CDG-Id caused by homozygosity for an ALG3 mutation due to segmental maternal isodisomy UPD3(q21.3-qter).
We report on a patient with a congenital disorder of glycosylation type Id (CDG-Id) caused by a homozygous mutation in the ALG3 gene, which results from a de novo mutation in combination with a segmental maternal uniparental isodisomy (UPD). The patient presented with severe psychomotor delay, primary microcephaly, and opticus atrophy, compatible with a severe form of CDG. Isoelectric focusing of transferrin showed a type I pattern and lipid-linked oligosaccharide analysis showed an accumulation of dol-PP-GlcNAc2Man5 in patient's fibroblasts suggesting a defect in the ALG3 gene. A homozygous ALG3 missense mutation p.R266C (c.796C > T) was identified. Further evaluation revealed that neither the mother nor the father were carrier of the p.R266C mutation. Marker analysis revealed a segmental maternal isodisomy for the chromosomal region 3q21.3-3qter. UPD for this region has not been described before. More important, the combination of UPD with a de novo mutation is an exceptional coincidence and an extraordinary observation.


Ammonia formation and soil pH increase caused by decomposing fruitbodies of macrofungi.
The formation of gaseous compounds from decomposing fruibodies of three common macrofungi was qualitatively analysed. It was shown that significant production of ammonia took place. When the fruitbodies were decomposing on the surface of a podzolic forest floor more than 90% of the ammonia produced was absorbed by the soil, causing soil pH to increase.


Emerging non-invasive approaches for diagnosis and monitoring of portal hypertension.
Clinically significant portal hypertension is associated with an increased risk of developing gastro-oesophageal varices and hepatic decompensation. Hepatic venous pressure gradient measurement and oesophagogastroduodenoscopy are the gold-standard methods for assessing clinically significant portal hypertension (hepatic venous pressure gradient ≥10 mm Hg) and gastro-oesophageal varices, respectively. However, invasiveness, cost, and feasibility limit their widespread use, especially if repeated and serial evaluations are required to assess the efficacy of pharmacotherapy. Although new techniques for non-invasive portal pressure measurement have been pursued for many decades, only recently have new tools been assessed and validated for larger clinical application. This Review focuses on the recent advances in non-invasive approaches for the diagnosis and serial monitoring of portal hypertension and varices for clinical practice.


Thrombin receptor (PAR-1) antagonists. Heterocycle-based peptidomimetics of the SFLLR agonist motif.
The thrombin receptor (PAR-1) is activated by alpha-thrombin to stimulate various cell types, including platelets, through the tethered-ligand sequence SFLLRN. A series of azole-based carboxamides, designed after SFLLR, were synthesized and evaluated in vitro. The compounds inhibited platelet aggregation induced by SFLLRN-NH2 or alpha-thrombin, and blocked the binding of [3H]-S-(p-F-Phe)-Har-L-Har-KY-NH2 to a CHRF membrane preparation of PAR-1. Oxazole 30 bound to PAR-1 with an IC50 of 1.6 microM, and gave IC50 values of 25 microM and 6.6 microM against alpha-thrombin- and SFLLRN-NH2-induced platelet aggregation, respectively.


Improving part-of-speech tagging in Amharic language using deep neural network.
To date, several POS taggers have been introduced to facilitate the success of semantic analysis for different languages. However, the task of POS tagging becomes a bit intricate in morphologically complex languages, like Amharic. In this paper, we evaluated different models such as bidirectional long short term memory, convolutional neural network in combination with bidirectional long short term memory, and conditional random field for Amharic POS tagging. Various features, both language-dependent and -independent, have been explored in a conditional random field model. Besides, word-level and character-level features are analyzed in deep neural network models. A convolutional neural network is utilized for encoding features at the word and character level. Each model's performance has evaluated on the dataset that contained 321 K tokens and manually tagged with 31 POS tags. Lastly, the best performance obtained by an end-to-end deep neural network model, convolutional neural network in combination with bidirectional long term short memory and conditional random field, is 97.23% accuracy. This is the highest accuracy for Amharic POS tagging task and is competent with contemporary taggers currently existing in different languages.


Interaction and Emotional Connection with Pets: A Descriptive Analysis from Puerto Rico.
The study of human-animal interactions has become a prominent research field. The presence of pets in our daily lives has meant a change in the perception of our relationship with pets. One of the new lines of research that has opened up in this area analyzes the possible physical, emotional, and psychological benefits of a human-animal bond. In this context, two main objectives were pursued in this study, whose sample (N = 1436) was investigated in Puerto Rico: (PO1) determining the characteristics of the owners and the care of the pets within Puerto Rican society and (PO2) to analyzing the benefits of living with pets for health and personal well-being, especially at the psychological level. We sought to identify the feelings that arose in pet caretakers as a result of human-animal interactions. The methodology used, which was descriptive and not experimental, was based on a questionnaire of 86 questions with a Likert scale. After the descriptive analysis was undertaken through a frequency analysis, a binary logistic regression was carried out to establish whether the feelings and emotions of the subjects toward their companion pets were determined by sociodemographic variables and were related to the type of coexistence with their pets. The two main results from this study are as follows: for most owners, their pets are very important beings, and those who establish an emotional connection with their pets experience love, joy, and peace. Pets are part of human life through very intense relationships and interactions that, in most cases, increase personal welfare by providing improvements to the human-animal biopsychosocial system. In this sense, a relationship with a pet has a positive impact on the mental health of the owner. Pets are a part of our family lives and are regulators of the most elementary feelings and emotions in humans.


Inferior caval venography in the assessment of renal carcinoma.
Inferior caval venography by a non-catheter technique was carried out in 30 cases of renal cell carcinoma. Occlusion of the renal vein was shown in 15 of these and occlusion of the inferior vena cava in a further three. Deformity of the vena cava by adjacent growth was found in nine instances. Renal arteriography was performed in 27 of these patients and the demonstration of the renal vein by this method has been compared with that of caval venography. The incidence of collateral veins on the arteriogram and the finding of impaired renal function as an index of renal vein occlusion has been discussed.


Orientation-dependency of perceptual surround suppression and orientation decoding of centre-surround stimuli are preserved with healthy ageing.
A key visual neuronal property that is mirrored in human behaviour is centre-surround contrast suppression, which is orientation-dependent. When a target is embedded in a high-contrast surround, the centre appears reduced in contrast, the magnitude of which depends on the relative orientation between centre and surround. Previous reports demonstrate changes in perceptual surround suppression with ageing; however, whether the orientation-dependency of surround suppression is impacted by ageing has not been explored. Here, we tested 18 younger (aged 19-33) and 18 older (aged 60-77) adults. Perceptual surround suppression was stronger for parallel than orthogonal stimuli; however contrary to previous work, here we found no difference in perceptual suppression strength between age-groups. In the same participants, we measured event-related potentials (ERPs) and conducted multivariate pattern analysis to confirm that parallel and orthogonal centre-surround stimuli elicit distinguishable brain activity, predominantly over occipital areas. Despite a delay in the first prominent ERP component (P1) in response to each pattern, older adults showed similar decoding of orientation information (i.e. distinguish between parallel and orthogonal centre-surround stimuli from 70 ms post-stimulus onset) as younger adults. This suggests that sufficient information to distinguish orientation in centre-surround stimuli becomes available to the older human brain as early as in younger adults.


MicroRNA-124 mediates the cholinergic anti-inflammatory action through inhibiting the production of pro-inflammatory cytokines.
The vagus nerve can control inflammatory response through a 'cholinergic anti-inflammatory pathway', which is mediated by the α7-nicotinic acetylcholine receptor (α7nAChR) on macrophages. However, the intracellular mechanisms that link α7nAChR activation and pro-inflammatory cytokine production remain not well understood. In this study, we found that miR-124 is upregulated by cholinergic agonists in LPS-exposed cells and mice. Utilizing miR-124 mimic and siRNA knockdown, we demonstrated that miR-124 is a critical mediator for the cholinergic anti-inflammatory action. Furthermore, our data indicated that miR-124 modulates LPS-induced cytokine production by targeting signal transducer and activator of transcription 3 (STAT3) to decrease IL-6 production and TNF-α converting enzyme (TACE) to reduce TNF-α release. These results also indicate that miR-124 is a potential therapeutic target for the treatment of inflammatory diseases.


Anaerobic digestion of microalgal biomass: Challenges, opportunities and research needs.
Integration of anaerobic digestion (AD) with microalgae processes has become a key topic to support economic and environmental development of this resource. Compared with other substrates, microalgae can be produced close to the plant without the need for arable lands and be fully integrated within a biorefinery. As a limiting step, anaerobic hydrolysis appears to be one of the most challenging steps to reach a positive economic balance and to completely exploit the potential of microalgae for biogas and fertilizers production. This review covers recent investigations dealing with microalgae AD and highlights research opportunities and needs to support the development of this resource. Novel approaches to increase hydrolysis rate, the importance of the reactor design and the noteworthiness of the microbial anaerobic community are addressed. Finally, the integration of AD with microalgae processes and the potential of the carboxylate platform for chemicals and biofuels production are reviewed.


Evaluation of RU-27987 as a ligand to determine the progesterone receptor.
RU-27987, a synthetic progestin, which was recently developed by Roussel Uclaf, Paris, was tested for its validity as a ligand to determine the progesterone receptor in breast cancer. The results were compared to those obtained with R-5020 and ORG-2058, two ligands that are already in use worldwide. The intra- and interassay variation of receptor determination was similar for all 3 ligands. Receptor levels were analyzed with each of the 3 progestins in control cytosols and in 26 mammary carcinoma samples. A good correlation between receptor levels was found although the values of ORG-2058 were somewhat lower, but not significantly. This resulted in a lower proportion of receptor positive samples for ORG-2058 (11/26) compared to R-5020 (13/26) and RU-27987 (14/26). The affinity to the progesterone and to the glucocorticoid receptor, as well as the precision of the Scatchard plot analysis were comparable for the 3 ligands tested. Intra- and interassay variation of receptor determination were also similar. We therefore conclude, that RU-27987 is a suitable ligand to determine progesterone receptor in mammary carcinoma.


Acute kidney injury after hip fracture in organ transplant recipients.
This study aimed to investigate the incidence and risk factors of acute kidney injury (AKI) after hip fracture in organ transplant recipients. In this single-center retrospective cohort study, 795 elderly patients who underwent hip fracture surgery were enrolled. AKI was defined according to Acute Kidney Injury Network criteria. Among the 795 patients, 23 underwent kidney transplantation (KT) and 20 underwent liver transplantation (LT). The incidence of AKI, dialysis requirement, and renal recovery rate were investigated. AKI occurred in 83 patients (10.5%), of whom 9 (39.1%), 3 (15%), and 71 (9.5%) were in the KT, LT, and nontransplantation groups, respectively. The incidence rates of AKI and severe AKI (17.4% vs. 1.4%) were significantly higher in the KT group than in the nontransplantation group (P = .001 for both). The renal recovery rate was significantly lower in the KT group than in the nontransplantation group (P = .033). The multivariate analysis revealed that male; body mass index; CKD; alkaline phosphatase; intraoperative hypotension; and history of KT were independent predictors of AKI development. AKI and severe AKI after hip fracture occurred more frequently in the KT recipients with lower renal recovery rates. Transplanted kidneys are more vulnerable to AKI after hip fracture.


Galanin in the trinitrobenzene sulfonic acid rat model of experimental colitis.
Neuropeptides are molecules produced by a variety of cells that modulate several biological processes and modify the activity of cells responsible either to trigger tissue damage and to promote healing in the intestine. Galanin is a neuropeptide present in enteric nerves lining the gastrointestinal tract and involved in the secretion and contractility regulation. The aim of this study is to investigate its potential therapeutic experimental use in an immunological disorder, such as experimental trinitrobenzensulfonic acid (TNBS)-induced colitis in rats. Galanin (10, 20 and 40 microg/kg/day) was administered by intraperitoneal route 48, 24 and 1 h prior to the induction of colitis and 24 h later, and the animals were sacrificed 48 h after. The lesions were blindly scored according to macroscopic and histological scales. The inflammatory response was assessed by histological analysis and by myeloperoxidase activity (MPO) and tumour necrosis factor-alpha (TNF-alpha) production. The results indicated that Galanin prevented the morphological alteration and reduced ulcer index associated with TNBS. In addition, Galanin reduced MPO and TNF-alpha values significantly. In order to elucidate some of the mechanisms, cycloxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression was analyzed by Western blotting. COX-2 was not modified, but iNOS protein was significantly reduced accompanied by a diminished nitrite production, in a dose-dependent manner, in comparison to the TNBS group. In conclusion, Galanin treatment has a significant preventive effect in the TNBS-induced acute model of colitis with reduction of the analyzed inflammatory parameters. Moreover, the results obtained demonstrated by the first time that Galanin administration promotes an important reduction in NO-related mechanisms.


Reimagining Postdiagnostic Care and Support in Young-Onset Dementia.
Although dementia has a profound impact in general, young-onset dementia causes additional problems and challenges as people are affected in their prime years. Awareness has increased that people with young-onset dementia and their families have specific care needs and dedicated services are necessary to accommodate those needs. However, in many countries, age-appropriate care and support for people with young-onset dementia is still largely unavailable. In this special article, barriers as well as facilitators for the development of postdiagnostic care and support in young-onset dementia are addressed. Drawing from the experiences in the Netherlands, the establishment of an appropriate infrastructure has proven a corner stone in service development in young-onset dementia. The establishment of a center at the national level for the development and dissemination of knowledge and affiliated regional centers that coordinate and offer care and support at the regional level has helped to reimagine, redefine, but more importantly also rearrange, postdiagnostic care and support in young-onset dementia in the Netherlands. This has resulted in care standards for service provision in young-onset dementia that have been incorporated in the dementia standard at the national level. Also, a quality hallmark has been developed to guide the arrangement of age-appropriate services at the local level. Moreover, specific training programs are in place for health care professionals involved in young-onset dementia. To be able to prioritize topics in research for the upcoming years, a scientific agenda has been established. The strong collaboration between organizations that provide a voice for people with dementia, care providers and research centers, that all strive to support people to live well with young-onset dementia has boosted these developments and may inspire other countries searching for ways to improve postdiagnostic care and support in young-onset dementia.


The oxygen uptake response of sprint- vs. endurance-trained runners to severe intensity running.
We compared the oxygen uptake (VO2) response of sprint- and endurance-trained runners for an exhaustive square wave run lasting approximately 2 minutes. Six sprinters and six middle- and long-distance runners each performed two exhaustive square wave runs lasting approximately 2 min and two exhaustive ramp tests. VO2 was determined breath-by-breath (QP9000; Morgan Medical, Rainham, UK) and averaged across the two repeats of each test; for the square wave test, the averaged VO2 response (excluding the first 15 s) was then modelled using a monoexponential function. Both VO2peak for the ramp test (67.5+/-3.3 vs. 54.5+/-8.5 mlxkg(-1)xmin(-1); P= 0.006) and the asymptotic VO2 for the square wave run (59.6+/-2.7 vs. 50.7+/-4.6 mlxkg(-1)xmin(-1); P= 0.002) were higher for the endurance than for the sprint group. However, as a percentage of VO2peak, this asymptotic VO2 did not differ between the groups (90.1+/-3.2% (endurance) vs. 96.2+/-9.0% (sprint); P= 0.145). Across all 12 subjects, the %VO2peak attained in the square wave run was negatively correlated with VO2peak (Pearson's r= -0.811, P= 0.001). We conclude that VO2max is more important than training history as a determinant of the %VO2max attained in exhaustive square wave running lasting approximately 2 min.


Enzymatic nitrate assay by a kinetic method employing Escherichia coli nitrate reductase.
An enzymatic assay system for nitrate employing the membrane-bound nitrate reductase (EC 22.214.171.124) of E. coli is described. Contrary to previous enzymatic assay systems, the present method is a kinetic one, i.e. the substrate, nitrate, is assayed by measuring the reaction rate of the nitrate reductase-catalyzed reaction. Based on the observation that the nitrate reductase-catalyzed reaction obeys pseudo-first order kinetics, a test system is described allowing the assay of nitrate at a concentration as low as 1 ppm. The relatively high Michaelis-Menten constant for nitrate (0.3 mM) of the E. coli nitrate reductase favours nitrate assay by the kinetic method.


Relationship Between Unmet Social Needs and Care Access in a Veteran Cohort.
The association between unmet social needs (e.g., food insecurity) and adverse health outcomes is well-established, especially for patients with and at risk for cardiovascular disease (CVD). This has motivated healthcare systems to focus on unmet social needs. Yet, little is known about the mechanisms by which unmet social needs impact health, which limits healthcare-based intervention design and evaluation. One conceptual framework posits that unmet social needs may impact health by limiting care access, but this remains understudied. Examine the relationship between unmet social needs and care access. Cross-sectional study design using survey data on unmet needs merged with administrative data from the Veterans Health Administration (VA) Corporate Data Warehouse (September 2019-March 2021) and multivariable models to predict care access outcomes. Pooled and separate rural and urban logistic regression models were utilized with adjustments from sociodemographics, region, and comorbidity. A national stratified random sample of VA-enrolled Veterans with and at risk for CVD who responded to the survey. No-show appointments were defined dichotomously as patients with one or more missed outpatient visits. Medication non-adherence was measured as proportion of days covered and defined dichotomously as adherence less than 80%. Greater burden of unmet social needs was associated with significantly higher odds of no-show appointments (OR = 3.27, 95% CI = 2.43, 4.39) and medication non-adherence (OR = 1.59, 95% CI = 1.19, 2.13), with similar associations observed for rural and urban Veterans. Social disconnection and legal needs were especially strong predictors of care access measures. Findings suggest that unmet social needs may adversely impact care access. Findings also point to specific unmet social needs that may be especially impactful and thus might be prioritized for interventions, in particular social disconnection and legal needs.


The influence of short-term water storage on the flexural properties of unidirectional glass fiber-reinforced composites.
The aim of this study was to determine flexural properties of unidirectional E-glass fiber-reinforced composite (FRC) with polymer matrices of different water sorption properties. Rhombic polymer and FRC test specimens made of three commercially available diacrylate resin (Sinfony Activator, Triad Gel, 3M Scotchbond Adhesive) and different volume fractions of fibers were tested with three-point bending test according to ISO 10477 after storing in water for 30 days. Water sorption of specimens was also measured. Flexural strength of specimens with 45 vol% fraction E-glass fibers varied from 759 to 916 MPa in dry conditions. Water-stored specimens showed flexural strengths of 420-607 MPa. ANOVA analysis revealed that the fiber-volume fraction and the water sorption of the polymer matrix had a significant effect (p < 0.001) on the flexural properties. Dehydration of specimens recovered the mechanical properties. Decrease of flexural properties after water immersion was considered to be mainly caused by the plasticizing effect of water and the decrease depended on water sorption. Use of polymers with low-water sorption seems to be beneficial in order to optimize the flexural properties of FRC.


Review article: the pathogenesis and management of eosinophilic oesophagitis.
Eosinophilic oesophagitis is a clinicopathological disease affecting both children and adults that is characterized by symptoms of gastro-oesophageal reflux disease (feeding refusal, vomiting, heartburn, dysphagia and food impaction) and dense oesophageal eosinophilia both of which are unresponsive to proton pump inhibition. To present a review of the recent literature examining the pathogenesis and treatments of eosinophilic oesophagitis. We performed a PubMed search for eosinophilic oesophagitis, pathogenesis and treatments. Translational and basic studies suggest that this disease is sparked by food or by aeroallergens. To date, effective treatments include systemic/topical corticosteroids, specific food elimination or an elemental diet. While several studies identified oesophageal strictures as potential complications of unbridled eosinophilia, the natural history of the disease is still not certain. Recent studies suggest a role for interleukin-5 and eotaxin-3 in the pathogenesis of eosinophilic oesophagitis and suggest an impact of future targeted therapeutic agents. Eosinophilic oesophagitis represents a immune-mediated disease of undetermined pathogenesis. While many patients develop clinicopathological findings following ingestion of foods, others do not. Natural history studies will be critical to defining future treatment paradigms.


Antioxidative, antimicrobial and cytotoxic effects of the phenolics of Leea indica leaf extract.
This study investigated the phytochemical, antioxidative, antimicrobial and cytotoxic effects of Leea indica leaf ethanol extract. Phytochemical values namely total phenolic and flavonoid contents, total antioxidant capacity, DPPH radical scavenging effect, FeCl3 reducing power, DMSO superoxide scavenging effect and Iron chelating effects were studied by established methods. Antibacterial, antifungal and cytotoxic effects were screened by disk diffusion technique, food poison technique and brine shrimp bioassay, respectively. Results showed the total phenolic content 24.00 ± 0.81 g GAE/100 g, total flavonoid content 194.68 ± 2.43 g quercetin/100 g and total antioxidant capacity 106.61 ± 1.84 g AA/100 g dry extract. Significant (P < 0.05) IC50 values compared to respective standards were recorded in DPPH radical scavenging (139.83 ± 1.40 μg/ml), FeCl3 reduction (16.48 ± 0.64 μg/ml), DMSO superoxide scavenging (676.08 ± 5.80 μg/ml) and Iron chelating (519.33 ± 16.96 μg/ml) methods. In antibacterial screening, the extract showed significant (P < 0.05) zone of inhibitions compared to positive controls Ampicillin and Tetracycline against Gram positive Bacillus subtilis, Bacillus cereus, Bacillus megaterium, and Staphylococcus aureus and Gram negative Salmonella typhi, Salmonella paratyphi, Pseudomonas aeroginosa, Shigella dysenteriae, Vibrio cholerae, and Escherichia coli. Significant minimum inhibitory concentrations compared to tetracycline were obtained against the above organisms. In antifungal assay, the extract inhibited the growth of Aspergillus flavus, Candida albicans and Fusarium equisetii by 38.09 ± 0.59, 22.58 ± 2.22, and 22.58 ± 2.22%, respectively. The extract showed a significant LC50 value compared to vincristine sulfate in cytotoxic assay. The results evidenced the potential antioxidative, antimicrobial and cytotoxic capacities of Leea inidica leaf extract to be processed for pharmaceutical use.


Determination of cisplatin and its hydrolytic metabolite in human serum by capillary electrophoresis techniques.
Cisplatin is for a long time in clinical use as efficient antitumor drug. The success in cisplatin-based chemotherapy, however, strongly depends on how careful the drug's dosages are monitored in order to reduce severe side-effects and overcome cellular resistance. The use of micellar electrokinetic chromatography with direct UV detection is described for the determination of intact cisplatin in human serum. The main product of drug's hydrolytic metabolism, cis-diammineaquachloroplatinum(II), was quantified using capillary zone electrophoresis in combination with indirect UV detection and on-line transient isotachophoresis preconcentration. The detection limits of platinum species studied were about 2-3 micromol l(-1) that allows the proposed methods to be applied for quantification of the administered levels of cisplatin as well as drug's active metabolite. Changes in the speciation of cisplatin occurring after intravenous administration can also be monitored using these simple and convenient CE techniques.


Re-evaluating the role of axillary lymph node dissection in screen-detected breast cancer patients.
The American College of Surgeons Oncology Group (ACOSOG), Z0011 trial, demonstrated that there was no therapeutic benefit from completion lymphadenectomy in early stage breast cancer patients with positive sentinel node (SLN) biopsy. Patients with asymptomatic screen-detected tumors may represent a subgroup where completion axillary dissection with its attendant morbidities is unacceptable. Therefore, the aim of this study was to evaluate the role of ALND in an asymptomatic screen-detected breast cancer cohort. Patients were recruited from the national screening program which offers women (aged 50 to 65) biannual digital mammography. Over a 1 year period 519 screen-detected breast cancer patients were recruited of which 110 had a positive SLN. Of 519 patients in a national screening program that were clinically/radiologically identified as axillary node negative, 110 (21.2%) had a positive SLN. All 110 (T1 = 68, T2 = 42) patients proceeded to have an axillary clearance. 68 (59%) had T1 tumors and of these 40 (60%), despite a positive SLN, had no metastatic nodes on final pathological analysis of their axilla. In addition, 21 (50%) patients with T2 tumors had no metastatic nodes except for a positive SNB. Furthermore, only 6 (8.8%) of T1 tumors with a positive SLN had 4 or more metastatic axillary lymph nodes. 55.45% of patients with a screen-detected T1/T2 tumor had negative completion lymphadectomy. These findings compel us to re-evaluate the role of axillary dissection in the screen-detected asymptomatic breast cancer population to avoid unnecessary ALND with its attendant morbidities.


Clinical results of various reconstructions employed after total gastrectomy.
Methods of restoring continuity after total gastrectomy, particularly those creating a "reservoir," have led to many publications over the last 20 years. These publications are herein reviewed in an attempt to answer questions regarding the clinical value of a jejunal "reservoir". The conclusion we reached from this review was that such a reconstruction does reduce unpleasant symptoms, aids weight maintenance, and is a valuable operative approach.


Hyperuricemia is accompanied by elevated peripheral CD4+ T cells.
Hyperuricemia (HUA) makes a chronic inflammation status, which affects immune cells. The association between HUA and immune cells, such as monocytes and neutrophils, has been extensively studied. However, studies on HUA and lymphocytes are still limited. We selected 1543 healthy participants and 258 individuals with HUA to analyze the correlation between serum uric acid (SUA) levels and immune cells, and 98 healthy participants and 16 individuals with HUA were used to study the relationship between SUA levels and cytokine levels. Then, we used soluble UA to stimulate peripheral blood mononuclear cells in vitro and examined lymphocyte subset counts and activation by flow cytometry. The results revealed that the number of lymphocytes in the HUA group was significantly increased, particularly CD4+ T cell numbers, which were higher than those in the total population (P = 0.0019), females (P = 0.0142), and males (P = 0.0199) of the healthy control group. Concomitantly, interleukin (IL)-4 and IL-10 levels significantly increased in people with HUA (P = 0.0254; P = 0.0019). In vitro, soluble UA promoted the proliferation and activation of CD4+ T and CD19+ B cells. Thus, HUA is accompanied by elevated peripheral CD4+ T cells and may cause a Th2-dominant immune status.


15-deoxy-Δ12, 14-prostaglandin J2 enhances anticancer activities independently of VHL status in renal cell carcinomas.
Renal cell carcinoma (RCC) is relatively resistant to chemotherapy and radiotherapy. Clear cell RCC (ccRCC) accounts for the majority of RCC, which have mutations or epigenetic silencing of the von Hippel-Lindau (VHL) gene. VHL-positive Caki-2 cells are killed by an endogenous anticancer substance, 15-deoxy-Δ12, 14-prostaglandin J2 (15d-PGJ2). The MTT reduction assay reflecting mitochondrial succinate dehydrogenase activity was employed for assessment of cell viability. We confirmed anticancer activities of camptothecin (topoisomerase I inhibitor), etoposide (topoisomerase II inhibitor), doxorubicin (topoisomerase II inhibitor) in VHL-positive Caki-2 cells. Combination of topoisomerase inhibitors with 15d-PGJ2 exhibited the synergistic effect in VHL-positive Caki-2 cells. However, 15d-PGJ2 did not increase cytotoxicities of topoisomerase inhibitors on VHL-negative 786-O cells. In addition, the 15d-PGJ2-enhanced antitumor activity of topoisomerase inhibitors was detected in neither VHL-positive nor VHL-negative RCC4 cells. Our finding indicated that 15d-PGJ2 enhanced the antitumor activity of topoisomerase inhibitors independently of VHL.


Is dental phobia a blood-injection-injury phobia?
Dental phobia is part of the Blood-Injection-Injury (B-I-I) phobia subtype of specific phobia within DSM-IV-TR. To investigate the conceptual validity of this classification, the purpose of the present study was to determine the co-occurrence of dental phobia, typical dental (and B-I-I related) fears, vasovagal fainting, and avoidance of dental care. Data were collected by an online survey in Dutch twin families (n = 11,213). Individuals with a positive screen of dental phobia (0.4% of the sample) rated typical B-I-I-related stimuli as relatively little anxiety provoking (e.g. of all 28 fears the stimulus "the sight of blood" was ranked lowest). Presence of dental phobia was significantly associated with a history of dizziness or fainting during dental treatment (OR = 3.4; 95% CI: 1.5-8.1), but of the dental phobic individuals only 13.0% reported a history of dizziness or fainting during dental treatment. Presence of dental phobia (OR = 5.0; 95% CI: 2.8-8.8) was found to be associated with avoidance of dental care, but a history of dizziness or fainting during dental treatment was not (OR = 1.0; 95% CI: 0.8-1.2). The present findings converge to the conclusion that dental phobia should be considered a specific phobia subtype independent of the B-I-I cluster within the DSM classification system.


Modifying the self-injurious behavior of an infant with spina bifida and diminished pain sensitivity.
This clinical case study extends the literature on behavioral treatment of self-injury to an intellectually normal infant with spina bifida and diminished sensitivity to pain. After treatment by attention-play periods plus an aversive tasting substance applied to the injured finger, severe biting of the index finger was eliminated and the finger healed. Follow-up inquiries 2 months, 2 and 3 yr later revealed no biting and no substantial tissue damage.


Neurochemical mechanisms for cancer anorexia.
Under normal conditions, the homeostasis of energy intake is maintained in the hypothalamus by 1) transducing metabolic and sensorial inputs arising from the periphery into neuronal response, 2) integrating the information originating from different tissues, and 3) triggering the appropriate feeding responses. If cancer anorexia is considered a disruption of the physiologic mechanisms controlling energy intake, it is conceivable that its pathogenesis may lie in an abnormal input of information to the hypothalamus, its defective transduction and integration, or the induction of exaggerated and inappropriate feeding responses. Currently available data suggest that the pathogenesis of cancer anorexia is multifactorial and involves most of the neuronal signaling pathways modulating energy intake. Thus, a number of factors has been proposed as putative mediators of cancer anorexia, including hormones (e.g., leptin), neuropeptides (e.g., neuropeptide Y), cytokines (e.g., interleukin-1, interleukin-6, tumor necrosis factor), and neurotransmitters (e.g., serotonin and dopamine). However, it is unlikely that they represent separate and distinct pathogenic mechanisms; rather, it appears that close interrelationships may exist among them. In line with this reasoning, consistent experimental and human data suggest that hypothalamic monoaminergic neurotransmission and serotonergic activity in particular may represent a major target on which different anorexia-related factors converge. Thus, interfering pharmacologically with hypothalamic serotonin synthesis and activity has been tested as a therapeutic strategy in anorectic cancer patients with encouraging results. However, more clinical options will be available by revealing the complex interactions between the many factors participating in controlling energy intake under normal and pathologic conditions. Further, modulation of hypothalamic activity also might result in reduced catabolic signals to skeletal muscles, thus improving the cachexia associated with cancer.


Contrast-enhanced magnetisation transfer MRI in metastatic lesions of the brain.
Our purpose was to compare prospectively the sensitivity of contrast-enhanced magnetisation transfer (MT) MRI and gradient-echo (GE) T1-weighted images in metastatic disease of the brain. We studied 52 patients with brain metastases, using conventional T1-weighted GE and MT spin-echo (SE) images after the same standard dose of gadolinium. Axial 5-mm reconstructions of GE data were compared with 5-mm MT images in the same plane. Metastases were counted independently by two neuroradiologists. In 12 patients (23%) MT imaging showed more metastases than GE images (P = 0.03). We detected 68 more metastases with the former technique.


Cost-Effectiveness of Shortening Treatment Duration Based on Interim PET Outcome in Patients With Diffuse Large B-cell Lymphoma.
Guideline recommendations for diffuse large-B-cell lymphoma (DLBCL) treatment are shifting from long to short treatment duration, although it is still unclear whether shortening treatment duration does not cause any harm. As interim PET (I-PET) has high negative predictive value for progression, we evaluated the cost-effectiveness of shortening treatment duration dependent on I-PET result. We developed a Markov cohort model using the PET Re-Analysis (PETRA) database to evaluate a long treatment duration (LTD) strategy, ie 8x R-CHOP or 6x R-CHOP plus 2 R, and a short treatment duration (STD) strategy, ie 6x R-CHOP. Strategies were evaluated separately in I-PET2 positive and I-PET2 negative patients. Outcomes included total costs and quality-adjusted life-years (QALYs) per patient (pp) from a societal perspective. Net monetary benefit (NMB) per strategy was calculated using a willingness-to-pay threshold of €50,000/QALY. Robustness of model predictions was assessed in sensitivity analyses. In I-PET2 positive patients, shortening treatment duration led to 50.4 additional deaths per 1000 patients. The STD strategy was less effective (-0.161 [95%CI: -0.343;0.028] QALYs pp) and less costly (-€2768 [95%CI: -€8420;€1105] pp). Shortening treatment duration was not cost-effective (incremental NMB -€5281). In I-PET2 negative patients, shortening treatment duration led to 5.0 additional deaths per 1000 patients and a minor difference in effectiveness (-0.007 [95%CI: -0.136;0.140] QALY pp). The STD strategy was less costly (-€5807 [95%CI: -€10,724;-€2685] pp) and led to an incremental NMB of €5449, indicating that it is cost-effective to shorten treatment duration. Robustness of these findings was underpinned by deterministic and probabilistic sensitivity analyses. Treatment duration should not be shortened in I-PET2 positive patients whereas it is cost-effective to shorten treatment duration in I-PET2 negative patients.


The influence of nutrition on white matter development in preterm infants: a scoping review.
White matter (WM) injury is the most common type of brain injury in preterm infants and is associated with impaired neurodevelopmental outcome (NDO). Currently, there are no treatments for WM injury, but optimal nutrition during early preterm life may support WM development. The main aim of this scoping review was to assess the influence of early postnatal nutrition on WM development in preterm infants. Searches were performed in PubMed, EMBASE, and COCHRANE on September 2022. Inclusion criteria were assessment of preterm infants, nutritional intake before 1 month corrected age, and WM outcome. Methods were congruent with the PRISMA-ScR checklist. Thirty-two articles were included. Negative associations were found between longer parenteral feeding duration and WM development, although likely confounded by illness. Positive associations between macronutrient, energy, and human milk intake and WM development were common, especially when fed enterally. Results on fatty acid and glutamine supplementation remained inconclusive. Significant associations were most often detected at the microstructural level using diffusion magnetic resonance imaging. Optimizing postnatal nutrition can positively influence WM development and subsequent NDO in preterm infants, but more controlled intervention studies using quantitative neuroimaging are needed. IMPACT: White matter brain injury is common in preterm infants and associated with impaired neurodevelopmental outcome. Optimizing postnatal nutrition can positively influence white matter development and subsequent neurodevelopmental outcome in preterm infants. More studies are needed, using quantitative neuroimaging techniques and interventional designs controlling for confounders, to define optimal nutritional intakes in preterm infants.


Incidence of postoperative pain after canal shaping by using Reciproc and Twisted File Adaptive systems: a prospective, randomized clinical trial.
The aim of this prospective clinical trial was to investigate the incidence of postoperative pain after initial root canal treatment using Twisted File Adaptive (TFA) and Reciproc systems. A total of sixty-four previously initiated or necrotic posterior teeth were randomly assigned to two groups based on the rotary system used; TFA (SybronEndo, Orange, Ca) (n = 35) and Reciproc (VDW, Munich, Germany) (n = 29). All teeth were treated in a single visit. Patients were contacted to assess the level of postoperative pain on a visual analog scale after treatment by 6 h, 24 h, 48 h, 72 h, and 1 week. Patients were also asked to report if any medication was taken during the follow-up period. The postoperative pain scores were analyzed by Mann-Whitney test with respect to follow-up interval at a significance level of 0.05. Patients treated with TFA reported significantly lower postoperative pain levels at 24 h, 48 h, and 72 h compared with those in Reciproc group (p < 0.01). There were no significant differences between the two groups at 6 h and 1-week follow-up intervals (p > 0.05). About 11% (TFA) and 24% (Reciproc) of the treated patients took analgesics, but none of them took antibiotics during the follow-up period. The tested rotary systems induced postoperative pain after root canal treatment. The TFA system was found to induce less pain scores compared with the Reciproc system after the treatment by 24 h, 48 h, and 72 h. The level of postoperative pain was low after the root canal treatment with the Twisted File Adaptive system compared with the Reciproc system.


Early secreted antigenic target 6-kDa from Mycobacterium tuberculosis enhanced the protective innate immunity of macrophages partially via HIF1α.
Early secreted antigenic target 6-kDa protein (ESAT6) is an essential virulence factor of Mycobacterium tuberculosis (MTb). However, ESAT6 helped fighting MTb infection according to vaccine studies. It's unclear whether ESAT6 confers protection via enhancing the innate immunity of macrophages, which are the first-line defense against MTb. We profiled the global transcriptional changes and characterized the innate immunity of THP-1 macrophages treated with ESAT6. We found ESAT6 promoted the phagocytosis ability, enhanced reactive oxygen species (ROS) generation and accelerated glucose metabolism in macrophages. Meanwhile, ESAT6 induced a distinctive phenotype of macrophages with a concurrence of pro-inflammatory and anti-inflammatory cytokines and chemokines. ESAT6 increased the expression of HIF1α mRNA and protein. Interfering HIF1α with siRNA defected the capacity of phagocytosis and ROS generation as well as glucose metabolism. Thus, ESAT6 enhanced the protective innate immunity of macrophages partially via HIF1α. This study provided clues for developing therapies against tuberculosis by targeting ESAT6.


Evaluation of degenerative disease of the lumbar spine: MR/MR myelography versus conventional myelography/post-myelography CT.
To compare the use of magnetic resonance (MR)/MR myelography (MRM) with conventional myelography/post-myelography CT (convM) for detailed surgery planning in degenerative lumbar disease. Twenty-six patients with suspected complex lumbar degenerative disease underwent MRM in addition to convM as preoperative workup. Surgery was planned based on convM-as usual at our department. Post hoc, surgical planning was repeated planned again-now based on MRM. Furthermore, the MRM-based planning was performed by six independent neurosurgeons (three groups) of different degrees of specialisation. In only 31 % of the patients, post hoc MRM-based planning resulted in the same surgical decision as originally performed, whereas in 69 % (n = 18) a different procedure was indicated. In patients with non-concurring convM- and MRM-based surgical plans, a less extended procedure was the result of MRM in six patients (23 %), a more extended one in five (19 %), and a related to side/level of decompression or nucleotomy different plan in six patients (23 %). In one patient (4 %), the MRM-based planning would have led to a completely different surgery compared to convM. Overall interobserver agreement on the MRM-based planning was substantial. Detailed planning of operative procedures for complex lumbar degenerative disease is highly dependent on the image modality used.


Management of bone complications in patients with genitourinary malignancies.
Skeletal metastases are common in genitourinary malignancies-including prostate cancer, renal cell carcinoma, and urothelial cancer-and portend significant morbidity and poor prognosis. The presence of skeletal metastases can result in decreased quality of life and increased morbidity. Strategies can be employed to prevent bone-related complications including lifestyle modifications and dietary supplementation. Additionally, pharmacologic agents exist to prevent bone loss and may be appropriate for patients at high risk of fragility-related or skeletal complications, such as pathologic fracture related to bone metastases. Finally, advancement in effective systemic treatments, particularly novel hormone-targeted agents and immunotherapies, may limit the morbidity of advanced disease and delay the onset of skeletal-related complications.


A new gamma spectroscopy methodology based on probabilistic uncertainty estimation and conservative approach.
The gamma spectroscopy technique is commonly used in many applications to evaluate the activity of gamma emitters in a given sample. This assessment of activity is of particular interest for the disposal of radioactive waste or for clearance purposes. However, for these specific applications, one needs to show that the evaluated activities are reasonably conservative. This paper shows an application of a methodology developed to quantify the efficiency calibration curve uncertainties originating from a test case sample and its associated geometry modelling. Therefore, the effects of enclosing geometries on the activity measurement results are discussed. The purpose is to provide an example of uncertainty analysis for an approach that could be applied to other studies in which a conservative estimation of the activity is required.


Effects of end-expired pressure on phrenic output in servo-ventilated dogs.
The pattern of breathing induced by increases in end-expired lung volume (EEVL) was determined in 9 anesthetized dogs. The pulmonary and systemic circulations were separately pump-perfused and the lungs were ventilated with a servo-ventilator actuated from the phrenic neurogram. EEVL was increased as a continuous ramp by slowly raising end-expired transpulmonary pressure from 1.5 to 12 cm H2O. Tidal volume (VT), inspiratory time (TI), and expiratory time (TE) were measured at vagal temperatures of 39 degrees C and 7 degrees C and following vagotomy. At a vagal temperature of 39 degrees C, increasing EEVL produced significant reductions in VT and TI while greatly prolonging TE. Vagal cooling to 7 degrees C, substantially altered the reflex response to increased EEVL. At 7 degrees C, VT decreased as EEVL increased, but the reduction was not so pronounced as at 39 degrees C. In addition, both TI and TE shortened. Increasing EEVL following vagotomy had no consistent effects on breathing pattern. We conclude that increasing EEVL stimulates tachypneic promoting pulmonary afferent nerves, most likely pulmonary C-fibers, but at normal vagal temperature their effect is masked by the stronger reflex inhibition of slowly adapting pulmonary stretch receptors.


Integrative Evaluation of the Clinical Significance Underlying Protein Arginine Methyltransferases in Hepatocellular Carcinoma.
HCC is a major contributor to cancer-related mortality worldwide. Curative treatments are available for a minority of patients diagnosed at early stages; however, only a few multikinase inhibitors are available and are marginally effective in advanced cases, highlighting the need for novel therapeutic targets. One potential target is the protein arginine methyltransferase, which catalyzes various forms of arginine methylation and is often overexpressed in various cancers. However, the diverse expression patterns and clinical values of PRMTs in HCC remain unclear. In the present study, we evaluated the transcriptional expression of PRMTs in HCC cohorts using publicly available datasets. Our results revealed a significant association between PRMTs and prognosis in HCC patients with diverse clinical characteristics and backgrounds. This highlights the promising potential of PRMTs as prognostic biomarkers in patients with HCC. In particular, single-cell RNA (scRNA) sequencing analysis coupled with another human cohort study highlighted the pivotal role of PRMT1 in HCC progression, particularly in the context of Tex. Translating these findings into specific therapeutic decisions may address the unmet therapeutic needs of patients with HCC.


Non-reducing end alpha-mannosylated glycolipids as potent activators for invariant Valpha19 TCR-bearing natural killer T cells.
A novel invariant Valpha19-Jalpha33 T cell receptor alpha chain, first found in mammalian blood cells, was primarily expressed by natural killer T cell repertoire (Valpha19 NKT cell). Attempts have been made to find specific antigens for Valpha19 NKT cells. A series of alpha- and beta-glycosyl ceramides were synthesized and tested whether they had potential to stimulate the cells isolated from invariant Valpha19-Jalpha33 TCR transgenic mice (where the development of Valpha19 NKT cells is facilitated). Comprehensive examinations revealed substantial antigenic activity in alpha-ManCer that was presented by MR1, one of the MHC class Ib molecules. Next, naturally occurring and synthetic alpha-mannosyl glycolipids were further analyzed to determine structural requirements for natural ligands for Valpha19 NKT cells. As a result, alpha-mannosyl phosphatidyl inositols (PI) such as (alpha-Man)(2)-PI and alpha-Man-alpha-GlcNH(2)-PI (a partial structure of mycobacterial lipoarabinomannan and GPI-anchors) as well as alpha-ManCer derivatives were found to activate Valpha19 NKT cells in vivo and in vitro. Thus, Valpha19 NKT cells are possibly responsive to certain alpha-mannosyl glycolipids and may have roles in the innate and adaptative immune systems to protect against various antigens expressing alpha-mannosyl glycolipids and to regulate the adaptive immune system responding to the intracellular ligands.


Perigastric lymph node metastases in gastric cancer: comparison of different staging systems.
BACKGROUND: Perigastric lymph node metastases in gastric cancer are classified differently by different staging systems: the distance of positive nodes from the primary tumor is considered by the 1987 International Union Against Cancer (UICC)-TNM system, but not by the Japanese staging system (of the Japanese Research Society for Gastric Cancer [JRSGC]); the new UICC-TNM system of 1997 is based on the number of involved nodes without differentiating perigastric from regional nodes. The aim of the present study was to assess which classification was more useful to predict prognosis in gastric cancer patients with metastases to the perigastric nodes.METHODS: The results for 107 patients with lymph node metastases to the first and second tiers who underwent curative gastrectomy for gastric cancer from March 1988 to October 1997 were analyzed. In particular, we compared the clinical characteristics and the survival probabilities of: (1) patients with metastases to perigastric nodes located within 3 cm from the primary tumor, classified as N1; (2) patients with metastases to perigastric nodes located 3 cm beyond the primary tumor (N2 in the UICC-TNM and N1 in the Japanese classification), classified by us as N1-N2; and (3) patients with metastases to the second tier (classified by us as N2). We also assessed the number of positive nodes dividing the patients into groups according to the 1997 UICC TNM system.RESULTS: On multivariate survival analysis, the mortality risks in the N1 and N1-N2 patients were comparable (relative risk [RR], N1-N2 versus N1, 1.32; 95% confidence interval [CI], 0.53-3.51) and were half the mortality risk in N2 patients (RR, N2 versus N1, 2.52; 95% CI, 1.33-4.79). The N1 and N1-N2 categories, while presenting markedly different distributions in the number of metastatic nodes (patients with more than seven metastatic nodes constituted less than 20% of the N1 group and more than 60% of the N1-N2 group), showed similar prognostic significance.CONCLUSION: In the present series, the distance of perigastric nodes from the primary tumor did not seem to exert a significant effect on prognosis, and the use of a combined classification based on anatomical location (JRSGC) and number of node metastases (UICC-TNM 1997) could be more useful than either system alone for prognostic purposes.


White matter microstructure and impulsivity in methamphetamine dependence with and without a history of psychosis.
Methamphetamine (MA) use may lead to white matter injury and to a range of behavioral problems and psychiatric disorders, including psychosis. The present study sought to assess white matter microstructural impairment as well as impulsive behavior in MA dependence and MA-associated psychosis (MAP). Thirty patients with a history of MAP, 39 participants with MA dependence and 40 healthy controls underwent diffusion tensor imaging (DTI). Participants also completed the UPPS-P impulsive behavior questionnaire. We applied tract-based spatial statistics (TBSS) to investigate group differences in mean diffusivity (MD), fractional anisotropy (FA), axial (λ‖ ) and radial diffusivity (λ⊥ ), and their association with impulsivity scores and psychotic symptoms. The MAP group displayed widespread higher MD, λ‖ and λ⊥ levels compared to both controls and the MA group, and lower FA in extensive white matter areas relative to controls. MD levels correlated positively with negative psychotic symptoms in MAP. No significant DTI group differences were found between the MA group and controls. Both clinical groups showed high levels of impulsivity, and this dysfunction was associated with DTI measures in frontal white matter tracts. MAP patients show distinct patterns of impaired white matter integrity of global nature relative to controls and the MA group. Future work to investigate the precise nature and timing of alterations in MAP is needed. The results are further suggestive of frontal white matter pathology playing a role in impulsivity in MA dependence and MAP. Hum Brain Mapp 37:2055-2067, 2016. © 2016 Wiley Periodicals, Inc.


Papillomavirus associated skin lesions in a cat seropositive for feline immunodeficiency virus.
A cat was presented with skin lesions consisting of slightly raised pigmented plaques, 2-7 mm in diameter with a rough slightly verrucous surface. Histologically these lesions were identified as papillomas. A papillomavirus infection was demonstrated: virus-like particles were present in the nuclei of cells within the lesions, and staining with an anti-bovine papillomavirus (BPV-1) antibody was obtained. An infection with feline immunodeficiency virus was diagnosed in this cat; this condition had probably enhanced the development of papillomas. This is the first report of a papillomavirus infection in a cat in Europe.


Elasticity measurement of living cells with an atomic force microscope: data acquisition and processing.
Elasticity of living cells is a parameter of increasing importance in cellular physiology, and the atomic force microscope is a suitable instrument to quantitatively measure it. The principle of an elasticity measurement is to physically indent a cell with a probe, to measure the applied force, and to process this force-indentation data using an appropriate model. It is crucial to know what extent the geometry of the indenting probe influences the result. Therefore, we indented living Chinese hamster ovary cells at 37 degrees C with sharp tips and colloidal probes (spherical particle tips) of different sizes and materials. We furthermore developed an implementation of the Hertz model, which simplifies the data processing. Our results show (a) that the size of the colloidal probe does not influence the result over a wide range (radii 0.5-26 microm) and (b) indenting cells with sharp tips results in higher Young's moduli ( approximately 1,300 Pa) than using colloidal probes ( approximately 400 Pa).


Ion-selective enrichment of tyrosine-sulfated peptides from complex protein digests.
We have developed a novel procedure for concentrating sulfated peptides, as a front end to mass spectrometric analysis, based on ion-selective interaction of sulfate ions with anion exchangers. Ions with a higher charge and smaller solvated ion radius, such as sulfate ions, have higher retention in an ion exchanger due to their greater degree of coulombic interactions. We tested the effectiveness of this approach for enrichment and identification of sulfated peptides using a tryptic digest of bovine serum albumin spiked with model sulfated peptide (molar ratio 20:1) and using a tryptic digest of bovine fibrinogen. Sulfated peptides are identified by mass spectrometry in which both the molecular ion and its specific fragment ion produced by facile loss of SO(3) are detected. In both experiments, sulfated peptides were strongly retained on the anion exchanger and were eluted by higher concentrations of competing ion with minimal contamination of nonsulfated peptides. Using this procedure, we determined that the 13-amino acid C-terminal peptide of the minor gamma'-chain of bovine fibrinogen contains sulfated tyrosine.


Preparation- or intention-to-act, in relation to pre-event potentials recorded at the vertex.
Pre-event potentials were compared in the same subject, for 3 types of forewarned events, in which the foreperiod for orienting or attention began several seconds before the event. All of these trials involved similar non-motor components (expectancy, attentiveness, general orienting to a salient stimulus) but differed in whether motor or non-motor responses were required. A prominent and consistent slow negative shift preceded the pre-set time for a motor response, even when the subject 'vetoed' his intention to act shortly before the pre-set time. Pre-event potentials were absent, or small and brief, when the event was a task-related skin stimulus not involving preparation to move. The findings selectively support the view that mental preparation/intention to act is a necessary and perhaps dominant process associated with the vertex-recorded pre-event, slow negative potential. They also show that such a pre-event potential can appear even when the subject knows he is going to veto his developing intention to act and does not actually move.


Pseudoepidemics of heroin addiction.
Smooth unimodal skewed distributions, sometimes referred to as "epidemic-like" curves, are often used as evidence of time to time changes in incidence. Data on year of onset from groups of treated heroin addicts are generally alleged to reflect incidence, and this distribution is used to evaluate effectiveness and predict future needs. This paper describes the development of simple demographic models which demonstrate the production of epidemic-like curves without changes in incidence, ascertainment or duration of disorder. These graphic models are relevant to other non-infectious disorders where there is continuing exposure to the etiologic agents and where intervals between onset and ascertainment are not uniformly distributed.


Serious post-tonsillectomy hemorrhage with and without lethal outcome in children and adolescents.
Serious post-tonsillectomy hemorrhage (PTH) is an uncommon complication requiring immediate and adequate medical treatment. This study was undertaken to describe and evaluate the clinical data and courses of serious PTH, with and without lethal outcome in children and adolescents. Bleeding episodes accompanied by hemorrhagic shock requiring resuscitation and/or major medical treatment were labeled as serious PTH, with or without lethal outcome. Personal experiences as surgeons and expert reports in connection with lawsuits and Professional Boards, as well as reports collected after a published request contributed to the data collection. Thirty-one boys and 21 girls (gender not stated for three patients) younger than 18 years of age were enrolled in our study (mean: 8.47; median: 6; S.D.: 4.73 years). Thirty-three children were 8 years of age or younger (60%). Lethal outcome was reported for 19 patients of whom 11 had experienced repeated episodes of bleeding. The majority of the surviving children experienced serious PTH without remaining sequelae (32), however, four children suffered from remaining sequelae. Forty-three children experienced repeated episodes of PTH. The first episode of PTH occurred either at home (32) or in the hospital (22; location not stated for one child). Primary hemorrhage (<24h) was reported for three, secondary bleeding (>24h) for 52 children (94.5%). A total of 169 bleeding episodes was reported of whom 149 were specified as massive (56), major (31), minor (15), diffuse (12), with spontaneous cessation (19) or vomiting of considerable amounts of blood (16). Aspiration was confirmed at the autopsy of seven patients. Ligature of greater arteries in the neck was performed in 35 cases, suturing of the faucal pillars in four and packing of the oropharynx in six patients. Twenty-four children received blood transfusions. Resuscitation was performed in 17 cases but remained ineffective in seven patients. Repeated episodes of bleeding should be considered as a warning sign of serious PTH. Inpatient observation does not eliminate the risk of lethal outcome. Children up to 8 years of age seem to be more susceptible to serious PTH, whereas gender remained irrelevant as a contributing risk factor. Life-threatening PTH is likely to occur as secondary PTH.


Human ocular filariasis: further evidence on the zoonotic role of Onchocerca lupi.
Among ocular vector-borne pathogens, Onchocerca volvulus, the agent of the so-called "river blindness", affects about 37 million people globally. Other Onchocerca spp. have been sporadically reported as zoonotic agents. Cases of canine onchocerciasis caused by Onchocerca lupi are on the rise in the United States and Europe. Its zoonotic role has been suspected but only recently ascertained in a single case from Turkey. The present study provides further evidence on the occurrence of O. lupi infesting human eyes in two patients from Turkey (case 1) and Tunisia (case 2). The importance of obtaining a correct sample collection and preparation of nematodes infesting human eyes is highlighted. In both cases the parasites were identified with morpho-anatomical characters at the gross examination, histological analysis and anatomical description and also molecularly in case 1. The nematode from the first case was obviously O. lupi based on their morphology at the gross examination, histological analysis and anatomical description. In the second case, although the diagnostic cuticular characters were not completely developed, other features were congruent with the identification of O. lupi. Furthermore, the morphological identification was also molecularly confirmed in the Turkish case. The results of this study suggest that O. lupi infestation is not an occasional finding but it should be considered in the differential diagnosis of other zoonotic helminths causing eye infestation in humans (e.g., D. immitis and Dirofilaria repens). Both cases came from areas where no cases of canine onchocerciasis were previously reported in the literature, suggesting that an in depth appraisal of the infestation in canine populations is necessary. Physicians and ophthalmologists are advised on how to preserve nematode samples recovered surgically, to allow a definitive, correct etiological diagnosis.


Lymphocytic infundibulo- neurohypophysitis with hypothalamic and optic pathway involvement: report of a case and review of the literature.
Lymphocytic adenohypohysitis and lymphocytic infundibulo-neurohypophysitis are rare auto-immune mediated diseases of the anterior and posterior pituitary, respectively. The former usually manifests as insufficiency of anterior pituitary hormone secretion, associated in many patients with disturbances of vision. The latter presents as diabetes insipidus of central origin. They present most commonly in pregnant or postpartum females. There have been infrequent reports in females with no association with pregnancy, and in males. We present a nulliparous female with central diabetes insipidus, pan-hypopituitarism, and severely impaired vision. Magnetic resonance imaging demonstrated a large mass involving the hypothalamus, infundibulum, optic nerves, chiasm, and tracts. At operation, the optic pathways were found to be grossly involved in the inflammatory mass. Histological examination of a biopsy demonstrated a nonspecific, mixed inflammatory infiltrate, composed predominantly of lymphocytes and plasma cells. She responded dramatically to treatment with dexamethasone, with disappearance of the mass on serial imaging studies and improvement in vision. In addition, she received hormone replacement therapy. We present a case of lymphocytic infundibulo-neurohypophysitis unique in the degree of optic pathway inflammatory involvement, with a documented response to steroids.


Pregnancy during adolescence has lasting adverse effects on blood lipids: a 10-year longitudinal study of black and white females.
Primiparity has been associated with 3 to 4 mg/dL lower high-density lipoprotein cholesterol concentrations in black and white adult women that persist several years after delivery. To examine the lasting effects of adolescent pregnancy on blood lipids, an early risk factor for future cardiometabolic diseases. The National Heart Lung and Blood Institute's Growth and Health Study is a multicenter prospective cohort that measured fasting blood lipids for 1013 (513 black, 500 white) participants at baseline (1987-1988) ages 9-10, and again at follow-up (1996-1997) ages 18-19. Change in fasting plasma total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol, defined as the difference between baseline and follow-up measurements, was compared among 186 (145 black, 41 white) primi- or multiparas, 106 (55 black, 51 white) nulliparous, gravidas versus 721 (313 black, 408 white) nulligravidas. Fully adjusted multiple linear regression models estimated blood lipid changes among these pregnancy groups adjusted for race, age at menarche, baseline lipids, physical inactivity, body mass index, and family sociodemographics. In the 10-year study period, adolescent paras compared with nulligravidas had greater decrements in high-density lipoprotein cholesterol (mg/dL; fully adjusted mean [95% confidence interval] group differences in black -4.3 [-6.7, -2.0]; P < .001 and white: -4.5 [-8.2, -0.7]; P = .016) and greater increments in fasting triglycerides (mg/dL; adjusted mean [95% confidence interval] group differences in black: 10.4 [3.9, 16.8]; P < .001, and white: 11.6 [-3.6, 26.8]; P = .167). Adolescent pregnancy contributes to pro-atherogenic lipid profiles that persist after delivery. Further research is needed to assess whether adolescent pregnancy has implications for future cardiovascular disease risk in young women.


Associations of Sarcopenic Obesity and Dynapenic Obesity with Bone Mineral Density and Incident Fractures Over 5-10 Years in Community-Dwelling Older Adults.
The purpose of this study is to determine whether low muscle mass (sarcopenia) or strength (dynapenia), in the presence of obesity, are associated with increased risk for osteoporosis and non-vertebral fracture over 5-10 years in community-dwelling older adults. N = 1089 volunteers (mean ± SD age 62 ± 7 years; 51 % female) participated at baseline and 761 attended follow-up clinics (mean 5.1 ± 0.5 years later). Total body, total hip and spine BMD, and appendicular lean and total fat mass were assessed by DXA. Sarcopenic obesity and dynapenic obesity were defined as the lowest sex-specific tertiles for appendicular lean mass or lower-limb strength, respectively, and the highest sex-specific tertile for total fat mass. Fractures were self-reported on three occasions over 10.7 ± 0.7 years in 563 participants. Obese alone participants had significantly higher BMD at all sites compared with non-sarcopenic non-obese. Sarcopenic obese and dynapenic obese men had lower spine and total body BMD, respectively, and sarcopenic obese women had lower total hip BMD, compared with obese alone (all P < 0.05). Sarcopenic obese men had higher non-vertebral fracture rates compared to non-sarcopenic non-obese (incidence rate ratio: 3.0; 95 % CI 1.7-5.5), and obese alone (3.6; 1.7-7.4). Sarcopenic obese women had higher fracture rates compared with obese alone (2.8; 1.4-5.6), but this was non-significant after adjustment for total hip BMD. Sarcopenic and dynapenic obese older adults may have increased risk of osteoporosis and non-vertebral fracture relative to obese alone counterparts. Sarcopenic and dynapenic obese individuals potentially represent a subset of the obese older adult population who require closer monitoring of bone health during ageing.


Knockdown THOC2 suppresses the proliferation and invasion of melanoma.
Melanoma is a potentially fatal form of skin cancer with great metastatic potential. THOC2 plays a vital role in human biological progression, however, the roles of THOC2 in melanoma tumorigenesis are still unknown. In the present study, our data demonstrated that THOC2 expression was significantly increased in melanoma tissues, and high THOC2 expression was associated with poor overall survival of melanoma patients. THOC2 reduction repressed melanoma cell proliferation and invasion, and induced cell apoptosis in vitro. Microarray data revealed that the cAMP signaling pathway was significantly downregulated in A375 cells transfected with si-THOC2, which was further confirmed by RT-qPCR and bioinformatics analysis. In conclusion, our data indicated that THOC2 might act as an oncogene in melanoma progression through cAMP signaling pathway regulation, which may offer a therapeutic target for melanoma treatment.


Disruption of immune cell function by mutant huntingtin in Huntington's disease pathogenesis.
Innate immune dysfunction is increasingly recognised as a key characteristic of neurodegenerative disease. In the fatal inherited neurological disorder, Huntington's disease, altered innate immune cell function and increased inflammation are observed in the brain and the periphery of disease gene carriers many years before symptom onset, suggesting a potentially early and important role in disease pathogenesis. This is due, at least in part, to the intrinsic effects of the disease-causing protein, mutant huntingtin, expressed in innate immune cells themselves. Understanding whether such innate immune dysfunction in Huntington's disease can be targeted to slow the onset and/or the progression of the disease has significant therapeutic implications and is the subject of much current research.


Coordination-induced decomposition of luminescent gold nanoparticles: sensitive detection of H2O2 and glucose.
The surface inert of luminescent gold nanoparticles (AuNPs) toward biomolecules set a challenge to further exploit their bioanalytical applications using the direct luminescence response. Herein, we report a novel approach to induce significant luminescence quenching of the AuNPs upon the interaction with a metal coordination ligand tris(2-carboxyethyl)phosphine (TCEP), providing a strategy for the detection of H2O2 with a limit of detection (LOD) of 14 nM through the reaction between H2O2 and TCEP to protect the luminescence quenching of the AuNPs. Furthermore, this strategy is also extended for sensitive and selective detection of glucose with a LOD of 1.1 μM based on monitoring the production of H2O2 catalyzed from the oxidation of glucose. The highly extendable feature of this strategy can have great potential in the sensitive detection of other biomolecules. Graphical Abstract A facile and extendable strategy has been developed for the sensitive detection of H2O2 and glucose based on the interaction between luminescent gold nanoparticles and TCEP, a metal coordination ligand.


Research in the Netherlands on a theory of child abuse: a preliminary report.
A three-factor theory of child abuse has been developed which includes: (1) a high level of parental aggression; (2) a low level of parental inhibition of overt aggression; and (3) the focusing of parental aggression on the child. In the theory each factor is the outcome of a subfactor "path." A high level of parental aggression is the outcome of seven subfactors. A low level of parental inhibition of overt aggression is the outcome of three subfactors. The focusing of parental aggression on the child is the outcome of ten subfactors. The theory posits that the type of child abuse that occurs is determined by the ratio of total parental aggression to total parental inhibition of overt aggression. High numerical values of the ratio result in battering. Lower numerical values result, in descending order, in non-organic failure to thrive, physical neglect and emotional abuse. The theory and 50 hypotheses derivable from it are being tested on a sample of 150 child-abuse families and 150 control families.


Andrographolide attenuates complete freund's adjuvant induced arthritis via suppression of inflammatory mediators and pro-inflammatory cytokines.
Traditional plant-derived medicines have enabled the mankind in curing the wide spectrum of diseases throughout the ages. Andrographis paniculata (Burm.f.) Nees, is one of the traditional plant used as a folk medicine for the management of inflammation, arthritis, viral-bacterial infections and other ailments in India, China, Malaysia and other South-East Asian countries. Its major bioactive compound; andrographolide, a diterpenoid, also exerts cytoprotective properties and is reported to be effective in neuroprotection, hepatoprotection, etc. AIM: The study is aimed to explore the role of andrographolide in treatment of complete freund's adjuvant (CFA) induced arthritis. The influx of immune cells, release of pro-inflammatory cytokines and subsequent accumulation of synovial fluid (swelling) and pain manifest into the disease. The present study used CFA induced Balb/c mice model and treated them intraperitoneally with andrographolide and dexamethasone (used as a positive control) on alternate days for six days. After 6 days, blood and peritoneal macrophages were collected to evaluate the expression of various arthritic markers and paw edema was measured on all days. The in vitro and ex vivo experiments showed that andrographolide treated animal group had reduced paw edema, cell cytotoxicity and nitric oxide production than dexamethasone treated animal group. Further, the study revealed the mechanistic role of andrographolide in treatment of arthritis by suppressing battery of molecules like COX-2, NF-κB, p-p38, CD40, TNF-α, IL-1β and IL-6 involved in arthritis. The study showed the potent anti-arthritic effects of andrographolide and warrants further investigations on andrographolide for the development of safe and effective anti-arthritic drug.


Efficacy of empiric antibiotic treatment of late-onset neonatal sepsis caused by Enterobacteriaceae: A systematic review.
Neonatal sepsis is a serious condition, where an adequate empiric antibiotic treatment is crucial. The objective of this systematic review is to assess whether the World Health Organization's recommended treatment regime remains applicable for late-onset neonatal sepsis caused by Enterobacteriaceae, in the time of increased antimicrobial resistance. PubMed was searched for articles from 2009 to 2020. A total of 49 articles were eligible for inclusion. The review was carried out in accordance with PRISMA guidelines. For Klebsiella spp. 100, 68 and 63% of the studies found sensitivity to ampicillin, gentamicin and third-generation cephalosporin in <50% of the isolates. For Escherichia coli, the corresponding values were 88, 50 and 42% respectively, whilst for Enterobacter spp. 100, 70 and 94% of the studies found <50% sensitivity to these antibiotics. Overall, there is low sensitivity to all agents in the WHO's recommended empiric treatment regimes (WHO recommends ampicillin plus gentamicin as first-line treatment and third-generation cephalosporin as second-line treatment). A revised guideline for empiric antibiotic treatment of neonatal sepsis is urgently needed due to the increased threat of antimicrobial resistant Enterobacteriaceae causing neonatal sepsis.


Semen analysis in post-pubertal patients with posterior urethral valves: a pilot study.
The issues of sexual function and fertility are becoming relevant in patients with posterior urethral valves (PUV), as more of them reach adulthood. To evaluate the semen of post-pubertal patients with PUV as a determinant of future fertility, all such patients (age >16 years) attending the follow-up urology clinic of our department from 1985 to December 1999 were contacted. Of the nine patients contacted, eight agreed to form the study group. All eight patients were asked to provide a post-masturbation semen sample and urine. Semen was analysed for pH, viscosity, liquefaction time, sperm morphology, sperm count, motility, and agglutination. The patients ages ranged from 16 to 21 years (mean 17.5 years). One patient with chronic renal failure awaiting a renal transplant refused to give a semen sample; two tried but failed to ejaculate on three consecutive visits. Their urine was negative for sperm. Of the five patients who gave semen, the liquefaction time was high in two. pH ranged from 7.2 to 8, sperm counts were 24-80 million. None of the patients had oligospermia. Abnormal sperm agglutination was present in four cases; a higher percentage of immotile sperm was also present in four. Semen abnormalities in the form of increased liquefaction time, abnormal sperm agglutination, and a high percentage of immotile sperm were thus seen in the present study. The bearing of these findings on subsequent sexual function and fertility remains a matter of speculation.


Relevant factors in the eutrophication of the Uruguay River and the Río Negro.
In recent decades, there has been increasing eutrophication of rivers and lagoons in Uruguay and solutions leading to water purification are being sought. The growing pollution has been attributed to nitrogen and phosphorus compounds exported from the river basins with intensification of agricultural production and the absence of tertiary treatment for urban and industrial effluents. Although nitrogen and phosphorus are relevant to eutrophication, there are also other factors that can promote eutrophication and algal blooms. This paper reports a broad analysis of water quality variables recorded over 9 years (2009-2018) at 17 sampling stations on the Uruguay River and 16 sampling stations on the Río Negro, and explores their relationship with the changes of chlorophyll a (Chl-a) concentrations using a generalized linear model and a neural network simulation (NNS). The input variables were total phosphorus; total suspended solids; electrical conductivity of water (ECw); alkalinity; water temperature (T); water pH (pH) and sampling month. The NNS explained 79% of Chl-a variations and showed the most relevant variables to be T, ECw, and pH. Moreover, the NNS showed that replacement of current land uses by natural prairie would not significantly reduce Chl-a concentrations. The results showed that the main factors that drive Chl-a concentrations (i.e., algae) are not directly linked to agriculture land use.


Low-concentration N-acetylaspartylglutamate suppresses the climbing fiber response of Purkinje cells in guinea pig cerebellar slices and the responses to excitatory amino acids of Xenopus laevis oocytes injected with cerebellar mRNA.
Whether N-acetylaspartylglutamate (NAAG) at micromolar concentrations shows a modulatory action on the synaptic transmission mediated by excitatory amino acids was investigated using Guinea pig cerebellar slices and the Xenopus laevis oocytes injected with mRNA from Guinea pig cerebellum. The climbing fiber response consisted of an excitatory postsynaptic potential (EPSP) and a plateau potential intracellularly recorded from Purkinje cell dendrite was depressed by 30 microM NAAG; the EPSP was decreased by about 21% in amplitude and the plateau potential was depressed by about 42% in duration. The depolarization induced by L-aspartate, L-glutamate, N-methyl-D-aspartate and quisqualate in mRNA-injected Xenopus oocytes were non-selectively antagonized by 0.5 microM-5 microM NAAG, the mean % blockade by 5 microM NAAG being about 38%. Higher concentrations (greater than 100 microM) of NAAG alone by 33% on average by 10 microM NAAG. These results suggest the possibility that micromolar concentrations of NAAG may attenuate the synaptic transmission mediated by glutamate receptors not only by blocking postsynaptic receptors but also by facilitating the high-affinity re-uptake of transmitter amino acids.


Nursing students' attitudes towards death and caring for dying patients.
To examine the attitudes of undergraduate Jordanian nursing students towards death and caring for dying patients. A cross-sectional correlational design. The Frommelt Attitude Toward Care of the Dying and Death Attitude Profile-Revised scales were used in this study with a convenience sample of 555 students from nursing schools in Jordan. Nursing students had positive attitudes towards death (M = 153.7, SD = 21.5) and a positive attitude towards caring for dying patients (M = 98.1, SD = 9.2). Fear of death, escape acceptance and death avoidance were significant negative predictors, while neutral acceptance, higher academic level and female gender were significant positive predictors of caring for dying patients (F = 4.5). Nursing students had positive attitudes towards caring for dying patients that was influenced by university type, academic level and gender. Nursing education must further focus on death, dying and end-of-life care across the core courses of nursing curricula, theory and practicum.


Transcription-coupled global genomic repair in E. coli.
The nucleotide excision repair (NER) pathway removes helix-distorting lesions from DNA in all organisms. Escherichia coli has long been a model for understanding NER, which is traditionally divided into major and minor subpathways known as global genome repair (GGR) and transcription-coupled repair (TCR), respectively. TCR has been assumed to be mediated exclusively by Mfd, a DNA translocase of minimal NER phenotype. This review summarizes the evidence that shaped the traditional view of NER in bacteria, and reviews data supporting a new model in which GGR and TCR are inseparable. In this new model, RNA polymerase serves both as the essential primary sensor of bulky DNA lesions genome-wide and as the delivery platform for the assembly of functional NER complexes in living cells.


Characterization of m6A-related lncRNA signature in neuroblastoma.
N6-methyladenosine (m6A) constitutes one of the most common modifications in mRNA, rRNA, tRNA, microRNA, and long-chain noncoding RNA. The influence of modifications of m6A on the stability of RNA depends upon the expression of methyltransferase ("writer") and demethylase ("eraser") and m6A binding protein ("reader"). In this study, we identified a set of m6A-related lncRNA expression profiles in neuroblastoma (NBL) based on the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) program. Thereupon, we identified two subgroups of neuroblastoma (high-risk group and low-risk group) by applying consensus clustering to m6A RNA methylation regulators ("Readers,", "Writer," and "Erase"). Relative to the low-risk group, the high-risk group correlates with a poorer prognosis. Moreover, the present study also revealed that the high-risk group proves to be significantly positively enriched in the tumor-related signaling pathways, including the P53 signaling pathway, cell cycle, and DNA repair. This finding indicates that these molecular prognostic markers may also be potentially valuable in early diagnosis, which provides a new research direction for the study of molecular mechanisms underlying the development of NBL. In conclusion, this study constructed a new model of NBL prognosis based on m6a-associated lncRNAs. Ultimately, this model is helpful for stratification of prognosis and development of treatment strategies.


Outcomes of treatment of fractures of the frontal sinus: review from a tertiary multispecialty craniofacial trauma service.
There are no agreed national guidelines for the treatment of fractures of the frontal sinus and the naso-orbitoethmoid complex. The Oxford University Hospitals Craniofacial Trauma unit was set up five years ago as a joint oral and maxillofacial, ENT, and neurosurgical service, and we present our experience to date in the treatment of patients with such fractures. The study includes 91 patients with data collected from a prospective database. Patients underwent cranialisation if they met the criteria of persistent leak of cerebrospinal fluid (CSF), displaced fracture of the posterior wall or obstruction of the nasofrontal outflow tract. The mean follow-up time was 42 months (range 1-10 years). Three groups of patients were analysed. Group 1 met the criteria for, and were treated by, cranialisation (n=50). Group 2 met the criteria for cranialisation, but were treated conservatively because of coexisting conditions (n=8). Group 3 did not match the criteria for treatment, and were managed conservatively (n=33). The numbers of patients with complications or who required further operation were: group 1 (4/50), group 2 (3/8), and group 3 (3/33). There were significantly fewer complications among those patients who met the operative criteria and were treated by cranialisation than among those treated conservatively (p=0.04). These outcomes from one dedicated multispecialist craniofacial trauma unit in the UK may help surgeons who care for patients with this specific group of injuries. Our morbidity was in keeping with published figures.


Audit of carotid doppler sonography: Spectrum of findings at a tertiary hospital in Northwestern Nigeria.
Doppler sonography of the cervical segment of the carotid arteries is becoming a popular tool for evaluating atherosclerosis of the carotid artery. We present the audit of findings on carotid ultrasound examination among patients with clinical suspicion and risks for cerebrovascular disease and possible correlates in Northern Nigeria. We performed carotid ultrasound examination on all patients referred for screening and clinical suspicion of cerebrovascular disease within the year 2017. The patients' characteristics, risk factors, presence of atheroma and characteristic of the atheroma, degree of stenotic disease as well as the presence of incidental ultrasound findings were reviewed and documented. Out of the 62 patients, 55 (88.7%) of them had various degrees and types of atheromatous plaques in different segments of the cervical carotid arteries, whereas 7 (11.3%) were normal. The predominant risk factor was smoking followed by diabetes mellitus, whereas the highest indication for the scan was transient ischemic attack. Incidental thyroid lesions such as nodules and cysts were encountered in 14 (22.6%) of the patients. There is a statistically significant difference between sex and age with the side of lesion, degree of stenosis, segment involved, and type of atheromatous plaque. There is a statistically significant difference between sex and age with the side of lesion, degree of stenosis, segment involved, and type of atheromatous plaque. About one-fifth of our patients had incidental thyroid lesions. Therefore, routine screening of population at risk is highly recommended.


Near-peer teaching in simulation.
Development, implementation and evaluation of a simulation curriculum is time and resource intensive. Limited faculty time and training are cited as primary barriers to adopting simulation into medical education. Near-peer teaching is a potential solution to manage the increased teaching demands that occur with simulation use. In 2022, we implemented a near-peer simulation curriculum for teaching junior physical medicine and rehabilitation (PM&R) residents high-acuity low-opportunity events commonly seen on the inpatient rehabilitation unit. The curriculum was taught by senior residents to supplement faculty lectures. Senior residents completed facilitator training on simulator logistics, debriefing and formative assessment. Residents completed an end-of-course questionnaire evaluating teaching effectiveness and perceived knowledge acquisition. All items were scored on a 5-point Likert-type scale. Learners rated their near-peers as having good clinical teaching effectiveness (mean [SD], 4.66[0.38]). Senior residents (n = 6) disclosed feeling knowledgeable about the topics they instructed (baseline 3.9[3.2-4.4]; after 4.6[4.1-4.9]; p = 0.19), and junior residents (n = 6) felt they gained knowledge and improved their ability to manage patients as a result of the near-peer curriculum (baseline 2.4[2.3-2.5]; after 3.9[3.5-4.2]; p = 0.005). This educational programme is an example of how near-peer teaching can be used in simulation. Our simulation curriculum taught by near-peers was valued by learners as well taught and educational. Research is needed that directly compares the effectiveness of near-pear teaching to faculty instruction. We hope that by sharing our work, educators will feel inspired to use near-peer teachers for simulation instruction when faculty availability for teaching is scarce.


Boric acid tolerant Vibrio cholerae: biological and physical properties.
Two boric acid tolerant variants were developed by passage in boric acid containing media from a mouse virulent parent Vibrio cholerae strain. The variants were stable, exhibited increased acid resistance, were less virulent to mice, but protected against challenge with the mouse virulent parent strain.


Effects of exercise on the physical fitness and functionality of people with amputations: Systematic review and meta-analysis.
systematic review and meta-analysis. Despite existing scientific evidence alluding to the positive effects of physical exercise on people with amputations, there is a lack of consistency between the results of past studies. To identify if people with amputations taking part in an exercise training programme can benefit from improvements in their health status as measured by changes in their physiological fitness and functionality levels. A systematic review and meta-analysis of randomized controlled trials (RCTs) were performed after searching within several databases up to October 2019. Ten RCTs with satisfactory methodological quality were found. Five RCTs were pooled in the meta-analysis. Exercise programmes with a combination of activities were most commonly delivered. Exercise had positive effects on aerobic and muscular fitness parameters. Findings from the meta-analysis indicated that exercise improved distance walked but did not have a significant impact on functional mobility or self-reported functional capacity. Combined exercise of muscular endurance and functional physical exercise appear to have greater positive effects on cardiorespiratory fitness, muscular fitness and functionality levels in adult prosthesis users with unilateral lower limb amputation. Future studies should include different profiles of patients with amputations that are poorly represented in the current scientific literature.


Effect of packing on orientation and cis-trans isomerization of azobenzene chromophore in Langmuir-Blodgett film.
Photoactive film material of long-chain azobenzene derivative, p-(omega-trimethylammoniodecyloxy)-p'-octyloxyazobenzene bromide (TAOAB), was fabricated into a Langmuir-Blodgett (LB) film by a polyion-complex technique using poly(sodium 4-styrenesulfonate) as a polyanion. To investigate the effect of the packing state of the azobenzene chromophore on its orientation and cis-trans isomerization, TAOAB was mixed with methyl stearate in the LB film matrix at various mole fractions (X(TAOAB)), and structural characterizations were subsequently carried out by means of Fourier transform infrared and ultraviolet-visible spectroscopies, X-ray diffraction analysis, and atomic force microscopy. The results obtained show that as the degree of packing increases, both the azobenzene chromophores and the hydrocarbon chains orient more perpendicularly to the surface of the LB film. In addition, reversible cis-trans photoisomerization of TAOAB took place upon alternate irradiation with UV and visible light even in a mixed LB film with the chromophores in a dense lateral packing state. In the process of thermal cis-to-trans isomerization, we found that the reaction rate is strongly affected by the packing state of TAOAB at 20 degrees C, reflecting the differences in steric hindrance among LB films of various X(TAOAB). In addition, higher activation energy was obtained for thermal cis-to-trans isomerization when the free volume around the chromophores became smaller.


Cardiovascular risk score, cognitive decline, and dementia in older Mexican Americans: the role of sex and education.
The purpose of this study was to examine the associations of cardiovascular disease (CVD) risk with cognitive decline and incidence of dementia and cognitive impairment but not dementia (CIND) and the role of education as a modifier of these effects. One thousand one hundred sixteen Mexican American elderly were followed annually in the Sacramento Area Latino Study on Aging. Our sex-specific 10-year CVD risk score included baseline age, systolic blood pressure, total cholesterol, high-density lipoprotein, smoking, body mass index, and diabetes. From adjusted linear mixed models, errors on the Modified Mini-Mental State Exam (3MSE) were annually 0.41% lower for women at the 25th percentile of CVD risk, 0.11% higher at the 50th percentile, and 0.83% higher at the 75th percentile (P value of CVDrisk×time <0.01). In men, 3MSE errors were annually 1.76% lower at the 25th percentile of CVD risk, 0.96% lower at the 50th percentile, and 0.12% higher at the 75th percentile (P value of CVDrisk×time <0.01). From adjusted linear mixed models, the annual decrease in the Spanish and English Verbal Learning Test score was 0.09 points for women at the 25th percentile of CVD risk, 0.10 points at the 50th percentile, and 0.12 points at the 75th percentile (P value of CVDrisk×time=0.02). From adjusted Cox models in women, compared with having <6 years of education, having 12+ years of education was associated with a 76% lower hazard of dementia/CIND (95% CI, 0.08 to 0.71) at the 25th percentile of CVD risk and with a 45% lower hazard (95% CI, 0.28 to 1.07) at the 75th percentile (P value of CVDrisk×education=0.05). CVD risk score may provide a useful tool for identifying individuals at risk for cognitive decline and dementia.


Apoptosis: mechanisms and relevance in cancer.
Apoptosis or programmed cell death is a process with typical morphological characteristics including plasma membrane blebbing, cell shrinkage, chromatin condensation and fragmentation. A family of cystein-dependent aspartate-directed proteases, called caspases, is responsible for the proteolytic cleavage of cellular proteins leading to the characteristic apoptotic features, e.g. cleavage of caspase-activated DNase resulting in internucleosomal DNA fragmentation. Currently, two pathways for activating caspases have been studied in detail. One starts with ligation of a death ligand to its transmembrane death receptor, followed by recruitment and activation of caspases in the death-inducing signalling complex. The second pathway involves the participation of mitochondria, which release caspase-activating proteins into the cytosol, thereby forming the apoptosome where caspases will bind and become activated. In addition, two other apoptotic pathways are emerging: endoplasmic reticulum stress-induced apoptosis and caspase-independent apoptosis. Naturally occurring cell death plays a critical role in many normal processes like foetal development and tissue homeostasis. Dysregulation of apoptosis contributes to many diseases, including cancer. On the other hand, apoptosis-regulating proteins also provide targets for drug discovery and new approaches to the treatment of cancer.