A2B pathway.
Neurogenic detrusor overactivity (NDO) is among the most challenging complications of spinal cord injury (SCI). A recent report by us demonstrated an improvement in NDO in SCI rats following chronic systemic treatment with the purine nucleoside inosine. The objective of this study was to investigate the mechanism of action of inosine underlying improvement of NDO. Male Sprague-Dawley rats underwent complete spinal cord transection at T8. Inosine (1 mM) delivered intravesically to SCI rats during conscious cystometry significantly decreased the frequency of spontaneous non-voiding contractions. In isolated tissue assays, inosine (1 mM) significantly decreased the amplitude of spontaneous activity (SA) in SCI bladder muscle strips. This effect was prevented by a pan-adenosine receptor antagonist CGS15943, but not by A1 or A3 receptor antagonists. The A2A antagonist ZM241385 and A2B antagonist PSB603 prevented the effect of inosine. The effect of inosine was mimicked by the adenosine receptor agonist NECA and the A2B receptor agonist BAY60-6583. The inhibition of SA by inosine was not observed in the presence of the BK antagonist, iberiotoxin, but persisted in the presence of KATP and SK antagonists. These findings demonstrate that inosine acts via an A2B receptor-mediated pathway that impinges on specific potassium channel effectors.


Development of a patient decision aid for the management of superficial basal cell carcinoma (BCC) in adults with a limited life expectancy.
Basal cell carcinoma (BCC) is a slow-growing, rarely lethal skin cancer that affects people 65 years or older. A range of treatment options exist for BCC, but there is little evidence available to guide patients and providers in selecting the best treatment options. This study outlines the development of a patient decision aid (PDA) for low-risk BCC that can be used by patients and providers to assist in shared decision-making. In accordance with the International Patient Decision Aids Standards (IPDAS) Collaboration framework, feedback from focus groups and semi-structured interviews with patients and providers, an initial prototype of the PDA was developed. This was tested using cognitive interviews and iteratively updated. We created eighteen different iterations using feedback from 24 patients and 34 providers. The key issues identified included: 1) Addressing fear of cancer; 2) Communicating risk and uncertainty; 3) Values clarification; and 4) Time lag to benefit. The PDA does not include all possible treatment options and is currently paper based. Our PDA has been specifically adapted and designed to support patients with a limited life expectancy in making decisions about their low risk BCC together with their doctors.


Comparative clinical dosimetry with X-knife and gamma knife.
X-knife and gamma knife techniques are well-established for cranial stereotactic radiosurgery (SRS). Due to differences in their radiation delivery methods, some of the dosimetric parameters of these two techniques differ which may have clinical significance. There are many dosimetric studies comparing linear accelerator based techniques such as X-knife with gamma knife but generally from different institutions. We carried out a retrospective comparative study of the dosimetric parameters of the SRS treatments performed at our centre with X-knife (circular cones) and gamma knife. Our results indicate that the dose conformity and dose fall-off in the vicinity of the target volumes were better for patients treated with gamma knife as compared to X-knife. However, the dose fall-off pattern shows a reversal at a larger distance from the target. It was better for the X-knife as compared to gamma knife in the low dose region.


Effect of Dietary Intervention, with or without Cointerventions, on Inflammatory Markers in Patients with Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.
Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of disease from simple steatosis to nonalcoholic steatohepatitis, with inflammatory cytokines and adipokines identified as drivers of disease progression. Poor dietary patterns are known to promote an inflammatory milieu, although the effects of specific diets remain largely unknown. This review aimed to gather and summarize new and existing evidence on the effect of dietary intervention on inflammatory markers in patients with NAFLD. The electronic databases MEDLINE, EMBASE, CINAHL, and Cochrane were searched for clinical trials which investigated outcomes of inflammatory cytokines and adipokines. Eligible studies included adults >18 y with NAFLD, which compared a dietary intervention with an alternative diet or control (no intervention) group or were accompanied by supplementation or other lifestyle interventions. Outcomes for inflammatory markers were grouped and pooled for meta-analysis where heterogeneity was allowed. Methodological quality and risk of bias were assessed using the Academy of Nutrition and Dietetics Criteria. Overall, 44 studies with a total of 2579 participants were included. Meta-analyses indicated intervention with an isocaloric diet plus supplement was more effective in reducing C-reactive protein (CRP) [standard mean difference (SMD): 0.44; 95% CI: 0.20, 0.68; P = 0.0003] and tumor necrosis factor-alpha (TNF-α) (SMD: 0.74; 95% CI: 0.02, 1.46; P = 0.03) than an isocaloric diet alone. No significant weighting was shown between a hypocaloric diet with or without supplementation for CRP (SMD: 0.30; 95% CI: -0.84, 1.44; P = 0.60) and TNF-α (SMD: 0.01; 95% CI: -0.43, 0.45; P = 0.97). In conclusion, hypocaloric and energy-restricted diets alone or with supplementation, and isocaloric diets with supplementation were shown to be most effective in improving the inflammatory profile of patients with NAFLD. To better determine the effectiveness of dietary intervention alone on a NAFLD population, further investigations of longer durations, with larger sample sizes are required.


Transthoracic echocardiography for right ventricular function late after the Mustard operation.
The aim of the study was to assess echocardiographic measurements of right ventricular function in 24 patients aged 10.7 to 28.9 years (mean 18.9 years) receiving the Mustard baffle repair for transposition of the great arteries. Right ventricular ejection fraction (RVEF) from single-plane areas and area length volumes, pulsed Doppler mean aortic acceleration, and tricuspid annular plane systolic excursion were correlated with first-pass radionuclide RVEF. The mean radionuclide RVEF was 39%, the mean echocardiographic apical four-chamber RVEF was 41%, and the mean short-axis RVEF was 37%. Echocardiographic apical four-chamber right ventricular end-diastolic volumes were 102 +/- 24 ml/m2, and RVEF interobserver and intraobserver correlation coefficients were 0.73 and 0.81, respectively. Radionuclide and echocardiographic RVEF correlation coefficients were short axis, 0.40; apical four-chamber, 0.24; average four-chamber and short axis, 0.38; mean aortic acceleration, 0.26; and tricuspid annular plane systolic excursion, 0.06. The range of echocardiographic right ventricular volumes for young adults receiving the Mustard repair is established allowing serial observation of dilatation. However, simple and reliable echocardiographic prediction of RVEF remains elusive in this age group.


Catalytic conversion of cellulose to chemicals in ionic liquid.
A simple and effective route for the production of 5-hydroxymethyl furfural (HMF) and furfural from microcrystalline cellulose (MCC) has been developed. CoSO(4) in an ionic liquid, 1-(4-sulfonic acid) butyl-3-methylimidazolium hydrogen sulfate (IL-1), was found to be an efficient catalyst for the hydrolysis of cellulose at 150°C, which led to 84% conversion of MCC after 300min reaction time. In the presence of a catalytic amount of CoSO(4), the yields of HMF and furfural were up to 24% and 17%, respectively; a small amount of levulinic acid (LA) and reducing sugars (8% and 4%, respectively) were also generated. Dimers of furan compounds were detected as the main by-products through HPLC-MS, and with the help of mass spectrometric analysis, the components of gas products were methane, ethane, CO, CO(2,) and H(2). A mechanism for the CoSO(4)-IL-1 hydrolysis system was proposed and IL-1 was recycled for the first time, which exhibited favorable catalytic activity over five repeated runs. This catalytic system may be valuable to facilitate energy-efficient and cost-effective conversion of biomass into biofuels and platform chemicals.