Low mindfulness is related to poor sleep quality from middle adolescents to emerging adults: a process model involving resilience and emotional dysfunction.
Transitions from middle adolescence into merging adulthood, a life stage between age 15-25, has a high prevalence of sleep problems. Mindfulness is a trait defined as being attentive to the present moment which positively relates to sleep quality. In this study, we aimed to investigate how resilience and emotional dysfunction may influence the relationship between trait mindfulness and sleep quality. The Five Facet Mindfulness Questionnaire, Connor-Davidson Resilience Scale, Pittsburgh Sleep Quality Index and Depression Anxiety Stress Scales were used to measure the key variables through an online survey of 497 participants between middle adolescence and emerging adults (317 females, mean age 18.27 ± 0.76 years). A process model was built to investigate the mediating roles of resilience and emotional dysfunction in the impact of trait mindfulness on sleep quality, together with the relationships between their specific components. We found a positive association between mindfulness and sleep quality through resilience and through emotional dysfunction, and through the sequential pathway from resilience to emotional dysfunction. Of note, acting with awareness (mindfulness facet) showed significant indirect effects on sleep quality, mediated by resilience and emotional dysfunction. Our findings may unveil the underlying mechanisms of how low mindfulness induces poor sleep quality. The findings indicate that conceiving mindfulness as a multifaceted construct facilitates comprehension of its components, relationships with other variables, and underscores its potential clinical significance given its critical implications for mental health.


Muscle group specific changes in the electromechanical delay following short-term resistance training.
The time delay between the onset of a muscle's electrical activity and force is believed to have important functional implications, and has been shown to decrease following resistance training in males. The purpose of this investigation was to examine changes in the voluntary electromechanical delay (EMD) for the leg extensors and flexors following a short-term resistance training intervention in females. Pretest/posttest control group experiment. Twenty-two previously untrained females (mean±SD age=21±2 years; mass=65.4±13.3kg) were randomly assigned to training (n=10) and control (n=12) groups. The training group performed barbell back squats and deadlifts twice per week for four weeks. EMD for the vastus lateralis (extensors) and biceps femoris (flexors) was examined during maximal voluntary contractions at pre- and posttesting. Data were examined using analyses of covariance (ANCOVAs) with the pretest and posttest scores serving as the covariate and dependent variable, respectively, and by evaluating the number of participants that exceeded the minimal difference statistic. For the leg extensors, the adjusted EMD posttest mean for the training group was significantly lower than that for the control group (74.3 vs. 91.8ms; p=0.015; ή(2)=0.275), and five training participants displayed decreases that exceeded the minimal difference. The ANCOVA for the leg flexors was not significant (adjusted means=98.0 vs. 90.0ms; p=0.487; ή(2)=.026). Four weeks of multi-joint resistance training resulted in decreased EMD for the leg extensors, but not the flexors.


Synthesis of Substituted Tropones by Sequential Rh-Catalyzed [5+2] Cycloaddition and Elimination.
Highly substituted tropones are prepared from cycloheptatrienes derived from Rh-catalyzed intermolecular [5+2] cycloaddition of 3-acyloxy-1,4-enynes and propargylic alcohols. The intermolecular [5+2] cycloaddition is highly regioselective for a variety of propargylic alcohols. Elimination of the cycloaddition products afforded various substituted tropones.


Bone mineral density in children with juvenile chronic arthritis.
The aim of this study was to evaluate bone mineral density changes in patients with juvenile chronic arthritis (JCA) and to determine the most likely causes of osteoporosis in these patients. Eighteen (11 male, 7 female) patients suffering from JCA and 14 healthy controls (10 male, four female) were included in this study. The mean age of the patients and control groups were 11.0 +/- 3.2 and 10.9 +/- 2.9 years respectively. Disease activity was determined by clinical and laboratory evaluation and 'Articular Disease Severity Score' (ADSS). Bone mineral density (BMD) of the femoral neck and lumbar spine was measured by dual photon absorptiometry. BMD of the patients at the lumbar spine was significantly lower than the control group (p < 0.05). This difference was more marked in patients treated with steroids. Femoral neck BMD was also lower in the patient group but this difference was not statistically significant. There was a negative correlation between ADSS and BMD at the spine. In conclusion, trabecular bone loss is characteristic for osteoporosis in JCA. Our results indicate that steroid treatment and disease severity are important factors in the development of osteoporosis in JCA.


The Race toward Equity: Increasing Racial Diversity in Cancer Research and Cancer Care.
Cancer research and cancer care require deliberate attention to racial diversity. Here we comment on the ongoing issues of diversity and racism in cancer research.


Health-Related Quality of Life and Living Costs of HIV-Infected Patients.
The aim of this study was the evaluation of health-related quality of life (HRQoL) of HIV-infected patients and the effect of their illness in their living costs. This is a cross-sectional study and the study sample, which was a sample of convenience, included 98 HIV-infected patients from March to May 2019 at the General Oncology hospital "Oi Agioi Anargyroi" in Greece. The main tools of the survey were the Greek version of the MOS-HIV and a questionnaire used for measuring rehabilitation costs in trauma patients adjusted for the needs of the this study. A total of 98 patients were inducted in our study aged 49.3 ± 11.3 years, most of them males (68.3%). HRQoL was assessed in 11 individual dimensions. The highest score was found in the dimensions of role functioning (73.47 ± 36.93), physical functioning (72.53 ± 26.65), and social functioning (71.63 ± 32.3). Regarding the patients' living costs over the last month due to their illness, the highest burden comes from other expenses (152.4 ± 179.5), services provided by a psychologist (142.8 ± 170.6) and medical visits (142.8 ± 170.6). As the HIV infection is characterized as a chronic disease, the economic cost due to the illness needs to be studied as it affects the extent to which an HIV-infected patient can access medical care and meet emerging needs. Therefore, future research should focus in the economic dimension of the illness in relation with the quality of life of these patients and their relatives, so that new health policies may arise.


Site-directed mutagenesis by complementary-strand synthesis using a closing oligonucleotide and double-stranded DNA templates.
An approach for generating structures capable of directing full-length complementary-strand synthesis for double-stranded plasmid DNA is described. The structures are formed following heat denaturation and cooling of linearized plasmid DNA molecules in the presence of what is referred to as a "closing" oligonucleotide. Consisting of a sequence complementary to the free ends of one of the two plasmid strands, the closing oligonucleotide functions as an agent for recircularization of a DNA strand and generation of a primer-circular template structure suitable for polymerase-dependent full-length complementary-strand synthesis and ligation into a covalently closed heteroduplex molecule. When combined with a mutagenic oligonucleotide and uracil-substituted DNA templates, this approach allows site-directed mutagenesis to be performed directly on double-stranded DNA with a mutant formation efficiency of about 50%, a level amenable to rapid screening by DNA sequencing.


[Immunoglobulins M, G and A as prognostic criteria of the treatment outcome in uveal melanoblastoma].
The level of immunoglobulins M, G, A in 30 patients with uveal melanoblastomas has been compared with results after treatment, different cellular types of uveal melanomas before enucleation and in various terms after it. It was found that for prognosing the outcomes of tumors the determination of the level of immunoglobulins M and G proved to be informative. It becomes lower after combined treatment; higher in spindle cell melanomas, than in mixed and epithelioid ones; lower in the patients survived, than in cases with a lethal outcome.


Draft genome sequence of a lipopeptide-producing Bacillus amyloliquefaciens strain isolated from wheat field soil with antagonistic activity against azole-resistant Fusarium graminearum.
Lipopeptides have been revealed as good potential biocontrol agents against various pathogenic microbes. In the present work, we report the draft genome sequence of a lipopeptide-producing strain of Bacillus amyloliquefaciens (7D3) that showed good antifungal activity against the azole-resistant pathogenic fungus Fusarium graminearum. Whole-genome sequencing of strain 7D3 was performed on an Illumina MiSeq 300 platform. Raw data were cleaned using Trim Galore v.0.4.0 and were checked for quality using FastQC. De novo assembly was performed using the SOAPdenovo2 package. Genes responsible for the biosynthesis of secondary metabolites were identified using antiSMASH. Bacillus amyloliquefaciens 7D3 genome assembly resulted in a total genome size of 3 913 220 bp with a G+C content of 46.13%. There were 3998 predicted genes with 72 tRNAs and 9 rRNAs. A total of ten gene clusters were found to be related to secondary metabolite biosynthesis, of which five were identified as lipopeptide synthesis clusters. This study presents the genome sequence of B. amyloliquefaciens 7D3, which exhibited intense antagonistic activity against azole-resistant fungi. The whole genome sequence will help in the search for novel antifungal peptides against drug-resistant pathogens.


Acceptability of donated breast milk among pregnant women in selected hospitals in central Uganda: a cross-sectional study.
Donated breast milk is considered beneficial to vulnerable infants. Thus, Uganda launched its first human milk bank in November 2021 to provide breast milk to preterm, low birthweight and sick babies. However, there is a scarcity of information on the acceptability of donated breast milk in Uganda. The study sought to assess the acceptability of using donated breast milk and associated factors among pregnant women at a private and a public hospital in central Uganda. This cross-sectional study enrolled pregnant women attending antenatal care at the selected hospitals between July and October 2020. All pregnant women recruited had already given birth to at least one child. Data were collected using a semi-structured questionnaire, and we recruited participants through systematic sampling. Used frequencies, percentages and means with standard deviations to summarize variables. Assessed the association between the acceptability of donated milk and selected factors by comparing their arithmetic means using a generalized linear model to allow for clustering at the health facility level. Used a normal distribution and an identity link and calculated the adjusted mean differences together with 95% CIs [generated using robust variance estimators to correct for model misspecification]. A total of 244 pregnant women with a mean age of 30 (± 5.25) years were enrolled. Sixty-one-point 5% (150/244) of the women reported that they would accept donated breast milk. Higher education (adjusted mean difference, technical versus primary level: 1.33; 95% CI 0.64, 2.02), being Muslim (adjusted mean difference, Muslim versus Christian: 1.24; 95% CI 0.77, 1.70), having heard of donated breast milk banking (adjusted mean difference, ever versus never: 0.62; 95% CI 0.18, 1.06) and presence of a serious medical condition (adjusted mean difference, preference of donated milk versus other feeds in a serious medical condition: 3.96; 95% CI, 3.28, 4.64) were associated with acceptability of donated breast milk. The acceptability of using donated breast milk for infant feeding was high among pregnant women. Public sensitization and education campaigns are indispensable for the acceptability of donated milk. These programs should be designed to include women with lower education levels.


[Analysis of composite therapy and effect on 36 patients with nasal polyposis].
To observe the long term effect of composite therapy on patients with nasal polyposis. All 36 cases with nasal polyposis accepted antibiotic for a week and systemic corticosteroids for 3 days before operation, then underwent ESS. Systemic corticosteroids were used for 5 days and topic corticosteroids for 6 months after operation, then they were followed up by endoscopy for more than 3 years. The symptoms were significantly improved after composite therapy. The effective rates of ventilation and headache were respectively 100% and 95%, the improvement of dysosmia is relatively poor. Catch cold and no use of topic corticosteroids can lead recurrence of nasal polyposis. Composite therapy is effective in the treatment of nasal polyposis. Using antibiotic for a week and systemic corticosteroids for 3 days before operation, making use of systemic corticosteroids for 5 days and topic corticosteroids for 6 months after operation , and a reasonable regular following-up by endoscopy , a suitable and prompt postoperative treatment are indispensable to improve the effect of treatment.


Index metacarpal fracture after tightrope suspension following trapeziectomy: case report.
Trapeziectomy, by itself or combined with ligament reconstruction/interposition arthroplasty, is commonly performed for advanced trapezial-metacarpal arthritis. Several methods and materials, both autogenous and artificial, are commonly used for ligament reconstruction and interposition arthroplasty. Harvesting autologous tendons adds to operative time and could increase potential surgical complications. Using an artificial material would, in theory, avoid some of these problems. However, this approach is not without its problems. We present a case of index metacarpal fracture after using the Arthrex Mini TightRope (Arthrex, Naples, FL) suture button fixation of the thumb and index metacarpals after complete trapeziectomy.


Noninvasive Moisture Detection in Lyophilized Drug Product Using NIR Spectrometer and Headspace Moisture Analyzer.
Utilization of laser headspace and near-infrared (NIR) methods provides rapid and non-destructive approaches for moisture detection of lyophilized drug products to facilitate lyophilization formulation characterization and process development. In the present study, the NIR method was developed based on a partial least square regression (PLSR) model calibrated and validated with Karl Fisher (KF) data, whereas the laser headspace method was developed with aid of dynamic vapor sorption (DVS) method so that the water vapor pressure measured from the headspace of a lyophilized drug product vial can be converted directly to water content value through the water vapor sorption isotherm of the lyophilized drug product bypassing KF calibration. The water contents of lyophilized samples obtained from both methods agreed well with KF data, with a root mean squared error of prediction (RMSEP) of less than 0.15%. The pros and cons of NIR and laser headspace method were evaluated. The results suggest that traditional off-line KF method can be potentially replaced by at-line laser headspace method combined with water sorption isotherm data from DVS. Further studies may be needed to evaluate the quantitation limit and generality of this method to a variety of lyophilized formulations.


Eosinophilic Granulomatosis with Polyangiitis after mRNA-1273 SARS-CoV-2 Vaccine.
During one of the worst global health crises, millions of people were vaccinated against SARS-CoV-2. In rare cases, new onset systemic inflammatory diseases were reported with temporal coincidence to the vaccination. We describe a case of severe Eosinophilic Granulomatosis with Polyangiitis (EGPA) in a young asthmatic woman, occurring after a second dose of the mRNA-1273 vaccine. She presented with multisystem EGPA with cardiac and central nervous system involvement, complicated by secondary immune thrombocytopenia (ITP). We review the reported cases of EGPA coinciding with SARS-CoV-2 mRNA vaccination. All potentially vaccine-related EGPA cases reported so far occurred within 14 days from immunization. EGPA is very rare with an incidence of 1:1,000,000 inhabitants, and the number of reported post-vaccination EGPA cases lies within the expected incidence rate for the period. While we cannot prove a causal relationship between the vaccine and EGPA onset, the temporal relationship with the vaccine immune stimulation is intriguing, in a disease occurring almost always in adults with asthma and/or chronic rhinosinusitis and driven by an aberrant Th2 lymphocyte activation with hypereosinophilia; nevertheless, cases of inflammatory diseases (IMIDs) emerging in the context of vaccination remain rare and the benefits of preventing severe COVID presentations with SARS-CoV-2 mRNA vaccines remain unquestionable.


Transection of carotid sinus nerve inhibits the turnover of dopamine and norepinephrine in long-term hypoxic carotid bodies: a biochemical and morphometric study.
To assess the efferent influence of the carotid sinus nerve on the catecholamine function and the vascularity in long-term hypoxic carotid bodies, rats were exposed to hypoxia (10% O2 in nitrogen for 1 and 3 weeks) after unilateral transection of the sinus nerve. In the intact carotid bodies, long-term hypoxia elicited several biochemical and morphological alterations: increased turnover of dopamine and norepinephrine, increased volume density of blood vessels, decreased volume density of glomic tissue. Transection of the sinus nerve reduced but did not abolish the increase in turnover of dopamine and norepinephrine evoked by hypoxia without preventing the structural alterations. Immunocytochemical studies revealed the presence of nerve fibres exhibiting neuropeptide Y-like immunoreactivity which persisted after the excision of the carotid sinus nerve. Nerve fibres showing substance P-like immunoreactivity were found in the intact carotid bodies but not in the carotid bodies deprived of sinus nerve. It is concluded that the sinus nerve exerts a stimulatory efferent control on the synthesis and release of dopamine and norepinephrine in rat carotid body during long-term hypoxia, but no appreciable vasodilatory influence on the glomic vasculature. A possible role of substance P contained in the endings of the carotid sinus nerve is discussed.


Elucidating critical mechanisms of deregulated stem cell turnover in the chronic phase of chronic myeloid leukemia.
Chronic myeloid leukemia (CML) has been studied intensively for many years; yet its treatment remains problematic and its biology remains elusive. In chronic phase, the leukemic clone appears to be maintained by a small number of BCR-ABL-positive hematopoietic stem cells that differentiate normally and amplify slowly. In contrast, as these cells enter the intermediate stages of lineage restriction, their progeny are selectively expanded and generate an enlarged pool of neoplastic progenitors. Recent analyses of purified subsets of primitive CML cells have provided a coherent explanation for this dichotomous behavior of BCR-ABL-positive stem and progenitor cells based on the discovery of an unusual autocrine IL-3/G-CSF mechanism activated in them. This only partially counteracts in vivosignals that maintain normal stem cells in a quiescent state but, when active in CML stem cells, promotes their differentiation in favor of their self-renewal. In more differentiated CML progenitors, the same mechanism has a more potent mitogenic effect which is then extinguished when the cells enter the terminal stages of differentiation. Thus, further expansion of the clone is limited until inevitably additional mutations are acquired that further distort or override the regulatory mechanisms still operative in the chronic phase.


HIF-1α dependent RhoA as a novel therapeutic target to regulate rheumatoid arthritis fibroblast-like synoviocytes migration in vitro and in vivo.
The purpose of this work is to investigate how the Rho family of GTPases A (RhoA) mediates the pathogenesis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS). The expression of RhoA in the synovial tissues of RA and Healthy people (Control) was detected using immunohistochemistry methods. The expression of RhoA and hypoxia-inducible factor-1α (HIF-1α) is inhibited by small interfering RNAs (siRNAs). The inhibition effect on RA-FLS migration was further investigated. The protein expression level of HIF-1α, RhoA, focal adhesion kinase (FAK), and myosin light chain (MLC) was also analysed using western blotting (WB). DBA1 mice were immunised with the mixture of bovine type II collagen and Freund's adjuvant to establish collagen induced arthritis (CIA) mouse model. Lip-siRhoA is administered through joint injection every two days. Micro-computed tomography (micro-CT) was used to detect mouse ankle joint destruction and evaluate the bone loss of the periarticular side. Destruction of the ankle articular cartilage was tested by histology. Expressions of P-RhoA, P-FAK and P-MLC in the ankle joint was detected by immunohistochemistry assay. The expression level of RhoA in the synovial tissues of RA patients was significantly higher than that in control group. Hypoxia was able to up-regulate the expression of RhoA. Whereas, HIF-1α siRNA (siHIF-1α) could down-regulate the expression of RhoA. Additionally, both of siHIF-1α and RhoA siRNA (siRhoA) delivered by liposome (Lip-siHIF-1α and Lip-siRhoA) were found to suppress FAK and MLC phosphorylation in vitro. In CIA mouse model, Lip-siRhoA was demonstrated to ameliorate the destruction of ankle joint and reduce the severity of ankle joint cartilage damage by micro-CT and histological staining, respectively. Therefore, inhibition of FLS cell migration can protect articular bone from destruction. Furthermore, the expression of P-RhoA, P-FAK and P-MLC was evaluated and found to be down-regulated by Lip-siRhoA in vivo. The results demonstrated that under hypoxic environment, HIF-1α dependent RhoA pathway played an important role on cytoskeleton remodelling and RA-FLS migration. Through down-regulating RhoA expression, it could effectively treat RA in vitro and in vivo. Our study provides new evidence for the potential clinical application of RhoA as a candidate for the treatment of RA.


Linking ecosystem service flow to water-related ecological security pattern: A methodological approach applied to a coastal province of China.
Water security is a critical concern due to intensifying anthropogenic activities and climate change. Delineating a water-related ecological security pattern can help to optimize spatial configuration, which in turn can inform sustainable water management. However, the methodology remains unclear. In this study, we developed a framework linking ecosystem service flow to water-related ecological security pattern; hence, we identified the sources, sinks, key corridors, and vulnerable nodes in Fujian Province, China. Our results revealed that the sources were located inland at high altitudes with a decreasing area trend in the south and an increasing area trend in the north, whereas the sinks were spread in coastal areas and exhibited a decreasing trend with relatively stable spatial distribution. The water-related ecological security has degraded as represented by a decreasing ecological supply-demand ratio over the last 30 years. Key corridors were identified in 17.12% of the rivers, and 22.5% of the vulnerable nodes were recognized as early warning nodes. Climate variability affected source distribution, while anthropogenic activities drove sink dynamics. These findings have important implications including landscape pattern planning and sustainable water management in the context of accelerated land use/cover and climate changes.


Monomelic macrodystrophia lipomatosa. A case report.
There are many reports of macrodystrophia lipomatosa involving the hands or feet, but here we report an unusual case where the whole of the left lower limb was affected.


Temporo-spatial patterns of pre-ictal spike activity in human temporal lobe epilepsy.
The statistical properties of pre-ictal EEG spike activity in medial temporal lobe sites were analyzed in 6 patients with medically refractory complex partial seizures. A total of 24 1 h pre-ictal periods (2-6 periods per patient) were evaluated by quantifying the rate of occurrence of individual spatial patterns of spike activity derived from a subset (n = 6) of the recording channels. The channels chosen for analysis always included those medial temporal lobe sites which were documented to be most likely to initiate seizures, as well as their respective contralateral homologues. Each 1 h pre-ictal period was divided into 360 10 sec bins which were then visually classified into 1 of 64 possible spatial patterns of spike activity. These patterns, in turn, were grouped into 1 of 5 general spatial patterns and evaluated for trends across 3 20 min pre-ictal segments. Pooling these data across patients yielded the following results: (1) Focal patterns of spike activity tended to decline significantly in rate of occurrence several minutes prior to seizures, while the rate of independent contralateral patterns did not change. (2) The rate of occurrence of patterns of bilateral loosely coupled spike activity (involving focal and contralateral sites) increased significantly across the 20 min pre-ictal segments and was clearly augmented during the 20 min prior to seizures. These findings indicate that the degree of bilateral independence in medial temporal lobe spike activity tends to decrease several minutes prior to the localized onset of temporal lobe seizures; such changes may reflect the mechanisms responsible for the inter-ictal-ictal transition.


Impact of histological variants on oncological outcomes of patients with urothelial carcinoma of the bladder treated with radical cystectomy.
To investigate the impact of variant histologies of urothelial carcinoma of the bladder (UCB) on oncologic outcomes after radical cystectomy (RC). Data from 1984 UCB patients treated by RC without preoperative chemo- or radiotherapy were reviewed for histological differentiation and variants. We analysed the differences between pure UCB and UCB with variant histology, and those between the different histological variants using various stratifications. Overall, 488 (24.6%) patients had UCB variants with squamous cell (11.4%) and glandular differentiation (3.8%) being the most common. Histological UCB variants were associated with advanced tumour stage, lymphovascular invasion and lymph node metastasis (all p-values<0.01) when compared to pure UCB. In univariable analyses, patients with non-squamous UCB variants were at significantly higher risk for disease recurrence and cancer-specific mortality than those with pure UCB patients (p-values=0.001) and those with squamous cell differentiated UCB (p-values=0.04); the latter two had the same risk. In multivariable analyses that adjusted for the effects of standard clinicopathologic characteristics, variant UCB histology was not associated with both survival end-points. In patients treated with adjuvant chemotherapy (n=492) there was no difference in cancer-specific survival between pure UCB, squamous cell differentiated UCB and other histological UCB variants. A quarter of UCB patients treated with RC harboured histological UCB variants. Variant UCB histologies were associated with features of biologically aggressive disease. While variant UCB histology was associated with worse outcomes in univariable analyses, this effect did not remain significant in multivariable analyses.


Determinants of healthy eating in Canada: an overview and synthesis.
This article uses a population health perspective to examine the complex set of interactions among the determinants of healthy eating. An overview of current knowledge on determinants of healthy eating was organized as follows: 1) individual determinants of personal food choices and 2) collective determinants, including a) environmental determinants as the context for eating behaviours and b) public policies as creating supportive environments for healthy eating. A conceptual synthesis of the literature revealed that individual determinants of personal food choice (physiological state, food preferences, nutritional knowledge, perceptions of healthy eating and psychological factors) are necessary, but not sufficient, to explain eating behaviour, which is highly contextual. Collective determinants of eating behaviour include a wide range of contextual factors, such as the interpersonal environment created by family and peers, the physical environment, which determines food availability and accessibility, the economic environment, in which food is a commodity to be marketed for profit, and the social environment, in which social status (income, education and gender) and cultural milieu are determinants of healthy eating that may be working "invisibly" to structure food choice. Policy is a powerful means of mediating multiple environments. There are gaps in our understanding of the process of intervening in macro-level environments and the impact of such interventions on the promotion of healthy eating. Collective determinants of food choice and policy contexts for promoting healthy eating, therefore, require investment in research. Applying a population health promotion lens to understanding the multiple contexts influencing healthy eating provides insight into prioritizing research and action strategies for the promotion of healthy eating.


Hypolipidaemic and antioxidant effects of various Chinese dark tea extracts obtained from the same raw material and their main chemical components.
In order to investigate the hypolipidaemic and antioxidant effects of various dark teas produced from different post-fermentation using the same raw material, a hyperlipidaemia zebrafish model combined with binding bile salts assay and antioxidant assays were performed in this study. Results showed that the hypolipidaemic effect of dark tea extracts increased significantly (p < 0.05) while the antioxidant ability decreased sharply compared with raw material. Particularly, Liupao tea (50%) and Pu-erh tea (48%) showed promising hypolipidaemic potential; however, the antioxidant capacity of Pu-erh tea decreased (31-49%) most dramatically. Besides, the levels of total polyphenols and catechins decreased sharply, but theabrownin, gallic acid, and caffeine increased significantly after post-fermentation. Moreover, the potential mechanisms of regulating hyperlipidaemia by dark tea extracts were discussed. These results suggest that microbial fermentation significantly affects the bioactivity of dark teas, and provide theoretical basis for processing and improving of dark tea products for hyperlipidaemia therapy.


A study of bovid herpesvirus 2 infection in calves inoculated intradermally or intranasally.
Bovid herpesvirus 2 infection was studied in calves exposed to the virus by intradermal inoculation of the skin of the left cheek or by nasal spray. In either case a localised infection developed and virus replication was shown to occur mostly in the tissues of its primary localisation, i.e. the skin of the left cheek or the nasal mucosa. There were neither secondary lesions, except at the site of virus injection, nor any serious systemic involvement on the part of the animals. The virus was also recovered from some areas of the skin (right cheek, perineum and scrotum) that were free of macroscopic lesions; moreover, intranuclear inclusions were found in several tissues of the nervous system (brain, superior cervical, stellate and Gasserian ganglia) which did not show any signs of inflammatory or degenerative changes. These findings suggest that the skin and the nervous system play an important role in the naturally-occurring disease since they could be the sites where the virus is maintained latently in the host.


Image guided, adaptive, accelerated, high dose brachytherapy as model for advanced small volume radiotherapy.
Brachytherapy has consistently provided a very conformal radiation therapy modality. Over the last two decades this has been associated with significant improvements in imaging for brachytherapy applications (prostate, gynecology), resulting in many positive advances in treatment planning, application techniques and clinical outcome. This is emphasized by the increased use of brachytherapy in Europe with gynecology as continuous basis and prostate and breast as more recently growing fields. Image guidance enables exact knowledge of the applicator together with improved visualization of tumor and target volumes as well as of organs at risk providing the basis for very individualized 3D and 4D treatment planning. In this commentary the most important recent developments in prostate, gynecological and breast brachytherapy are reviewed, with a focus on European recent and current research aiming at the definition of areas for important future research. Moreover the positive impact of GEC-ESTRO recommendations and the highlights of brachytherapy physics are discussed what altogether presents a full overview of modern image guided brachytherapy. An overview is finally provided on past and current international brachytherapy publications focusing on "Radiotherapy and Oncology". These data show tremendous increase in almost all research areas over the last three decades strongly influenced recently by translational research in regard to imaging and technology. In order to provide high level clinical evidence for future brachytherapy practice the strong need for comprehensive prospective clinical research addressing brachytherapy issues is high-lighted.


Intradural extramedullary tuberculoma of the spinal cord in patient of tubercular meningitis - an uncommon scenario.
Intradural extramedullary tuberculoma of the spinal cord (IETSC) is a rare and unanticipated manifestation of CNS tuberculosis. A 28 years old female diagnosed case of tubercular meningitis (TBM), already on antitubercular therapy (ATT) for last nine months, developed sensory and motor weakness in lower limbs along with saddle anaesthesia. Magnetic resonance imaging (MRI) with contrast of the spine revealed the presence of multiple space occupying lesions in dorsal spinal cord. She received oral steroid therapy for six weeks with escalation of ATT after which neurological functions improved remarkably.


An evaluation of ethyl-6-ethoxybenzothiazole-2-carbamate (Sch 18099) for anthelmintic activity in domestic animals.
Ethyl-6-ethoxybenzothiazole-2-carbamate (Sch 18099) was evaluated for efficacy against natural helminth infections in ponies, pigs, lambs and chickens. Sixteen critical trials were conducted in ponies at dosages of 15 to 150 mg/kg. At 15 mg/kg, efficacy against adult and larval Oxyuris equi was 100% and 91% and against small strongyles it was 98%. Efficacy levels were 95% against Strongylus vulgaris and S. edentatus at the 20 mg/kg dosage. In two trials at 100 mg/kg efficacy against Parascaris equorum was 77%. No efficacy was observed against Gastrophilus spp. or Anoplocephala spp. In swine single oral doses of 10 to 100 mg/kg were not effective. 500 ppm Sch 18099 in the diet for seven days resulted in 100% efficacy against Ascaris suum and Trichuris suis but had no effect on Stongyloides ransomi. Efficacy at 250 ppm against A. suum was 77%. Efficacy at 200 mg/kg in lambs was greater than 90% for Haemonchus contortus, Trichostrongylus axei, Marshallagia marshalli, Bunostomum trignocephalum, Oesophagostomum columbianum, Trichuris ovis, and Chabertia spp. Efficacy was less than 80% for Trichostrongylus vitrinus, Nematodirus filicollis, Ostertagia circumcinta and Cooperia curticei. Except for O. circumcinta and C. curticei, drug efficacy was reduced for these worms in lambs treated at 100 mg/kg. Efficacies of 14.3-89% against Ascaridia galli were obtained with dietary levels of 125-1000 ppm Sch 18099 fed for 7 days. Efficacy of 100% was recorded against Heterakis gallinarum at the 1000 ppm dietary drug level.


Effectiveness of a 4-week sophrology program for primary care patients with moderate to high anxiety levels: a randomised controlled trial.
he aim of this study is to determine the effectiveness of an intensive four-week structured group re- laxation-training program (sophrology's dynamic relaxation) on anxiety and depression symptoms in primary care patients with moderate and high anxiety levels.


In vivo blockade of Ca(+2)-dependent nitric oxide synthases impairs expressions of L-selectin and PECAM-1.
Interactions of leukocytes with endothelium play a role for the immune system modulated by endogenous agents, such as glucocorticoids and nitric oxide (NO). Glucocorticoids inhibit leukocyte-endothelial interactions whereas the role of NO is still controversial. In this study, the activity of Ca(+2)-dependent nitric oxide synthases was in vivo blocked in male Wistar rats by given l-NAME, 20mgkg(-1) for 14 days dissolved in drinking water and expression of adhesion molecules involved in leukocyte-endothelial interactions was investigated. Expressions of L-selectin and PECAM-1 in peripheral leukocytes and PECAM-1 in endothelial cells were reduced by l-NAME treatment. Only L-selectin expression was controlled at transcriptional levels. These effects were not dependent on endogenous glucocorticoids, as corticosterone levels were not altered in l-NAME-treated rats. Our results show that NO, produced at physiological levels, controls expression of constitutive adhesion molecules expressions in cell membranes by different mechanisms of action.


Adverse Childhood Experiences and Mental Health Conditions Among Adolescents.
Adverse childhood experiences (ACEs) have been linked with poor physical and mental health. This study examined adult respondents' (e.g. parental) reports from the 2016-17 National Survey of Children's Health, a nationally representative study of health outcomes and social contexts of U.S. households with noninstitutionalized children. Logistic regression was used to examine associations between ACEs and reports of current depression, anxiety, conduct/behavioral problems, attention-deficit/hyperactivity disorder, and substance use disorder among youth (n = 29,617; 49% female) aged 12-17 years. ACEs were associated with an increased likelihood of all current mental health diagnoses, particularly for youth exposed to four or more ACEs. Although data relied on cross-sectional adult reports, results provide evidence of a graded association between ACEs exposure and adolescents' mental health conditions; associations with substance use disorder were particularly marked. Early childhood, multilevel, trauma-informed interventions are needed to prevent negative youth outcomes associated with ACEs.


Spinal nociceptive reflexes are sensitized in the monosodium iodoacetate model of osteoarthritis pain in the rat.
Evidence suggests that osteoarthritis (OA) is associated with altered central pain processing. We assessed the effects of experimentally induced OA on the excitability of spinal nociceptive withdrawal reflexes (NWRs), and their supraspinal control in a preclinical OA model. Experimental OA was induced in rats with knee injection of monosodium iodoacetate (MIA) and pain behaviour was assessed. 14/28 days post-MIA or saline injection, rats were anaesthetised for spinal NWR recording from tibialis anterior (TA) and biceps femoris (BF) hind limb muscles during plantar hind paw stimulation. Thresholds, receptive field sizes and wind up (incremental increase to repetitive stimulation) were measured in intact (d14/28) and spinalised (severed spinal cord; d28) MIA- and saline-injected rats. MIA reduced BF mechanical thresholds at day 28. Spinalisation of MIA rats did not prevent this hyperexcitability, and failed to produce the reduction in reflex receptive field (RRF) size observed in saline rats. These data indicate that MIA induces a hyperexcitability of BF NWR circuits that is maintained at the spinal level. In contrast, MIA appeared to have no effect on NWRs evoked by mechanical stimuli in the ankle flexor TA in intact rats, however spinalisation revealed hyperexcitability. Thus, 28 days following MIA-treatment, descending supraspinal inhibition normalised TA NWRs and was only overcome following repetitive noxious stimulation during wind up. We demonstrate that spinal nociceptive reflex pathways are sensitized following the development of OA, suggesting the presence of central sensitization. Further, our data reflect OA-induced alterations in the descending control of reflex responses. Our findings contribute to a mechanism-based understanding of OA pain.


Eutopic and ectopic stromal cells from patients with endometriosis exhibit differential invasive, adhesive, and proliferative behavior.
To study immunophenotype, differential proliferation capacity, invasiveness, adhesion, and cytokine production in ectopic and eutopic endometrial stromal cells (EESCs and EuESCs) from patients with endometriosis. In vitro study. Academic research center. Patients with ovarian endometriosis (endometrioma) and nonendometriotic controls. None. EESCs and EuESCs from 25 patients with endometrioma and ESCs from 20 nonendometriotic controls (CESCs) were isolated, and their immunophenotype, proliferation, invasion, adhesion, and cytokine production were assessed and compared. Isolated ESCs from all three sources expressed markers specific for cells of mesenchymal origin but were negative for hematopoietic markers. EESCs exhibited a significantly lower proliferation rate in fibronectin-coated plates and less invasive capacity compared with CESCs or EuESCs. Among all stromal cell groups studied, EuESCs showed the highest invasive behavior. EESCs adhered more firmly to extracellular matrix than EuESCs or CESCs in all time intervals examined. The levels of interleukin (IL) -6 and IL-8 production by EESCs were significantly higher compared with those of EuESCs or CESCs. The results of the present study demonstrated that retrograde menstruation alone does not account for the pathogenesis of endometriosis as eutopic and ectopic counterparts of ESCs from patients with endometriosis exhibit differential invasive, adhesive, and proliferative behavior.


Ibrutinib restores immune cell numbers and function in first-line and relapsed/refractory chronic lymphocytic leukemia.
Ibrutinib positively modulates many T-cell subsets in chronic lymphocytic leukemia (CLL). To understand ibrutinib's effects on the broader landscape of immune cell populations, we comprehensively characterized changes in circulating counts of 21 immune blood cell subsets throughout the first year of treatment in patients with relapsed/refractory (R/R) CLL (n = 55, RESONATE) and previously untreated CLL (n = 50, RESONATE-2) compared with untreated age-matched healthy donors (n = 20). Ibrutinib normalized abnormal immune cell counts to levels similar to those of age-matched healthy donors. Ibrutinib significantly decreased pathologically high circulating B cells, regulatory T cells, effector/memory CD4+ and CD8+ T cells (including exhausted and chronically activated T cells), natural killer (NK) T cells, and myeloid-derived suppressor cells; preserved naive T cells and NK cells; and increased circulating classical monocytes. T-cell function was assessed in response to T-cell receptor stimulation in patients with R/R CLL (n = 21) compared with age-matched healthy donors (n = 18). Ibrutinib significantly restored T-cell proliferative ability, degranulation, and cytokine secretion. Over the same period, ofatumumab or chlorambucil did not confer the same spectrum of normalization as ibrutinib in multiple immune subsets. These results establish that ibrutinib has a significant and likely positive impact on circulating malignant and nonmalignant immune cells and restores healthy T-cell function.


Optimising the use of transoesophageal echocardiography in diagnosing suspected infective endocarditis.
We evaluated the clinical indication and incremental diagnostic yield gained by transoesophageal echocardiography (TOE) performed after transthoracic echocardiography (TTE) in patients with suspected infective endocarditis (IE). We retrospectively analysed 60 pairs of TOE and TTE exams for suspected IE, performed between July 2011 and July 2013 in our district general hospital. The TOE results were classified as 'positive' or'negative' based on the Duke criteria, while TTEs were classified as 'no vegetation', 'vegetation', 'suspected vegetation' and 'cannot exclude vegetation' according to the final reports. Pre-existent valve disease and Greaves clinical criteria (prosthetic valve, IVDU, positive blood cultures, embolic phenomena and central lines) were also recorded. Among 22/60 (36%) patients, there was no additional diagnostic yield from further TOE after TTE. Of these 22 patients, 6 had negative Greaves criteria while 16 were Greaves positive but had no evidence of lE on TTE in the presence of good image quality.TOE had a higher diagnostic yield in the remaining 38 patients especially in the presence of prosthetic valves, calcified aortic valves, myxomatous/prolapsing mitral valves and poor TTE image quality. TOE is not required in patients with low clinical suspicion of IE, when TTE images are of good quality, as there is no additional diagnostic yield. TOE has a higher diagnostic yield and remains a useful tool in patients with intermediate to high suspicion of IE in the presence of poor TTE image quality, calcified aortic valve, myxomatous mitral valve and prosthetic valves.


Effects of DL-3-n-butylphthalide on vascular dementia and angiogenesis.
3-n-Butylphthalide (NBP) is a compound extracted from Chinese celery and is used as an anti-hypertensive herbal medicine for treating stroke patients. The aim of this study is to demonstrate the effects and mechanisms of this compound through in vitro and in vivo experiments. Culture experiments were performed by adding hydrogen peroxide (H(2)O(2)) to SH-SY5Y cells. From the MTT assay result, enhanced cell survival was observed with DL-NBP treatment, regardless of whether they are added before, simultaneously with or after the addition of H(2)O(2). For the in vivo experiment, Spontaneously Hypertensive rats and Wistar Kyoto control rats with chronic cerebral ischemia, which were induced by bilateral transection of the common carotid arteries, were given DL-NBP. Their performances in the place navigation test and spatial probe test in the Morris Water Maze have significantly improved compared with the DL-NBP untreated animals, indicating an improvement in spatial learning and memory in the ischemic-animals. In addition, in the chick embryonic chorioallantoic membrane assay, angiogenesis was more vigorous under the effects of DL-NBP, together with increased expression of growth factors, VEGF, VEGF-receptor and bFGF. All these suggested that one of the mechanisms of DL-NBP might be ameliorating vascular dementia and promoting angiogenesis.


Decidualisation of human endometrial stromal cells is associated with increased expression and secretion of prorenin.
In pregnancy, the decidualised endometrium expresses high levels of prorenin and other genes of the renin-angiotensin system (RAS) pathway. In this study we aimed to determined if the RAS was present in endometrial stromal cells and if decidualisation upregulated the expression of prorenin, the prorenin receptor ((P)RR) and associated RAS pathways. Immortalised human endometrial stromal cells (HESCs) can be stimulated to decidualise by combined treatment with medroxyprogesterone acetate (MPA), 17β-estradiol (E2) and cAMP (MPA-mix) or with 5-aza-2'-deoxycytidine (AZA), a global demethylating agent. HESCs were incubated for 10 days with one of the following treatments: vehicle, MPA-mix, a combination of medroxyprogesterone acetate (MPA) and estradiol-17β alone, or AZA. Messenger RNA abundance and protein levels of prorenin (REN), the (P)RR (ATP6AP2), angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin II type 1 receptor (AGTR1), vascular endothelial growth factor (VEGF), and plasminogen activator inhibitor-1 (PAI-1) were measured by real-time PCR and ELISA's, respectively. Promyelocytic zinc finger (PLZF) and phospho-inositol-3 kinase (PIK3R1) mRNA abundances were also measured. HESCs expressed the prorenin receptor (ATP6AP2), REN, AGT, ACE and low levels of AGTR1. MPA-mix and AZA stimulated expression of REN. Prorenin protein secretion was increased in MPA-mix treated HESCs. E2 + MPA had no effect on any RAS genes. MPA-mix treatment was associated with increased VEGF (VEGFA) and PAI-1 (SERPINE1) mRNA and VEGF protein. An endometrial prorenin receptor/renin angiotensin system is activated by decidualisation. Since (P)RR is abundant, the increase in prorenin secretion could have stimulated VEGF A and SERPINE1 expression via Ang II, as both ACE and AGTR1 are present, or by Ang II independent pathways. Activation of the RAS in human endometrium with decidualisation, through stimulation of VEGF expression and secretion, could be critical in establishing an adequate blood supply to the developing maternal placental vascular bed.


Young female with abdominal pain and intra-abdominal free fluid: The risk of confirmation bias associated with point-of-care ultrasound.
Confirmation bias is an ever-present risk to the rapid decision-making required in emergency departments (EDs). We present a case of a young woman who was brought to ED by ambulance with hypotension, syncope and vaginal bleeding, with a presumptive pre-hospital diagnosis of ruptured ectopic pregnancy. On arrival in ED, she was found to have intra-abdominal free fluid on bedside ultrasound. This finding could have been used by clinicians to confirm their suspicion of a ruptured ectopic; however, with further investigations, it was found that anaphylaxis was the most likely cause of the patient's symptoms. This case highlights that point-of-care ultrasound findings can play a potentially dangerous role in confirmation bias and that we should maintain an open mind when making a diagnosis by treating the patient, rather than the ultrasound picture.


Demonstration of the role of cell wall homeostasis in Staphylococcus aureus growth and the action of bactericidal antibiotics.
Bacterial cell wall peptidoglycan is essential, maintaining both cellular integrity and morphology, in the face of internal turgor pressure. Peptidoglycan synthesis is important, as it is targeted by cell wall antibiotics, including methicillin and vancomycin. Here, we have used the major human pathogen Staphylococcus aureus to elucidate both the cell wall dynamic processes essential for growth (life) and the bactericidal effects of cell wall antibiotics (death) based on the principle of coordinated peptidoglycan synthesis and hydrolysis. The death of S. aureus due to depletion of the essential, two-component and positive regulatory system for peptidoglycan hydrolase activity (WalKR) is prevented by addition of otherwise bactericidal cell wall antibiotics, resulting in stasis. In contrast, cell wall antibiotics kill via the activity of peptidoglycan hydrolases in the absence of concomitant synthesis. Both methicillin and vancomycin treatment lead to the appearance of perforating holes throughout the cell wall due to peptidoglycan hydrolases. Methicillin alone also results in plasmolysis and misshapen septa with the involvement of the major peptidoglycan hydrolase Atl, a process that is inhibited by vancomycin. The bactericidal effect of vancomycin involves the peptidoglycan hydrolase SagB. In the presence of cell wall antibiotics, the inhibition of peptidoglycan hydrolase activity using the inhibitor complestatin results in reduced killing, while, conversely, the deregulation of hydrolase activity via loss of wall teichoic acids increases the death rate. For S. aureus, the independent regulation of cell wall synthesis and hydrolysis can lead to cell growth, death, or stasis, with implications for the development of new control regimes for this important pathogen.


Combination treatment of high-dose pyridoxal phosphate and low-dose ACTH in children with West syndrome and related disorders.
Combination therapy of high-dose pyridoxal phosphate (PAL-P, 40-50 mg/kg/day) and low-dose ACTH beta 1-24-Z (tetracosactide acetate-Zn, Cortrosyn Z, 0.01 mg/kg/day) was instituted in 26 children suffering from West syndrome and related disorders--pretreated without success with high-dose PAL-P alone; 18 with West syndrome (14 with symptomatic and 4 with cryptogenic types), 2 with symptomatic Lennox-Gastaut syndrome, 5 with cerebral palsy with hypsarhythmia or diffuse slow spike-waves and one with myoclonic seizures (secondary generalized epilepsy). Clinical, electroencephalographic and neurochemical investigations were carried out. The results were summarized as follows. 1) Only one of 27 children with West syndrome and related disorders pretreated using high-dose PAL-P alone before ACTH showed a clinically excellent response. 2) Clinical seizures were completely suppressed in 19 of 21 children who initially had seizures (90%) after this combination therapy. 3) Twenty-one of the total 26 children (80%) had disappearance of hypsarhythmia or diffuse slow spike-waves in EEG after this therapy. 4) During PAL-P treatment alone transient increases in liver enzymes occurred in 37 percent. The brain shrinkage of CT and the significant rise in CSF NSE were seen in 95% and 78% after ACTH, respectively. 5) Twenty-three children have been followed for one to 29 months after tapering off of ACTH. No relapses were experienced in 11 of 18 who initially had seizures (61%) and 13 of 23 with hypsarhythmia or diffuse slow spike-waves (57%). 6) Postictal PRL elevations were suppressed during high-dose PAL-P. 7) No significant changes in the CSF levels of HVA and 5-HIAA were seen during this combination therapy. The CSF levels of HVA were significantly lower than the controls. 8) Daily ACTH therapy transiently suppressed the secretion of anterior pituitary hormones (GH, TSH, PRL, LH and FSH) and thyroid hormones (T3 free T3, T4 and free T4). It is recommended that the combination therapy of high-dose PAL-P and low-dose ACTH is a promising new method and should be tried in children with West syndrome and related disorders. The mechanism of action of this combination therapy remains obscure although some information has been obtained from our investigations.


Knowing the fetal gender and its relationship to seeking prenatal care: results from Jordan.
The purpose of this study was to examine the relationship between knowing fetal gender and seeking prenatal care. Four-hundred and eighty-four postpartum mothers identified before discharge from the maternity unit participated in this study. We collected data from the women using two sources: a demographic data questionnaire and reviews of hospital records. The number of prenatal care visits during pregnancy was determined to assess the adequacy of prenatal care. In the current study, we defined less-than-adequate prenatal care as less than nine prenatal care visits. The data showed that Jordanian women had a strong preference for male babies. The findings suggested that knowing the fetal gender was significantly related to the mean number (7.01+/-2.75) of prenatal care visits by the mother. When the prenatal gender was known the mean number of prenatal care visits of women pregnant with male fetuses (8.91+/-1.25) was significantly higher than that of female fetuses (5.32+/-2.64). Knowledge of fetal gender may thus increase the risk of less-than-adequate care among pregnant women with female fetuses (52.7%) compared to male fetuses (29%). Jordanian women had a strong preference for male babies. Given prenatal knowledge of the gender is related to adequate prenatal care seeking behavior.


Persistent embryonic veins in the arteriovenous malformation of the telencephalon.
The arterial components of the telencephalic arteriovenous malformations arise from the anterior cerebral and middle cerebral arteries. The complexity of the development process in this region obscures the fundamental segmental pattern. There are three regions where the primitive pial vessels cross at right angles. They are: a) over the convexity of the cerebral hemispheres, b) in the Sylvian territory, c) in the region of the basal ganglia. The malformations over the surface drain into the superior sagittal sinus. The Sylvian and deep telencephalic malformations drain primarily into the tentorial sinus, and this is often replaced by a medial drainage into the internal cerebral vein through the tributaries of the basal vein.


Surgical treatment of brachial plexus injuries in adults.
We carried out a retrospective review of 32 consecutive patients (30 adults and two children) with total or partial lesions of the brachial plexus who had surgical repair using nerve grafting, neurotisation, and neurolysis between January 1991 and December 2003. The outcome measures of muscular strength were correlated with the type of lesion, age, preoperative time, length and number of grafts, and time to reinnervation of the biceps. The function of the upper limb was also evaluated. There was a significant correlation between muscular strength after surgical repair and both the preoperative time and the length of the nerve graft. There was also a significant correlation between muscular strength and the number of grafts. Muscular strength was better when the neurolysis was done before six months. When neurosurgical repair and reconstructive procedures were performed, the function of the upper limb was improved.


Ionic interactions determine the morphology of dried alkali/liposome suspension droplets.
We sought to understand why saline drops produce intriguing patterns when drying in the presence of zwitterionic liposomes. Specifically, we would like to comprehend why the nature of such patterns is hierarchically driven by the Hofmeister series. The liposome suspension is made of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) with alkali metal chlorides. A complexity analysis of the patterns gives a fractal dimension around 1.71, which means that the drying process resembles a DLA mechanism. A physicochemical study, including the determination of zeta potential, molecular dynamics simulations, microrheology, and calorimetry, supports the fact that electrostatic interactions among head groups of phospholipids with alkali cations are the driven forces behind the assembling of the observed structures. Moreover, we found that the morphology of the dried droplets is sensitive to the substrate. Our findings could be used in a biological context, for example, to characterize cells in ionic media.


3D simulation of percutaneous sustentaculum tali screw insertion in calcaneal fractures.
In calcaneal fractures, the percutaneous screw fixation (PSF) is currently considered to be the better choice, but it is difficult to accurately place the screw into the sustentaculum tali (ST) during the operation. In this study, the ideal entry point, angle, diameter and length of the screw were calculated by simulating the operation process. We retrospectively collected the calcaneus computed tomography (CT) scans of 180 adults, DICOM-formatted CT-scan images of each patient were imported into Mimics software to establish calcaneus model. Virtual screws were placed on the lateral of the posterior talar articular surface (PTAS), the lateral edge of the anterior process of calcaneus (APC), and the calcaneal tuberosity, respectively, the trajectory and size of the screws were calculated. The mean maximum diameter of the PTAS screw was 42.20 ± 3.71 mm. The vertical distance between the midpoint of the APC optimal screw trajectory and the lowest point of the tarsal sinus was 10.67 ± 1.84 mm, and the distance between the midpoint of the APC optimal screw trajectory and the calcaneocuboid joint was 5 mm ~ 19.81 ± 2.08 mm. The mean maximum lengths of APC screws was 44.69 ± 4.81 mm, and the Angle between the screw and the coronal plane of the calcaneus from proximal to distal was 4.72°±2.15° to 20.52°±3.77°. The optimal point of the maximum diameter of the calcaneal tuberosity screw was located at the lateral border of the achilles tendon endpoint. The mean maximum diameters of calcaneal tuberosity screws was 4.46 ± 0.85 mm, the mean maximum lengths of screws was 65.31 ± 4.76 mm. We found gender-dependent differences for the mean maximum diameter and the maximum length of the three screws. The study provides effective positioning for percutaneous screw fixation of calcaneal fractures. For safer and more efficient screw placement, we suggest individualised preoperative 3D reconstruction simulations. Further biomechanical studies are needed to verify the function of the screw.


Molecular cloning of the cDNA for rat phosphatase inhibitor-2 and its wide gene expression in the central nervous system.
Inhibitor-2 (I-2) is the cytosolic regulatory subunit of type 1 protein phosphatase. We cloned and sequenced a cDNA for rat I-2 from rat brain cDNA library. By in situ hybridization histochemistry, I-2 mRNA was expressed throughout the adult rat brain (on the postnatal 7th week) at various hybridization intensities: high expression signals were detected in the hippocampal formation, olfactory neuronal layers, choroid plexus and cerebellar Purkinje and granule cell layers. Moderate expression signals were detected homogeneously through the layers II-VI of the neocortex. On the embryonic day 15, 1-2 mRNA was expressed moderately in both ventricular and mantle zones of the fore-, mid-, hindbrain and spinal cord, suggesting the possible involvement of I-2 together with type 1 protein phosphatase (PP-1) in the regulation of various early neuronal events including mitosis, migration and differentiation.


Studies on the attachment of herpes simplex virus. Effect of trypsin treatment.
The adsorption of herpes simplex virus (HSV) to monolayers of trypsinized and mock-treated GMK-AH1 cells was studied by means of a microplaque technique. Plaque formation was nearly abolished for c:a 20 minutes and full sensitivity regained at 6--8 hours post trypsinization. The return of sensitivity to HSV was inhibited by cycloheximide and incubation at 4 degrees C. The sum of PFU in the supernatant and PFU successe modifying agents were without effect on the adsorption of HSV.


Urocortin 1-containing neurons in the human Edinger-Westphal nucleus.
The topographical location of neurons containing urocortin 1, a peptide related to corticotropin-releasing factor was investigated in human postmortem brain by immunohistochemistry, and compared with the location of neurons containing choline acetyltransferase, a marker for cholinergic cells. A three-dimensional computer reconstruction of the urocortin 1 and choline acetyltransferase-positive population of neurons within the oculomotor area was made. It was shown that the urocortin 1-positive neurons are located within the area identified as the Edinger-Westphal nucleus according to the human brain stem atlas, and that the neurons identified as Edinger-Westphal nucleus in the atlas are not choline acetyltransferase-positive. This finding agrees with recent animal studies showing that urocortin 1-positive neurons are not identical with the parasympathetic cholinergic neurons projecting to the ciliary ganglion. They indicate that the neurons identified as Edinger-Westphal nucleus in the human brain stem atlas belong to the non-preganglionic Edinger-Westphal nucleus, whereas the location of preganglionic Edinger-Westphal nucleus remains unidentified.


Parachute mitral valve, coarctation of aorta, radius aplasia, and omphalocele in an infant with the trisomy 18 syndrome.
A premature infant with trisomy 18 had cardiac defects including parachute mitral valve, coarctation of the aorta, and a subcristal ventricular septal defect. The parachute mitral valve was funnel-shaped with a moderately-thick cone of fibrous tissue around the annulus and an eccentric orifice. Many forms of congenital cardiac defects have been described in the 18 trisomy syndrome. However, parachute mitral valve has not, to our knowledge, been part of the spectrum of cardiac defects in trisomy 18. Other anomalies were absent radii, omphalocele, and cleft palate and cleft lip; these have been observed previously in the 18 trisomy syndrome.


Malakoplakia. Two unusual cases which presented diagnostic problems.
Two unusual cases of malakoplakia are presented. Both cases occurred outside the urinary tract (retroperitoneum and anus) and were diagnostic problems due to the paucity of Michaelis-Guttman bodies. One case mimicked a retroperitoneal malignant fibrous histiocytoma and the other a common perianal abcess.


Associations between intake of added sugars and intakes of nutrients and food groups in the diets of German children and adolescents.
The aim of the present analysis was to evaluate the effect of intake of added sugars on intakes of nutrients and food groups. We used a mixed linear model (PROC MIXED) to analyse data from the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study (an ongoing longitudinal cohort study between infancy and adulthood). Between July 1985 and August 2001, 3 d weighed dietary records (n 4993) from 849 children and adolescents (416 male, 433 female) aged 2-18 years were collected and evaluated. Overall mean intake of added sugars was 12.4 (SD 5.3) (median 12.0) % energy. Fat intake (% energy) and intake of all analysed nutrients (as % reference values for nutrient intakes) fell across quintiles 1-5 of energy intake from added sugars (P<0.001). With the exception of 'Sugary foods' and 'Beverages' (significant increase, P<0.0001) and 'Dairy' (NS), intake of all other food groups decreased with increasing intake of added sugars (P<0.0001). In conclusion, we found a slight, but statistically significant, nutrient-dilution effect of added sugars and a significant reduction in intake of important nutrient-bearing food groups. However, the DONALD study gives no clear indicator on grounds of micronutrient dilution for a quantitative limit on intake of added sugars.


Orbital apex anatomy: relationship between the optic foramen and anterior face of sphenoid sinus - a radiological study.
This study aims to identify radiologically the position of the optic foramen in relation to the anterior face of the sphenoid sinus, to aid surgeons in their planning for orbital decompression. CT scans of 100 orbits from 50 adult patients without any abnormality were assessed. Primary outcome measures included: position and measurement of the distance from the optic foramen to the anterior face of the sphenoid sinus. Secondary outcomes included: medial orbital wall length, distance from the optic foramen and the anterior face of the sphenoid sinus to the carotid prominence in the sphenoid sinus, and the thickness of bone anterior to the optic foramen. The mean location of the optic foramen was just posterior to the position of the anterior face of sphenoid sinus, with an average distance of +0.4 +/- 3.5 mm. In 54% of orbits the optic foramen was positioned posterior to the anterior face of the sphenoid sinus. The finding was symmetrical in 80% of patients. Our study identifies that the optic foramen lies posterior to the anterior face of sphenoid sinus in approximately half of cases. The position may be asymmetric in 20% of individuals.


Intraocular pressure in patients with human immunodeficiency virus and treated with highly active antiretroviral therapy.
To compare the intraocular pressure (IOP) of patients infected with human immunodeficiency virus (HIV) and treated with highly active antiretroviral therapy (HAART) to a control group and to determine whether HAART reverses the previously reported reduction in IOP associated with HIV infection. Retrospective case control study. Review of patients with HIV infection on HAART compared with a matched control group. Among 64 patients and 56 control subjects, no significant difference in IOP was found (P =.520), nor was correlation noted between IOP and either CD4+ T-lymphocyte counts, or viral load. When HIV infection is treated with HAART, IOP is not significantly different from that of control subjects.


Public health implications of endocrine disrupting chemicals in drinking water and aquatic food resources in Nigeria: A state-of-the-science review.
This state-of-the-science review is aimed at identifying the sources, occurrence, and concentrations of EDCs, including potential public health risks associated with drinking water and aquatic food resources from Nigerian inland waters. A total of 6024 articles from scientific databases (PubMed, Scopus, Web of science, ScienceDirect, Google Scholar, and African Journals Online) were identified, out of which, 103 eligible articles were selected for this study. Eleven (11) classes of EDCs (OCPs, PCBs, PBDEs, PAHs, BPA, OTs, PEs, PCs, PPCPs, sterols and n-alkanes) were identified from drinking waters, river sediments and aquatic food species from Nigerian rivers, showing that OCPs were the most studied and reported EDCs. Analytical methods used were HPLC, LC-MS/MS, GC-FID, GC-ECD and GC-MS with all EDCs identified to originate from anthropogenic sources. Carcinogenic, mutagenic, and teratogenic effects were the highest (54.4 %) toxicological effects identified, while reproductive/endocrine disruptive effects (15.2 %) and obesogenic effects (4.3 %) were the least identified toxicological effects. The targeted hazard quotient (THQ) and cancer risk (CR) were generally highest in children, compared to the adult populations, indicating age-specific toxicity. PEs produced the highest THQ (330.3) and CR (1.2) for all the EDCs in drinking water for the children population, suggesting enhanced vulnerability of this population group, compared to the adult population. Due to associated public health, wildlife and environmental risk of EDCs and their increasing concentrations in drinking water and food fish species from Nigerian inland waters, there is an urgent need for focused and strategic interventions, sensitization and policy formulation/implementation towards public health and aquatic food safety in Nigeria.


Childhood obesity and cardiovascular dysfunction.
Obesity-related cardiovascular disease in children is becoming more prevalent in conjunction with the rise in childhood obesity. Children with obesity are predisposed to an increased risk of cardiovascular morbidity and mortality in adulthood. Importantly, research in children with obesity over the last decade has demonstrated that children may exhibit early signs of cardiovascular dysfunction as a result of their excess adiposity, often independent of other obesity-related comorbidities such as dyslipidemia and insulin resistance. The clinical evidence is accumulating to suggest that the cardiovascular damage, once observed only in adults, is also occurring in obese children. The objective of this review is to provide a synopsis of the current research on cardiovascular abnormalities in children with obesity and highlight the importance and need for early detection and prevention programs to mitigate this potentially serious health problem.


Uterine hyperemia simulating rapid urinary excretion.
Uterine hyperemia in a menstruating adolescent girl was visualized on a renal transplant evaluation. This mimicked early excretion into the urinary bladder.


CEP63 upregulates YAP1 to promote colorectal cancer progression through stabilizing RNA binding protein FXR1.
Abnormal regulation of centrosome components can induce chromosome instability and tumorigenesis. Centrosomal protein 63 (CEP63) is a vital member for assembling centrosome. Yet, the involvement of CEP63 in cancer pathogenesis remains unclear. Here we identify CEP63 as an important mediator for RNA-binding proteins (RBPs) to facilitate regulation on their RNA targets in colorectal cancer (CRC). We demonstrate that CEP63 protein is upregulated in a large cohort of colorectal cancer tissues and predicts poor prognosis, and USP36 is identified for stabilizing CEP63 by enhancing its K48-dependent deubiquitination. CEP63 overexpression promotes the proliferation and tumor growth of CRC cells in vitro and in vivo. Furthermore, we find that CEP63 can promote cancer stem-like cell properties by enhancing YAP1 expression through binding with and inhibiting the K63-ubiquitylation degradation of RBP FXR1 in CRC cells. Importantly, we further verify that the KH domain of FXR1 is necessary for the interaction between CEP63 and FXR1. Moreover, microtube motor proteins can form a complex with CEP63 and FXR1 to mediate the regulation of FXR1 on RNA targets. Additionally, we also confirm that CEP63 can bind and regulate multiple RBPs. In conclusion, our findings unveil an unrecognized CEP63/RBPs/RNA axis that CEP63 may perform as an adapter facilitating the formation of RBPs complex to regulate RNA progression and discover the role of CEP63 involved in signal transduction and RNA regulation, providing potential therapeutic target for CRC patients.


How do the stay-at-home (SAH) orders affect air quality? Evidence from the northeastern USA.
This paper examines whether the SAH orders, implemented in the USA from mid-March to late May 2020, improved air quality in the northeastern states. The estimates are based on panel data from the Environmental Protection Agency and an identification strategy that exploits the exogenous variation in the timing of the SAH orders. We find that the SAH orders reduced the concentrations of the air pollutants nitrogen dioxide ( NO 2 ) and carbon monoxide (CO), whose dominant source is motor vehicle emissions, by approximately 24% and 13%, respectively. The effects were larger for areas of high population density and areas near major roads. We also find that the reductions got smaller, and air pollution gradually approached normal levels, after the orders were lifted. This suggests that the air quality improvements were temporary.


SPINE20 recommendations 2021: spine care for people's health and prosperity.
The focus of SPINE20 is to develop evidence-based policy recommendations for the G20 countries to work with governments to reduce the burden of spine disease, and disability. On September 17-18, 2021, SPINE20 held its annual meeting in Rome, Italy. Prior to the meeting, the SPINE20 created six proposed recommendations. These recommendations were uploaded to the SPINE20 website 10 days before the meeting and opened to the public for comments. The recommendations were discussed at the meeting allowing the participants to object and provide comments. In total, 27 societies endorsed the following recommendations. SPINE20 calls upon the G20 countries: (1) to expand telehealth for the access to spine care, especially in light of the current situation with COVID-19. (2) To adopt value-based interprofessional spine care as an approach to improve patient outcomes and reduce disability. (3) To facilitate access and invest in the development of a competent rehabilitation workforce to reduce the burden of disability related to spine disorders. (4) To adopt a strategy to promote daily physical activity and exercises among the elderly population to maintain an active and independent life with a healthy spine, particularly after COVID-19 pandemic. (5) To engage in capacity building with emerging countries and underserved communities for the benefit of spine patients. (6) To promote strategies to transfer evidence-based advances into patient benefit through effective implementation processes. SPINE20's initiatives will make governments and decision makers aware of efforts to reduce needless suffering from disabling spine pain through education that can be instituted across the globe.


Recurrent Donath-Landsteiner hemolytic anemia: a pediatric case report.
Paroxysmal cold hemoglobinuria (PCH) is a form of autoimmune hemolytic anemia caused by the Donath-Landsteiner antibody (D-L antibody). In children, this is typically a transient immune-mediated hemolysis that follows a viral illness and does not recur. Recurrent acute or chronic PCH due to D-L antibody is very rare. We have reported a unique case of recurrent PCH in a 5-year-old boy with two acute episodes of hemolysis separated by 21 months of hematologic remission. Each episode was severe requiring red blood cell transfusions, intravenous methylprednisolone, and intravenous immunoglobulin during the second episode. Testing identified recurrence of the D-L antibody with the classic anti-P biphasic hemolysis. This demonstrates that PCH can be a recurrent disease in the pediatric population (in the absence of syphilis) with the classical D-L antibody.


How Imaging Membrane and Cell Processes Involved in Electropermeabilization Can Improve Its Development in Cell Biology and in Clinics.
Cell membranes can be transiently permeabilized under the application of electric pulses. This process, called electropermeabilization or electroporation, allows hydrophilic molecules, such as anticancer drugs and DNA, to enter into cells and tissues. The method is nowadays used in clinics to treat cancers. Vaccination and gene therapy are other fields of application of DNA electrotransfer. A description of the mechanisms can be assayed by using different complementary systems with increasing complexities (models of membranes, cells cultivated in 2D and 3D culture named spheroids, and tissues in living mice) and different microscopy tools to visualize the processes from single molecules to entire animals. Single-cell imaging experiments revealed that the uptake of molecules (nucleic acids, antitumor drugs) takes place in well-defined membrane regions and depends on their chemical and physical properties (size, charge). If small molecules freely cross the electropermeabilized membrane and have a free access to the cytoplasm, larger molecules, such as plasmid DNA, face physical barriers (plasma membrane, cytoplasm crowding, nuclear envelope) which reduce transfection efficiency and engender a complex mechanism of transfer. Gene electrotransfer indeed involves different steps that include the initial interaction with the membrane, its crossing, transport within the cytoplasm, and finally gene expression. In vivo, additional very important effects of electric pulses are present such as blood flow modifications. The full knowledge on the way molecules are transported across the electropermeabilized membranes and within tissues is mandatory to improve the efficacy and the safety of the electropermeabilization process both in cell biology and in clinics.


Mercury drives microbial community assembly and ecosystem multifunctionality across a Hg contamination gradient in rice paddies.
Soil microbial communities are critical for maintaining terrestrial ecosystems and fundamental ecological processes. Mercury (Hg) is a heavy metal that is toxic to microorganisms, but its effects on microbial community assembly and ecosystem multifunctionality in rice paddy ecosystems remain largely unknown. In the current study, we analyzed the microbial community structure and ecosystem multifunctionality of paddy soils across a Hg contamination gradient. The results demonstrated that Hg contamination significantly altered the microbial community structure. The microbial communities were predominantly driven by deterministic selection rather than stochastic processes. The random forest model and variation partition analysis demonstrated that the Hg level was the most important predictor of microbial profiles. Ecosystem multifunctionality decreased across the Hg concentration gradient, and multifunctionality was significantly correlated with soil biodiversity, suggesting that Hg-induced reductions in soil biodiversity led to reduced ecosystem services. A structural equation model showed that Hg contamination directly and indirectly affected ecosystem multifunctionality. The present work broadens our knowledge of the assembly of the microbiome in rice paddies across a Hg contamination gradient and highlights the significance of soil biodiversity in regulating ecosystem functions, especially in Hg-polluted rice paddies.


Concurrent hypersecretion of aldosterone and cortisol from the adrenal cortical adenoma.
Hypertension, hypokalemia, suppressed plasma renin activity and increased plasma aldosterone were found in a middle-aged woman. Following removal of the tumor in the left adrenal gland these abnormalities disappeared. Concurrently, however, the plasma cortisol level did not show normal diurnal change, although the value at 6 A.M. was within the normal range. Administration of 2 mg dexamethasone failed to depress the plasma cortisol level and urinary 17-OHCS concentrations. Postoperatively, plasma cortisol and urinary 17-OHCS were below normal. Histologic examination of the tumor indicated the presence of two types of adenoma cells; one was a large watery clear cell with rich lipid and possibly with aldosterone secretion and the other was an acidophilic cell with poor lipid and possibly with cortisol secretion. It is suggested that, in addition to oversecretion of aldosterone, the tumor autonomously secreted cortisol, although the amount of cortisol secreted was not large enough to produce typical Cushing's syndrome.


Effect of hyperlipidemia on femoral biomechanics and morphology in low-density lipoprotein receptor gene knockout mice.
The objective of this study was to evaluate the effect of hyperlipidemia on the biomechanical and morphological properties of the femur of low-density lipoprotein receptor gene knockout mice (LDLr-/-) mice. Ten wild-type mice (C57BL6) and 10 LDLr-/- mice generated on a C57BL6 background were used. Male 3-month-old animals were divided into four groups (n = 5): group W (wild type) and group L (LDLr-/-) receiving low-fat commercial ration, and group WH (wild type) and group LH (LDLr-/-) receiving a high-fat diet. After 60 days, blood samples were collected for laboratory analysis of calcium, triglycerides, and cholesterol. The femur was excised for mechanical testing and morphometric analysis. LDLr-/- mice receiving the high-fat diet presented more marked alterations in the mechanical and morphological properties of femoral cortical and trabecular bone. Changes in the plasma levels of calcium, triglycerides, cholesterol, and fractions were also more pronounced in this group. The present results demonstrate that hyperlipidemia causes alterations in the structure and mechanical properties of the femur of LDLr-/- mice. These effects were more pronounced when associated with a high-fat diet.


Effects of silicon on the distribution of cadmium compartmentation in root tips of Kandelia obovata (S., L.) Yong.
The Effects of silicon (Si) on the distribution of cadmium (Cd) compartmentation in root tips of Kandelia obovata (S., L.) Yong were investigated by pot experiments. Cd concentrations in the apoplastic saps and symplastic fractions of the root tips of K. obovata seedlings were decreased at both Si-supplied treatments. Si addition reduced the concentrations of BaCl(2-)extractable cell-wall-Cd in root tips, but increased the concentrations of Na(3)citrate-extractable cell-wall-Cd and HCl-extractable cell-wall-Cd in root tips. The total root-tip contents of Cd were mainly distributed in the apoplast and most of the Cd in the apoplast was bound to the cell wall. Our experiment found that Si increased the ratio of apoplast Cd (>87.08%) and reduced the ratio of Cd in the symplast (<12.92%). This suggested that Si enhanced binding of Cd to the cell walls and restricted the apoplastic transport of Cd.


Clonal Hematopoiesis and Mosaicism Revealed by a Multi-Tissue Analysis of Constitutional TP53 Status.
Though germline TP53 pathogenic/likely pathogenic variants (PV) are associated with Li-Fraumeni syndrome, many detected by multigene panels represent aberrant clonal expansion (ACE), most due to clonal hematopoiesis (CH). Discerning ACE/CH from germline variants and postzygotic mosaicism (PZM) is critically needed for risk assessment and management. Participants in the Li-Fraumeni & TP53 Understanding & Progress (LiFT UP) study with a TP53 PV were eligible. Demographics, personal/family cancer history, and clinical laboratory test reports were obtained. DNA from multiple tissues was analyzed using a custom QIAseq assay (ACE panel) that included TP53 and other CH-associated genes; the ACE panel and eyebrow follicles were assessed in a workflow to discern TP53 PV clinical categories. Among 134 participants there was a significant difference for the age at diagnosis (P < 0.001), component cancers (P = 0.007), and clinical testing criteria (P < 0.001), comparing germline with PZM or ACE. ACE panel analysis of DNA from 55 sets of eyebrow follicles (mean 1.4 ug) and 36 formalin-fixed, paraffin imbedded tissues demonstrated low variance (SE, 3%; P = 0.993) for TP53 variant allele fraction, with no significant difference (P = 0.965) between tissue types, and detected CH gene PVs. Of 55 multi-tissue cases, germline status was confirmed for 20, PZM in seven, ACE for 25, and three were indeterminate. Additional CH variants were detected in six ACE and two germline cases. We demonstrated an effective approach and tools for discerning germline TP53 status. Discernment of PZM and TP53-driven CH increases diagnostic accuracy and enables risk-appropriate care.


Effect of captopril on norepinephrine vascular contractility.
In isolated aortic rings and in vitro perfused mesenteric arteries of Wistar rats the vasoconstrictor responses to norepinephrine (NE) were not affected by captopril (2 X 10(-4) M). However, captopril (1 mg/kg i.v.) in pithed Wistar rats attenuated significantly the increases in diastolic blood pressure induced by NE. In pithed rats the effect of captopril on NE diastolic blood pressure responses disappeared either in the presence of an angiotensin II (5 ng X kg-1 X min) infusion or when the rats were previously nephrectomized. These findings suggest that the effect of captopril on vascular responses to norepinephrine is mediated by an inhibition of the renin-angiotensin system and not by an antagonistic effect on alpha-adrenergic receptors.


Postirradiation fibrosarcoma following radical mastectomy.
A case of fibrosarcoma arising in the scar of the radical mastectomy with postoperative irradiation of breast carcinoma is reported. The tumors arose five times in spite of the extirpations including surrounding tissue since 11 years after radical mastectomy and postoperative irradiation. All of arisen tumors were diagnosed fibrosarcoma histologically and with every recurrence the aggravation of malignancy of tumors was shown. In this case, the primary tumor of the breast was infiltrating carcinoma and no sign of fibrosarcoma was noted histologically. The mastectomy scar was indicated the irradiation therapy postoperatively and fibrosarcoma developed 11 years after postoperative irradiation. Namely, this case agreed to the strict criteria of the postirradiation sarcoma proposed by Cahan et al. In this paper, a case of postirradiation fibrosarcoma arising in the scar of radical mastectomy for carcinoma is presented.


Synthesis and Anticonvulsant Properties of New 3,3-Diphenyl-2,5-dioxo-pyrrolidin-1-yl-acetamides and 3,3-Diphenyl-propionamides.
The focused library of new amides derived from 3,3-diphenyl-2,5-dioxo-pyrrolidin-1-yl-acetic acid (2a-t) and 3,3-diphenyl-propionic acid (3a-t) as potential anticonvulsant agents was synthesized. The final products were obtained in the amidation reaction of the given carboxylic acid (2, 3) with appropriate secondary amines in the presence of carbonyldiimidazole (CDI) as a coupling reagent. The initial anticonvulsant screening was performed in mice intraperitoneally (i.p.) using the "classical" maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure models, whereas the acute neurological toxicity was determined applying the rotarod test. Additionally, several compounds were studied also in the 6-Hz seizures recognized as the animal model of human pharmacoresistant epilepsy. In this series, compound 3q displayed a broad spectrum of activity across the preclinical seizure models (ED50 MES = 31.64 mg/kg; ED50 scPTZ = 75.41 mg/kg, ED50 6-Hz (32 mA) = 38.15 mg/kg). Consequently, compound 3q revealed a wider spectrum of protection, higher activity or/and a better safety profile than the commonly used antiepileptic drugs such as phenytoin, ethosuximide, valproic acid, or/and levetiracetam. Notably, the in vitro studies showed that the most possible mechanism of action of 3q may be connected to the interaction with neuronal voltage-sensitive sodium channels (site 2). Other substances were active predominantly in the chemically induced seizures. The results of the current studies indicate that the presence of the pyrrolidine-2,5-dione ring is important but not indispensable for anticonvulsant activity.


A collaborative robot for COVID-19 oropharyngeal swabbing.
The coronavirus disease 2019 (COVID-19) outbreak has increased mortality and morbidity world-wide. Oropharyngeal swabbing is a well-known and commonly used sampling technique for COVID-19 diagnose around the world. We developed a robot to assist with COVID-19 oropharyngeal swabbing to prevent frontline clinical staff from being infected. The robot integrates a UR5 manipulator, rigid-flexible coupling (RFC) manipulator, force-sensing and control subsystem, visual subsystem and haptic device. The robot has strength in intrinsically safe and high repeat positioning accuracy. In addition, we also achieve one-dimensional constant force control in the automatic scheme (AS). Compared with the rigid sampling robot, the developed robot can perform the oropharyngeal swabbing procedure more safely and gently, reducing risk. Alternatively, a novel robot control schemes called collaborative manipulation scheme (CMS) which combines a automatic phase and teleoperation phase is proposed. At last, comparative experiments of three schemes were conducted, including CMS, AS, and teleoperation scheme (TS). The experimental results shows that CMS obtained the highest score according to the evaluation equation. CMS has the excellent performance in quality, experience and adaption. Therefore, the proposal of CMS is meaningful which is more suitable for robot-sampling.


Discovery of potent and stable conformationally constrained analogues of the MCH R1 antagonist SB-568849.
A strategy of systematically targeting more rigid analogues of the known MCH R1 receptor antagonist, SB-568849, serendipitously uncovered a binding mode accessible to N-aryl-phthalimide ligands. Optimisation to improve the stability of this compound class led to the discovery of novel N-aryl-quinazolinones, benzotriazinones and thienopyrimidinones as selective ligands with good affinity for human melanin-concentrating hormone receptor 1.


The potentiation of spinal analgesia by leucine enkephalin.
In two strains of rats, intrathecal administration of morphine and met-enkephalin was found to produce a dose-dependent analgesic effect as measured by the tail-flick assay. Prior administration of leu-enkelphalin at a dose which had no analgesic effect was found to reduce significantly the analgesic ED50 of both morphine and met-enkephalin. Met-enkephalin pretreatment, at a similar sub-analgesic dose, was without effect. Thus, a differential interaction of the enkephalins with morphine is evident at spinal structures.


A minor laryngeal cleft (type 1-a) diagnosed in infancy.
We report a case of laryngeal cleft. The patient showed tachypnea, stridor, and cyanosis with feeding, when the diagnosis was made by laryngo-fiberscopy at 2 days of life. At the age of 7 months, a direct laryngoscopy showed a 5 mm length of cleft behind the vocal cord at the level of the interarytenoid portion. Gastrostomy and tracheostomy were performed at the same time. For small type 1 clefts, some authors have proposed the possibility of treatment without surgery. In this case, we tried to minimize the defect by injecting collagen into the sub-mucosal space of the arytenoids. The patient was decanulated at the age of 2 years and 2 months. This case represents an example of earliest diagnosis of minimal laryngeal clefts (Armitage's type 1-a), which has been usually identified at older ages.


Immobilization of tris(1,10-phenanthroline)ruthenium with graphene oxide for electrochemiluminescent analysis.
Electrochemiluminescence (ECL) of ruthenium complexes has broad applications and the immobilization of Ru(bpy)(3)(2+) has received extensive attention. In comparison with Ru(bpy)(3)(2+), Ru(phen)(3)(2+) can be immobilized more easily because of its better adsorbability. In this study, immobilization of Ru(phen)(3)(2+) for ECL analysis has been demonstrated for the first time by using graphene oxide (GO) as an immobilization matrix. The immobilization of Ru(phen)(3)(2+) is achieved easily by mixing Ru(phen)(3)(2+) with GO without using any ion exchange polymer or covalent method. The strong binding of Ru(phen)(3)(2+) with GO is attributed to both the π-π stacking interaction and the electrostatic interaction. The Ru(phen)(3)(2+)/GO modified electrode was characterized by using tripropylamine (TPA) as the coreactant. The linear range of TPA is from 3×10(-7) to 3×10(-2) mol L(-1) with the detection limit of 3×10(-7) mol L(-1). The ECL sensor demonstrates outstanding long-term stability. After the storage in the ambient environment for 90 days, the ECL response remains comparable with its original signal.


The use of sodium hyaluronate-carboxymethylcellulose to prevent postoperative mastication pain from harvesting of temporalis fascia.
To evaluate the anti-adhesive and anti-inflammatory effects of sodium hyaluronate-carboxymethylcellulose (HA-CMC) in reducing postoperative pain after temporalis fascia harvest during tympanomastoid surgery. Between January and December 2009, 27 patients underwent tympanoplasty and open cavity mastoidectomy involving the harvesting of temporalis fasciae (more than 3×4cm). At the end of surgery, patients were injected with 1.5g HA-CMC or normal saline around the fascia harvest area. Beginning immediately postoperatively and for 2 months after surgery, patients scored their pain in the temporal area on a visual analogue scale (VAS). There were no significant postoperative complications, such as bleeding or hematoma, in either control group. VAS scores of both groups decreased over time and were negligible after 2 months. VAS scores of the HA-CMC and control groups differed significantly (p<0.001 by repeated measures ANOVA for all VAS scores). HA-CMC can decrease immediate postoperative pain arising from tissue adhesion and inflammation, thus reducing postoperative mastication pain.


Immunization with a synthetic consensus hepatitis C virus E2 glycoprotein ectodomain elicits virus-neutralizing antibodies.
Global eradication of hepatitis C virus (HCV) infection will require an efficacious vaccine capable of eliciting protective immunity against genetically diverse HCV strains. Natural spontaneous resolution of HCV infection is associated with production of broadly-neutralizing antibodies targeting the HCV glycoproteins E1 and E2. As such, production of cross-neutralizing antibodies is an important endpoint for experimental vaccine trials. Varying success generating cross-neutralizing antibodies has been achieved with immunogens derived from naturally-occurring HCV strains. In this study the challenge of minimising the genetic diversity between the vaccine strain and circulating HCV isolates was addressed. Two novel synthetic E2 glycoprotein immunogens (NotC1 and NotC2) were derived from consensus nucleotide sequences deduced from samples of circulating genotype 1 HCV strains. These two synthetic sequences differed in their relative positions in the overall genotype 1a/1b phylogeny. Expression of these constructs in Drosophila melanogaster S2 cells resulted in high yields of correctly-folded, monomeric E2 protein, which were recognised by broadly neutralizing monoclonal antibodies. Immunization of guinea pigs with either of these consensus immunogens, or a comparable protein representing a circulating genotype 1a strain resulted in high titres of cross-reactive anti-E2 antibodies. All immunogens generated antibodies capable of neutralizing the H77 strain, but NotC1 elicited antibodies that more potently neutralized virus entry. These vaccine-induced antibodies neutralized some viruses representing genotype 1, but not strains representing genotype 2 or genotype 3. Thus, while this approach to vaccine design resulted in correctly folded, immunogenic protein, cross-neutralizing epitopes were not preferentially targeted by the host immune response generated by this immunogen. Greater immunofocussing of vaccines to common epitopes is necessary to successfully elicit broadly neutralizing antibodies.


Neutrophils, dendritic cells and Toxoplasma.
Toxoplasma gondii rapidly elicits strong Type 1 cytokine-based immunity. The necessity for this response is well illustrated by the example of IFN-gamma and IL-12 gene knockout mice that rapidly succumb to the effects of acute infection. The parasite itself is skilled at sparking complex interactions in the innate immune system that lead to protective immunity. Neutrophils are one of the first cell types to arrive at the site of infection, and the cells release several proinflammatory cytokines and chemokines in response to Toxoplasma. Dendritic cells are an important source of IL-12 during infection with T. gondii and other microbial pathogens, and they are also specialized for high-level antigen presentation to T lymphocytes. Tachyzoites express at least two types of molecules that trigger innate immune cell cytokine production. One of these involves Toll-like receptor/MyD88 pathways common to many microbial pathogens. The second pathway is less conventional and involves molecular mimicry between a parasite cyclophilin and host CC chemokine receptor 5-binding ligands. Neutrophils, dendritic cells and Toxoplasma work together to elicit the immune response required for host survival. Cytokine and chemokine cross-talk between parasite-triggered neutrophils and dendritic cells results in recruitment, maturation and activation of the latter. Neutrophil-empowered dendritic cells possess properties expected of highly potent antigen presenting cells that drive T helper 1 generation.