The Impact of Epilepsy on Complication Rates After Total Joint Arthroplasty: A Propensity Score-Matched Cohort Study.
It is unclear how epilepsy may affect total joint arthroplasty outcomes. The purpose of this study is to analyze the impact of epilepsy on prosthesis-related complications following primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). A retrospective cohort study was conducted using a national database. Patients who have epilepsy underwent a primary THA (n = 6,981) and TKA (n = 4,987) and were matched 1:4 (THA, n = 27,924; TKA, n = 19,948). Rates of low-energy falls and prosthesis-related complications within 2 years postoperatively were compared for patients who did and did not have epilepsy with multivariable logistic regression. After primary TKA, patients who have epilepsy exhibited significantly higher rates of aseptic revision (4.3% versus 3.5%, odds ratio [OR] 1.21, P = .017) and revision for prosthetic joint infection (1.8% versus 1.3%, OR 1.29, P = .041). THA patients who have epilepsy exhibited significantly higher rates of prosthetic dislocation (3.2% versus 1.9%, OR 1.54, P < .001), periprosthetic fracture (2.2% versus 0.8%, OR 2.39, P < .001), and aseptic loosening (1.7% versus 1.1%, OR 1.40, P = .002). Rates of low-energy falls within 2 years after TKA (14.1% versus 6.4%, OR 2.19, P < .001) and THA (33.6% versus 7.5%, OR 5.95, P < .001) were also significantly higher for patients who have epilepsy. Epilepsy was associated with significantly higher rates of falls (P < .001) and prosthesis-related complications after primary THA (P < .05) and TKA (P < .05). Precautions should be implemented in this population during intraoperative and perioperative decision-making to reduce complication risk. Level III.


Follicular dendritic cell sarcoma of the neck: report of two cases complicated by pulmonary metastases.
Follicular dendritic cell (FDC) sarcoma is an uncommon neoplasm occurring primarily in lymph nodes but also in extranodal sites. A correct diagnosis can be difficult to make, especially in the latter sites. Two patients with FDC sarcoma of the cervical soft tissues that metastasized to the lungs are reported. Both were initially misdiagnosed as having CASTLE (carcinoma showing a thymus-like element). Additional immunohistochemical stains were performed. The primary tumors showed jigsaw puzzle-like lobulation resembling thymic epithelial tumor and consisted of spindly cells arranged in fascicles, whorls, and a storiform pattern. The spindly cells had indistinct cell borders, vesicular nuclei, and distinct nucleoli. Perivascular spaces were present. Lymphocytes were sprinkled throughout the tumor in one case but were sparse in the other. The metastatic deposits in the lungs appeared 27 and 2 years, respectively, after the initial presentation and were histologically similar to the original tumors. The FDC nature of the primary and metastatic tumors was confirmed by positive staining with CD21/CD35 cocktail and CD23 and by negative staining for cytokeratin. In one case, in direct continuity with the main tumor, there was a lobulated lesion composed of small lymphocytes punctuated by large cells with vesicular nuclei, histologically reminiscent of thymoma. The large cells were shown by immunohistochemistry to represent FDCs forming complex interconnecting meshworks. It is unclear whether this contiguous mass represents a precursor lesion or an unusual-looking component of the neoplasm. FDC sarcoma can look deceptively like a thymic epithelial tumor histologically. A correct diagnosis requires a high index of suspicion and immunohistochemical evaluation. The tumor shows a propensity to metastasize to the lungs, which can be delayed until more than 20 years after initial presentation.


Germin like protein genes exhibit modular expression during salt and drought stress in elite rice cultivars.
Germin-like proteins (GLPs) are ubiquitous plant proteins, which play significant role in plant responses against various abiotic stresses. However, the potential functions of GLPs in rice (Oryza sativa) against salt and drought stress are still unclear. In this study, transcriptional variation of eight OsGLP genes (OsGLP3-6, OsGLP4-1, OsGLP8-4, OsGLP8-7, OsGLP8-10, OsGLP8-11 and OsGLP8-12) was analyzed in leaves and roots of two economically important Indica rice cultivars, KS282 and Super Basmati, under salt and drought stress at early seedling stage. The relative expression analysis from qRT-PCR indicated the highest increase in expression of OsGLP3-6 in leaves and roots of both rice varieties with a significantly higher expression in KS282. Moreover, relative change in expression of OsGLP8-7, OsGLP8-10 and OsGLP8-11 under salt stress and OsGLP8-7 under drought stress was also commonly higher in leaves and roots of KS282 as compared to Super Basmati. Whereas, OsGLP3-7 and OsGLP8-12 after salt stress and OsGLP8-4 and OsGLP8-12 after drought stress were observed with higher relative expression in roots of Super Basmati than KS282. Importantly, the OsGLP3-6 and OsGLP4-1 from chromosome 3 and 4 respectively showed higher expression in leaves whereas most of the OsGLP genes from chromosome 8 exhibited higher expression in roots. Overall, as a result of this comparative analysis, OsGLP genes showed both general and specific expression profiles depending upon a specific rice variety, stress condition as well as tissue type. These results will increase our understanding of role of OsGLP genes in rice crop and provide useful information for the further in-depth research on their regulatory mechanisms in response to these stress conditions.


Heart rate variability in human immunodeficiency virus-positive individuals.
Heart rate variability (HRV) is a marker of cardiac autonomic tone. Depressed HRV has been reported in patients with AIDS. We conducted this study to find out if HRV is depressed in human immunodeficiency virus (HIV)-positive individuals without AIDS. We studied prospectively HRV by spectral analysis of short-term electrocardiography (ECG) monitoring in 21 HIV-positives (33+/-11 years) and in 18 healthy volunteers (31+/-9 years). None of the HIV-positives had any clinical evidence of autonomic or cardiac dysfunction. Echocardiography was also performed in HIV-seropositives to rule out left ventricular (LV) systolic dysfunction. All these individuals did not have any evidence of AIDS. Mean CD4+ lymphocyte count was 426+/-166/mm(3). The ejection fraction (EF%) of HIV patients was 62.4+/-6.4. The total power of HRV was reduced significantly in HIV-positive individuals (p<0.00001). All the components of HRV were reduced. HRV is reduced in HIV-seropositive individuals in early stages of infection as well without any clinical evidence of autonomic dysfunction. This may serve as an early marker of future global sympatho-vagal imbalance.


Characteristics of older patients with postmenopausal osteoporosis who developed loss of muscle mass during the COVID-19 pandemic - a case-control study.
Under the restriction of social activities during the coronavirus disease 2019 (COVID-19) pandemic, there was concern about the loss of muscle mass due to a decrease in physical activity for the elderly. The purpose of this study was to investigate the characteristics of older patients with postmenopausal osteoporosis who developed loss of muscle mass during the COVID-19 pandemic in Japan. A total of 54 patients with postmenopausal osteoporosis were evaluated in this study. Whole-body dual-energy X-ray absorptiometry was performed pre- and post-COVID-19 pandemic to measure trunk and lower limb muscle mass. At the time of the post-COVID-19 pandemic, we conducted a survey to compare lifestyle before pandemic (the frequency of going out, the frequency of meeting acquaintances or families living apart, regular exercise habits, walking time, family structure), and comorbidities between the muscle mass loss (ML) group and the muscle mass maintenance (MM) group. The ML group consisted of patients with at least a 5% decrease in lower limb muscle mass or trunk muscle mass. A significant difference was found only for the family structure (P = 0.0279); in the ML group, those living alone were the largest group, while in the MM group they were the smallest group. The ML group was significantly more likely to live alone than the MM group. The current study showed that loss of muscle mass was more common in patients living alone.


Integration of shape and motion cues in biological motion processing in the monkey STS.
To correctly perceive biological actions, the movement pattern generated in the course of the action has to be linked to the configuration of the actor. Recently, we showed that in humans, motion and configuration cues are processed separately in occipito-temporal cortex, and that both cues are integrated in the extrastriate (EBA) and fusiform (FBA) body areas (Jastorff and Orban, 2009). Using the same factorial design as in our human study, we performed fMRI experiments in awake monkeys to compare biological motion processing in the two species. Point-light displays of monkeys engaged in various actions were presented in a 2×2 factorial design. One factor manipulated the configuration of the stimuli, the other, the kinematics. As in humans, the two factors were anatomically segregated in the superior temporal sulcus (STS) rostral to the MT/V5 complex, with the effect of configuration significant along the lower bank and that of kinematics significant in the fundus and the upper bank of the STS. Moreover, voxels showing a significant interaction between the two factors were mainly confined to body-selective patches within the STS, mimicking our human findings. Importantly, this study reports for the first time differential activation for biological actions presented as point-light displays in the monkey. Moreover, our results suggest that the processing mechanisms of biological actions are remarkably similar in humans and macaque monkeys, and provide the basis for linking existing and future single-cell physiology in the monkey with human functional imaging.


The mutations previously designated as flightless-I3, flightless-O2 and standby are members of the W-2 lethal complementation group at the base of the X-chromosome of Drosophila melanogaster.
By using a well defined panel of chromosomal deficiencies, duplications and lethals, we have mapped three mutations causing flightlessness, flightless-I3, flightless-O2 and standby, to a single lethal complementation group (termed W-2) at the base of the X-chromosome of D. melanogaster. We also show that a fourth flightless mutation, termed grounded, previously mapped near to the base of the X-chromosome, is distal to the cytogenetic interval 18F to 20F. Mutants homozygous for the flightless-I3, flightless-O2 and standby mutations exhibit abnormalities of myofibrillar arrangements in the indirect flight muscles. They have distorted Z-bands and the myofibrils are often displaced from their normal parallel arrangement. These viable flightless mutations are all hypomorphs since the homozygous deficiency of the W-2 X-chromosomal region is lethal to the organism.


Interaction of emotion and cognitive control along the psychosis continuum: A critical review.
To better understand how emotion impacts cognitive control is important as both influence adaptive behavior in complex real-life situations. Performance changes in emotion and cognitive control as well as in their interaction are often described in psychotic patients as well as in non-clinical participants who experience psychosis-like symptoms. These changes are linked to low motivation and limited social interaction. However, it is unclear whether these changes are driven by emotion, cognitive control, or an interaction of both. This review provides an overview of neuroimaging evidence on the potential interaction of emotion and cognitive control along the psychosis continuum. The literature confirms that over-sensitivity towards negative and lowered sensitivity towards positive emotional stimuli in tasks exploring emotion-cognitive control interaction are associated with the severity of positive and negative symptoms in psychosis. Changes in the dynamic interplay between emotion and context-sensitive cognitive control, mediated by arousal, motivation, and reward processing may underlie poor interpersonal communication and real-life skills in psychosis. In addition, structural and functional changes in subcortical and cortical associative brain regions (e.g., thalamus, basal ganglia, and angular gyrus) may contribute to alterations in emotion and cognitive control interaction along the psychosis continuum. There is limited evidence on how antipsychotic medication and age at illness-onset affect this interaction.


Bidirectional placental transfer of glucose and its turnover in fetal and maternal sheep.
Glucose biokinetics were assessed simultaneously in the pregnant ewe and its fetus by a primed constant infusion of 2-3H glucose and U-14C glucose. Late in gestation fetal glucose turnover was 27.3 +/- 3.7 mg/min; expressed in terms of fetal weight this is 6 to 10 mg/kg/min. In the fed state the results indicated that all of the fetal glucose turnover was derived from the mother via placental transfer and there was no evidence that the fetus was capable of glucose production. Maternal glucose turnover was 145.6 +/- 9.3 mg/min (2.8 mg/kg/min). There was a significant amount of glucose (16.3 +/- 2.3 mg/min) transferred from the fetus to the mother. This feto-maternal transfer of glucose accounted for 11% of the maternal glucose turnover and approximately 50% of the total glucose coming to the fetus from the mother. This study provides the first in vivo simultaneous quantification of the bidirectional glucose transfer across the placenta.


Expandable Cardiovascular Progenitor Cells Reprogrammed from Fibroblasts.
Stem cell-based approaches to cardiac regeneration are increasingly viable strategies for treating heart failure. Generating abundant and functional autologous cells for transplantation in such a setting, however, remains a significant challenge. Here, we isolated a cell population with extensive proliferation capacity and restricted cardiovascular differentiation potentials during cardiac transdifferentiation of mouse fibroblasts. These induced expandable cardiovascular progenitor cells (ieCPCs) proliferated extensively for more than 18 passages in chemically defined conditions, with 10(5) starting fibroblasts robustly producing 10(16) ieCPCs. ieCPCs expressed cardiac signature genes and readily differentiated into functional cardiomyocytes (CMs), endothelial cells (ECs), and smooth muscle cells (SMCs) in vitro, even after long-term expansion. When transplanted into mouse hearts following myocardial infarction, ieCPCs spontaneously differentiated into CMs, ECs, and SMCs and improved cardiac function for up to 12 weeks after transplantation. Thus, ieCPCs are a powerful system to study cardiovascular specification and provide strategies for regenerative medicine in the heart.


Commentary: Are there good reasons to adopt dynamic systems approaches for explaining deductive reasoning?
The focus of this commentary is twofold. First, I examine Faiciuc's attempts to counter symbolic computationalism as a major theoretical framework for the study of deductive reasoning. Second, I wish to see how far the author goes in her defense of Dynamic Systems Approaches (DSAs) as a more promising framework for explaining logical reasoning. When reading her work, I posed two versions of the same for/against question to myself: How strong is the case against symbolic computationalism? And, on the basis of the author's argumentation, would one feel justified in adopting DSAs instead? I examine each question in turn, and come to similar conclusions. The article by Faiciuc tackles issues of relevance to any serious effort toward reflecting on the two perspectives being compared. Unfortunately, however, references to studies supporting her claims are rather thin. A better-informed answer to the question raised in the title of the article is still to be given.


Identifying a transport mechanism of dust aerosols over South Asia to the Tibetan Plateau: A case study.
Dust aerosol, one of the important light-absorbing impurities in snow and ice sheets in the Tibet Plateau (TP), can significantly affect the magnitude and timing of snow melting and glacier recession by altering the surface albedo. It is thus of great importance to understand the potential source and transport mechanism of the dust aerosol over the TP. A typical dust storm case, erupted from the Thar Desert (ThD) in South Asia on 1 to 4 May 2018, was selected to understand synoptic causes and a transport mechanism to the TP using the latest Second Modern-Era Retrospective analysis for Research and Applications (MERRA-2) reanalysis data. Comparing with active/passive satellite-based and AERONET-based observations, the MERRA-2 data provide both the spatio-temporal distribution and evolution process of the dust aerosol more accurately. This study also found that the entire Indian-Gangetic Plain (IGP), Southern India, the Bay of Bengal, and even the TP were influenced by the dust event. The synoptic analysis showed that the dust storm was caused jointly by an upper-level jet stream (ULJS), an upper trough and the subtropical high. A typical south-north secondary circulation adjacent its exit zone, mainly triggered by the ULJS, promoted much stronger and higher vertical uplift of the dust aerosols over the ThD. Consequently, those uplifted dust particles were easily transported to the TP across the majestic Himalayas by the southerly airflows in front of the low-pressure trough over Afghanistan and the southern branch trough over the Bengal Bay. These results indicate that dust aerosol and anthropogenic pollutions constrained and driven by the typical atmospheric circulation condition from South Asia are likely to be transported to the TP. Therefore, it is necessary to further pay attention to the influence of dust aerosols from South Asia on the weather and climate in the TP and its downstream areas.


Timosaponin AIII induces apoptosis and autophagy in human melanoma A375-S2 cells.
Timosaponin AIII (AIII), a steroidal saponin isolated from Anemarrhena asphodeloides Bge. Our study showed that AIII induced both apoptosis and autophagy, and autophagy inhibited apoptosis in A375S2 cells. Furtherly, this study was carried out to investigate what kind of cytokines plays an important role in this process. The results revealed that AIII induced apoptosis through activating c-Jun N-terminal protein kinase (JNK) or extracellular signal related kinase (ERK) signaling pathway and generating NO. However, JNK or ERK inhibited autophagy, while NO had no effect on autophagy. Therefore, JNK, ERK or NO regulates two programmed death processes in different ways. AIII did not show obvious cytotoxic effect on human peripheral blood mononuclear cells, which indicated that AIII has less side effects on normal cells, and could be considered as a leading compound for developing novel anticancer drug.


A contravention of Ohno's law in mice.
The chloride channel gene, CLCN4, has been previously mapped to the X chromosome in humans. We isolated a cDNA clone for mouse Clcn4 and used this to map the gene in an interspecific backcross. This revealed the surprising finding that the gene maps to the X chromosome in Mus spretus but to chromosome 7 in C57BL/6 mice. This is the first example of a gene that contravenes Ohno's law--it is a gene unique to the X chromosome in one eutherian species but autosomal in another. The consequence of this chromosomal rearrangement is that the gene is lost by mendelian segregation in a subset of the male progeny of a (C57BL/6 x Mus spretus) x Mus spretus backcross.


Haplotype-specific suppressor T cells mediating linked suppression of immune responses elicited by third-party H-2 alloantigens.
Specific suppressor T cells (Ts) were induced in vitro by incubation of mouse spleen/lymph node cells with allogeneic heat-treated cells. These Ts inhibit mixed lymphocyte reaction (MLR) in a haplotype-specific manner. Ts also suppress cell proliferation induced by third-party H-2 alloantigens provided these are expressed on the same cell surface as at least some of the H-2 antigens used for Ts activation. Ts activated by H-2 plus non-H-2 alloantigens suppress an MLR induced by irrelevant H-2 alloantigens if these are expressed on the same cell surface as the non-H-2 alloantigens used for Ts activation. Products of the H-2 region or non-H-2 alloantigens which are not able to stimulate cell proliferation do not activate Ts. These Ts are first demonstrable after 4 days of incubation of lymphoid cells with heat-treated allogeneic cells and they inhibit MLR only if added at the very beginning of the culture. Exogenous interleukin 2 does not overcome suppression and the suppression is not due to a cytotoxic effect, since heat-treated cells do not elicit cell proliferation or cytotoxic cells. Moreover, the specific Ts differ in their Thy-1+,Ly-1+,2-phenotype from Ly-2+ allospecific cytotoxic cells. Thus specific Ts could be induced in vitro, which demonstrate linked suppression for third-party H-2 alloantigens provided these are expressed on the same cell surface as the antigens used for Ts activation.


The healthcare seeking behaviour of adult patients with asthma at Chitungwiza Central Hospital, Zimbabwe.
Although asthma is a serious public health concern in Zimbabwe, there is lack of information regarding the decision to seek for healthcare services among patients. This study aimed to determine the health care seeking behaviour of adult patients with asthma attending Chitungwiza Central Hospital in Zimbabwe. A cross-sectional study was conducted among 400 patients with asthma. A questionnaire with four thematic areas (i) patients' demographic characteristics, (ii) types of health seeking behaviours (iii) knowledge of asthma treatment and (iv) attitudes on asthma treatment was used. We determined the sequence of remedial action that people undertake to rectify perceived ill health commonly referred to as health care seeking behaviours in 400 adult patients with asthma. This behaviour was considered good if the patient sought care at the hospital/clinic and or private practitioners. Poor health seeking behaviour was adjudged if patients sought no treatment, self-treated or resorted to traditional or faith healers for care.The majority 261(65.3%) of the study participants were females mainly between ages 29-39 years who lived in the urban setting. Distance to health facility, perception of supportive roles of healthcare providers, perceived good quality of service and knowledge of asthma complications were key determinants for health seeking behaviour. The results showed that majority 290 (72.5%) reported good health seeking behaviour. The correlates of good health seeking behaviour included financial capacity to pay for medical care [OR: 0.50 (CI: 0.31-0.83); p = 0.008)] and receiving good quality of asthma treatment [OR: 0.59 (CI: 0.37-0.93); p = 0.03)]. The inability to voluntarily seek own asthma treatment [OR: 1.68 (CI: 1.05-2.70); p = 0.03) was a significant risk factor (68% more likely) for poor health seeking behaviour. We concluded that prior to scaling up asthma treatment programmes in Zimbabwe, there is need to address, individual-level, community-level and health service level barriers to health seeking among asthma patients.


Mechanical and thermal properties of mud dauber nests under atmospheric drying.
Mud dauber wasps construct soil nests to protect their offspring from predators, extreme temperatures, and rainwater. The mechanical and thermal properties of these nests are important for the reproductive success of mud daubers. The previous study showed that the high densities and strengths of mud dauber nests were due to the repetitive tapping and atmospheric drying used by mud daubers during nest construction. This study investigated the effect of atmospheric drying on the mechanical and thermal properties of mud dauber nests. The soil shrinkage curve, elastic modulus, suction stress characteristic curve, soil water retention curve, shear strength, and thermal conductivity function of mud dauber nest soils were measured by performing drying cake tests, direct shear tests, unconfined compression tests, and thermal conductivity measurements. This study showed atmospheric drying could increase Young's moduli (from hundreds to thousands of kPa), the magnitudes of suction stress (up to 64 kPa), and shear strengths (e.g., unconfined compressive strength increased up to 2100 kPa) of mud dauber nests. The thermal conductivity was reduced by 47% due to atmospheric drying. Investigation of mud dauber nests under atmospheric drying could provide insights and inspiration to improve human manufacturing and manipulation of soils for earthen building construction.


Glucose-regulated protein 78 binds to and regulates the melanocortin-4 receptor.
The melanocortin-4 receptor (MC4R) belongs to the G protein-coupled receptor (GPCR) family and plays an essential role in the control of energy homeostasis. Here, we identified a novel MC4R-interacting protein, glucose-regulated protein 78 (GRP78), from a pulldown assay using hypothalamic protein extracts and the third intracellular loop of MC4R. We found that MC4R interacted with GRP78 in both the cytosol and at the cell surface and that this interaction increased when MC4R was internalized in the presence of the agonist melanotan-II (MTII). Downregulation of GRP78 using a short interfering RNA approach attenuated MTII-mediated receptor internalization. Reduction in GRP78 expression during tunicamycin-induced endoplasmic reticulum stress also suppressed MTII-mediated internalization of MC4R and cAMP-mediated transcriptional activity. Furthermore, lentiviral-mediated short hairpin RNA knockdown of endogenous GRP78 in the paraventricular nucleus (PVN) of the hypothalamus resulted in an increase in body weight in mice fed a high-fat diet. These results suggest that GRP78 in the PVN binds to MC4R and may have a chaperone-like role in the regulation of MC4R trafficking and signaling.


Neurologically normal development of a patient with severe methionine adenosyltransferase I/III deficiency after continuing dietary methionine restriction.
There is not much information on established standard therapy for patients with severe methionine adenosyltransferase (MAT) I/III deficiency. We report a boy with MAT I/III deficiency, in whom plasma methionine and total homocysteine, and urinary homocystine were elevated. Molecular genetic studies showed him to have novel compound heterozygous mutations of the MAT1A gene: c.191T>A (p.M64K) and c.589delC (p.P197LfsX26). A low methionine milk diet was started at 31 days of age, and during continuing dietary methionine restriction plasma methionine levels have been maintained at less than 750 μmol/L. He is now 5 years old, and has had entirely normal physical growth and psychomotor development. Although some severely MAT I/III deficient patients have developed neurologic abnormalities, we report here the case of a boy who has remained neurologically and otherwise normal for 5 years during methionine restriction, suggesting that perhaps such management, started in early infancy, may help prevent neurological complications.


The carmaphycins: new proteasome inhibitors exhibiting an α,β-epoxyketone warhead from a marine cyanobacterium.
Two new peptidic proteasome inhibitors were isolated as trace components from a Curaçao collection of the marine cyanobacterium Symploca sp. Carmaphycin A (1) and carmaphycin B (2) feature a leucine-derived α,β-epoxyketone warhead directly connected to either methionine sulfoxide or methionine sulfone. Their structures were elucidated on the basis of extensive NMR and MS analyses and confirmed by total synthesis, which in turn provided more material for further biological evaluations. Pure carmaphycins A and B were found to inhibit the β5 subunit (chymotrypsin-like activity) of the S. cerevisiae 20S proteasome in the low nanomolar range. Additionally, they exhibited strong cytotoxicity to lung and colon cancer cell lines, as well as exquisite antiproliferative effects in the NCI60 cell-line panel. These assay results as well as initial structural biology studies suggest a distinctive binding mode for these new inhibitors.


Epidural lipomatosis and renal transplantation.
A 34-year-old man presented with progressive myelopathy 4 months after cadaveric renal transplant for endstage renal disease. Radiographic evaluation gave findings consistent with epidural lipomatosis and compression of the thoracic thecal sac. Decompressive laminectomy resulted in dramatic improvement of his neurologic deficit. This case is unusual in the brevity of steroid treatment prior to onset of the myelopathy, as well as the relatively small dose. The 10 previous cases of epidural lipomatosis are also reviewed.


Understanding the role of tumor stem cells in glioblastoma multiforme: a review article.
It has been hypothesized that cancer stem cells (CSC) may account for the pathogenesis underlying various tumors, including GBM. Markers of these CSCs can be potentially used as therapeutic targets. In this review, we discuss the most recent information regarding CSCs, their molecular biology and their potential role in GBM.


Rehabilitation Needs of Stroke Survivors After Discharge From Hospital in India.
To assess the rehabilitation needs of stroke survivors in Chennai, India, after discharge from the hospital. Mixed-methods research design. Home-based. Stroke survivors (n=50; mean age ± SD, 58.9±10.5y) and primary caregivers of these stroke survivors (n=50; mean age ± SD, 43.1±11.8y) took part in the quantitative survey. A subsample of stroke survivors (n=12), primary caregivers (n=10), and health care professionals (n=8) took part in the qualitative in-depth interviews. Not applicable. Rehabilitation needs after hospital discharge. About 82% of the needs expressed by stroke survivors and 92% of the needs expressed by caregivers indicated that they had a substantial need for information. The proportion of financial needs reported by the stroke survivors and the caregivers was 70% and 75%, respectively. The qualitative data revealed major gaps in access to stroke rehabilitation services. Service providers identified availability and affordability of services as key problems. Stroke survivors and their caregivers identified lack of information about stroke as major barriers to accessibility of stroke rehabilitation services. Caregivers expressed a tremendous need for support to manage family dynamics. The study highlights a considerable unmet need for poststroke rehabilitation services. Given the lack of rehabilitation resources in India, developing an accessible, innovative, patient-centered, culturally sensitive rehabilitation intervention is of public health importance. It is crucial for low- and middle-income countries like India to develop technology-driven stroke rehabilitation strategies to meet the growing rehabilitation needs of stroke survivors.


Safety and Feasibility of ≤24-h Short-Stay Right Colectomies for Primary Colon Cancer.
Hospital length of stay (LOS) has been used as a surgical quality metric. This study seeks to determine the safety and feasibility of right colectomy as a ≤24-h short-stay procedure for colon cancer patients. This was a retrospective cohort study using the ACS-NSQIP database and its Procedure Targeted Colectomy database (2012-2020). Adult patients with colon cancer who underwent right colectomies were identified. Patients were categorized into LOS ≤1 day (≤24-h short-stay), LOS 2-4 days, LOS 5-6 days, and LOS ≥7 days groups. Primary outcomes were 30-day overall and serious morbidity. Secondary outcomes were 30-day mortality, readmission, and anastomotic leak. The association between LOS and overall and serious morbidity was assessed using multivariable logistic regression. 19,401 adult patients were identified, with 371 patients (1.9%) undergoing short-stay right colectomies. Patients undergoing short-stay surgery were generally younger with fewer comorbidities. Overall morbidity for the short-stay group was 6.5%, compared to 11.3%, 23.4%, and 42.0% for LOS 2-4 days, LOS 5-6 days, and LOS ≥7 days groups, respectively (p < 0.001). There were no differences in anastomotic leak, mortality, and readmission rates in the short-stay group compared to patients with LOS 2-4 days. Patients with LOS 2-4 days had increased odds of overall morbidity (OR 1.71, 95% CI 1.10-2.65, p = 0.016) compared to patients with short-stay but no differences in odds of serious morbidity (OR 1.20, 95% CI 0.61-2.36, p = 0.590). ≤24-h short-stay right colectomy is safe and feasible for a highly-select group of colon cancer patients. Optimizing patients preoperatively and implementing targeted readmission prevention strategies may aid patient selection.


Intermolecular aminotrifluoromethylation of alkenes by visible-light-driven photoredox catalysis.
Intermolecular aminotrifluoromethylation of alkenes catalyzed by [Ru(bpy)3](2+) under visible light irradiation has been explored. The present photocatalytic protocol achieves highly efficient and regioselective difunctionalization of C═C bonds, leading to a variety of β-trifluoromethylamines. The reaction is applied to "late-stage aminotrifluoromethylation" of steroid and amino acid scaffolds.


Confirmed case of feline mycetoma due to Microsporum canis.
The first case of feline true mycetoma because of a dermatophyte has been reported in this manuscript, although pseudomycetoma has been described in dogs and cats. The patient was a 9-year-old castrated male Persian cat weighing 4.2 kg with subcutaneous nodules on the dorsal trunk. Physical examination revealed two subcutaneous nodules (2.5 x 5.0 cm and 3.5 x 5.0 cm in size) that drained purulent exudates with cement-like substances containing yellowish granules. The impression smear of the yellowish granules demonstrated by PAS staining that they were masses of fungal septated hyphae (3-4 mum of width). From the nodular inflammation with fibrosis, fistulae draining from deep tissue and many grains containing abundant hyphal filaments, the case was diagnosed as mycetoma, complying with the definitive criteria of mycetoma. The etiologic fungus was molecularly as well as morphologically identified as Microsporum canis.


Modelling thrombin generation in human ovarian follicular fluid.
A mathematical model is constructed to study thrombin production in human ovarian follicular fluid. The model results show that the amount of thrombin that can be produced in ovarian follicular fluid is much lower than that in blood plasma, failing to reach the level required for fibrin formation, and thereby supporting the hypothesis that in follicular fluid thrombin functions to initiate cellular activities via intracellular signalling receptors. It is also concluded that the absence of the amplification pathway to thrombin production in follicular fluid is a major factor in restricting the amount of thrombin that can be produced. Titration of the initial concentrations of the various reactants in the model lead to predictions for the amount of tissue factor and phospholipid that is required to maintain thrombin production in the follicle, as well as to the conclusion that tissue factor pathway inhibitor has little effect on the time that thrombin generation is sustained. Numerical experiments to determine the effect of factor V, which is at a much reduced level in follicular fluid compared to plasma, and thrombomodulin, illustrate the importance for further experimental work to determine values for several parameters that have yet to be reported in the literature.


Stroke topography in diabetic and nondiabetic patients by magnetic resonance imaging.
Stroke is more frequent in diabetic than in nondiabetic patients. We studied lesion topography in 61 stroke patients with diabetes mellitus and 77 without diabetes using magnetic resonance imaging. Location, number and size of infarcts were investigated. Prevalence of hypertension did not differ between diabetic and nondiabetic patients. In elderly subgroups (> or = 65 years), infratentorial infarcts > or = 5 mm in diameter were more frequent in diabetic than in nondiabetic patients (32 vs. 12%, P < 0.05), while supratentorial infarcts were not different (56 vs. 68%, ns). Asymptomatic hemorrhage combined with silent infarction was significantly less frequent in diabetic than in nondiabetic patients (5 vs. 22%, P < 0.05). In nondiabetic patients with significant stenosis in the carotid system, supratentorial infarction measuring > or = 15 mm was more frequent than in those without stenotic lesions, but the number of infarcts per patient irrespective of size was smaller when stenosis was present. On the other hand, the number of infarcts in diabetic patients was similar between those with and without carotid system stenosis. The present study demonstrated that infratentorial infarcts were more common in elderly diabetic patients, suggesting the vulnerability of vertebrobasilar circulation in diabetes.


Draft Genome Sequence of Cyclobacterium qasimii Strain M12-11BT, Isolated from Arctic Marine Sediment.
A 6.29-Mb genome sequence of Cyclobacterium qasimii strain M12-11B(T), isolated from an Arctic marine sediment sample, is reported.


Effects of radiochemotherapy and splenectomy on cellular immunity in long-term survivors of Hodgkin's disease and non-Hodgkin's lymphoma.
Thirty-six patients treated for Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) who had been in complete remission and off all therapy for greater than two years were examined for evidence of immunosuppression. All patients were found to have marked depression of their lymphocyte blastogenic response to phytohemagglutinin (PHA) and of their skin test responses. No abnormalities of serum protein or immunoglobulins were found. T cells were significantly lower than normal in patients who had had Hodgkin's disease, but not in those who had had NHL. B cells, on the other hand, were significantly elevated in both groups. Splenectomy elevated the total lymphocyte count, while those who had not had a splenectomy had lower than normal lymphocyte counts. B cells were elevated while T cells tended to be lower in both splenectomy and nonsplenectomy groups, though only in the nonsplenectomized patients did this reach statistical significance. PHA response tended to be higher in patients with less advanced disease and less extensive treatment than in those with more advanced disease and more extensive treatment, although there was no statistically significant difference. Skin test response though, was shown to correlate well with both stage of disease at diagnosis and extent of treatment.


Comparing asymmetric price efficiency in regional ESG markets before and during COVID-19.
The ever-emerging environmental, social, and governance (ESG) concerns have received significant attention of policymakers, governments, regulation bodies, and investors. Considering the markets volatilities due to economic and financial uncertainties that can drive the informational price inefficiencies across the markets, this study compares the asymmetric price efficiency of regional ESG markets by using an asymmetric multifractal detrended fluctuation analysis before and during COVID-19 crisis. We then examine whether global factors influence the asymmetric efficiency of regional ESG markets. Our findings reveal that COVID-19 outbreak reduced the efficiency of regional ESG markets, except for Europe, which sustained its efficiency even during the pandemic. Moreover, global factors drive the efficiency of regional ESG markets significantly before and during COVID-19. A major implication of our findings stems from the fact that a contagion reduces the efficiency of the markets while stable economic conditions make those markets informationally efficient.


Depression and its association with peritonitis in long-term peritoneal dialysis patients.
Depression is the most common psychological disorder among patients with end-stage renal disease and has been associated with mortality in patients maintained on hemodialysis therapy. Peritonitis is the leading cause of technique failure among long-term peritoneal dialysis (PD) patients. This prospective study is designed to examine the relationship between depression and peritonitis. All patients on long-term PD therapy in our unit between January 1, 1997, and January 31, 2002, completed a Beck Depression Inventory (BDI) assessment at 6-month intervals. BDI scores were analyzed 2 ways. First, patients were placed into either group I (BDI score < 10) or group II (BDI score > or = 11) and were reclassified based on subsequent scores. Second, multivariable analysis was performed looking at initial BDI score as a risk factor for peritonitis, adjusting for age older than 65 years, diabetes, coronary artery disease, and race. One hundred sixty-two patients were enrolled, and 281 individual BDI assessments were completed. There was a significantly greater incidence of diabetes and coronary artery disease in group II. Rates for overall and gram-positive peritonitis were significantly greater in group II patients compared with group I patients. Using Cox regression, only BDI score of 11 or greater was associated with the development of peritonitis (hazard ratio, 2.7; 95% confidence interval, 1.2 to 6.0). There is an association between BDI score of 11 or greater and the development of peritonitis. Whether treatment of depression can impact on the rate of peritonitis remains to be examined.


Misappropriation of the 1986 WHO analgesic ladder: the pitfalls of labelling opioids as weak or strong.
Opioids have a vital role in alleviating pain from cancer and surgery. Despite good intentions, it is now recognised that the original WHO Cancer Pain Relief guidance from 1986, in which opioids were classified as either weak or strong, has been both inadvertently and purposefully misused, thereby contributing to harm from opioid use and misuse. However, the recommendation in the 2018 update of the WHO analgesic ladder that a combination of a high-potency opioid with simple analgesics is better than alternative analgesics for the maintenance of pain relief is also applicable to patients who require short-term opioids. Furthermore, because potential harm through opioid use and misuse is intrinsic to all opioids, whether weak or strong, we argue that the arbitrary classification of opioids either as weak or strong should be discontinued, as this description is not helpful to either prescribers or consumers.


Proteolytic activity associated with human erythrocyte membranes. Self-digestion of isolated human erythrocyte membranes.
At least two kinds of enzymes are active in the proteolytic self-digestion of erythrocyte membranes. The specific activities of these enzymes do not decrease with repeated washings of purified stroma. The effects of a variety of inhibitors on the membrane preparation's capacity to digest 125-I-labelled casein, covalently linked to latex beads, have been examined. Pepstatin-inhibitable enzyme, active at low pH, digests the membrane extensively to small polypeptide fragments. Spectrin, located at the internal part of the membrane, is readily degraded. Diisopropylfluorophosphate-inhibitable enzyme, active at pH 8-9, has only limited digestive capacity. Some of the membrane components, such as the small molecular weight glycoproteins, are resistant to digestion. The restricted capacity of digestion is due to the membrane molecular arrangement; increased disaggregation removes the restriction and increases the activity. Spectrin is not digested unless the membrane topography is disrupted by NP-40 neutral detergent. These observations suggest that the enzymes active at basic pH are located external to the cell. Intact cells do possess a limited capacity to degrade 125-I-labelled casein when their surfaces are brought into contact with substrate-coated beads.


Effects of beta-/Tyr9/melanotropin-/9-18/ on apomorphine-induced stereotyped cage-climbing and on striatal dopamine release in mice. Comparative studies with amphetamine.
beta-/Tyr9/melanotropin-/9-18/ significantly increased apomorphine-induced cage-climbing, while only a tendency towards an increase was observed after supersensitization with haloperidol. Amphetamine also enhanced apomorphine-induced climbing behavior. The peptide showed only a tendency to increase dopamine release from striatal slices, while amphetamine elevated this significantly. The results suggest that the striatal dopamine system is involved in the behavioral action of beta-/Tyr9/melanotropin-/9-18/.


A recommended protocol for pacemaker follow-up: analysis of 1,705 implanted pacemakers.
This study, developed for the purpose of establishing an appropriate protocol for general follow-up of the paced patient, is based on clinical experience with patients derived from diverse specialties, geographical locations and protocol preferences. The analysis represents a four-year study of the transtelephonic follow-up of 1,705 implanted cardiac pacers, which represents 44,616 pacer-months of experience. There were 340 system malfunctions, 41% (141) due to battery exhaustion and 59% (199) due to other causes. Of all observed system failures 9.7% (33) occurred within 1 month of implantation, with the rate declining sharply thereafter until battery failures began to occur at approximately the twenty-fourth month. Only 10.9% (37) of all system failures were accompanied by clinical symptoms. Of the clinical failures, 62% (23) occurred in patients who were tested at intervals greater than 10 weeks. Our analysis indicates that testing should be performed weekly for the first month following lead manipulation. Thereafter, tests should be performed at 8- to 10-week intervals for the first 24 months of pacemaker life. During the third postimplant year tests should be conducted more frequently, depending on the energy source of the generator.


Physicochemical changes of 'Phulae' pineapple fruit treated with short-term anoxia during ambient storage.
The effects of short-term anoxia exposure for 16h on physicochemical changes of 'Phulae' pineapple fruit stored at ambient temperature (25±2°C) were investigated. The respiratory rate of the fruit was induced by the anoxia treatment. However, it retarded the increase in moisture loss and maintained both flesh and pulp colour by inhibiting polyphenol oxidase (PPO) activity of the both tissues. The anoxia exposure delayed the increase in total sugar content and enhanced total ascorbic acid content during storage. The half-cut pineapple fruit showed that the anoxia exposure completely inhibited internal transparency of the flesh tissue adjacent to core during the storage. In conclusion, the short-term anoxia exposure for 16h maintained postharvest quality, retarded physiological disorder and enhanced nutritional values of the pineapple fruit stored at ambient temperature (25±2°C).


Textbook Oncological Outcome in European GASTRODATA.
To assess the rate of textbook outcome (TO) and textbook oncological outcome (TOO) in the European population based on the GASTRODATA registry. TO is a composite parameter assessing surgical quality and strongly correlates with improved overall survival. Following the standard of treatment for locally advanced gastric cancer, TOO was proposed as a quality and optimal multimodal treatment parameter. TO was achieved when all the following criteria were met: no intraoperative complications, radical resection according to the surgeon, pR0 resection, retrieval of at least 15 lymph nodes, no severe postoperative complications, no reintervention, no admission to the intensive care unit, no prolonged length of stay, no postoperative mortality and no hospital readmission. TOO was defined as TO with the addition of perioperative chemotherapy compliance. Of the 2558 patients, 1700 were included in the analysis. TO was achieved in 1164 (68.5%) patients. The use of neoadjuvant chemotherapy [odds ratio (OR) = 1.33, 95% CI: 1.04-1.70] and D2 or D2+ lymphadenectomy (OR = 1.55, 95% CI: 1.15-2.10) had a positive impact on TO achievement. Older age (OR = 0.73, 95% CI: 0.54-0.94), pT3/4 (OR = 0.79, 95% CI: 0.63-0.99), ASA 3/4 (OR = 0.68, 95% CI: 0.54-0.86) and total gastrectomy (OR = 0.56, 95% CI: 0.45-0.70), had a negative impact on TO achievement. TOO was achieved in 388 (22.8%) patients. Older age (OR = 0.37, 95% CI: 0.27-0.53), pT3 or pT4 (OR = 0.52, 95% CI: 0.39-0.69), and ASA 3 or 4 (OR = 0.58, 95% CI: 0.43-0.79) had a negative impact on TOO achievement. Despite successively improved surgical outcomes, stage-appropriate chemotherapy in adherence to the current guidelines for multimodal treatment of gastric cancer remains poor. Further implementation of oncologic quality metrics should include greater emphasis on perioperative chemotherapy and adequate lymphadenectomy.


Investigating the effects of herbaceous root systems on the soil detachment process at the species level.
Plant root growth significantly affect soil detachment process, whereas the mechanism of how roots affect the soil detachment process by overland flow at species level is not fully understood. This study was conducted to investigate the soil detachment rate responds to plant-induce soil properties and root traits at species level. Two typical herbaceous plants, Bothriochloa ischcemum (Linn.). Keng (BI; fibrous root system) and Artemisia vestita Wall. ex Bess (AG; tap root system), from the Loess Plateau were studies for one year under six planted densities of 5 plants m-2, 10 plants m-2, 15 plants m-2, 20 plants m-2, 25 plants m-2, and 30 plants m-2. In total, 24 steel tanks were planted, and two plots were used as bare soil controls. Their soil detachment rates were tested under a constant overland flow (1.5 l s-1) on a 26.2 % slope. The results showed that soil detachment rate under the six planted densities ranged from 0.034 kg m2 s-1 to 0.112 kg m2 s-1 for BI and was ranged from 0.053 kg m2 s-1 to 0.132 kg m2 s-1 for AG, which all greatly reduced soil detachment rate and were 68.17 % to 92.33 % and 69.20 % to 87.27 % less than that of the control. In general, BI was more effective in reducing soil detachment rate than AG, achieving a mean soil detachment rate that was 23.75 % lower. With increasing plant density, soil detachment rate decreased as a power function. The overland flow hydraulic characteristics, soil properties and root traits influenced by plant density were positively or negatively correlated with soil detachment rate. Specifically, soil detachment rate decreased with velocity, bulk density, root length density, and increased with shear stress and Darcy-Weisbach friction factor as power or exponential functions. On this basis, the soil detachment rate (Dr) can be satisfactorily estimated by overland flow velocity (v), soil bulk density (BD) and root length density (RLD) as a power function (Dr = 63.03v0.174 × BD-20.712 × RLD-0.233R2 = 0.65; NSE = 0.60; p < 0.01).


Individual and community-level factors associated with early initiation of antenatal care: Multilevel modelling of 2018 Cameroon Demographic and Health Survey.
Early initiation of antenatal care (ANC) provided by skilled personnel is essential as it enables pregnant women to receive comprehensive reproductive health services. Early ANC utilisation could prevent complications related to pregnancy and improve maternal and neonatal health outcomes. Regardless of this, only forty-one in every hundred women in Cameroon seek early ANC services. Studies on the uptake of antenatal care in Cameroon have not focused on individual and community-level factors that influence early initiation of ANC. This study aimed at investigating the association between individual and community-level factors and early ANC uptake in Cameroon. This study was a cross-sectional survey design. Data was extracted from the women's file of the 2018 Cameroon Demographic and Health Survey (CDHS). A sample of 4,183 women aged 15-49 who had complete information on variables of interest to the study was used. The outcome variable was early ANC (i.e. women whose first ANC occurred between 0-3 months of pregnancy). Eighteen explanatory variables consisting of fifteen individual-level variables and three community-level variables were selected for the study. At 95% confidence interval (95% CI), two-level multilevel models were built. The results for the fixed effects were presented in adjusted odds ratio (aOR) and the random effects were expressed in terms of Intra-Class Correlation (ICC) and Primary Sampling Units (PSUs) variance. Descriptively, 46% [CI = 45.0-48.0] of the women aged 15-49 attended ANC earlier. The median age at which women started utilising early ANC was 28 (15 to 48) years. For the fixed effects results, it was found that the odds of seeking early ANC increased among those aged 35-39 [aOR = 1.78, CI = 1.24-2.57], the richest [aOR = 2.43, CI = 1.63-3.64] and those with secondary/higher education [aOR = 1.38, CI = 1.05-1.82]. Muslims [aOR = 0.73, CI = 0.60-0.88] and women at parity four or more had lesser odds to seek early ANC [aOR = 0.63, CI = 0.49-0.82]. The study found that primary sampling unit (community/cluster) [σ2 = 0.53, CI = 0.40-0.72] and individual [σ2 = 0.16, CI = 0.09-0.29] level variations exist in early initiation of ANC. About 14% (intra-class correlation (ICC) = 0.14) and 5% (ICC = 0.05) variability in early initiation of ANC were attributable to variations in the primary sampling unit (community/cluster) and individual-level factors, respectively. Individual-level factors (maternal age, wealth status, educational attainment and religious affiliation) were associated with early initiation of ANC whereas variations in cluster/community characteristics contributed to the variations in early initiation of ANC seeking. The Departments of Health Promotion, Health Information Center and eHealth under the Ministry of Public Health, Cameroon, have to strengthen mass sensitisation programs on early ANC uptake and such programs should consider individual differences such as age, wealth status, education, and religious affiliation in its program design.


Preoperative Hematocrit Level and Associated Risk of Transfusion for Myomectomy Based on Myoma Burden and Surgical Route.
To determine the association between preoperative hematocrit level and risk of blood transfusion for laparotomic and laparoscopic myomectomy based on myoma burden and surgical route. A cohort study of prospectively collected data. American College of Surgeons National Surgical Quality Improvement Program participating institutions. A total of 26 229 women who underwent a laparotomic or laparoscopic myomectomy from 2010 to 2020. The primary outcome assessed was the risk of transfusion based on preoperative hematocrit level. This was evaluated with respect to myoma burden and surgical route. There were 26 229 women who underwent a myomectomy during the study interval, 2345 women (9%) of whom required a blood transfusion. Compared with patients who did not require transfusion, those who did had lower median preoperative hematocrit levels (34.7 vs 38.2). Patients were stratified by surgical approach (laparotomic vs laparoscopic) and myoma burden (1-4 myomas/weight ≤250 g or ≥5 myomas/weight >250 g) using Current Procedural Terminology codes (58140, 58146, 58545, 58546). In all categories, there was an inverse relationship between blood transfusion and preoperative hematocrit level with increasing risk depending on preoperative hematocrit range. The odds ratios comparing hematocrit level of 29% with 39% were 6.16 (95% confidence interval [CI], 5.15-7.36), 4.92 (95% CI, 4.19-5.78), 4.85 (95% CI, 3.72-6.33), and 5.2 (95% CI, 3.63-7.43) for patients with laparotomic (1-4 myomas/≤250 g, ≥5 myomas/>250 g) and laparoscopic myomectomy (1-4 myomas/≤250 g, 5 myomas/>250 g), respectively. Incremental increases in hematocrit result in a significantly decreased risk of blood transfusion at the time of myomectomy.


The effect of mixed live vaccines of Newcastle disease and infectious bronchitis on the chicken respiratory tract.
The effect of mixed live vaccines of Newcastle disease (ND) and infectious bronchitis (IB) on specific pathogen-free chickens aged 7 days was investigated. The chickens were inoculated intranasally with mixed live vaccines with and without Escherichia coli, or with E. coli alone. "Vaccine 1" consisted of ND virus strain B1 and IB virus strain ON; "vaccine 2" consisted of ND virus strain B1 and IB virus strain H120. The tracheas of chickens inoculated with the vaccines and E. coli and with the vaccines alone showed multiplication of E. coli and histological lesions (loss of cilia, degeneration and hyperplasia in epithelial cells and cellular infiltration of subepithelial tissues). In the tracheas of chickens inoculated with vaccines and E. coli, multiplication of E. coli was greater than in chickens given vaccine alone. There were no histological lesions, and only mild, transient multiplication of E. coli in chickens inoculated with E. coli alone. The results suggest that these mixed live vaccines, especially vaccine 2, play a role in inducing or enhancing colibacillosis in the chicken.


Tumor necrosis factor-α gene polymorphism relationship to seminal variables in infertile men.
To assess the tumor necrosis factor (TNF)-α gene polymorphism relationship with seminal variables in fertile men (N) and those with asthenozoospermia (A), asthenoteratozoospermia (AT), and oligoasthenoteratozoospermia (OAT). A total of 50 infertile men without a female factor who were attending a fertility clinic and 48 fertile men were randomly screened for semen analysis, analysis of the TNF-α promoter region for polymorphism, seminal caspase-9, acrosin activity, α-glucosidase, and reproductive hormones. The TNF-α GG genotype was present in 83.9%, 72.7%, 66.7%, and 59.5%, the TNF-α AA genotype in 3.2%, 6.8%, 10.4%, and 11.9%, and TNF-α AG genotype in 12.9%, 20.5%, 22.9%, and 28.6% in the N, A, AT, OAT groups, respectively. The occurrence of A allele was significantly greater among infertile patients than among fertile controls (21.6% vs 9.7%; odds ratio 0.388, 95% confidence interval 0.2 to 0.75, P = .005). Men with the TNF-α AA genotype demonstrated a significant decrease in the sperm count, sperm motility, normal sperm morphology, acrosin activity, and seminal α-glucosidase and a significant increase in seminal caspase-9 compared with those with the TNF-α GG genotype. This single nucleotide polymorphism in the TNF-α(-308) gene was associated with significantly increased seminal caspase-9 and a significantly decreased sperm count, sperm motility, normal sperm morphology, acrosin activity, and seminal α-glucosidase.


Effect of Statins on Recurrent Venous Thromboembolism (from the COMMAND VTE Registry).
Statins, which are considered as essential for primary and secondary prevention of atherosclerotic diseases, were also reported to reduce first venous thromboembolism (VTE). However, the effect of statins on VTE recurrence remains conflicting. We aimed to examine the association between statin use and VTE recurrence in a large observational study in Japan. The COMMAND VTE Registry is a multicenter registry enrolling consecutive 3027 patients with acute symptomatic VTE in 29 centers in Japan between January 2010 and August 2014. In the current study, the entire cohort was divided into statin group (N = 437) and no-statin group (N = 2590) according to the status of statin use at baseline. The statin group as compared with the no-statin group was older (statin group 71.2 vs no-statin group 66.5 years, p <0.001), included more women (67% vs 60%, p = 0.008), and less frequently had active cancer (12% vs 25%, p <0.001). There was no significant difference in the clinical presentation of VTE (pulmonary embolism, 58% vs 56%, p = 0.44). The cumulative 3-year incidence of recurrent VTE was significantly lower in the statin group than the no-statin group (3.8% vs 8.8%, p <0.001). After adjusting for confounders including active cancer, statin use was associated with significantly lower risk for recurrent VTE (Hazard ratio 0.49, 95% confidence interval 0.29 to 0.78, p = 0.002). The results were consistent in a sensitivity sub-group analysis with and without active cancer. In conclusion, statin use was associated with significantly lower risk for the recurrent VTE in patients with VTE.


Adaptation to social-evaluative threat: Effects of repeated acceptance and status stressors on cardiovascular reactivity.
Social-evaluative threat plays a key role in research on stress, health and related psychophysiological mechanisms such as cardiovascular reactivity (CVR). Social-evaluative threats can activate two broad social motives: striving for status, achievement and influence, and/or striving for acceptance, inclusion, and connection. Prior research emphasizes threats related to status (e.g., task performance) or combined threats to status and acceptance, obscuring their independent effects. Further, because prior research has mostly utilized single stressors, it is not clear if effects of social-evaluative threats involving status and acceptance on CVR persist or adapt quickly over repeated exposures. To address these issues, 139 undergraduates (93 females) were randomly assigned to undergo two repetitions of a stressful role-played interaction with a pre-recorded antagonistic partner under one of four conditions in a factorial design: low evaluative threat, high status threat only, high acceptance threat only, or a combined threat. In a single laboratory session, systolic and diastolic blood pressure (SBP, DBP) and heart rate (HR) were recorded during baseline and two stressor exposures. Task-induced CVR demonstrated significant adaptation across exposures. Both forms of social evaluative threat produced additional CVR, and these differences between high and low social-evaluative threat were generally maintained across exposures. Hence, threats to social status and acceptance have independent and sustained effects on CVR across multiple stressor exposures, even in the context of overall adaptation of cardiovascular responses.


A rare case of long-term survival from metachronous bilateral adrenal metastasis of lung adenocarcinoma after combined surgical removal and immunochemotherapy.
The prognosis of adrenal metastasis from non-small cell lung cancer is very poor. A recent report described the efficacy of the surgical removal of adrenal metastasis when solitary. However, metachronous bilateral adrenal metastasis is extremely rare, and a treatment strategy has not been established. Herein, we describe a 52-year-old Asian male who presented with a right adrenal metastasis of non-small cell lung cancer 8 months after immunochemotherapy and surgical resection of the lung. He underwent combined systemic treatment and a laparoscopic right adrenalectomy; however, after 9 months, a metachronous left adrenal metastasis emerged. A subsequent laparoscopic left adrenalectomy and systemic treatment led to long-term progression-free survival. The appropriate surgical indication and combined systemic treatment of a metachronous bilateral adrenal metastasis in non-small cell lung cancer may extend the prognosis.


Crystal structure of 6,7-dimeth-oxy-1-(4-nitro-phen-yl)quinolin-4(1H)-one: a mol-ecular scaffold for potential tubulin polymerization inhibitors.
The protein tubulin is central for maintaining normal cellular processes, and mol-ecules inter-fering with the tubulin dynamics have potential in the treatment of cancerous diseases. The title compound, C17H14N2O5, was prepared as a lead compound in a project dedicated to the development of therapeutic agents binding to the colchicine binding site on tubulin, thereby inter-fering with the cell division in cancer cells. It holds many of the main structural characteristics for colchicine binding and has the potential for further modification and functionalization. In the title mol-ecule, the benzene ring is inclined to the quinoline ring by 76.10 (8)°. In the crystal, mol-ecules are linked by two pairs of C-H⋯O hydrogen bonds, forming tubular-like arrangements, propagating along the direction of the diagonals of the ab plane, and enclosing R22(26) and R22(16) ring motifs.


Aortopulmonary window and aortic isthmic hypoplasia. Operative management in newborn infants.
Aortopulmonary window with aortic isthmic hypoplasia is an unusual combination of congenital heart lesions that usually causes severe heart failure, poor systemic perfusion, and death shortly after birth. In 21 previously reported cases, survival beyond infancy was uncommon, yet only one neonate survived operation. This report describes three cases of aortopulmonary window and aortic isthmic hypoplasia and a two-stage operative approach that proved successful in both infants in which it was tried. During the first step the isthmic obstruction is relieved, the ductus is ligated, and the aortopulmonary window is plicated via a left thoracotomy. The second stage consists of definitive closure of the aortopulmonary window using the technique of deep perfusion hypothermia.


Application of neural networks for the analysis of intravascular ultrasound and histological aortic wall appearance-an in vitro tissue characterization study.
The role of tissue characterization by intravascular ultrasound (IVUS) imaging of the aortic wall has not been well established. The artificial neural networks (ANNs) are a promising tool for image classification. The aim of the study was to assess the texture correlation between matching IVUS and histologic images of the aortic wall. The computer-based discrimination of pathology within the data sets was also evaluated. In vitro IVUS images and histologic sections from 36 aortic segments were compared using texture parameters that produced the best correlation or the highest discriminative value. The images were classified as normal or abnormal with variable degrees of pathology. Tissue characterization was performed by a nearest neighbor classifier, linear discriminant analysis (LDA) and the ANN-based approach. Good agreement was observed between IVUS and the histologic reference with a correlation coefficient of r = 0.89, r = 0.76 and r = 0.71 for the three most successful texture parameters. The ANN-based approach was the most effective in discriminant analysis, with a correct classification rate of 87.5% for histologic images and 79.2% for IVUS data. The study shows that ANNs are a potentially effective tool for assessment of IVUS aortic images.


A potential acyltransferase regulates swarming in Serratia marcescens.
Swarming in Serratia marcescens is a specialized form of bacterial populational surface migration behavior. A precocious swarming mutant S. marcescens O6 whose rssC is interrupted by mini-Tn5 transposon was obtained. The 364 amino-acid RssC showed a high identity to members of acyltransferase family. Characterization of the rssC knock-out mutant S. marcescens PC105 showed aberrant and hypervirulent phenotypes including precocious swarming behavior, reduced cell attachment ability and increase in swimming motility, flagellin synthesis, capsular polysaccharide (CPS) production, hemolysin activity, and cytotoxicity activity. Besides a more intense pattern of O-antigen sugar unit ladder, S. marcescens PC105 also showed an altered cell surface topology. A potential FlhDC binding site was identified at the rssC promoter region. In accordance, rssC transcriptional activity was up-regulated by FlhDC(Sm). Briefly, rssC is hierarchically classified as class II members in FlhDC(Sm) regulon, and reciprocally defect in rssC results in aberrant swarming and hypervirulence in S. marcescens.


Plant species diversity, community structure and invasion status in insular primary forests on the Sekimon uplifted limestone (Ogasawara Islands).
Native forests on oceanic islands are among the most threatened ecosystems. The forests formed on Sekimon uplifted limestone in Haha-jima Island (Ogasawara Islands) have not yet been destroyed by human activities and remain as primary forests harboring several narrow endemic endangered plants. In this paper, we described the plant species diversity, community structure, and status of invasion by alien plants in the mesic forests of Sekimon. The Sekimon forest was characterized by low tree diversity (37 species), high stem density (1731 ha-1), and high basal area (63.9 m2 ha-1), comparing with natural forests in world islands. The forests were dominated in the number of stems by the sub-tree Ardisia sieboldii followed by the trees Pisonia umbellifera and Elaeocarpus photiniifolius. The invasive tree Bischofia javanica ranked fourth for basal area and third for the number of stems (DBH ≥ 10 cm), and its distribution expanded, especially near a past plantation site. Surveys of forest floor vegetation revealed that species richness of vascular plants was 109 species and that many alien plants had already invaded the forests. Despite the low species richness of alien (16% for vascular flora and 8% for trees), the high frequency of aliens on the forest floor suggests that they have colonized successfully in the Sekimon forest. Extrapolation analysis based on the rarefaction curves predicted that the vascular plants in the Sekimon (25 ha) accounted for 135 species (29.9% of the vascular flora of the Ogasawara Islands) and endemic plants were 85 species (62.0%). The fact that the 39 vascular species recorded in our plots were listed in Japanese Red List suggests that the Sekimon forest should be conserved as a sanctuary of biodiversity. Because alien plants are invading the forests without apparent anthropogenic disturbance, immediate action to eradicate these invaders is highly needed.


The Western Sydney Health Study: results of the shopping-centre survey.
The Western Sydney Health Study is a two-phase descriptive study that is designed to provide data on the health-related knowledge, attitudes and behaviour of persons in the Western Metropolitan health region, which has higher-than-average death rates of many disorders that are associated with life-style. In the first phase of the study, 2164 respondents were interviewed in six shopping centres in the region. The prevalence rates of self-reported cardiovascular disease and diabetes were about twice those that were found in the Australia-wide National Heart Foundation Risk Factor Prevalence Study in 1983. The prevalence rates of smoking and self-reported raised blood lipid levels were also high. Doctors and nurses were the main sources of health information, and the media was less important as a source of health information than was found in the Better Health Commission's national survey in 1985. Over 80% of respondents believed that a lowering of the dietary fat intake and an increase in exercise were health-enhancing behaviours. Given this high level of health knowledge, the major aims for health promotion in the region should be a social change to facilitate choices towards healthy behaviour and the provision of skills to enable individual behavioural changes.


The long-term mental health of Australia's tertiary students.
The objective of the current study was to quantify the extent to which Australia's tertiary students have reported poorer mental health in comparison with the general community between 2001 and 2017. Data were derived from the Household, Income and Labour Dynamics in Australia Survey, a longitudinal household-based panel study. There were 29,124 participants who provided at least one observation over the study period. On average, participants provided 7.4 observations. Mental Health was assessed with the SF-36 mental health and vitality subscales. There was little evidence for differences in mental health and vitality between those studying at tertiary levels and those not in tertiary education. Age-stratified analyses revealed that any differences were reported by older students. Interactions between education level and time revealed that the association between tertiary study and mental health outcomes has been consistent over time. There were very few differences between those in and those not in tertiary education. The magnitude of any differences was very small and does not necessarily reflect substantial poor mental health outcome. Overall, the most consistent finding was that there was little risk for poor mental health outcomes attributed to tertiary study.


Pancreatic necrosis and acute pancreatitis.
With reference to 115 cases of acute pancreatitis which were either operated on or confirmed, the authors stress the seriousness of the lesion to the glandular parenchyma; it is also difficult to recognise during peroperative exploration. The necrosis, which is sometimes limited to the peripheral and interstitial tissue, sparing the gland itself (its prognosis is less serious) has led many surgeons to perform surgical excision. However, the problems encountered postoperatively have given rise to doubts a posteriori as to whether this is legitimate. Reference is made to the decapsulation of the pancreas described by Romanian authors, and a method for future operative diagnosis of glandular necrosis is proposed.


Aberrant Methylation of FOXE1 Contributes to a Poor Prognosis for Patients with Colorectal Cancer.
Hypermethylation of DNA silences gene expression and is an important event in colorectal cancer (CRC). This study aimed to identify aberrantly methylated genes that contribute to a poor prognosis for patients with CRC. The study comprehensively explored DNA methylation microarray profiles from 396 CRC samples and 45 normal control samples in a database and selected aberrantly methylated transcription factors associated with prognosis and metastasis. Using quantitative reverse transcription polymerase chain reaction, the identified genes in 140 patients with CRC were validated to assess the relationship between expression of methylated genes and prognosis. In the study, FOXE1 was newly identified as a gene associated with prognosis and metastasis in CRC. Expression of FOXE1 in CRC tissues was significantly lower than in normal colorectal tissues (p = 0.01). The survival rate for the patients with low expression of FOXE1 was significantly lower than that for patients with high expression of FOXE1 in uni- and multivariate analyses. Inhibition of DNA methylation recovered FOXE1 expression in CRC cells. Methylation-mediated silencing of FOXE1 expression was shown to be a potential prognostic factor in CRC.


Regulation of Apoptosis and Autophagy During Anoxia in the Freshwater Crayfish, Faxonius virilis.
The ability of an animal to survive prolonged periods of oxygen deprivation is a critical area of study, both in terms of its importance to better understanding the physiology of these incredible animals and to its potential applicability to medical fields. The freshwater crayfish, Faxonius virilis, is one such animal capable of resisting anoxia, but it remains understudied and much of the metabolic mechanisms underlying this anoxia tolerance remain largely unprofiled. This study examines the activity and regulation of apoptosis and autophagy in F. virilis in response to 20-h anoxia. Apoptosis signaling was assessed through pro- and anti-apoptosis targets, whereas autophagy was assessed via expression response of multiple autophagy proteins. An anoxia-triggered, tissue-specific result arose, potentially based on the importance of individual organ integrity through hypometabolism. Tail muscle, which showed increased expression profiles of all three target groups, contrasted with hepatopancreas, which appeared to not be susceptible to either apoptotic or autophagic signaling during anoxia. This is likely due to the importance of the hepatopancreas, given that apoptosis or autophagy of this organ at any significant level could be fatal to the organism. The data provides a comprehensive overview of the responses and integration of multiple stress-responsive signaling pathways in F. virilis that provide a novel contribution to our understanding of pro-survival mechanisms supporting invertebrate anoxia resistance.


The effects of distension of the small intestine on myocardial blood flow in anaesthetised cats: possible relevance to coronary vasospasm.
The haemodynamic effects of distending the small intestine (with a balloon in the lumen) were examined in cats anaesthetised with chloralose. Particular attention was paid to blood flow changes in localised areas of the left ventricular wall (as assessed using the heated thermocouple technique). Intestinal distension led to an increase in systemic blood pressure but usually to a reduction in myocardial blood flow; no cardiac dysrhythmias were observed. When the effect of increased systemic (perfusion) pressure on blood flow was eliminated (using partial correlation coefficients) flow then bore a negative relationship to intestinal pressure, probably indicating constriction of the myocardial blood vessles. This may indicate that distension of hollow organs can lead to a visceral-cardiac reflex. The resulting coronary vasospasm might be one cause of pain in certain patients with angina pectoris.


Acute Kidney Injury and Abnormalities on Brain Magnetic Resonance Imaging or Death in Infants with Hypoxic-Ischemic Encephalopathy: A Case-Control Study.
This study aimed to analyze the association between acute kidney injury (AKI) and abnormalities on brain magnetic resonance imaging (MRI) or death in neonates treated with therapeutic hypothermia for hypoxic-ischemic encephalopathy (HIE). This is a retrospective case-control analysis of 380 neonates born at ≥35 weeks' gestation treated with therapeutic hypothermia for HIE. Death or abnormal brain MRI using the basal ganglia watershed scoring system was compared between neonates with and without AKI. A total of 51 (13.4%) neonates had AKI. Infants with AKI had higher rates of the composite of death or abnormal brain MRI (74.5 vs. 38.3%; p < 0.001). Rate of death (21.6 vs. 5.5%; p < 0.001) and severe abnormalities on MRI or death (43.1 vs. 19.1%; p < 0.001) were also higher in neonates with AKI. AKI is strongly associated with abnormalities on brain MRI or death in neonates with HIE. Identification of AKI in this patient population may be helpful in guiding clinical management and predicting potential neurodevelopmental impairment. · Neonates with HIE are at increased risk for AKI.. · AKI is associated with hypoxic-ischemic injury on brain MRI or death among neonates with HIE.. · Identification of AKI in infants with HIE may help predict neurodevelopmental impairment..


Expression of laminin isoforms by peripheral nerve-derived connective tissue cells in culture. Comparison with epitope distribution in normal human nerve and neural tumors in vivo.
Laminins are a family of multifunctional glycoproteins that play a role in various aspects of cell biology. Three different isoforms of laminin have been described, and each comprises a molecule consisting of three subunit polypeptides, the A, B1, B2, M or S chain. The expression pattern of laminin isoforms was studied by indirect immunofluorescence staining of human peripheral nerve in situ or cell cultures derived from such nerve by using monoclonal antibodies recognizing the subunit epitopes. Selective expression of the subunit polypeptides of laminin isoforms in endoneurium and perineurium was demonstrated. Specifically, an intense immunoreaction for A, B2 and S chain epitopes could be detected in perineurium, whereas endoneurium revealed the presence of B1, B2, M and S chains. Examination of the laminin isoform expression in perineurial cells, Schwann cells, and fibroblasts in cultures derived from normal human nerve indicated, however, that these cells under in vitro conditions were capable of expressing all five laminin chains. Cutaneous neurofibromas, tumors characterized by the presence of mixed cell populations consisting of Schwann cells, perineurial cells, and fibroblasts, demonstrated the expression of B1, B2 and M chain epitopes, whereas only a weak immunostaining could be detected with antibodies recognizing the A and S chains. Similar observations were made on schwannomas, a Schwann cell tumor. Collectively, the observations of this study attest to the plasticity of neural-derived connective tissue cells with respect to laminin isoform expression. Such plasticity may relate to the cell-cell and cell-matrix interactions during development of peripheral nerves and the potential for neural regeneration.


Pregastric and postabsorptive inhibitory effects of water on angiotensin-induced Fos in rat brain.
Intraventricularly (ICV)-injected Ang II activates cells in several forebrain structures of rats, including SFO, OVLT, PVN and SON, and produces a spectrum of physiological and behavioral responses. It has been reported that the Fos-like immunoreactivity (FLI; a marker of cell activation) that is induced in PVN and SON by exogenous Ang II is prevented by allowing rats to ingest water after injection. The present study tests whether this inhibitory effect of water is due to either preabsorptive (oral) or postingestive factors, or both. Rats received cerebroventricular injection of Ang II (100 ng) and were killed 1 h later. One group received no water after the injection, another group drank water, a third group drank water but had it drain from a gastric fistula (sham drinking), and a fourth group received an intragastric infusion of water. In confirmation of a previous study, rats allowed to drink water after Ang II showed an almost complete absence of FLI in SON and PVN, compared with those not allowed access to water. Both sham drinking and intragastrically-infused rats showed less FLI in SON and PVN than nondrinkers. The reduction was greater in the infused group than the sham drinkers, but was not as great as in those allowed to drink water and absorb it. This suggests that both orally-mediated as well as postabsorptive factors can inhibit Ang II-induced FLI by impinging upon cells in the SON and PVN. In contrast, Ang II-induced FLI in OVLT and SFO was not affected by any of the oral or gastric water conditions.


Dengue hepatitis: Incidence, spectrum and outcome.
While dengue infection is common in India, there is scarce information on dengue hepatitis. The aim of this study was to analyze the incidence, spectrum and outcome of dengue hepatitis. We retrospectively analyzed consecutive patients, who had hepatitis among those with dengue infection admitted to two tertiary care hospitals in western India from January 2016 to March 2021. Diagnosis of dengue infection was made by serology. Dengue hepatitis was diagnosed and the severity of dengue was categorized by standard criteria. Of 1664 patients admitted with dengue fever during the study period, 199 patients had hepatitis (i.e. incidence of dengue hepatitis was 11.9%). Of the 199 dengue hepatitis patients (age: 29 [13 - 80] years, median [range], 67% males), 100 patients (50%) had severe dengue, 73 (36%) had severe dengue hepatitis, 32 (16%) had dengue shock syndrome and eight (4%) had acute liver failure. Forty-five patients (23%) had acute lung injury and 32 (16%) had acute kidney injury. The dengue hepatitis patients were treated with standard medical care, including vital organ support, as needed-166 (83%) patients survived, while 33 patients (17%) died (cause of death: multi-organ failure: 24 patients, septic shock: nine patients). The presence of shock independently predicted mortality (odds ratio 6.4, 95% confidence interval: 1.2 - 34). Among patients with dengue hepatitis, mortality rate was higher in those with severe dengue (23%), dengue shock syndrome (47%), severe dengue hepatitis (24%) and acute liver failure (38%). In this large series of hospitalized patients with dengue infection, the incidence of dengue hepatitis was 11.9%. Among 199 dengue hepatitis, 17% died; multi-organ failure was the commonest cause for death and death rate was higher in patients with more severe disease. The presence of shock at presentation independently predicted mortality.


Very low-dose coronary artery calcium scanning with high-pitch spiral acquisition mode: comparison between 120-kV and 100-kV tube voltage protocols.
Effective radiation dose from a single coronary artery calcification CT scan can range from 0.8 to 10.5 mSv, depending on the protocol. Reducing the effective radiation dose to reasonable levels without affecting diagnostic image quality can result in substantial dose reduction in CT. We prospectively compared tube voltages of 120 and 100 kV in a low-dose CT acquisition protocol for measuring coronary artery calcified plaque with prospectively electrocardiogram (ECG)-triggered high-pitch spiral acquisition. In 150 consecutive patients, measurement of coronary artery calcified plaque was performed with prospectively ECG-triggered high-pitch spiral acquisition. Imaging was first done with tube voltage of 120 kV voltage and subsequently repeated with 100 kV and otherwise unchanged parameters. CT was performed with a dual-source CT system with 280 milliseconds of rotation time, 2 × 128 slices, pitch of 3.4, triggered at 60% of the R-R interval. Tube current for both protocols was set at 80 mAs. With the use of a medium sharp reconstruction kernel (Siemens B35f), cross-sectional images were reconstructed with 3.0-mm slice thickness and 1.5-mm increment. Agatston scores were determined per patient for both scan settings by 2 independent readers with the use of a standard threshold of 130 HU for calcium detection. In addition, the Agatston score was calculated with a previously proposed threshold of 147 HU for 100-kV acquisitions. Mean image noise was 20 ± 5 and 27 ± 7 for 120 and 100 kV, respectively (P < 0.0001). Mean dose length product was 24 ± 6 cm · cGy for the 120-kV protocol and 14 ± 4 cm · cGy for the 100-kV protocol, corresponding to average estimated effective doses of 0.3 and 0.2 mSv (P < 0.0001). Five patients were excluded from the analysis. In the remaining 145 patients, using the standard tube voltage of 120 kV, any coronary calcium was detected in 76 identical patients by both observers. In 75 of these patients, calcium was also identified by both observers in 100-kV data sets, whereas 1 patient was scored negative by 1 reader and was assigned an Agatston score of 0.7 (threshold, 130 HU) and 0.2 (threshold, 147 HU) by the other. Interobserver disagreement for assigning a patient a zero Agatston score was the same for both scan settings (each 4 patients). The mean Agatston scores for 120-kV and 100-kV (threshold, 147 HU) scans were 105 ± 245 (range, 0-1865) and 116 ± 261 (range, 0-1917), respectively (P < 0.0001). Bland-Altman analysis indicated a systematic overestimation of the Agatston score with tube voltage of 100 kV and threshold of 147 HU (mean difference, 11; 95% limits of agreement, 62 to -40). Similar results were observed for coronary calcium volume scores. High-pitch spiral acquisition allows coronary calcium scoring with effective doses below 0.5 mSv. The use of 100-kV tube voltage further reduces effective radiation dose compared with the standard of 120 kV; however, it leads to significant overestimation of the Agatston score when the standard threshold of 130 HU is used. Adjusting the threshold to 147 HU leads to a better agreement compared with standard 120 kV protocols yet with a remaining systematic bias toward overestimation of the Agatston score. For high-pitch spiral acquisition mode, effective radiation dose reduction when using a 100-kV setting is minimal compared with the standard 120-kV setting and may be considered nonsignificant in a clinical setting.


Traditional food knowledge of local people and its sustainability in mountains of Uttarakhand State of India.
With homogenisation of various cultural groups due to outside forces and the effect of globalisation, many traditional foods, as developed by various cultural groups, have been lost or on the verge of elimination. In this context, the present study aims to examine and document the traditional food knowledge of local people in Uttarakhand State of India. Interviews and interactions with the local people resulted in documentation of 38 cuisines traditionally prepared by the local people of selected study regions in Uttarakhand. Apart from boiled rice and chapattis (flatbread) of wheat flour, chapattis and porridge of finger millet flour and boiled barnyard and foxtail millets were frequently consumed dishes in combination with dishes made with locally grown pulses such as horse gram and black gram and vegetables such as potato, radish and other leafy vegetables. The supplementary dishes were locally called as fanu, chaisu, gathoni, thechwani, kafli and kadhi. Plants formed the major ingredients in making traditional cuisines. The present study documented 41 plant species comprising of cereals, millets, pulses and spices. With a view to enhance the taste of the dishes, different spices and condiments such as Allium humile, Allium wallichii, Cleome viscosa, Cannabis sativa, Perilla frutescens and Cinnamomum tamala were used by the local people. These dishes possessed some unique characteristics and ethno-medicinal values; hence, when required, they were used to cure a number of ailments as well. Since most of the mountain region in the study area was once inaccessible and health facilities were not much developed till recent times, the traditional health-care system was supported by the traditional food systems. The findings of the present study are further discussed in the context of sustainability of socio-ecological systems of Uttarakhand.


Variant Characterization of a Representative Large Pedigree Suggests "Variant Risk Clusters" Convey Varying Predisposition of Risk to Lynch Syndrome.
Recently, worldwide incidences of young adult aggressive colorectal cancer (CRC) have rapidly increased. Of these incidences diagnosed as familial Lynch syndrome (LS) CRC, outcomes are extremely poor. In this study, we seek novel familial germline variants from a large pedigree Tunisian family with 12 LS-affected individuals to identify putative germline variants associated with varying risk of LS. Whole-genome sequencing analysis was performed to identify known and novel germline variants shared between affected and non-affected pedigree members. SNPs, indels, and structural variants (SVs) were computationally identified, and their oncological influence was predicted using the Genetic Association of Complex Diseases and Disorders, OncoKB, and My Cancer Genome databases. Of 94 germline familial variants identified with predicted functional impact, 37 SNPs/indels were detected in 28 genes, 2 of which (MLH1 and PRH1-TAS2R14) have known association with CRC and 4 others (PPP1R13B, LAMA5, FTO, and NLRP14) have known association with non-CRC cancers. In addition, 48 of 57 identified SVs overlap with 43 genes. Three of these genes (RELN, IRS2, and FOXP1) have a known association with non-CRC digestive cancers and one (RRAS2) has a known association with non-CRC cancer. Our study identified 83 novel, predicted functionally impactful germline variants grouped in three "variant risk clusters" shared in three familiarly associated LS groups (high, intermediate and low risk). This variant characterization study demonstrates that large pedigree investigations provide important evidence supporting the hypothesis that different "variant risk clusters" can convey different mechanisms of risk and oncogenesis of LS-CRC even within the same pedigree.


Interobserver agreement of the modified Paris classification and histology prediction of colorectal lesions in patients with inflammatory bowel disease.
SCENIC (International Consensus Statement on Surveillance and Management of Dysplasia in IBD) guidelines recommend that visible dysplasia in patients with longstanding inflammatory bowel disease (IBD) should be endoscopically characterized using a modified Paris classification. This study aimed to determine the interobserver agreement (IOA) of the modified Paris classification and endoscopists' accuracy for pathology prediction of IBD visible lesions. One hundred deidentified endoscopic still images and 30 videos of IBD visible colorectal lesions were graded by 10 senior and 4 trainee endoscopists from 5 tertiary care centers. Endoscopists were asked to assign 4 classifications for each image: the standard Paris classification, modified Paris classification, pathology prediction, and lesion border. Agreement was measured using Light's kappa coefficient. Consensus of ratings was assessed according to strict majority. The overall Light's kappa for all study endpoints was between .32 and .49. In a subgroup analysis between junior and senior endoscopists, Light's kappa continued to be less than .6 with a slightly higher agreement among juniors. Lesions with the lowest agreement and no consensus were mostly classified as Is, IIa, and mixed Paris classification and sessile and superficial elevated for modified Paris classification. Endoscopist accuracy for prediction of dysplastic, nondysplastic, and serrated pathology was 77%, 56%, and 30%, respectively. There was a strong association (P < .001) between the given morphology classification and the predicted pathology with Ip lesions carrying a much lower expectation of dysplasia than Is/IIc/III and mixed lesions. The agreement for border prediction was .5 for junior and .3 for senior endoscopists. This study demonstrates very low IOA for Paris and modified Paris classifications and low accuracy and IOA for lesion histopathology prediction. Revisions of these classifications are required to create a clinically useful risk stratification tool and enable eventual application of augmented intelligence tools.


[Ceramic 55S as a substrate for the regeneration of bone defects; an in vitro study].
The purpose of this work is to evaluate the in vitro behaviour and the capacity to induce osteoblastic differentiation of a 55S vitro-ceramic (Vc) on a population of adult rabbit mesenchymal stem-cells (MSCs). The material was obtained using the sol-gel method. The cells were obtained from rabbit bone-marrow aspirate and seeded over the Vc, and over plastic (control). The MSCs were cultivated in two culture media; one a standard DMEM (growth medium), and the other an osteoblastic phenotype inducer, composed of DMEM complemented with dexamethasone, ß-glycerophosphate and ascorbic acid-2-phosphate (osteogenic medium). The morphology of the cells that grew was assessed using a scanning electronic microscope. The tetrazolium salt reduction test was used for evaluating the cell growth. For cell differentiation, osteocalcin production and loss of CD90 bone surface antigen, characteristic of MSCs, were quantified. During the culture time the MSCs adhered, proliferated and formed a mineralised extracellular matrix over the Vc. An osteoblastic phenotype finally being shown, producing osteocalcin and decreasing the expression of the CD90 antigen, regardless of the culture medium used. Based on these results we can state that Vc 55S behaved like a material capable of supporting adhesion and growth of MSCs and, in turn, inducing the differentiation of the MSCs to osteoblastic cell lines, thus showing osteoconduction and osteoinduction properties.


A constitutively active G protein-coupled acetylcholine receptor regulates motility of larval Schistosoma mansoni.
The neuromuscular system of helminths controls a variety of essential biological processes and therefore represents a good source of novel drug targets. The neuroactive substance, acetylcholine controls movement of Schistosoma mansoni but the mode of action is poorly understood. Here, we present first evidence of a functional G protein-coupled acetylcholine receptor in S. mansoni, which we have named SmGAR. A bioinformatics analysis indicated that SmGAR belongs to a clade of invertebrate GAR-like receptors and is related to vertebrate muscarinic acetylcholine receptors. Functional expression studies in yeast showed that SmGAR is constitutively active but can be further activated by acetylcholine and, to a lesser extent, the cholinergic agonist, carbachol. Anti-cholinergic drugs, atropine and promethazine, were found to have inverse agonist activity towards SmGAR, causing a significant decrease in the receptor's basal activity. An RNAi phenotypic assay revealed that suppression of SmGAR activity in early-stage larval schistosomulae leads to a drastic reduction in larval motility. In sum, our results provide the first molecular evidence that cholinergic GAR-like receptors are present in schistosomes and are required for proper motor control in the larvae. The results further identify SmGAR as a possible candidate for antiparasitic drug targeting.


The finding of invasive cancer after a preoperative diagnosis of ductal carcinoma-in-situ: causes of ductal carcinoma-in-situ underestimates with stereotactic 14-gauge needle biopsy.
For the evaluation of nonpalpable lesions of the breast, image-guided 14-gauge automated needle biopsy is increasingly replacing wire-localized excision. When ductal carcinoma-in-situ (DCIS) is diagnosed at core biopsy, invasive cancer is found in approximately 17% of excision specimens. These so-called DCIS underestimates pose a problem for patients and surgeons, because they generally cause extension of treatment. We evaluated DCIS underestimates in detail to assess reasons for missing the invasive component at core biopsy. This evaluation also included a histological comparison with true DCIS (DCIS at core biopsy and excision). Between 1997 and 2000, DCIS was diagnosed at 14-gauge needle biopsy in 255 patients. In 41 cases (16%), invasive cancer was found at excision. We performed a thorough histopathological and radiological review of all these DCIS underestimates, including a histological comparison with core biopsy specimens of 32 true DCIS cases. We assessed the main reason for missing the invasive component at core biopsy. Causes for DCIS underestimates were categorized into "mainly radiological" (n = 20), "mainly histopathological" (n = 15), and "histological disagreements" (n = 6). High-grade DCIS and periductal inflammation in core biopsies made a DCIS underestimate 2.9 and 3.3 times more likely, respectively. A variety of radiological and histopathological reasons contribute to the DCIS underestimate rate. Approximately half of these are potentially avoidable.