Coping with auditory hallucinations: a cross-cultural comparison between western (British) and non-western (Saudi Arabian) patients.
The majority of schizophrenic patients from Western backgrounds develop strategies to cope with the positive symptoms of their condition. However, there is little evidence to indicate how these coping mechanisms are affected by cultural background. Seventy schizophrenic patients from Saudi Arabia (SA) and the United Kingdom (UK) who reported auditory hallucinations were interviewed to explore the ways in which they coped with their voices and sounds. Patients from both cultures had several coping mechanisms, but these varied between cultures. The majority of SA patients used strategies associated with their religion whereas UK patients were more likely to use distraction or physiologically based approaches. The majority of patients were slightly or not at all confident about the effectiveness of their coping strategies. This study suggests that clinicians, when they attempt to facilitate the use of such strategies, may find greater patient acceptance and efficacy if they are familiar with culturally specific factors.


Health issues among foreign born uninsured children visiting an inner city pediatric emergency department.
To study the demographic and socio-economic characteristics of foreign born children visiting an inner city pediatric emergency department (PED) and to assess their access to care, unmet health care needs, barriers to care and follow-up care. A cross-sectional study was conducted in October and November 2006; parents of children visiting an inner city PED underwent face-to-face interview regarding their socio-economic status, access to health care, unmet medical needs and barriers to care. A follow-up telephonic interview was conducted within 1 week of the ED visit to assess compliance with follow-up care. 385 patients (Mean age 4.63 years, 51.9% male) were enrolled prospectively. 297 (77%) children had health insurance and 88 (23%) were uninsured. 38 (43%) uninsured children were foreign born. Of those uninsured, 53 (60%) were uninsured for >a year and 35 (40%) had been uninsured part year. Compared with insured children, fewer uninsured children had a regular place for medical care (89 vs. 46%, P < 0.001), a regular Primary Care Provider (95 vs. 68%, P < 0.001), and regular dental care (46 vs. 26%, P < 0.001). Almost one-third of parents of uninsured children reported a perceived barrier to care (31 vs. 8%, P < 0.001). Uninsured children, who were foreign born, were older (mean age 8.9 vs. 4.9 years, P < 0.001), primarily Spanish speaking (95 vs. 76%, P < 0.02), poorer, with household income less than 100% of the Federal poverty level and had poorer access to care. They also used the PED as their primary source of care more frequently (87 vs. 66%, P < 0.03). In a multivariate logistic regression analysis, children with no health insurance, and those children who were foreign born were more likely to have poor access to care with odds ratio (95% CI) of 0.19 (0.08-0.46) and 0.35 (0.13-0.95), respectively. Significant proportions of uninsured children visiting our PED are born in Mexico and from low income immigrant families, many do not qualify for public insurance, have poor access to care, and use the PED for their healthcare needs. This is likely to be a growing problem in certain regions of the country requiring targeted health policy intervention.


Mechanical Thrombectomy for Acute Ischemic Stroke Caused by Prosthetic Aortic Valve Endocarditis Due to Exophiala dermatitidis Infection: A Case Report.
Prosthetic valve endocarditis (PVE) can cause large cerebral vessel occlusion. Many reports suggested that mechanical thrombectomy (MT) is effective and useful for early diagnosis from the histopathological findings of thrombus. We present the case of a 62-year-old man, with a history of prosthetic aortic valve replacement and pulmonary vein isolation for his atrial fibrillation, who developed a high fever and an acute neurological deficit, with left hemiplegia and speech disorder. He was diagnosed as having an acute right middle cerebral artery embolism and underwent an MT. The embolic source was found to be a PVE vegetation. However, histopathological analysis of the thrombus could not detect the actual diagnosis. Although he was treated for bacterial endocarditis, his blood culture revealed a rare fungal infection with Exophiala dermatitidis not until >3 weeks after admission. Subsequently, a ß-D-glucan assay also indicated elevated levels. Although he underwent an aortic valve replacement on day 36, MRI showed multiple minor embolic strokes till that day. Early diagnosis of fungal endocarditis and detection of the causative pathogen are still challenging, and the disease has a high risk of occurrence of early and repeated embolic stroke. In addition to clinical findings and pathological studies, ß-D-glucan assay might be a good tool for the diagnosis and evaluation of fungal endocarditis.


Differential expression of trypsinogen and tumor-associated trypsin inhibitor (TATI) in bladder cancer.
Tumor-associated trypsin inhibitor (TATI) is a marker of mucinous ovarian carcinoma, but it is also widely expressed in other malignant tumors and normal human tissues. Elevated serum concentrations of TATI are of prognostic value in ovarian, kidney, and bladder cancer. Tumor-associated trypsin is co-expressed with TATI in many malignancies and is thought to be involved in tumor invasion. TATI mRNA has been shown to be overexpressed in bladder cancer. We therefore studied whether trypsinogen expression also can be detected in bladder cancer and how this and TATI expression are associated with the clinicopathological characteristics of the tumors. We used RT-PCR, in situ hybridization and immunohistochemistry to detect trypsinogen- and TATI mRNA and protein in tissue samples from 28 bladder cancer patients and ten benign urothelia. TATI expression was detected in all benign tissues and non-invasive tumors. However, the expression was lower in the muscle-invasive tumors (pT2; n=5), whereas trypsinogen expression was seen in all but one non-invasive tumor. We conclude that trypsinogen is expressed in both malignant and benign bladder epithelium, whereas TATI expression decreases with increasing stage and grade of the tumor. This may suggest that a balanced expression of TATI and trypsinogen is required in normal tissue and that this balance is disrupted during tumor progression.


The structure of substrate-free 1,5-anhydro-D-fructose reductase from Sinorhizobium meliloti 1021 reveals an open enzyme conformation.
1,5-Anhydro-D-fructose (1,5-AF) is an interesting building block for enantioselective and stereoselective organic synthesis. Enzymes acting on this compound are potential targets for structure-based protein/enzyme design to extend the repertoire of catalytic modifications of this and related building blocks. Recombinant 1,5-anhydro-D-fructose reductase (AFR) from Sinorhizobium meliloti 1021 was produced in Escherichia coli, purified using a fused 6×His affinity tag and crystallized in complex with the cofactor NADP(H) using the hanging-drop technique. Its structure was determined to 1.93 Å resolution using molecular replacement. The structure displays an empty substrate-binding site and can be interpreted as an open conformation reflecting the enzyme state shortly after the release of product, presumably with bound oxidized cofactor NADP⁺. Docking simulations indicated that amino-acid residues Lys94, His151, Trp162, Arg163, Asp176 and His180 are involved in substrate binding, catalysis or product release. The side chain of Lys94 seems to have the ability to function as a molecular switch. The crystal structure helps to characterize the interface relevant for dimer formation as observed in solution. The crystal structure is compared with the structure of the homologue from S. morelense, which was solved in a closed conformation and for which dimer formation in solution could not be verified but seems to be likely based on the presented studies of S. meliloti AFR.


Integrin overexpression induced by high glucose and by human diabetes: potential pathway to cell dysfunction in diabetic microangiopathy.
The nature of the process leading to the acellular nonperfused capillaries of diabetic microangiopathy remains unknown. Because these capillaries manifest thickened basement membranes, we asked whether the process causing deposition of excess extracellular matrix in diabetes modifies cell-matrix interactions in a direction that would compromise cell renewal. In 44 individual isolates of human umbilical vein endothelial cells we observed that high glucose concentrations (30 mM) induce coordinate increases in the levels of mRNAs encoding fibronectin and the fibronectin-specific integrin receptor alpha 5 beta 1 as well as in the cognate proteins. Expression of the integrin subunit alpha 3, component of the alpha 3 beta 1 polyspecific receptor for fibronectin, laminin, and collagen, was also up-regulated by high glucose. Overexpression of integrins correlated with increased cell attachment to exogenous fibronectin and laminin as well as to complex matrix. Moreover, cells exhibited firmer steady-state adhesion to their own matrix. To correlate these in vitro observations with events in human diabetic retinopathy we measured integrin levels in retinal trypsin digests prepared from 10 patients with 8.2 +/- 1.6 (mean +/- SE) years of diabetes and 10 age- and sex-matched nondiabetic controls. Microvessels of diabetic patients showed increased immunostaining for beta 1 integrin (P = 0.025) when compared with control microvessels. These data show that high glucose and diabetes increase integrin expression and thus alter the interaction of vascular endothelial cells with their basement membranes in the direction of firmer cell-matrix adhesion. This could compromise the migration and replication critical to the reendothelialization process and contribute to microvascular occlusion.


Construct validity of the Bruininks-Oseretsky Test of Motor Proficiency-short form for a sample of Greek preschool and primary school children.
The construct validity of the short form of the Bruininks-Oseretsky Test of Motor Proficiency for the assessment of gross and fine motor skills was assessed in 377 nondisabled Greek preschool and primary school children (age range 5 yr. to 8:3 mo.) from urban areas of northern Greece. Analysis showed the three factors accounted for 54.1% of the total score variance, agreeing with the earlier findings. Moreover, the item scores had statistically significant relationships with the total short-form score, except for that of copying a circle with the preferred hand. This latter item was also the only one with a small effect size. Age confirmed a statistically significant effect on the scores of the half items of the test battery, also an earlier finding. This test seemed to be a valid test of motor proficiency in normal Greek preschool and primary school children.


[Pathological features and treatment of T lymphoma].
T lymphomas are classified into two types from surface phenotype, thymic T (T1) and Peripheral T (T2) lymphoma, and T2 lymphomas, are furthermore subdivided to inducer/helper (Ti/h or T4) and cytotoxic/suppressor (Tc/s or T8) type. But even in ATLL (adult T cell leukemia/lymphoma) believed to be a model of Ti/h type, the heterogeneities of surface phenotype are reported frequently. All of the pleomorphic and lymphoblastic and a part of small cell, medium-sized cell, mixed and large cell types have a T-cell phenotype. In addition to these histologies, AILD/IBL/IBL-like T lymphoma, T-zone lymphoma and So-called Lennert's lymphoma also hold T-cell nature. The heterogenecity and the existence of the borderline area between neoplasm and reactive lymphadenitis or hyperplasia often confused the clinicians and hematopathologists. From our experience, forty nine percent 5 year survival of T lymphoma other than lymphoblastic and pleomorphic type suggests the propriety of classifying T lymphoma into high grade and intermediate grade malignancies. Treatment of T lymphomas are basically distinguishable to two categories, for T1 and T2 lymphomas. The treatment of T1 lymphoma should be an aggressive one including CNS prophylaxis. At present, the recommendable treatment of T2 lymphoma is to apply the best regimens obtained from B cell lymphoma study. As aggressive treatment for ATL does not always yield favorable results, the concept of therapy will become clear near future. An intensive supportive therapy including T-S prophylaxis should be combined actively in the treatment program.


Blood-based transcriptomics: leukemias and beyond.
In 1999, Golub et al. proposed for the first time microarray-based transcriptional profiling to be used as a new technology for the differential diagnosis of acute myeloid leukemias and acute lymphocytic leukemias. This very preliminary study sparked great enthusiasm beyond the leukemias. Over the last 10 years, numerous studies addressed the use of gene expression profiling of peripheral blood from patients with malignancies, infectious diseases, autoimmunity and even cardiovascular diseases. Despite this great effort, no single test has yet been established using microarray-based transcriptional profiling of peripheral blood. Here we highlight the advances in the field of blood transcriptomics during the last 10 years and also critically discuss the issues that need to be resolved before blood transcriptomics will become part of daily diagnostics in the leukemias, as well as in other diseases showing involvement of peripheral blood.


Eye preferences in common marmosets (Callithrix jacchus): influence of age, stimulus, and hand preference.
Eye preferences of the common marmoset ( Callithrix jacchus ) were examined, taking into account age, arousal, and hand preference. Monocular eye use for looking through a small hole at a stimulus was recorded. Of 21 marmosets, 20 displayed right-eye preferences for viewing a piece of familiar food. In subjects tested at 3-8, 12, 15-18, and 22 months, eye preferences were consistent across age. A group bias, indicative of right-eyedness, was also found for viewing other stimuli. The stimuli included a watch, mirror, model of a beetle, and the experimenter's hand. However, when the marmosets viewed a threatening stimulus, a model resembling two rearing snakes, they displayed increased arousal (indicated by longer duration between monocular viewing events and increased incidence of aroused vocalisations) and the eye preferences shifted away from a preference for the right eye to either no preference or a left-eye preference. No relationship between eye preference and hand preference for holding food was found. Therefore, we suggest that eye preferences may reflect hemispheric specialisations for perceptual processing, according to the emotional valence of the stimulus.


Hormonal regulation of aldose reductase in rat ovary during the estrous cycle.
The physiological roles of aldose reductase [alditol:NAD(P)+1-oxidoreductase] have not been fully elucidated yet, although it has been implicated in the pathogenesis of diabetic complications. In the rat ovary we found remarkable changes in the enzyme level during the 4-day estrous cycle. After diestrus, the activity and protein content of aldose reductase increased to the maximum level on proestrous morning and rapidly fell off to the lowest level on the early morning of estrus. At this time its mRNA level in the ovary was significantly decreased compared with that on the morning of proestrus. Immunohistochemical staining of the diestrous ovary demonstrated localization of the enzyme protein in the granulosa cells and in the oocytes. At the end of proestrus when its level was low, immunoreactive aldose reductase in the granulosa cells was localized preferentially to the antrum side, with lesser staining in the cells lining the follicles. Administration of chlorpromazine to the rats on proestrus significantly restored the enzyme level on the following morning of the expected estrus. This effect of chlorpromazine was abolished when human chorionic gonadotropin was administered to the chlorpromazine-treated rats. When chlorpromazine was administered to the rats treated with bromocriptine, an inhibitor of pituitary prolactin secretion, aldose reductase activity in the ovary was significantly elevated compared with that in the rats treated with chlorpromazine alone. These findings suggest that in the rat ovary it is under hormonal regulation during the estrous cycle. The enzyme may possess a new functional role in the reproductive system of the female rat, which can be disordered under diabetic conditions.


Predicted four-wave mixing and tripling rates for neonlike yttrium x-ray laser radiation in sodiumlike plasmas.
Presented are predicted conversion rates for four-wave mixing of the output of the Ne-like Y soft-x-ray laser (15.495 nm) with that of an optical laser in a Na-like Ca plasma to give radiation at ~ 7.8 nm (approximate frequency doubling). Also presented are frequency tripling rates of the Ne-like Y laser in a Na-like V plasma to give radiation at 5.165 nm. In each case the nonlinear susceptibilities and converted intensities are calculated, and phase-matching considerations are discussed.


Treatment of confluent and reticulated papillomatosis with azithromycin.
Confluent and reticulated papillomatosis (CRP) is a relatively rare disorder of unknown origin, mostly affecting young female adults. We here present the case of a 21-year-old male patient with confluent and reticulated papillomatosis. Skin examination revealed brownish, verrucous, hyperkeratotic, 2 to 5 mm papules, which formed confluent patches and plaques with a reticulate network on the interscapular area. The patient was initially treated with ketoconazole cream for two weeks without improvement. The disease can be rather persistent and resistant to topical therapy. Our case showed a satisfactory response to treatment with azithromycin. Although this treatment is known to be effective in some cases, the action mechanism of azithromycin on CRP is not fully understood.


A randomized controlled trial comparing amoxicillin and azithromycin for the treatment of Chlamydia trachomatis in pregnancy.
Our goal was to compare the efficacy of azithromycin with that of amoxicillin for the treatment of Chlamydia trachomatis infection during pregnancy. A randomized controlled trial of pregnant women with cervical C trachomatis infection receiving care at two inner-city, university-based prenatal clinics. Pregnant women were randomly assigned to receive either oral amoxicillin, 500 mg, three times daily for 7 days, or oral azithromycin, 1 g, in a single dose. Partners were referred for treatment. Tests of cure were scheduled 4 weeks after initiation of treatment. Statistical analysis was performed by using the Student t test and chi2 analysis. One hundred twenty-nine pregnant women were enrolled, and 110 (85%) completed the protocol. There was similar treatment efficacy between amoxicillin and azithromycin (58% vs 64%, respectively,P =.56). In the amoxicillin group 3 women (5.5%) were intolerant, compared with 6 (10.9%) in the azithromycin group (P =.31). Amoxicillin and azithromycin are equally efficacious in the treatment of cervical C trachomatis during pregnancy.


Scurvy. A case caused by peculiar dietary habits.
A 9-year-old girl had the insidious development of lethargy, gingival erosions, and follicular hyperkeratosis with perifollicular hemorrhage. A dietary history disclosed that she consumed only one kind of sandwich and beverage and took no other foods. A skin biopsy specimen was consistent with the diagnosis of scurvy, and marked improvement occurred with ascorbic acid therapy. Although it is an uncommon disorder in the United States, scurvy may occur in persons with prolonged and peculiar dietary habits.


GS6, a member of the GRAS gene family, negatively regulates grain size in rice.
Grain size is an important yield-related trait in rice. Intensive artificial selection for grain size during domestication is evidenced by the larger grains of most of today's cultivars compared with their wild relatives. However, the molecular genetic control of rice grain size is still not well characterized. Here, we report the identification and cloning of Grain Size 6 (GS6), which plays an important role in reducing grain size in rice. A premature stop at the +348 position in the coding sequence (CDS) of GS6 increased grain width and weight significantly. Alignment of the CDS regions of GS6 in 90 rice materials revealed three GS6 alleles. Most japonica varieties (95%) harbor the Type I haplotype, and 62.9% of indica varieties harbor the Type II haplotype. Association analysis revealed that the Type I haplotype tends to increase the width and weight of grains more than either of the Type II or Type III haplotypes. Further investigation of genetic diversity and the evolutionary mechanisms of GS6 showed that the GS6 gene was strongly selected in japonica cultivars. In addition, a "ggc" repeat region identified in the region that encodes the GRAS domain of GS6 played an important historic role in the domestication of grain size in rice. Knowledge of the function of GS6 might aid efforts to elucidate the molecular mechanisms that control grain development and evolution in rice plants, and could facilitate the genetic improvement of rice yield.


Mixed protection of threatened species traded under CITES.
The Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) regulates international legal trade to prevent the detrimental harvest of wildlife. We assess the volumes of threatened and non-threatened bird, mammal, amphibian, and reptile species in the CITES-managed trade and how this trade responded to category changes of species in the IUCN Red List between 2000 and 2018. In this period, over a thousand wild-sourced vertebrate species were commercially traded. Species of least conservation concern had the highest yearly trade volumes (excluding birds), whereas species in most Red List categories showed an overall decrease in trade reoccurrence and volume through time, with most species unlikely to reoccur in recent trade. Charismatic species with populations split-listed between Appendices I and II were traded in substantially lower yearly volumes when sourced from the more-threatened Appendix I populations. Species trade volumes did not systematically respond to changes in the Red List category, with 31.0% of species disappearing from trade before changing category and the majority of species revealing no difference in trade volumes from pre- to post-change. Just 2.7% (12/432) of species volumes declined and 2.1% (9/432) of volumes increased after a category change. Our findings highlight that non-threatened species dominate trade but reveal small numbers of highly threatened species in trade and a disconnect between species trade volumes and changing extinction risk. We highlight potential drawbacks in the current regulation of trade in listed species and urgently call for open and accessible assessments-non-detriment findings-robustly evidencing the sustainable use of threatened and non-threatened species alike.


Paperbark and pinard: A historical account of maternity care in one remote Australian Aboriginal town.
Maternity care in remote areas of the Australian Northern Territory is restricted to antenatal and postnatal care only, with women routinely evacuated to give birth in hospital. Using one remote Aboriginal community as a case study, our aim with this research was to document and explore the major changes to the provision of remote maternity care over the period spanning pre-European colonisation to 1996. Our research methods included historical ethnographic fieldwork (2007-2013); interviews with Aboriginal women, Aboriginal health workers, religious and non-religious non-Aboriginal health workers and past residents; and archival review of historical documents. We identified four distinct eras of maternity care. Maternity care staffed by nuns who were trained in nursing and midwifery serviced childbirth in the local community. Support for community childbirth was incrementally withdrawn over a period, until the government eventually assumed responsibility for all health care. The introduction of Western maternity care colonised Aboriginal birth practices and midwifery practice. Historical population statistics suggest that access to local Western maternity care may have contributed to a significant population increase. Despite population growth and higher demand for maternity services, local maternity services declined significantly. The rationale for removing childbirth services from the community was never explicitly addressed in any known written policy directive. Declining maternity services led to the de-skilling of many Aboriginal health workers and the significant community loss of future career pathways for Aboriginal midwives. This has contributed to the current status quo, with very few female Aboriginal health workers actively providing remote maternity care.


Biohydrogen production from cattle wastewater by enriched anaerobic mixed consortia: influence of fermentation temperature and pH.
Experiments were conducted to select a natural mixed microflora seed source and investigate the effect of temperature and pH on fermentative hydrogen (H2) production from cattle wastewater by sewage sludge. Sewage sludge was shown to have higher cumulative H2 production than other inoculum collected from cow dung compost, chicken manure compost, and river sludge. Experimental results show that H2 production from cattle wastewater was significantly affected by both pH and temperature of the culture. The maximum H2 yield was obtained at pH 5.5. H2 yield and the ratio of butyrate/acetate (Bu/Ac) followed a similar production trend, suggesting that butyrate formation might favor H2 production. The optimal temperature for H2 production from cattle wastewater was 45 degrees C with peak values of H2 production (368 ml), hydrogen yield of 319 ml H2/g chemical oxygen demand (COD) consumed, and butyrate/acetate ratio of 1.43. Presence of ethanol and propionic acid indicated decreased hydrogen production; their concentrations were also affected by pH and temperature. A modified Gompertz model adequately described H2 production and bacterial growth.


Altered Microbiota, Impaired Quality of Life, Malabsorption, Infection, and Inflammation in CVID Patients With Diarrhoea.
Background: Diarrhoea is the commonest gastrointestinal symptom in patients with common variable immunodeficiency (CVID). Objective: The aim of this study was to describe the prevalence and clinical presentation of chronic and recurrent diarrhoea in the Royal-Free-Hospital (RFH) London CVID cohort, including symptoms, infections, level of inflammation, and microbial diversity. Methods: A cross-sectional study of adult CVID patients (139 out of 172 diagnosed with CVID completed the screening questionnaire). Those with diarrhoea ≥6 days/month had stool and blood samples analysed and completed the short Inflammatory Bowel Disease Questionnaire (sIBDQ). BMI, spleen-size, lymphocytes and gut-microbial diversity were compared. Due to logistical and clinical restraints, not all patients could be analysed on all measures. Results: 46/139 (33.1%) patients had current significant diarrhoea. In patients with past or present diarrhoea, BMI was lower (median 23.7 vs. 26, p = 0.005), malabsorption more common (57.97 vs. 35.71%, p = 0.011). CD4+ lymphocytes were higher in patients with diarrhoea (p = 0.028; n = 138), but CD4+ naïve lymphocytes were significantly higher in non-diarrhoea patients (p = 0.009, N = 28). Nine patients had confirmed or probable current gastrointestinal infections. Calprotectin was >60 μg/g in 13/29 with significant diarrhoea including 9 without infection. SIBDQ revealed a low median score of 4.74. Microbial alpha diversity was significantly lower in CVID patients compared to healthy household controls. There was no significant difference in alpha diversity in relation to antibiotic intake during the 6 weeks prior to providing samples. Conclusion: Patients with CVID and significant diarrhoea had infections, raised calprotectin, malabsorption, a lower BMI, an impaired quality of life (comparable to active IBD), and they differed from non-diarrhoea patients in their lymphocyte phenotyping. Furthermore, microbial diversity was altered. These findings strongly imply that there may be an inflammatory nature and a systemic predisposition to diarrhoea in CVID, which necessitates further investigation.


Measurement of protein in natural rubber latex.
Latex from the Brazilian rubber tree (Hevea brasiliensis) is the source of virtually all commercial natural rubber (cis-1,4-polyisoprene). Products made from natural rubber latex include gloves, condoms, and hundreds of different medical devices. However, recent reports of widespread life-threatening latex-associated Type I allergies have focused attention on latex proteins as serious allergens. In this paper, we describe a method that permits accurate and reproducible determination of protein in latex and that includes a procedure for solubilizing latex proteins and removing rubber. Also, we show that interfering substances in latex can be removed by precipitating proteins with sodium deoxycholate and trichloroacetic acid, and that latex proteins can be recovered and quantified with 2,2'-bicinchoninic acid.


Unusual spread of liposarcoma.
The aim of our study was to investigate the unusual pattern of metastatic spread of liposarcoma. We retrospectively studied thirty-two patients with liposarcoma (in seventeen located in the retroperitoneum and in fifteen in the extremities) who were managed at our institution over a ten-year period. Six patients with extremity liposarcoma developed local recurrence and or distal metastases and in three the site of the distal spread was other than the lungs. In only one patient with retroperitoneal liposarcoma we observed extra-pulmonary spread. The histologic type of all four cases with unusual spread was myxoid, with small areas of round cell differentiation in two cases. The survival of the patients after the initial recurrence was relatively prolonged (6, 1.5, 8 and 3 years with the last patient alive and well). Physicians should maintain a low threshold for initiating evaluation of relatively minor symptoms in patients with liposarcoma, as these symptoms may reflect the first manifestation of an extrapulmonary metastasis. Such an approach should result in earlier detection and hopefully improve survival for patients with liposarcoma.


Inference of the phylogenetic position of the phylum Deferribacteres from gene order comparison.
The phylogenetic placement of the phylum Deferribacteres was investigated on the basis of gene order comparisons of completely sequenced bacterial genomes. Two completely sequenced Deferribacteres species share five sets of gene arrangements with a group of phyla, Proteobacteria, Aquificae, Planctomycetes, Spirochaetes, Bacteroidetes, Chlorobi, Acidobacteria, Verrucomicrobia, Elusimicrobia and Nitrospirae, while the other group of phyla, Synergistetes, Firmicutes, Actinobacteria, Thermotogae, Chloroflexi and Deinococcus-Thermus, Fusobacteria, shares alternative sets of gene arrangements, suggesting that the Deferribacteres is classified in the former group of phyla. Gene transfers that are thought to have occurred in a common ancestor of the Deferribacteres, Deltaproteobacteria and Nitrospirae exclusive of virtually all other phyla were identified, which suggests that the Deferribacteres is phylogenetically proximal to the Proteobacteria and Nitrospirae.


A novel antineuronal antibody in stiff-man syndrome.
Two-thirds of stiff-man syndrome (SMS) patients harbor an autoantibody specific for a 64-kD species of glutamic acid decarboxylase (GAD), the rate-limiting enzyme in GABA synthesis. We assayed SMS antisera from two patients with SMS for the presence of anti-GAD antibodies using Western blot, immunohistochemical, and enzymatic analyses. Both SMS antisera recognized an 80-kD antigen present in human and rat neuronal extracts, and failed to recognize the 64-kD GAD species. Immunohistochemistry demonstrated neuronal binding identical to that reported with anti-GAD antibodies. Both sera depleted GAD activity from brain extracts. Our analysis indicates that these SMS antisera differ from previously reported SMS antisera by recognizing a novel 80-kD antigen, and suggests that they contain antibodies directed against either a species of GAD different in size from the 64-kD enzyme, or a protein that co-immunoprecipitates with GAD.


Autoimmune adrenal insufficiency and autoimmune polyendocrine syndromes: autoantibodies, autoantigens, and their applicability in diagnosis and disease prediction.
Recent progress in the understanding of autoimmune adrenal disease, including a detailed analysis of a group of patients with Addison's disease (AD), has been reviewed. Criteria for defining an autoimmune disease and the main features of autoimmune AD (history, prevalence, etiology, histopathology, clinical and laboratory findings, cell-mediated andhumoral immunity, autoantigens and their autoepitopes, genetics, animal models, associated autoimmune diseases, pathogenesis, natural history, therapy) have been described. Furthermore, the autoimmune polyglandular syndromes (APS) associated with AD (revised classification, animal models, genetics, natural history) have been discussed. Of Italian patients with primary AD (n = 317), 83% had autoimmune AD. At the onset, all patients with autoimmune AD (100%) had detectable adrenal cortex and/or steroid 21-hydroxylase autoantibodies. In the course of natural history of autoimmune AD, the presence of adrenal cortex and/or steroid 21-hydroxylase autoantibodies identified patients at risk to develop AD. Different risks of progression to clinical AD were found in children and adults, and three stages of subclinical hypoadrenalism have been defined. Normal or atrophic adrenal glands have been demonstrated by imaging in patients with clinical or subclinical AD. Autoimmune AD presented in four forms: as APS type 1 (13% of the patients), APS type 2 (41%), APS type 4 (5%), and isolated AD (41%). There were differences in genetics, age at onset, prevalence of adrenal cortex/21-hydroxylase autoantibodies, and associated autoimmune diseases in these groups. "Incomplete" forms of APS have been identified demonstrating that APS are more prevalent than previously reported. A varied prevalence of hypergonadotropic hypogonadism in patients with AD and value of steroid-producing cells autoantibodies reactive with steroid 17alpha-hydroxylase or P450 side-chain cleavage enzyme as markers of this disease has been discussed. In addition, the prevalence, characteristic autoantigens, and autoantibodies of minor autoimmune diseases associated with AD have been described. Imaging of adrenal glands, genetic tests, and biochemical analysis have been shown to contribute to early and correct diagnosis of primary non-autoimmune AD in the cases of hypoadrenalism with undetectable adrenal autoantibodies. An original flow chart for the diagnosis of AD has been proposed.


Coping with Dementia in the Middle of the COVID-19 Pandemic.
Multiple neurological complications have been associated with the coronavirus disease-19 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2. This is a narrative review to gather information on all aspects of COVID-19 in elderly patients with cognitive impairment. First, the following three mechanisms have been proposed to underlie the neurological complications associated with COVID-19: 1) direct invasion, 2) immune and inflammatory reaction, and 3) hypoxic brain damage by COVID-19. Next, because the elderly dementia patient population is particularly vulnerable to COVID-19, we discussed risk factors and difficulties associated with cognitive disorders in this vulnerable population. We also reviewed the effects of the patient living environment in COVID-19 cases that required intensive care unit (ICU) care. Furthermore, we analyzed the impact of stringent social restrictions and COVID-19 pandemic-mediated policies on dementia patients and care providers. Finally, we provided the following strategies for working with elderly dementia patients: general preventive methods; dementia care at home and nursing facilities according to the activities of daily living and dementia characteristics; ICU care after COVID-19 infection; and public health care system and government response. We propose that longitudinal follow-up studies are needed to fully examine COVID-19 associated neurological complications, such as dementia, and the efficacy of telemedicine/telehealth care programs.


Pre-clinical evaluation of soybean-based wound dressings and dermal substitute formulations in pig healing and non-healing in vivo models.
In the last decade, a new class of natural biomaterials derived from de-fatted soybean flour processed by either thermoset or extraction procedures has been developed. These biomaterials uniquely combine adaptability to various clinical applications to proven tissue regeneration properties. In the present work, the biomaterials were formulated either as hydrogel or as paste formulation and their potential as wound dressing material or as dermal substitute was assessed by two in vivo models in pig skin: The healing full-thickness punch biopsy model and the non-healing full-thickness polytetrafluoroethylene (PTFE) chamber model. The results clearly show that collagen deposition is induced by the presence of these biomaterials. A unique pattern of early inflammatory response, eliciting neutrophils and controlling macrophage infiltration, is followed by tissue cell colonization of the wound bed with a significant deposition of collagen fibers. The study also highlighted the importance in the use of optimal formulations and appropriate handling upon implantation. In large size, non-healing wounds, wound dermis was best obtained with the paste formulation as hydrogels appeared to be too loose to ensure lasting scaffolding properties. On the contrary, packing of the granules during the application of paste reduced biomaterial degradation rate and prevent the penetration of newly vascularized tissue, thus impeding grafting of split-thickness autologous skin grafts on the dermal substitute base.


Adenosine prevents protein kinase C activation during hypothermic ischemia.
The cardioprotective properties of exogenous and endogenously produced adenosine during ischemia have been shown previously. The models used to demonstrate the efficacy and mechanism of effect have been primarily of normothermic ischemia where adenosine was given pre-ischemia in an effort to mimic the preconditioning phenomena. The proposed mechanisms responsible for the protective effects of adenosine include A2-receptor mediated vasodilation, A1-receptor mediated improvement of glycolysis during ischemia and early reperfusion, and interaction with protein kinase C (PKC) pre-ischemia. This study was designed to assess the dose-dependent effects of adenosine on myocardial recovery after prolonged hypothermic ischemia. Using an isolated Langendorff perfused rabbit heart model, we subjected hearts to 8 hours of hypothermic ischemia with crystalloid cardioplegia containing adenosine 0, 0.01, 0.25, or 5 mmol/L followed by reperfusion. Pre- and postischemic (30 minutes of reperfusion) diastolic and developed pressure were compared among the groups. Translocation of PKC from cytosol to membrane, tissue levels of ATP, and total lactate production during ischemia were also determined. ATP levels at end-ischemia were higher in all adenosine-treated hearts, along with significantly enhanced anaerobic glycolysis as measured by total lactate production. Recovery of left ventricular diastolic pressure and developed pressure, however, were improved significantly only in hearts exposed to higher adenosine concentrations (0.25 and 5 mmol/L). The higher dose adenosine cardioplegia also prevented translocation of PKC from cytosol to membrane during ischemia. We conclude that adenosine provides significant protection of the ischemic myocardium during prolonged hypothermic ischemia and that 0.25 mmol/L adenosine was equally as protective as 5 mmol/L. The mechanism of protection is most likely not related to ATP preservation or enhanced glycolysis but may be caused by prevention of PKC translocation during ischemia.


Organoids capture tissue-specific innate lymphoid cell development in mice and humans.
Organoid-based models of murine and human innate lymphoid cell precursor (ILCP) maturation are presented. First, murine intestinal and pulmonary organoids are harnessed to demonstrate that the epithelial niche is sufficient to drive tissue-specific maturation of all innate lymphoid cell (ILC) groups in parallel, without requiring subset-specific cytokine supplementation. Then, more complex human induced pluripotent stem cell (hiPSC)-based gut and lung organoid models are used to demonstrate that human epithelial cells recapitulate maturation of ILC from a stringent systemic human ILCP population, but only when the organoid-associated stromal cells are depleted. These systems offer versatile and reductionist models to dissect the impact of environmental and mucosal niche cues on ILC maturation. In the future, these could provide insight into how ILC activity and development might become dysregulated in chronic inflammatory diseases.


Extraction of anthocyanins and other phenolics from black currants with sulfured water.
Health benefits of fruits, vegetables, and red wine are attributed to anthocyanins and other phytochemicals. In this research, the extraction of phenolics from black currants was optimized using different SO(2) concentrations (28, 300, 700, 1100, and 1372 ppm), temperatures (6, 20, 40, 60, and 74 degrees C), and solvent to solid ratios (S/S) (6, 20, 40, 60, and 74 mL/g). Surface response methodology was used to optimize yields of anthocyanins and total phenolics, as well as their antiradical and antioxidant activities. The extraction of phenolics varied with the SO(2) concentration, S/S, and temperature. Maximum yields of total phenolics and anthocyanins were obtained at an SO(2) concentration of 1000-1200 ppm and 19 L of solvent/kg of milled frozen berries. The increase of extraction temperature increased the rate of extraction and, thus, times to reach equilibrium for the extraction of total phenolics and anthocyanins were reduced. However, for the extraction of anthocyanins it is recommended that temperatures of 30-35 degrees C be used, as higher temperatures will degrade these compounds. Antioxidant activity was affected by all three experimental variables evaluated; however, the main variable affecting it was S/S. The higher the S/S, the lower the antioxidant index.


Acute Aerobic Exercise Remodels the Adipose Tissue Progenitor Cell Phenotype in Obese Adults.
Adipose tissue pathology in obese patients often features impaired adipogenesis, angiogenesis, and chronic low-grade inflammation, all of which are regulated in large part by adipose tissue stromal vascular cells [SVC; i.e., non-adipocyte cells within adipose tissue including preadipocytes, endothelial cells (ECs), and immune cells]. Exercise is known to increase subcutaneous adipose tissue lipolysis, but the impact of exercise on SVCs in adipose tissue has not been explored. The purpose of this study was to assess the effects of a session of exercise on preadipocyte, EC, macrophage, and T cell content in human subcutaneous adipose tissue. We collected abdominal subcutaneous adipose tissue samples from 10 obese adults (BMI 33 ± 3 kg/m2, body fat 41 ± 7%) 12 h after a 60 min acute session of endurance exercise (80 ± 3%HRpeak) vs. no acute exercise session. SVCs were isolated by collagenase digestion and stained for flow cytometry. We found that acute exercise reduced preadipocyte content (38 ± 7 vs. 30 ± 13%SVC; p = 0.04). The reduction was driven by a decrease in CD34hi preadipocytes (18 ± 5 vs. 13 ± 6%SVC; p = 0.002), a subset of preadipocytes that generates high lipolytic rate adipocytes ex vivo. Acute exercise did not alter EC content. Acute exercise also did not change total immune cell, macrophage, or T cell content, and future work should assess the effects of exercise on subpopulations of these cells. We conclude that exercise may rapidly regulate the subcutaneous adipose tissue preadipocyte pool in ways that may help attenuate the high lipolytic rates that are commonly found in obesity.


Long noncoding RNA polymorphisms and colorectal cancer risk: Progression and future perspectives.
Colorectal cancer (CRC) is one of the most common cancers causing death worldwide. Many long noncoding RNAs (lncRNAs) have possible carcinogenic or tumor suppressor functions. Some lncRNA polymorphisms are useful for predicting cancer risk, and may help advance personalized therapy management. While the use of lncRNAs as biomarkers is promising, there are still drawbacks, and further studies are needed to verify the consistency of current outcomes in large-scale populations and different ethnicities. Single nucleotide polymorphisms (SNPs) can disrupt a lncRNAs' function, thus enhancing or hindering disease occurrence. SNPs can directly influence the lncRNA expression by interfering with transcription factor binding or affecting indirectly a regulatory factors' expression. Moreover, the association between lncRNAs and other RNAs or proteins may be disrupted by SNPs. This research sought to assess the association between lncRNA polymorphisms and CRC risk, as well as clinical and therapeutic consequences in certain cases.


Genomic evolution and adaptation of arthropod-associated Rickettsia.
Rickettsia species are endosymbionts hosted by arthropods and are known to cause mild to fatal diseases in humans. Here, we analyse the evolution and diversity of 34 Rickettsia species using a pangenomic meta-analysis (80 genomes/41 plasmids). Phylogenomic trees showed that Rickettsia spp. diverged into two Spotted Fever groups, a Typhus group, a Canadensis group and a Bellii group, and may have inherited their plasmids from an ancestral plasmid that persisted in some strains or may have been lost by others. The results suggested that the ancestors of Rickettsia spp. might have infected Acari and/or Insecta and probably diverged by persisting inside and/or switching hosts. Pangenomic analysis revealed that the Rickettsia genus evolved through a strong interplay between genome degradation/reduction and/or expansion leading to possible distinct adaptive trajectories. The genus mainly shared evolutionary relationships with α-proteobacteria, and also with γ/β/δ-proteobacteria, cytophagia, actinobacteria, cyanobacteria, chlamydiia and viruses, suggesting lateral exchanges of several critical genes. These evolutionary processes have probably been orchestrated by an abundance of mobile genetic elements, especially in the Spotted Fever and Bellii groups. In this study, we provided a global evolutionary genomic view of the intracellular Rickettsia that may help our understanding of their diversity, adaptation and fitness.


Significance of neither green nor red NGR bacilli in FDA-EB staining.
This Study deals with determination of viability by FDA-EB method. It has been observed that some of the bacilli do not take any colour in FDA-EB preparations. These can be called "neither green nor red" (NGR) bacilli. These non-staining bacilli should be taken into account when reporting viability by FDA-EB method.


Outcomes of elderly hip fracture patients in the Swiss healthcare system: A survey prior to the implementation of DRGs and prior to the implementation ofa Geriatric Fracture Centre.
PROBLEM AND QUESTIONS: The consequences for elderly patients with hip fractures are well known. In Switzerland, the introduction of diagnosis related groups (DRG) will bring additional challenges. New models of care, such as Geriatric Fracture Centres (GFC), may be the key to minimising negative outcomes. This study documents outcomes of hip fracture patients in the Swiss healthcare system, for use as baseline data prior to DRG- and GFC-implementation, and compares them to results reported in the literature, for example by Cooper (1997). This was a prospective cohort quality assurance survey with a one-year follow-up. Outcomes were mortality, living situation, required support and mobility. All patients 65 years of age or older with a proximal femoral fracture were included. Data were analysed by descriptive and interferential statistics. From 272 patients, 70% were community dwelling pre-fracture. Overall, one-year mortality was 22%. Pre-fracture community dwelling patients had better outcomes than nursing home patients with a one-year mortality rate of 12%. A total of 83% of pre-fracture community dwelling patients still lived in the community after one year but more needed help with activities of daily living (ADL) or mobility. Patients with dementia, ADL- and mobility dependency pre-fracture were significantly more at risk for being newly admitted to a nursing home. Our results reflect the clinical reality of the hip fracture population in Switzerland. Results one year after fracture were comparable to study findings in different health care systems. Our findings provide important baseline data prior to the implementation of DRG and GFC.


In vitro and in vivo expression of interleukin-1alpha and tumor necrosis factor-alpha mRNA in pemphigus vulgaris: interleukin-1alpha and tumor necrosis factor-alpha are involved in acantholysis.
Keratinocyte-derived cytokines have been implicated in the pathogenesis of a number of skin diseases. In this study we examined the possible role of keratinocyte-derived cytokines in the development of acantholysis in pemphigus vulgaris. Nineteen patients with pemphigus vulgaris, demonstrating the characteristic clinical, pathologic, and immunopathologic findings were studied. In situ immunolabeling demonstrated the presence of two cytokines interleukin-1alpha and tumor necrosis factor-alpha, in lesional and perilesional areas. Results were confirmed by reverse transcriptase-polymerase chain reaction, demonstrating overexpression of both cytokines in vivo. To study the role of these cytokines in the pathogenesis of pemphigus vulgaris both in vitro and in vivo studies were performed. The results of the in vitro study demonstrated that pemphigus vulgaris IgG induced interleukin-1alpha and tumor necrosis factor-alpha mRNA in the skin. The potential pathogenic role of these mediators was demonstrated by a blocking study using antibodies against human interleukin-1alpha and tumor necrosis factor-alpha in keratinocytes cultures. A combination of anti-interleukin-1alpha and anti-tumor necrosis factor-alpha antibodies inhibited in vitro pemphigus vulgaris IgG induced acantholysis. To confirm the role of interleukin-1 and tumor necrosis factor-alpha in pemphigus, we utilized passive transfer studies using interleukin-1 deficient mice (ICE-/-, interleukin-1beta-/-) and tumor necrosis factor-alpha receptor deficient mice (TNFR1R2-/-). Both groups demonstrated a decreased susceptibility to the passive transfer of pemphigus. Our data support the role of cytokines interleukin-1 and tumor necrosis factor-alpha in the pathogenesis of pemphigus vulgaris.


Surveys still teach vital non-technical lessons in General Surgery.
In general surgery, observational studies are disregarded and often seen as non-noteworthy research. We intend to defend the use of surveys in general surgery and colorectal surgery. This review highlights the historical importance and contemporary utility of surveys internationally and in our region, thus reminding Australasian surgeons and clinicians in numerous disciplines of the usefulness of this research tool. Well-constructed surveys often successfully capture qualitative data otherwise impossible to collect through randomized controlled trial. The results of these surveys may advise national policies and medical registration agencies thus having a direct influence on individuals and their public health. Samples from contemporary survey-based research publications from international and Australasian authors are used to illustrate some of the vital non-technical lessons learned in recent times.


Ca2+ oscillations and intercellular Ca2+ waves in ATP-stimulated articular chondrocytes.
Cytosolic Ca2+ oscillations are known to occur in many cell types stimulated with agonists linked to the phosphoinositide signaling pathway. Trains of repetitive short-lasting Ca2+ spikes could be induced in articular chondrocytes by extracellular ATP, an agonist potently effective in stimulating cartilage resorption. The mechanism of these Ca2+ oscillations was studied by computerized video imaging on primary cultures of articular chondrocytes. Few cycles of oscillatory activity could be evoked in the absence of extracellular Ca2+, while, for oscillations to be sustained, Ca2+ influx was required. Thapsigargin irreversibly blocked Ca2+ oscillations, thus demonstrating the crucial involvement of intracellular stores in triggering the rhythmic activity. Apart from activating intracellular Ca2+ release, extracellular ATP also induced a noncapacitive Ca2+ influx in these cells. This ATP-mediated influx modulates both the oscillation frequency and intracellular stores refilling. In monolayers of confluent cells, Ca2+ oscillations spread from cell to cell in the form of intercellular waves. Propagating waves could also be observed in the absence of extracellular Ca2+, demonstrating that Ca2+ itself is not required for signal coordination. These results demonstrate that complex spatiotemporal pathways of Ca2+ oscillations and intercellular Ca2+ waves could be activated in articular chondrocytes during degenerative diseases.


Binding of Butyl Gallate to Plant Mitochondria : II. Relationship to the Presence or Absence of the Alternative Pathway.
[(14)C]butyl gallate was used in binding studies to investigate the cyanide-resistant respiratory pathway in mitochondria isolated from a variety of sources displaying varying levels of cyanide resistance. Highly cyanide-resistant mitochondria were isolated from aroid spadices, while moderately cyanide-resistant mitochondria were isolated from either mung bean (Vigna radiata L.) hypocotyls or carbon dioxide/oxygen/ethylene-treated tubers. Totally cyanide-sensitive mitochondria were isolated from untreated tubers and rat liver. With one exception, all the plant mitochondria showed a reversible butyl gallate binding site which saturated at a level of 1.0 to 2.0 nanomoles per milligram protein. The exception, freshly harvested white potato tubers (<1 month from harvest), showed little specific butyl gallate binding, and also showed no appreciable induction of the cyanide-resistant pathway following carbon dioxide/oxygen/ethylene treatment. Only a low level, linear binding, well below that seen with plant mitochondria, was observed with rat liver mitochondria. Taken together, these results suggest a model for the interaction of the alternative pathway with the cytochrome pathway. In this model, the butyl gallate binding site (alternative oxidase) is a constitutive component in those mitochondria that are capable of developing the alternative pathway, and the binding sites associated with a second, inducible component that functions to couple the oxidase to the cytochrome pathway.


Characterization of a novel mouse cDNA, ES18, involved in apoptotic cell death of T-cells.
Using the modified screening approach in combination with expressed sequence tags, we have identified several novel cDNAs from mouse embryonic stem (ES) cells, whose expression is tissue-restricted and/or developmentally regulated. One of the cDNAs, ES18, is preferentially expressed in lymph node and thymus, and contains noteworthy features of transcriptional regulator. The expression of ES18 transcript was selectively regulated during the apoptosis of T-cell thymoma S49.1 induced by several stimuli. Interestingly, the ES18 transcript was differently regulated in the mutually antagonistic process, between dexamethasone- and A23187-induced cell death of T-cells. Moreover, the message level of ES18 was selectively enhanced by staurosporine, a broad protein kinase inhibitor, but not by other protein kinase inhibitors such as GF109203X and H89. In addition, ES18 transcript was induced by C2-ceramide, which is a mediator of both dexamethasone- and staurosporine-induced apoptotic signaling. We further showed that transient overexpression of ES18 in mouse T-cell lymphoma increased the apoptotic cell death. These data suggest that ES18 may be selectively involved in specific apoptotic processes in mouse T-cells.


Entrapment of individual DNA molecules and nanoparticles in porous alumina membranes.
Depth-resolved fluorescence imaging allows the motion of single DNA molecules and single nanoparticles at the liquid/solid interface to be recorded in real time. Porous alumina membranes were employed as model chromatographic packing material. Using a suitable pH and ionic strength, adsorptive interactions are suppressed. The effects of 3-dimensional topography, specifically the presence of nanopores, on DNA and nanoparticle migration across the surface are, thus, revealed. The residence times and the number of immobilized DNA molecules or particles increased as the pores size increased. Yet, we found that the pore diameter must be significantly larger than the particle diameter or the DNA short radius before entrapment can occur. Furthermore, the depth distribution of particles does not conform to one-dimensional diffusion in the pores, probably because of collisions with the walls. These observations provide new insights into conventional liquid chromatography as well as size-exclusion chromatography and membrane separations.


The diagnostic role of radionuclide imaging in evaluation of patients with nonhypersecreting adrenal masses.
The aim of this study was to evaluate the role of radionuclide imaging in the characterization of nonhypersecreting adrenal masses. A total of 54 patients (19 men, 35 women; mean age, 50 +/- 16 y) with nonhypersecreting unilateral adrenal tumors that had been originally detected on CT or MRI underwent adrenal scintigraphy using different radiotracers. None of the patients showed specific symptoms of adrenal hypersecretion. Screening tests for excess cortical and medullary products showed normal adrenal hormone levels. Radionuclide studies (n = 73) included (131)I-norcholesterol (n = 24), (131)I-metaiodobenzylguanidine (MIBG) (n = 23), and (18)F-FDG PET (n = 26) scans. Histology after surgery (n = 31) or adrenal biopsy (n = 23) was obtained. Adrenal lesions were represented by 19 adenomas, 4 cysts, 1 myelolipoma, 1 neurinoma, 2 ganglioneuromas, 5 pheochromocytomas, 4 pseudotumors, 6 carcinomas, 2 sarcomas, and 10 metastases (size range, 1.5- to 5-cm diameter; mean, 4.9 +/- 3.1 cm). For norcholesterol imaging, diagnostic sensitivity, specificity, and accuracy were 100%, 71%, and 92%, respectively; the positive predictive value (PPV) of the norcholesterol scan to characterize an adrenal mass as an adenoma was 89%, whereas the corresponding negative predictive value (NPV) to rule out this type of tumor was 100%. For MIBG imaging, diagnostic sensitivity, specificity, and accuracy were 100%, 94%, and 96%, respectively; the PPV of the MIBG scan to characterize an adrenal mass as a medullary chromaffin tissue tumor was 83%, whereas the corresponding NPV to rule out this type of tumor was 100%. For FDG PET, diagnostic sensitivity, specificity, and accuracy were 100%, 100%, and 100%, respectively; the PPV of FDG PET to characterize an adrenal mass as a malignant tumor was 100%, whereas the corresponding NPV to rule it out was 100%. Furthermore, in 7 patients with malignant adrenal tumors, FDG whole-body scanning revealed extra-adrenal tumor sites (n = 29), allowing an accurate diagnosis of the disease's stage using a single-imaging technique. In patients with nonhypersecreting adrenal masses, radionuclide adrenal imaging, using specific radiopharmaceuticals such as norcholesterol, MIBG, and FDG, may provide significant functional information for tissue characterization. Norcholesterol and MIBG scans are able to detect benign tumors such as adenoma and pheochromocytoma, respectively. Conversely, FDG PET allows for recognition of malignant adrenal lesions. Therefore, adrenal scintigraphy is recommended for tumor diagnosis and, hence, for appropriate treatment planning, particularly when CT or MRI findings are inconclusive for lesion characterization.


Automatic Dynamic Range Adjustment for Pedestrian Detection in Thermal (Infrared) Surveillance Videos.
This paper presents a novel candidate generation algorithm for pedestrian detection in infrared surveillance videos. The proposed method uses a combination of histogram specification and iterative histogram partitioning to progressively adjust the dynamic range and efficiently suppress the background of each video frame. This pairing eliminates the general-purpose nature associated with histogram partitioning where chosen thresholds, although reasonable, are usually not suitable for specific purposes. Moreover, as the initial threshold value chosen by histogram partitioning is sensitive to the shape of the histogram, specifying a uniformly distributed histogram before initial partitioning provides a stable histogram shape. This ensures that pedestrians are present in the image at the convergence point of the algorithm. The performance of the method is tested using four publicly available thermal datasets. Experiments were performed with images from four publicly available databases. The results show the improvement of the proposed method over thresholding with minimum-cross entropy, the robustness across images acquired under different conditions, and the comparable results with other methods in the literature.


Beta wave of the scotopic (rod) electroretinogram as a measure of the activity of human on-bipolar cells.
The beta wave of the human electroretinogram (ERG) is widely believed to reflect the activation of on-bipolar cells. However, the shape of the beta wave is also influenced by the activity of other cell types. To assess how the activity of on-bipolar cells is reflected in the human ERG, rod ERG's were recorded in the dark and on the steady fields. Derived P2 responses were obtained by computer subtraction of the receptor contribution to the ERG. The light-adapted derived P2 was shown to have properties similar to those predicted from previous studies of on-bipolar activity. This was also true of the dark-adapted derived P2 if a small (less than 10%) contribution from a negative potential was taken into consideration. The derived P2, and under certain conditions the beta wave, can be used to study rod on-bipolar activity.


Endothelin: a mediator of renal disease progression.
Glomerulosclerosis and tubulointerstitial damage are characteristics of progressive renal diseases associated with chronic proteinuria. Since numerous studies have demonstrated a correlation between proteinuria and the degree of renal damage, a causal role for proteinuria in the development of progressive renal failure has been postulated. Some in vitro data suggest that endothelins (ET), a family of endogenous peptides, could be involved in the genesis and progression of glomerular damage. Moreover, evidence that tubular cells exposed to high molecular weight proteins are induced to release ET toward the basolateral compartment, together with the capability of these peptides to influence events occurring in the interstitium, suggest that ET could also participate in interstitial inflammation. Data are now available that ET actually plays a role in the progression of chronic renal disease in different experimental models including renal mass reduction, lupus nephritis and streptozotocin-induced diabetes.


[An experimental study of regional spontaneous portasystemic shunt in cirrhotic rats].
CCl4 induced splenic portasystemic shunt (SPSS) was measured in 11 CCl4-induced cirrhotic rats and 10 controls, and mesenteric shunt (MPSS) was measured in 11 controls. 125I labeled albumin microspheres was used as nuclear markers for measurement of shunting rate. It was found that, portal resistance, free portal pressure, wedged hepatic venous pressure, portahepatic venous pressure gradient were all elevated markedly in cirrhotic rats, while the volume of portal flow had no significant difference between the two groups. SPSS and MPSS were higher remarkably those that in the normal controls, and SPSS was greater than MPSS significantly. It suggested that splenogastric venous bed is the main area for compensatory shunt and also the dangerous site of bleeding. Portaazygous disconnection is the operation of choice for control of bleeding. However it could impair the mechanism of spontaneous shunting compensation seriously. Disconnection operation combined with splenorenal shunt seems to be a reseasonable consideration.


Molecular and histological characteristics of bovine caudal nucleus pulposus by combined changes in hydrostatic and osmotic pressures in vitro.
Intervertebral disc degeneration is ubiquitous among aging patients, and altered matrix homeostasis is one of the key features of this condition. Physicochemical stresses have a significant impact on matrix homeostasis as they lead to progressive degeneration and may be associated with spinal pain and dysfunction. Thus, it is important to understand the cellular and matrix characteristics of nucleus pulposus in response to these stresses, which include hydrostatic and osmotic pressures during alternate loading conditions. We hypothesized that a combination of changes in hydrostatic pressure and in osmotic pressure that mimic normal, daily spinal stress would stimulate anabolic function, whereas a non-realistic combination of those stresses would stimulate catabolic function in nucleus pulposus cells. We examined the effects of these combined stresses, represented by 12 systematic conditions, on the metabolic activities of enzymatically isolated bovine caudal nucleus pulposus in vitro. We measured the gene expression of extracellular matrix (ECM) molecules and proliferating cell nuclear antigen (PCNA) and evaluated the quality of the matrix and the capability of cell proliferation immunohistologically. Combined cyclic hydrostatic pressure at 0.5 MPa, 0.5 Hz, and high osmotic pressure at 450 mOsm upregulated the aggrecan core protein and collagen type-II gene expression significantly (p < 0.05), and showed trends of upregulation of chondroitin sulfate N-acetylgalactosaminyltransferase 1, matrix metalloproteinase-13, and PCNA. ECM, however, contained empty spaces at a high osmotic pressure with and without hydrostatic pressure. Since ECM has highly specialized physicochemical properties, homeostasis should involve not only phenotypic cellular behavior but also turnover of ECM. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 37:466-476, 2019.


Opioid Prescription Clusters Associated With Early or Unplanned Military Separation.
Early/unplanned military separation in Active Component U.S. service members can result in reduced readiness during periods of high-tempo combat and increased demand for health care services within the Military Health System and Veterans Administration. Although current assessment tools leverage prescription data to determine deployment-limiting medication receipt and the need for interventions or waivers, there is a lack of understanding regarding opioid prescription patterns and subsequent early/unplanned military separation after return from deployment. As such, understanding these relationships could support future tool development and strategic resourcing. Therefore, the goal of the present study was to identify unique 12-month opioid prescription patterns and evaluate their relationship with early/unplanned military separation in Active Component service members who returned from deployment. This retrospective, IRB-approved cohort study included data from 137,654 Active Component Army service members who returned from deployment between 2007 and 2013, received a post-deployment (index) opioid prescription, and had at least 1 year of Active Component service post-opioid initiation. A k-means clustering analysis identified clusters using opioid prescription frequency, median dose, median days supply, and prescription breaks (≥30 days) over the 12-month post-initiation (monitoring) period. A generalized additive model examined whether cluster membership and additional covariates were associated with early/unplanned separation. In addition to the single opioid prescription (38%), the cluster analysis identified five clusters: brief/moderate dose (25%), recurrent breaks (16%), brief/high dose (11%), long/few prescriptions (8%), and high prescription frequency (2%). In the generalized additive model, the probability of early/unplanned military separation was higher for the high prescription frequency cluster (74%), followed by recurrent breaks (45%), long/few prescriptions (37%), brief/moderate dose (30%), and brief/high dose (29%) clusters, relative to the single prescription (21%) cluster. The probability of early/unplanned separation was significantly higher for service members with documented substance use disorders, mental health conditions, or traumatic brain injuries during the monitoring periods. Service members assigned male were more likely to have an early/unplanned separation relative to service members assigned female. Latinx service members and service members whose race was listed as Other were less likely to experience early/unplanned separation relative to white service members. Relative to Junior Officers, Junior Enlisted and Senior Enlisted service members were more likely to experience early/unplanned separation, but Senior Officers were less likely. Further evaluation to support the integration of longitudinal opioid prescription patterns into existing tools (e.g., a screening tool for deployment-limiting prescriptions) may enable more timely intervention and support service delivery to mitigate the probability and impact of early/unplanned separation.


Effects of short-term spaceflight and recombinant human growth hormone (rhGH) on bone growth in young rats.
The purpose of this study was to characterize the effects of short-term spaceflight and recombinant human growth hormone (rhGH) on bone growth in rapidly growing male rats. Bone growth was determined by dynamic bone histomorphometry and rhGH was administered using implanted ALZET osmotic pumps. Treatment with rhGH for 5 d had no effect on body weight but a 4-d spaceflight resulted in a small reduction in the rate of weight gain. Neither spaceflight nor rhGH altered bone length or the rate of bone elongation. In contrast, rhGH and spaceflight each resulted in site- and bone-specific increases (periosteal) and decreases (endocortical) in formation of cortical bone. The results demonstrate that: a) inhibition of periosteal bone formation observed during longer spaceflight is not apparent during a 4-d spaceflight; and b) infusion of rhGH stimulates cortical bone formation in weightless as well as in weight bearing animals.


The release of the endothelium derived relaxing factor from isolated human arteries.
Isolated human arterial segments have been used to demonstrate the presence and release of the endothelium derived relaxing factor (EDRF) in human vasculature. This has been shown in peripheral, splanchnic and coronary arteries. Agents which have been shown to promote the release of the human EDRF in these studies include acetylcholine (by a muscarinic mechanism), the calcium ionophore A23187, histamine and vasoactive intestinal peptide (VIP). Nordihydroguaretic acid (NDGA), methylene blue and haemoglobin reverse the effect of the EDRF. The EDRF effect is calcium-dependent and is not inhibited by indomethacin. Atheromatous disease in coronary arteries impairs the response to agents which release EDRF; its relative absence in this circumstance may play a role in the phenomenon of coronary artery spasm. The possibility of a specific alpha 2-adrenoceptor mechanism for the release of EDRF was investigated. This does not appear to be present in the human vasculature.


Fatty acid profile and acid phosphatase activity of fresh isolates of Pseudomonas pseudomallei.
Eighty-one fresh isolates of Pseudomonas pseudomallei from melioidosis patients were subjected to the analysis for the fatty acid composition by gas-liquid chromatography (GLC) and pH-dependent pattern of nonspecific phosphatase activity. All the test strains were identical in the GLC profile showing the three peaks of characteristic hydroxy acids (3-OH 14:0, 2-OH 16:0, 3-OH 16:0) and the two prominent peaks of cyclopropane acids (17:0 delta, 19:0 delta). They had also basically the same pH-dependent curves of the enzymatic activity with paranitrophenyl phosphate as substrate, showing two to three peaks or shoulders only in the acidic side of the curve. These two biochemical characteristics could differentiate P. pseudomallei distinctly from P. aeruginosa, but not from P. cepacia.


Insect-specific viruses in the Parvoviridae family: Genetic lineage characterization and spatiotemporal dynamics of the recently established Brevihamaparvovirus genus.
The analysis of the viruses allocated to the recently established Brevihamaparvovirus genus (Parvoviridae family), which includes all previously known brevidensoviruses, has not yet been carried out on an extensive basis. As a result, no detailed genetic lineage characterization has ever been performed for this group of insect-specific viruses. Using a wide range of molecular tools, we have explored this taxon by calculating Shannon entropy values, intra- and inter-taxon genetic distances, analysed sequence polymorphisms, and evaluated selective pressures acting on the viral genome. While the calculated Brevihamaparvovirus mutation rates were within the range of those of other parvoviruses, their genomes look to be under strong purifying selection, and are also characterized by low diversity and entropy. Furthermore, even though recombination events are quite common among parvoviruses, no evidence of recombination (either intra or intergenic) was found in the Brevihamaparvoviruses sequences analyzed. An extended taxonomic analysis and reevaluation of existing Brevihamaparvoviruses sequences, many still unclassified, was performed using cut-off values defining NS1 identity between viral sequences from the Parvovirus family. Two existing genetic lineages, Dipteran Brevihamaparvovirus 1 and Dipteran Brevihamaparvovirus 2, were rearranged and the creation of a new one, Dipteran Brevihamaparvovirus 3, was suggested. Finally, despite the uncertainties associated with both the time estimates of the most recent common ancestors, which could span from twenty thousand years before the current era to way earlier (in the last century), and the dispersal routes proposed for Brevihamaparvoviruses sequences by phylodynamic reconstruction, the analyses here presented could help define how future studies should be conducted as more isolates continue to be identified in the future, and contribute to eliminating possible analytical biases.


The effects of incident and persistent behavioral problems on change in caregiver burden and nursing home admission of persons with dementia.
The individual contributions of behavior problems to key and related outcomes in dementia, such as nursing home admission (NHA) or caregiver burden, remain unclear. This study sought to determine the ramifications of temporal change in individual behavior problems when accounting for increases in caregiver burden and time to NHA. Although burden is sometimes conceptualized as an antecedent to NHA, it has also emerged as a relevant outcome in dementia caregiving research. A sample of 4545 dementia caregivers who participated in the Medicare Alzheimer disease Demonstration Evaluation was selected for this secondary analysis. Various patterns of change in individual behavior problems were considered as predictors of increases in caregiver burden and time to NHA over a 3-year period via mixed effects and Cox proportional hazards models, respectively. Caregivers who did not indicate a care recipient's dangerous behavior initially but did so subsequently (ie, an "incident" behavior problem) were more likely to experience increases in burden (P < 0.0026). Alternatively, the persistent occurrence of behavior disturbances (particularly memory problems) emerged as the strongest predictors of time to NHA. The findings of this study suggest the benefit of examining temporal patterns of individual behavioral disturbances, and that incident and persistent problems account for different dementia outcomes over time. Considering the temporal ramifications and potency of specific behavior problems can facilitate the targeted and timely delivery of effective clinical interventions.


Non-invasive Model-Based Assessment of Passive Left-Ventricular Myocardial Stiffness in Healthy Subjects and in Patients with Non-ischemic Dilated Cardiomyopathy.
Patient-specific modelling has emerged as a tool for studying heart function, demonstrating the potential to provide non-invasive estimates of tissue passive stiffness. However, reliable use of model-derived stiffness requires sufficient model accuracy and unique estimation of model parameters. In this paper we present personalised models of cardiac mechanics, focusing on improving model accuracy, while ensuring unique parametrisation. The influence of principal model uncertainties on accuracy and parameter identifiability was systematically assessed in a group of patients with dilated cardiomyopathy ([Formula: see text]) and healthy volunteers ([Formula: see text]). For all cases, we examined three circumferentially symmetric fibre distributions and two epicardial boundary conditions. Our results demonstrated the ability of data-derived boundary conditions to improve model accuracy and highlighted the influence of the assumed fibre distribution on both model fidelity and stiffness estimates. The model personalisation pipeline-based strictly on non-invasive data-produced unique parameter estimates and satisfactory model errors for all cases, supporting the selected model assumptions. The thorough analysis performed enabled the comparison of passive parameters between volunteers and dilated cardiomyopathy patients, illustrating elevated stiffness in diseased hearts.


Global trends in total atmospheric ozone.
Analyses of the mean monthly global distributions of total ozone for the 13-year period from 1957 through 1970 reveal an upward trend of about 7.5 percent per decade in the Northern Hemisphere and about 2.5 percent per decade in the Southern Hemisphere. The increase seems to have started about March 1961 in the Northern Hemisphere and about September 1961 in the Southern Hemisphere. The cause of these trends is at present unknown.


PCV-15 and PPSV-23 coverage of invasive and respiratory tract Streptococcus pneumoniae, including MDR and XDR isolates: CANWARD 2007-20.
To compare the proportion of invasive and respiratory tract isolates of Streptococcus pneumoniae, including MDR and XDR strains, that demonstrated PCV-15 and PPSV-23 serotypes in Canada from 2007 to 2020. The CANWARD study collected 2984 S. pneumoniae isolates from 2007 to 2020 (1054 invasive, 1930 respiratory). Serotyping was performed using the Quellung reaction. Antimicrobial susceptibility testing was performed using CLSI methods. MDR/XDR was defined as resistance to ≥3/≥5 antimicrobial classes, respectively. Overall, the proportion of vaccine serotypes demonstrating a PCV-15/PPSV-23 serotype was significantly higher in blood isolates (54.6%/76.2%, respectively) than respiratory isolates (38.9%/55.3%; P < 0.0001). Similarly, PCV-15 and PPSV-23 vaccine coverage was higher for blood isolates for all demographic categories, including both genders, all regions and all age groups (P ≤ 0.0213). PCV-15/PPSV-23 coverage was also significantly higher for blood isolates demonstrating clarithromycin resistance (60.4/75.1% blood, 47.8/57.4% respiratory; P ≤ 0.009) and penicillin resistance (68.9/63.0% blood, 45.2/43.0% respiratory; P < 0.0001) and trimethoprim/sulfamethoxazole-resistant isolates for PPSV-23 only (82.6% blood, 64.3% respiratory; P = 0.0057). Vaccine coverage was numerically higher but not significantly different between specimen source for children <2 years of age, as well as ceftriaxone-, doxycycline- and levofloxacin-resistant isolates. PCV-15/PPSV-23 vaccine coverage for MDR isolates (61.8%/67.3% blood, 52.2%/56.2% respiratory) and XDR isolates (93.3% blood, 89.6% respiratory for both vaccines) was not significantly different between specimen sources. PCV-15 and PPSV-23 serotype coverage is generally greater for blood versus respiratory isolates but not for MDR and XDR isolates. Continued pneumococcal surveillance is warranted to determine future trends in vaccine coverage, serotype distribution and antimicrobial susceptibilities under the pressure of vaccine use.


The Relationship between Physical Activity, Self-Regulation and Cognitive School Readiness in Preschool Children.
(1) Background: Limited research exists on the pathways through which physical activity influences cognitive development in the early years. This study examined the direct and indirect relationships between physical activity, self-regulation, and cognitive school readiness in preschool children. (2) Method: Participants (n = 56) aged 3-5 years were recruited from the PLAYCE study, Perth, Western Australia. Physical activity was measured using 7-day accelerometry. Self-regulation was measured using the Head Toes Knees and Shoulders task and cognitive school readiness was assessed using the Bracken School Readiness Assessment. Baron and Kenny's method was used for mediation analysis. (3) Results: After adjustment for socio-demographic factors, total physical activity was positively and significantly associated with cognitive school readiness (B = 0.16, SE = 0.07, p ≤ 0.05). Moderate-vigorous physical activity (MVPA) was positively and significantly associated with self-regulation (B = 0.3, SE = 0.13, p ≤ 0.05) and cognitive school readiness score (B = 0.20, SE = 0.09, p ≤ 0.05). Self-regulation was found to be a partial mediator of the relationship between MVPA and cognitive school readiness. (4) Conclusion: These findings highlight the direct and indirect association between preschool children's physical activity, self-regulation, and cognitive school readiness. Further research is needed to determine the causal relationships between young children's physical activity and cognitive development, over time.


Laboratory-based multi-modal X-ray microscopy and micro-CT with Bragg magnifiers.
We report on the successful demonstration of X-ray phase contrast microscopy and micro computed tomography (CT) with a Bragg magnifier microscope (BMM) in a laboratory setup. The Bragg magnifiers, constituted by two channel-cut crystals in asymmetric diffraction, produced a 15X magnification of the X-ray beam, thus enabling high resolution imaging to be attained. The angular sensitivity of the crystals was used to implement analyzer-based phase contrast imaging: acquiring images at different angular positions and the three parametric images (apparent absorption, differential phase and scattering) have been obtained. Micro-CT, with resolution of about 5 μm is demonstrated with the same system. The main limitations, as well as the ways to mitigate them, are discussed with the aid of the experimental data. The technique demonstrated herein extends high-resolution, multi-modal, x-ray imaging and micro-CT to compact laboratory setups, with the potential of broadening the reach of these techniques outside the community of synchrotron users.


Controversies in modern evolutionary biology: the imperative for error detection and quality control.
The data from high throughput genomics technologies provide unique opportunities for studies of complex biological systems, but also pose many new challenges. The shift to the genome scale in evolutionary biology, for example, has led to many interesting, but often controversial studies. It has been suggested that part of the conflict may be due to errors in the initial sequences. Most gene sequences are predicted by bioinformatics programs and a number of quality issues have been raised, concerning DNA sequencing errors or badly predicted coding regions, particularly in eukaryotes. We investigated the impact of these errors on evolutionary studies and specifically on the identification of important genetic events. We focused on the detection of asymmetric evolution after duplication, which has been the subject of controversy recently. Using the human genome as a reference, we established a reliable set of 688 duplicated genes in 13 complete vertebrate genomes, where significantly different evolutionary rates are observed. We estimated the rates at which protein sequence errors occur and are accumulated in the higher-level analyses. We showed that the majority of the detected events (57%) are in fact artifacts due to the putative erroneous sequences and that these artifacts are sufficient to mask the true functional significance of the events. Initial errors are accumulated throughout the evolutionary analysis, generating artificially high rates of event predictions and leading to substantial uncertainty in the conclusions. This study emphasizes the urgent need for error detection and quality control strategies in order to efficiently extract knowledge from the new genome data.


Diagnosis of pneumonia in mechanically ventilated patients. Repeatability of the protected specimen brush.
The repeatability (i.e., the variation in repeated measurements of the same quantity) of the protected specimen brush (PSB) with quantitative cultures was assessed in 22 consecutive mechanically ventilated (MV) patients with suspected nosocomial pneumonia. Five PSB samples were collected in the same lung area during the same bronchoscopic procedure and processed for bacteriologic identification and quantitative culture. A laboratory control was also performed in order to assess the in vitro repeatability of the quantitative culture technique. The five PSB always recovered the same microorganisms, indicating a 100% qualitative repeatability for the PSB. Conversely, the quantitative repeatability was somewhat lower since in 59% of the patients the quantitative results varied by more than one log10, which is the minimal precision affordable with quantitative cultures. The distinction between presence or absence of infection based on the 10(3) cfu/ml recommended diagnostic threshold was, however, only moderately affected by the variability of the quantitative results since only three of 22 patients (13.6%) displayed results spread out on each side of the 10(3) cfu/ml break point. Intrasubject variability of quantitative results was not explained by problems with the quantitative culture technique, which proved excellent repeatability in the laboratory. This study indicated that, although the PSB technique with quantitative cultures displays an acceptable level of repeatability, caution is advisable when interpreting PSB results in critically ill patients with suspected pneumonia, especially if one refers to the 10(3) cfu/ml recommended diagnostic threshold and if a decision to treat or to abstain from treating is to be made.


Comparison of real-time PCR assay with a commercial rapid test based on the immunochromatographic principle for the detection of Chlamydia trachomatis in seminal fluid and urine specimens.
Chlamydia trachomatis is the most common sexually transmitted bacterial infection worldwide, with the highest prevalence in sexually active young women. Since most chlamydial infections are asymptomatic, facilitating the transmission of the pathogen in the population, regular screening is recommended for at-risk sexually active individuals. Hence, a sensitive, specific, inexpensive diagnostic test that can be executed efficiently and quickly to yield results would be helpful. In this study, we evaluated the performance (sensitivity and specificity) of the Chlamydia Rapid Test Device, an inexpensive rapid test based on immunochromatographic analysis. We then compared these results to those obtained using real-time PCR, the gold standard for C. trachomatis testing. Seminal fluid and urine specimens of male subjects were tested. The rapid test was applied to 220 seminal fluid samples, showing a sensitivity of 0%. On the other hand, used in 114 urine specimens, the rapid test showed 37.5% and 100% sensitivity and specificity, respectively. Hence, the Chlamydia Rapid Test Device was shown to be insufficiently sensitive to be recommended as a screening test and diagnostic method for the detection of C. trachomatis in symptomatic and asymptomatic subjects. Finally, the present investigation showed an infection prevalence of 5% calculated using seminal fluid, with a mean age of 28 years.


Synthesis of 3-oxa- and 3-azabicyclo[4.1.0]heptanes by gold-catalyzed cycloisomerization of cyclopropenes.
Allyl 3,3-dimethylcyclopropenylcarbinyl ethers or sulfonamides undergo gold-catalyzed cycloisomerization leading to 5-isopropylidene-3-oxa- and 3-azabicyclo[4.1.0]heptanes in excellent yields and with high diastereoselectivities. These reactions constitute the first examples of intramolecular cyclopropanation of an alkene by a gold carbene generated by electrophilic ring opening of a cyclopropene in the presence of gold(I) chloride.


Genetic control of male germ unit organization in Arabidopsis.
In flowering plants, the vegetative nucleus and the two sperm cells are proposed to form a functional assemblage, the male germ unit (MGU). Here, we describe the developmental pathway of MGU assembly in Arabidopsis and report two classes of mutations that affect the integrity and/or the positioning of the MGU in the mature pollen grain. In germ unit malformed (gum) mutants, the vegetative nucleus is positioned adjacent to the pollen grain wall, separate from the two sperm cells, whereas in MGU displaced (mud) mutants, the intact MGU is displaced to the pollen grain wall. mud and gum mutants correspond to male-specific gametophytic mutations that also reduce pollen fitness. Genetic mapping showed that the gum1 and gum2 mutations are genetically linked, possibly allelic, whereas the mud1 and mud2 mutations correspond to two unlinked loci mapping on different chromosomes. The hierarchical relationship between mud and gum mutations was investigated by phenotypic analysis of double mutants. gum1 appeared to act earlier than mud1 and mud2, affecting initial MGU assembly and its stability during pollen maturation. In contrast, mud1 and mud2 mutations appear to act only on MGU positioning during final maturation. From in planta analyses of pollen germination in mud and gum mutants, we conclude that the initial proximity and positioning of MGU components is not required for their entrance into the pollen tube, but the efficiency of MGU translocation is reduced.


Characteristics of maximum performance of pedaling exercise in recumbent and supine positions.
To determine the characteristics of maximum pedaling performance in the recumbent and supine positions, maximum isokinetic leg muscle strength was measured in eight healthy male subjects during pedaling at three velocities (300°/s, 480°/s, and 660°/s), and maximum incremental tests were performed for each position. The maximum isokinetic muscle strength in the recumbent position was 210.0 ± 29.2 Nm at 300°/s, 158.4 ± 19.8 Nm at 480°/s, and 110.6 ± 13.2 at 660°/s. In contrast, the muscle strength in the supine position was 229.3 ± 36.7 Nm at 300°/s, 180. 7 ± 20.3 Nm at 480°/s, and 129.6 ± 14.0 Nm at 660°/s. Thus, the maximum isokinetic muscle strength showed significantly higher values in the supine position than in the recumbent position at all angular velocities. The knee and hip joint angles were measured at peak torque using a goniometer; the knee joint angle was not significantly different between both positions, whereas the hip joint angle was greater in the supine position than in the recumbent position (Supine position: 137.3 ± 9. 33 degree at 300°/s, 140.0 ± 11.13 degrees at 480°/s, and 141.0 ± 9.61 degrees at 660°/s. Recumbent position: 99.5 ± 12.21 degrees at 300°/s, 101.6 ± 12.29 degrees at 480°/s, and 105.8 ± 14.28 degrees at 660°/s). Peak oxygen uptake was higher in the recumbent position (50.3 ± 4.43 ml·kg(-1)·min(-1)) than in the supine position (48.7 ± 5.10 ml·kg(-1)·min(-1)). At maximum exertion, the heart rate and whole-body rate of perceived exertion (RPE) were unaffected by position, but leg muscle RPE was higher in the supine position (19.5 ± 0.53 than in the recumbent position (18.8 ± 0.71). These results suggest that the supine position is more suitable for muscle strength exertion than the recumbent position, and this may be due to different hip joint angles between the positions. On the contrary, the endurance capacity was higher in the recumbent position than in the supine position. Since leg muscle RPE was higher in the supine position than in the recumbent position, it was suggested that different burdens imposed on active muscles in both positions exerted an impact on the result of the endurance capacity. Key pointsIsokinetic maximal peak torque measured in this study during pedaling showed higher values in the supine position than in the recumbent position at all angular velocities.Maximum oxygen uptake as evaluated by maximum incremental testing showed higher values in the recumbent position than in the supine position.No significant changes in the angle of peak torque for the knee joint or hip joint were observed in either the recumbent or supine position even at an increased angular velocity. These observations indicate the effectiveness of a cycle-type muscle strength assessment device for evaluating leg muscle strength.


New strategies in ovarian cancer: translating the molecular complexity of ovarian cancer into treatment advances.
An improved understanding of the genomics of ovarian cancer and the separation of ovarian cancer into histologically and molecularly defined subgroups have affected drug development and clinical trial design in ovarian cancer. Active therapies that have been tested in ovarian cancer include agents that inhibit angiogenesis and poly (ADP-ribose) polymerase inhibitors (PARPi). However, no FDA drug approvals for ovarian cancer have been granted since 2006, and overall survival improvements have been difficult to achieve with new agents. The genomic complexity of ovarian cancer and modest single-agent activity of many biologic agents in this disease have led to testing of biologic agent combinations. In this article, we review recent advances in the understanding of the molecular diversity of ovarian cancer as well as emerging therapeutic strategies such as new agents and biologic combinations that attempt to target multiple aberrant pathways in this cancer.


Metastatic cerebral choriocarcinoma coexistent with a viable pregnancy.
Gestational choriocarcinoma associated with a viable pregnancy is extremely rare, and such choriocarcinoma with metastases presenting during the pregnancy is even more exceptional. Metastases from this tumor may present in a variety of ways depending on the site of the metastatic lesion, and can be fatal before choriocarcinoma is even suspected. We describe a 32-year-old primigravida presenting at 31 weeks gestation with a grand mal seizure due to cerebral metastases secondary to gestational choriocarcinoma who was subsequently successfully treated with chemotherapy. To our knowledge this is the first reported case of choriocarcinoma presenting with signs due to cerebral metastases during pregnancy where both the mother and child survived. This paper emphasizes the need to consider metastatic choriocarcinoma in any gravid female who presents with unusual neurological signs because of the life-threatening nature of this potentially curable disease.


Enhancing Student Centered Active-Learning by "Flipped Classrooms" In a Histology Module.
Flipped learning has been the focus of significance and area of interest for medical educationists but accounts of the progression and the assessment of this pedagogical prototype are lacking. The present study describes how a histology module was delivered using the flipped learning approach. This qualitative and quantitative analysis was undertaken among First Professional MBBS students studying human anatomy at All India Institute of Medical Sciences, Jodhpur Rajasthan, India from 2016 to 2019. The participants were subjected to conventional and active learning approach i.e. flipped classroom for the various separate topics of histology with comparable level of difficulty. The students were assessed for subject knowledge by a short assessment which was taken after each session. A feedback from them in reference to use of flipped learning approach in regular teaching-learning and their experience was also obtained. Both the conventional and flipped classroom teaching showed significant changes in knowledge of participants, though mean test score was higher in the flipped learning activity. In the feedback analysis it was noted that majority of the medical students considered incorporation of active learning methods useful for learning histology. Use of active teaching-learning by flipped classroom can assist as a comprehensive tool in regular histology sessions.


K-shell emission x-ray imaging of Z-pinch plasmas with a pinhole and a logarithmic spiral crystal.
An in-chamber, mini x-ray imaging instrument employs a pinhole and a logarithmic spiral crystal has been developed for obtaining K-shell line images of the imploding aluminum wire array on the "Yang" accelerator. The logarithmic spiral crystal acts as a monochromator and a non-dispersive mirror that reflects the pinhole image to a x-ray film detector with a very narrow photon energy bandwidth (<1 eV, mainly determined by the width of rocking curve of the crystal). Two imaging configurations with the use of Quartz (10 ̅10) crystal and Mica (002) crystal are designed, respectively, to image the Al Ly(α2) line (1727.7 eV) emission and Al He(α) intercombination line (1588.3 eV) emission. The primary experimental data corresponding to these two configurations are presented and discussed.