Dispersion of Lutzomyia longipalpis and expansion of visceral leishmaniasis in São Paulo State, Brazil: identification of associated factors through survival analysis.
In Brazil, visceral leishmaniasis (VL) is a serious public health problem because of its magnitude, geographical expansion and potential harms caused by illnesses, including death. However, VL is largely ignored in discussions of tropical disease priorities. Thus, this study aimed to identify factors associated with the expansion of VL and the dispersion of its vector, Lutzomyia longipalpis, in the municipalities of the State of São Paulo, Brazil. Information about the date of vector detection and the confirmation of autochthonous VL occurrence in humans and canines in São Paulo were obtained between 1997 and 2014. Survival curves were calculated by the Kaplan-Meier and the Cox multiple regression models was used. The presence of the Marechal Rondon highway showed the highest positive association with vector dispersion and canine and human VL expansion. The monthly maximum and minimum temperature averages recorded in the municipalities during the study period were also positively associated with these events. The presence of transverse highways was positively associated with the presence of the vector; the border with the State of Mato Grosso do Sul, the presence of a prison, microregion headquarters, and the presence of the Tietê River were positively associated with the occurrence of canine cases, while only the presence of prison was positively associated with the occurrence of human cases. The construction of the Bolivia-Brazil gas pipeline was not associated with any events. Survival analysis enabled the identification of factors associated with vector dispersion and VL expansion, thus the results of this study may be useful to the improvement of VL surveillance and control activities in the State of São Paulo and throughout Brazil.


[Ischemic colitis and hemophagocytosis complicating Kawasaki disease].
Gastrointestinal manifestations of Kawasaki disease are usually limited to stomatitis, paralytic ileus, and hydrops of the gallbladder. We report a case of Kawasaki disease complicated with hemophagocytosis and ischemic colitis. A 5-year-old girl with Kawasaki disease presented with hemophagocytosis that responded to gamma-globulin therapy. On day 4 she had abdominal pain and diarrhea. CT scan showed features suggesting ischemic colitis. Symptoms resolved on total parenteral nutrition. Ischemic colitis and hemophagocytosis are potential severe complications of Kawasaki disease.


Task shifting roles, interventions and outcomes for kidney and cardiovascular health service delivery among African populations: a scoping review.
Human resources for health (HRH) shortages are a major limitation to equitable access to healthcare. African countries have the most severe shortage of HRH in the world despite rising communicable and non-communicable disease (NCD) burden. Task shifting provides an opportunity to fill the gaps in HRH shortage in Africa. The aim of this scoping review is to evaluate task shifting roles, interventions and outcomes for addressing kidney and cardiovascular (CV) health problems in African populations. We conducted this scoping review to answer the question: "what are the roles, interventions and outcomes of task shifting strategies for CV and kidney health in Africa?" Eligible studies were selected after searching MEDLINE (Ovid), Embase (Ovid), CINAHL, ISI Web of Science, and Africa journal online (AJOL). We analyzed the data descriptively. Thirty-three studies, conducted in 10 African countries (South Africa, Nigeria, Ghana, Kenya, Cameroon, Democratic Republic of Congo, Ethiopia, Malawi, Rwanda, and Uganda) were eligible for inclusion. There were few randomized controlled trials (n = 6; 18.2%), and tasks were mostly shifted for hypertension (n = 27; 81.8%) than for diabetes (n = 16; 48.5%). More tasks were shifted to nurses (n = 19; 57.6%) than pharmacists (n = 6; 18.2%) or community health workers (n = 5; 15.2%). Across all studies, the most common role played by HRH in task shifting was for treatment and adherence (n = 28; 84.9%) followed by screening and detection (n = 24; 72.7%), education and counselling (n = 24; 72.7%), and triage (n = 13; 39.4%). Improved blood pressure levels were reported in 78.6%, 66.7%, and 80.0% for hypertension-related task shifting roles to nurses, pharmacists, and CHWs, respectively. Improved glycaemic indices were reported as 66.7%, 50.0%, and 66.7% for diabetes-related task shifting roles to nurses, pharmacists, and CHWs, respectively. Despite the numerus HRH challenges that are present in Africa for CV and kidney health, this study suggests that task shifting initiatives can improve process of care measures (access and efficiency) as well as identification, awareness and treatment of CV and kidney disease in the region. The impact of task shifting on long-term outcomes of kidney and CV diseases and the sustainability of NCD programs based on task shifting remains to be determined.


Word and line bisection in typical and impaired readers and a cross-language comparison.
Observers exhibit larger leftward bias when bisecting words compared with lines. According to the Attentional Scaling Hypothesis, attempting to access lexical entries involves focusing attention on the initial letters of words to establish a cohort of potential matches with entries in the mental lexicon. We test this account by examining two predictions: (1) greater leftward bias for words should be evident in English readers in which the word beginning is on the left but not in Hebrew readers. (2) Dyslexics who have lexical impairments should show greater bias. Results reveal that word length modulated bisection bias differently for Hebrew and English readers, although the bias stays always leftward. Furthermore, dyslexics exhibited an exaggerated leftward bias than controls. We propose this effect arises from an interaction between reading and spatial attention rather than from the scaling of attention relative to the beginning of the word in the service of lexical access.


The clinical implications of telomerase activity in upper tract urothelial cancer and washings.
To measure telomerase activity in upper tract urothelial carcinomas (as renal pelvic tumours comprise nearly half of all kidney tumours in Taiwan, a much higher percentage than in other countries) and to determine whether telomerase activity could be used as an additional diagnostic marker in exfoliated cancer cells present in upper tract urothelial washing fluids, thus providing earlier diagnosis and treatment. Materials and methods Telomerase activity was assessed using the telomeric repeat amplification protocol assay in tissue samples from 31 upper tract urothelial carcinomas (from 29 patients). The feasibility of identifying cancer using telomerase activity in exfoliated cancer cells in 17 upper tract urothelial washing samples was also investigated. Telomerase activity was found in 30 (97%) of the 31 upper tract urothelial cancer tissue samples; telomerase activity was detectable in 95% of superficial cancers and in all 11 invasive tumours. The sensitivity of measuring telomerase activity was 100% for grade 1, 93% for grade 2 and 100% for grade 3 tumours. In contrast, telomerase activity was detected in only two (8%) of 26 normal adjacent tissue samples. When the telomerase activity of urothelial washing fluid was compared with that in the corresponding tumours, there was compatible telomerase activity in 15 of the 17 samples. Telomerase activity was more sensitive than voided urine cytology (15%) and washing fluid cytology (53%). In addition, the telomerase activity was high in metastatic lesions. Telomerase activity is present in most upper tract urothelial cancer tissues and may be present at an early stage of carcinogenesis. Telomerase activity can be detected in exfoliated cells in urothelial washing fluids in a high proportion of patients with upper tract urothelial cancer. These results suggest that measuring telomerase activity in the exfoliated cancer cells obtained from urothelial washing could be a potentially useful addition to the conventional diagnostic tools used to identify patients with upper tract urothelial carcinoma.


The role of statins in the prevention of preeclampsia.
Preeclampsia is a common hypertensive disorder of pregnancy associated with considerable neonatal and maternal morbidities and mortalities. However, the exact cause of preeclampsia remains unknown; it is generally accepted that abnormal placentation resulting in the release of soluble antiangiogenic factors, coupled with increased oxidative stress and inflammation, leads to systemic endothelial dysfunction and the clinical manifestations of the disease. Statins have been found to correct similar pathophysiological pathways that underlie the development of preeclampsia. Pravastatin, specifically, has been reported in various preclinical and clinical studies to reverse the pregnancy-specific angiogenic imbalance associated with preeclampsia, to restore global endothelial health, and to prevent oxidative and inflammatory injury. Human studies have found a favorable safety profile for pravastatin, and more recent evidence does not support the previous teratogenic concerns surrounding statins in pregnancy. With reassuring and positive findings from pilot studies and strong biological plausibility, statins should be investigated in large clinical randomized-controlled trials for the prevention of preeclampsia.


The role of uterine natural killer cells in recurrent pregnancy loss and possible treatment options.
This narrative review summarizes the current knowledge on the role of uterine natural killer (uNK) cells in recurrent pregnancy loss and possible treatment options. Recurrent pregnancy loss involves 2 or more consecutive miscarriages, affecting around 3% of couples attempting conception. Despite extensive investigation, causes often remain elusive. Uterine natural killer cells, critical in early gestation and implantation, may hold answers for treatment options. Properly designed and powered clinical trials are needed to provide more answers on the effect of treatment options in relation to uNK cells.


Comparative study of outcomes between allograft intervertebral disc transplantation and anterior cervical discectomy and fusion: a retrospective cohort study at least 5 years of follow-up.
Adjacent segment degeneration (ASDeg) after anterior cervical discectomy and fusion (ACDF) seriously affects the long-term efficacy of the operation. Therefore, our team has done a lot of research on allograft intervertebral disc transplantation (AIDT) to prove its feasibility and safety. This study will compare the efficacy between AIDT and ACDF in the treatment of cervical spondylosis. All patients who received ACDF or AIDT in our hospital from 2000 to 2016 and followed up for at least 5 years were recruited and divided into ACDF and AIDT groups. The clinical outcomes including functional scores and radiological data of both groups were collected and compared preoperatively and postoperatively at 1 week, 3 months, 6 months, 12 months, 24 months, 60 months and last follow-up. Functional scores included Japanese Orthopedic Association score (JOA), Neck Disability Index (NDI), Visual Analog Scale of Neck (N-VAS) and Arms (A-VAS) pain, the Short Form Health Survey-36 (SF-36) and imaging dates including digital radiographs in the lateral, hyperextension and flexion positions to assess the stability, sagittal balance and mobility of the cervical spine and magnetic resonance imaging (MRI) scans to assess the degeneration of adjacent segment. There were 68 patients with 25 in AIDT group and 43 in ACDF group. Satisfactory clinical results were obtained in both groups, but the long-term NDI score and N-VAS score in the AIDT group were better. The AIDT obtained the same stability and sagittal balance of the cervical spine as fusion surgery. The range of motion of adjacent segments can be restored to the preoperative level after transplantation, but this increases significantly after ACDF. There were significant differences in the superior adjacent segment range of motion (SROM) between two groups at 12 months (P = 0.039), 24 months (P = 0.035), 60 months (P = 0.039) and the last follow-up (P = 0.011). The inferior adjacent segment range of motion (IROM) and SROM had a similar trend in the two groups. The ratio value of the greyscale (RVG) of adjacent segments showed a downward trend. At the last follow-up, the RVG decreased more significantly in the ACDF group. At the last follow-up, there was a significant difference in the incidence of ASDeg between the two groups (P = 0.000). And the incidence of adjacent segment disease (ASDis) is 22.86% in the ACDF group. The allograft intervertebral disc transplantation may be as an alternative technique to traditional anterior cervical discectomy and fusion for the management of cervical degenerative diseases. For the more, the results showed it would improve cervical kinematics and reduce the incidence of adjacent segment degeneration.


Controllable degradation kinetics of POSS nanoparticle-integrated poly(ε-caprolactone urea)urethane elastomers for tissue engineering applications.
Biodegradable elastomers are a popular choice for tissue engineering scaffolds, particularly in mechanically challenging settings (e.g. the skin). As the optimal rate of scaffold degradation depends on the tissue type to be regenerated, next-generation scaffolds must demonstrate tuneable degradation patterns. Previous investigations mainly focussed on the integration of more or less hydrolysable components to modulate degradation rates. In this study, however, the objective was to develop and synthesize a family of novel biodegradable polyurethanes (PUs) based on a poly(ε-caprolactone urea)urethane backbone integrating polyhedral oligomeric silsesquioxane (POSS-PCLU) with varying amounts of hard segments (24%, 28% and 33% (w/v)) in order to investigate the influence of hard segment chemistry on the degradation rate and profile. PUs lacking POSS nanoparticles served to prove the important function of POSS in maintaining the mechanical structures of the PU scaffolds before, during and after degradation. Mechanical testing of degraded samples revealed hard segment-dependent modulation of the materials' viscoelastic properties, which was attributable to (i) degradation-induced changes in the PU crystallinity and (ii) either the presence or absence of POSS. In conclusion, this study presents a facile method of controlling degradation profiles of PU scaffolds used in tissue engineering applications.


Becoming involved: the nurse leader's role in encouraging teamwork.
This study explored why nurses enjoy and seek involvement in their work. Nurses from inpatient and outpatient units were surveyed. Results indicated that prior involvement, and meaningful involvement, served to predict further teamwork. Recommendations were made to the nurse leader who wished to promote increased work involvement.


Disease status, costs and quality of life of patients with rheumatoid arthritis in France: the ECO-PR Study.
To investigate resource consumption and quality of life (utility) in a sample of patients covering the full spectrum of the disease, modalities of patient management and geographic areas. Information on demographics, disease parameters, work capacity and resource consumption (in the past 1, 3 or 12 months depending on the resource) was collected in an anonymous mail survey from all members of a national patient association (ANDAR). Results are presented for the sample and by level of functional capacity, in 2005 euro. 1487 patients were included in the analysis (response rate 49%). Mean age was 62.7 years and 83.5% of respondents were female. Mean disease duration was 18 years; mean HAQ was 1.42; fatigue and pain ranked 5.6 and 4.8 on a scale between 0 and 10, respectively. Of patients below 60 years, 34% had taken early retirement due to RA, and only 15% of patients with a HAQ of 2 or higher were working. Productivity losses were estimated at 5076 euro, of which indemnity payments covered 1944 euro. Direct health care costs were 11,757 euro in the societal perspective and 9216 euro in the perspective of the national health insurance. Direct non-medical costs (including informal care) were 4857 euro and 136 euro respectively. Costs to society increased from 9400 euro in mild disease to 40,700 euro in severe disease, and to public payers from 6000 euro to 19,000 euro. Utility decreased simultaneously from 0.80 to 0.06. The study confirms overall findings in other studies in other countries, and provides the first estimate of all costs by disease severity in France.


On the protective mechanisms of nitric oxide in acute pancreatitis.
Ectopic protease activation, microcirculatory changes, and leucocyte activation are the main events in the pathogenesis of acute pancreatitis. Nitric oxide (NO) is known to be a key mediator in the normal and inflamed pancreas. To investigate the targets on which NO exerts its effect in caerulein induced pancreatitis. Acute pancreatitis was induced in rats which additionally received either the NO synthase substrate, L-arginine; the NO donor, sodium nitroprusside; or the NO synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME). At six hours, pancreatic injury (oedema, leucocyte content, ectopic trypsinogen activation) was analysed and pancreatic oxygenation and perfusion were determined. A direct influence of NO on amylase secretion and trypsinogen activation was evaluated separately in vitro. Both NO donors reduced the grade of inflammation. L-NAME increased the severity of inflammation, while decreasing pancreatic tissue oxygenation. Although neither amylase secretion nor intracellular trypsinogen activation in caerulein stimulated pancreatic acini was influenced by either NO donors or inhibitors, both NO donors decreased intrapancreatic trypsinogen activation peptide (TAP) and pancreatic oedema in vivo, and L-NAME increased TAP. NO protects against injury caused by pancreatitis in the intact animal but has no discernible effect on isolated acini. It is likely that in pancreatitis NO acts indirectly via microcirculatory changes, including inhibition of leucocyte activation and preservation of capillary perfusion.


Dolichoarteriopathia of Bilateral Common Carotid Artery Presenting as Mass in Pyriform Fossae Causing Dysphagia: An Anatomical Anomaly.
A rare case of aberrant tortuous common carotid artery (dolichoarteriopathia) presenting as submucosal swellings in bilateral pyriform sinuses, non-pulsatile, mimicking submucosal growths in an elderly female with complaints of dysphagia for solids, is described. CT with contrast by the radiologist opined the swellings as common carotid dolichoarteriopathia. We discussed the presentation of the anomaly in head and neck briefly by reviewing the literature and the hazards of biopsy in such a situation. Flexible fibreoptic videoendoscopy, CT with contrast of the head and neck, and the radiologist's opinion gave the clue to diagnosis. The non-pulsatile masses in the pyriform sinuses, is intriguing and minimally invasive procedure like biopsy would have been fatal. One should be careful in dealing with such non-pulsatile submucosal swellings in the laryngopharynx without proper investigations. Anomalies of common carotid artery (CCA) are rare in clinical experience. Choi et al. (Eur Arch Otorhinolaryngol 255(5):269-270, 1998) reported tortuous CCA in neck dissection for cancer but in clinical practice, the abnormal course of CCA presenting in pyriform sinus is extremely rare.


A systematic review and meta-analysis of neoadjuvant chemotherapy for bladder cancer between ddMVAC and GC regimen.
The purpose of this systematic literature review and meta-analysis was to compare the pathological response rate and prognosis of the dose dense Methotrexate, vinblastine, doxorubicin and cisplatin (ddMVAC) regimen and gemcitabine and cisplatin (GC) regimen as neoadjuvant chemotherapy choices for bladder cancer. A literature review of articles published before February 28, 2021, was conducted using the PubMed, Web of Sciences and Embase databases. Data for comparison included pathological response rate and overall survival. Five studies including 1,206 patients were identified and assessed for the meta-analysis. The pooled analysis yielded an odds ratio value of 1.29 (95% CI, 0.86-1.92) with a downstaging rate and an odds ratio value of 1.57 (95% CI, 1.10-2.25) with a complete response rate when comparing ddMVAC with the GC regimen. The pooled analysis yielded a hazard ratio of 0.47 (95% CI, 0.30-0.72) with regard to overall survival between the two regimens. Compared with the GC regimen, ddMVAC has a better pathological response rate, especially the complete response rate, and provides longer overall survival as a neoadjuvant chemotherapy regimen for bladder cancer.


Children in Beardslee's family intervention: relieved by understanding of parental mental illness.
Beardslee's family intervention (FI), which is a family-based preventive method for children of mentally ill parents, has been implemented on a national level in Sweden. Fourteen children and parents from nine families were interviewed about how the FI was for the children. Data were analysed by qualitative content analysis. A central finding was children's sense of relief and release from worry because of more knowledge and openness about the parent's illness in the family. The results indicating relief for the children are encouraging.


A review of screening mammography: The benefits and radiation risks put into perspective.
In medical imaging a benefit to risk analysis is required when justifying or implementing diagnostic procedures. Screening mammography is no exception and in particular concerns around the use of radiation to help diagnose cancer must be addressed. The Medline database and various established reports on breast screening and radiological protection were utilised to explore this review. The benefit of screening is well argued; the ability to detect and treat breast cancer has led to a 91% 5-year survival rate and 497 deaths prevented from breast cancer amongst 100,000 screened women. Subsequently, screening guidelines by various countries recommend annual, biennial or triennial screening from ages somewhere between 40-74 years. Whilst the literature presents different perspectives on screening younger and older women, the current evidence of benefit for screening women <40 and ≥75 years is currently not strong. The radiation dose and associated risk delivered to each woman for a single examination is dependent upon age, breast density and breast thickness, however the average mean glandular dose is around 2.5-3 mGy, and this would result in 65 induced cancers and 8 deaths per 100,000 women over a screening lifetime from 40-74 years. This results in a ratio of lives saved to deaths from induced cancer of 62:1. Therefore, compared to the potential mortality reduction achievable with screening mammography, the risk is small.


Partition of malathion in synthetic and native membranes.
Partition coefficients of [14C]malathion in model and native membranes are affected by temperature, cholesterol content, and lipid chain length. Partition in egg phosphatidylcholine bilayers decreases linearly with temperature, over a range (10-40 degrees C) at which the lipid is in the liquid-crystalline state. Addition of 50 mol% cholesterol severely decreases partition and practically abolishes the temperature dependence. First-order phase transitions of dimyristoyl-, dipalmitoyl- and distearoylphosphatidylcholines (DMPC, DPPC and DSPC) are accompanied by a sharp increase in malathion partition. Apparently, the insecticide is easily accommodated in bilayers of short-aliphatic-chain lipids, since the partitions were 225, 135 and 48 in DMPC, DPPC and DSPC, respectively, at temperatures 10 Cdeg below the midpoint of their transitions. Partition values in native membranes decrease sequentially as follows: sarcoplasmic reticulum, mitochondria, brain microsomes, myelin and erythrocytes. This dependence parallels the relative content of cholesterol and is similar in liposomes of total extracted lipids, although the absolute partitions showed decreased values.


Ascorbic acid status of female camels during different phases of reproduction.
There is suggestive evidence that a low status of ascorbic acid in camels enhances their risk for infectious diseases. This study was carried out to disclose the role of reproduction, if any, in affecting ascorbic acid status. The associations between the reproductive cycle and ascorbic acid contents in plasma and leukocytes were studied in Sudanese camels browsing on local vegetation. Ascorbic acid status was found to be lowest during pregnancy and highest during lactation. Estrus versus non-estrus was associated with high vitamin C status. Brucellosis-positive camels showed decreased levels of ascorbic acid in plasma and leukocytes. Possibly, the phases of non-estrus and pregnancy in camels invoke an increased susceptibility to infectious diseases due to a lower ascorbic acid status.


Autopsy proven cases of pulmonary thromboembolism: 18-year study at Ramathibodi Hospital.
Twelve cases of pulmonary embolism were found among 4,896 autopsies during 18 years in Ramathibodi hospital. This gives an incidence of 0.24 per 100 necropsies. Deep vein thrombosis occurred in two of the twelve cases and was not the main cause of pulmonary embolism in this series.


Impact of palifermin on intestinal mucositis of HSCT recipients after BEAM.
The matched-control study failed to show a clinical relevant impact of palifermin on intestinal mucositis, although there was a reduced inflammatory response and less febrile neutropenia among patients who had no bacteraemia.


Temporal delay and lexical retrieval in narratives: aphasiological observations.
Temporal delays in nonpathological speech have been mostly attributed to long-term planning and lexical access. In wake of the recent increased interest in lexicon in general, there have also been serious attempts to approach lexical processes through analyses of disrupted lexicon, most notably through the language of aphasics. In the present study we have analyzed the temporal delays and pauses associated with neologisms produced by Finnish posterior aphasics. It appears that delays and pauses correlate with the type of neology they precede. Moreover, the anomia theory of neologistic items will receive here further observational support.


Percutaneous Fixation of Pediatric Fractures of the Proximal Phalanx Neck: A Novel Technique.
Proximal phalanx neck fractures occur almost exclusively in children. Fractures of the proximal phalanx neck can be difficult to treat nonoperatively given the anatomic location and associated extrinsic forces. A divergent or crossed pin configuration is often utilized for the stabilization of these fractures. We present a surgical technique with a single Kirschner (K-wire) placed axially along the affected finger, with a hyperextension reduction maneuver, to reduce and fixate proximal phalanx neck fractures in children and adolescents. We performed a retrospective review of all pediatric proximal phalanx neck fractures treated by a single surgeon. Demographic data, as well as clinical and radiographic outcomes were recorded. We then directly compared axial pinning [14 patients; average age 6.63 y (9 mo to 17 y)] with nonoperative treatment [28 patients; average age 8.03 y (9 mo to 16 y)], and open treatment [8 patients; average age 8.13 y (1 to 14 y)]. Patients who underwent closed reduction and axial pinning had significantly improved final coronal alignment compared with nonoperative treatment. Compared with fractures which required open reduction, closed reduction with axial pinning resulted in significantly shorter surgical duration and time to radiographic healing. The final range of motion showed no difference between intervention types, as all patients regained full range of motion. We find this axial pinning technique to be simpler and faster than divergent pin fixation, with no significant differences in time to radiographic healing, time to full activity, final proximal interphalangeal active flexion or extension, loss of reduction, or radiographic parameters. Level III-Therapeutic.


Trypanosoma cruzi: origin of metacyclic trypomastigotes in the urine of the vector Triatoma infestans.
Population density and percentage of the different stages of an established infection of Trypanosoma cruzi were determined for two parts of the excretory system and for the rectum of fifth instars of Triatoma infestans unfed and 4 hr after feeding. These data were also evaluated for feces and urine of the fed bugs. In the first unfed group only small populations of the flagellate occurred in the Malpighian tubules and ampullae and not in all bugs. The three rectal populations (rectal lumen and anterior and posterior rectal wall) consisted of approximately equal numbers. About 10% were spheromastigotes and about 10% were stages intermediate to epimastigotes. Significantly fewer epimastigotes and more trypomastigotes were present on the rectal wall than in the lumen. Two intermediate forms leading to the trypomastigote stage occurred in similar numbers. In nearly all bugs the initial excretion (feces) contained the highest number of flagellates as compared to the following drops of urine. More flagellates were excreted through the urine than were contained in the excretory system of unfed bugs. The population in the feces reflected the percentage of forms present in the rectal lumen of unfed bugs, but in the urine the percentage of trypomastigotes increased up to 100%. Four hours after blood uptake, dissection of bugs still showed parasites in the Malpighian tubules and ampullae; the total number of parasites in the rectum was reduced by more than 50%. This reduction was more pronounced in the rectal lumen and on the posterior rectal wall. In stained smears from all three rectal populations there were rarely spheromastigotes but high percentages of epimastigotes. The intermediate stages leading to trypomastigotes mainly originated from short epimastigotes. Comparison of the T. cruzi populations before and after feeding demonstrates that the trypomastigotes in the urine should originate from the rectal wall, especially from the posterior part.


Putting the "No" in Non Nocere: Surgery, Anesthesia, and a Patient's Right to Withdraw Consent.
[Full article available at http://rimed.org/rimedicaljournal-2017-10.asp].


The metabolic syndrome: similar deleterious impact on all-cause mortality in hypertensive and normotensive subjects.
Few data are available on the impact of the metabolic syndrome on all-cause mortality risk according to the presence of hypertension. Our aim was to evaluate the 5-year impact of the metabolic syndrome, according to blood pressure status, on all-cause mortality risk in a large French population. The study population included 39 998 men and 20 756 women with no personal history of cardiovascular disease, who had a health check-up at the IPC Center (Paris, France) between 1999 and 2002, and who were followed up for 4.7 +/- 1.2 years. The metabolic syndrome was defined according to the National Cholesterol Educational Program classification (2001). Cox regression models were used to evaluate risk of all-cause mortality after adjustment for age, sex, classical risk factors and socioeconomic categories. Subjects were classified according to blood pressure status: hypertensive subject (systolic blood pressure > or =140 mmHg and/or diastolic blood pressure > or =90 mmHg or treatment) and normotensive subject. The risk of all-cause mortality associated with the metabolic syndrome was 1.50 (1.24-1.82) [hazard ratio (HR) (95% confidence interval)]. The risk of all-cause mortality associated with the presence of hypertension was 1.60 (1.38-1.85). During the 4.7 years of follow-up, the impact of the metabolic syndrome was similar among normotensive and hypertensive subjects [HR: 1.09 (0.68-1.75) and 1.40 (1.13-1.74), respectively, P for interaction = 0.35]. The findings from this study show that, in a large middle-aged French population, the metabolic syndrome has the same deleterious impact on all-cause mortality in hypertensive subjects and normotensive subjects.


'PartBreCon' study. A UK multicentre retrospective cohort study to assess outcomes following PARTial BREast reCONstruction with chest wall perforator flaps.
Partial breast reconstruction with a pedicled chest wall perforator flap (CWPF) enables breast conservation in a higher tumour: breast volume ratio scenario. Since there is limited evidence, this retrospective cohort study aimed to ascertain immediate (30-days) and medium-term (follow-up duration) surgical outcomes. STROBE-compliant protocol ascertained CWPF outcomes between March 2011-March 2021. UK centres known to perform CWPF were invited to participate if they performed at least 10 cases. Data were retrospectively collected, including patient demographics, tumour and treatment characteristics, and surgical and oncological outcomes. Statistical analysis (R™) included multivariable logistic regression and sensitivity analysis. Across 15 centres, 507 patients with median age (54 years, IQR; 48-62), body mass index (25.4 kg/m2, IQR; 22.5-29), tumour size (26 mm, IQR; 18-35), and specimen weight (62 g, IQR; 40-92) had following flap types: LiCAP (54.1%, n = 273), MiCAP/AiCAP (19.6%, n = 99), LiCAP + LTAP (19.8%, n = 100) and TDAP (2.2%, n = 11). 30-days complication rates were in 12%: haematoma (4.3%, n = 22), wound infection (4.3%, n = 22), delayed wound healing (2.8%, n = 14) and flap loss (0.6%, n = 3; 1 full) leading to readmissions (2.6%, n = 13) and re-operations (2.6%, n = 13). Positive margins (n = 88, 17.7%) led to 15.9% (n = 79) re-excisions, including 7.5% (n = 37) at the planned 2nd of 2-stage surgery and 1.8% (n = 9) mastectomy. At median 23 months (IQR; 11-39) follow-up, there were 1.2% (n = 6) symmetrisations; recurrences: local (1%), regional/nodal (0.6%) and distant (3.2%). This large multicentre cohort study demonstrates acceptable complication and margin re-excision rates. CWPF extends the range of breast conservation techniques. Further studies are required for long-term oncological outcomes.


Urea separation in flat-plate microchannel hemodialyzer; experiment and modeling.
Two flat-plate microchannel hemodialyzers were constructed consisting of two identical laminae separated by a 20[μm] thick ultrafiltration membrane (Gambro AN69). Each lamina contains a parallel array of microchannels 100[μm] deep, 200[μm] wide, and 5.6[cm] or 9.9[cm] in length respectively. Urea was removed from the aqueous stream containing 1.0[g] urea per liter de-ionized water in the blood side, by countercurrent contact with pure de-ionized water in the dialysate side of the flat-plate hemodialyzer. In all cases volumetric flow rate of water in the dialysate side was equal or less than the volumetric flow rate in the blood side, which is in large contrast to commercial applications of hollow-fiber hemodialyzers where dialysate flow is severalfold larger than blood flow rate. A three-dimensional finite volume mass transport model, built entirely from the first principles with no adjustable parameters, was written in FORTRAN. The results of the mathematical model excellently predict experimental results. The fractional removals of urea predicted by the model are within 2.7%-11% of experimentally obtained values for different blood and dialysate velocities/flow rates in microchannels, and for different transmembrane pressures. The overall mass transfer coefficient was calculated using the urea outlet concentrations obtained at various average velocities (1.0-5.0[cm/s]) in the blood and dialysate, and two nominal transmembrane pressures (∆P(tm) = 0 and 10,000.[Pa]). Overall mass transfer coefficients obtained experimentally ranged from 0.068 to 0.14 [cm/min]. The numerical model predicted an average overall mass transfer coefficient of 0.08 [cm/min]. This value is 60% higher than those found in commercial dialyzers (~0.05[cm/min]).


Duration of visual afterimages on modulated backgrounds: postreceptoral processes.
A foveal afterimage produced by a small photoflash increases in duration when the luminance of a 5.8 degrees diameter background on which it is seen is temporally modulated. At a modulation frequency of 1 Hz and a depth of modulation of 52%, the duration of the afterimage is prolonged by 335% compared to the duration obtained on a steady background. This increase has been attributed to the functional border resulting from the difference in excitability between bleached and unbleached photoreceptors. Afterimage duration is also prolonged, although only by 20%, when the luminance of the background is kept constant, while the luminance of an annular surround is modulated. This finding suggests a weak effect of neural lateral interaction (via area contrast). If the background luminance is modulated only in the contralateral eye (dichoptic presentation), afterimage duration increases by as much as 54% compared to the unmodulated state. This result indicates that afterimages, in part, are sustained by processes mediated by the visual cortex.


Autologous transplantation for primary systemic AL amyloidosis is feasible outside a major amyloidosis referral centre: the Calgary BMT Program experience.
Recent reports from large amyloidosis referral centers suggest that primary systemic AL amyloidosis patients treated with high-dose melphalan (HDM) and autologous stem cell transplantation (ASCT) survive longer than historical controls treated with less intensive chemotherapy, despite high transplant-related mortality (TRM) rates of >10%. A retrospective review was conducted to determine if the outcome of ASCT for AL amyloidosis at our institution was similar to that reported at major amyloidosis referral centers. Over a 7 year period, we treated a total of 15 AL amyloidosis patients with ASCT, including four with poor prognosis cardiac or multisystem involvement. No TRM was observed. Overall, 10 patients (67%) achieved a complete hematological response and four patients (27%) achieved a complete organ response. The 4-year event-free and overall survival rates were 60% (95% CI 32-89%) and 75% (95% CI 50-100%), respectively. One patient, who presented with cardiac failure and multiorgan involvement with colonic bleeding currently remains in complete remission 62 months post-ASCT. In conclusion, ASCT for primary AL amyloidosis can safely be performed at experienced transplant centers that are not associated with major amyloidosis referral centers, and is feasible for patients who have multisystem involvement, particularly for motivated patients with good performance status.


Reduction in brain immunoreactive corticotropin-releasing factor (CRF) in spontaneously hypertensive rats.
The brain CRF concentration of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) was examined by rat CRF radioimmunoassay. Anti-CRF serum was developed by immunizing rabbits with synthetic rat CRF. Synthetic rat CRF was also used as tracer and standard. The displacement of 125I-rat CRF by serially diluted extracts of male Wistar rats hypothalamus, thalamus, midbrain, pons, medulla oblongata, cerebral cortex, cerebellum and neurointermediate lobe was parallel to the displacement of synthetic rat CRF. In both WKY and SHR the highest levels of CRF immunoreactivity were shown by the hypothalamus and neuro-intermediate lobe, and considerable CRF immunoreactivity was also detected in other brain regions. The CRF immunoreactivity in the hypothalamus, neurointermediate lobe, midbrain, medulla oblongata and cerebral cortex was significantly reduced in SHR and it may suggest that CRF abnormality may be implicated in the reported abnormalities in the pituitary-adrenal axis, autonomic response and behavior of SHR.


Sheep cardiac Purkinje fibers: configurational changes during the cardiac cycle.
Previous attempts to study the cytoarchitecture of cardiac Purkinje fibers with the scanning electron microscope (SEM) have been limited by the surrounding dense connective tissue. In this study the connective tissue was removed by treatment with 8N HCl, after adult sheep hearts were fixed in diastole or systole and tissue taken for SEM and transmission electron microscopy (TEM). In SEM, Purkinje fibers freely anastomosed in false tendons and formed a subendocardial plexus. In systole, medium and small-sized Purkinje fibers formed deep clefts not observed in diastole. The clefts are thought to be due to sarcolemmal folding and fiber buckling and may therefore affect conduction. The myofibrils beneath the laterally apposed sarcolemmas of adjacent Purkinje cells when fixed in systole were often observed as tightly curved arches in series. Similar configurations with expanded arches were observed in diastole. The formation of arches by myofibrils is unique to Purkinje fibers and is interpreted as the mechanism responsible for their compliance to stretch. The significance of contraction in producing the observed geometric changes in Purkinje fibers and the implications of their cytoarchitecture with respect to conduction are discussed.


Pharmacokinetics of morphine and oxycodone following intravenous administration in elderly patients.
An increased and prolonged duration of pain relief after morphine administration has been found in elderly patients. Whether this is due to alterations in pharmacokinetics, receptor binding profile or other factors remains unsolved. The aims were to elucidate the pharmacokinetics after intravenous administration of morphine and oxycodone in elderly patients older than 70 years. A randomized non-blinded study with 16 patients aged older than 70 years scheduled for elective hip replacement receiving morphine or oxycodone 0.05 mg/kg as an IV infusion over 15 minutes. A 2-compartment pharmacokinetic model best described the disposition of morphine and oxycodone. The estimated elimination half-lives for morphine and oxycodone were (mean +/- SD) 2.7 +/- 3.6 (range 0.8-11.6) and 3.1 +/- 1.3 (range 1.1-4.8) hr, respectively. Volume of distribution at steady state was estimated to be 243 +/- 256 and 277 +/- 187 L, and clearance to be 1748 +/- 623 and 1206 +/- 546 ml/min for morphine and oxycodone, respectively. The increased and prolonged duration of pain relief after morphine administration seen in some elderly patients cannot, based on these findings, be ascribed to changes in the pharmacokinetic parameters between elderly and younger patients. Similar for oxycodone, no changes in the pharmacokinetic could be found when comparing the parameters found in elderly patients with those from younger healthy volunteers. A great variability within the individual pharmacokinetic parameters was seen for both drugs. Therefore, we recommend that treatment with morphine and oxycodone in elderly patients is initiated very conservatively and is titrated slowly to effect.


A rare presentation of a transethmoidal encephalocele at birth.
Transethmoidal encephalocele is a very rare condition. Herein, we report the case of a neonate with a transethmoidal encephalocele, who presented with an externally visible intranasal mass at birth. Clinical suspicion of intracranial extension was confirmed by radiological imaging. A bifrontal craniotomy was done to divide the narrow communicating duct. The mass was delivered through the nostril and duraplasty was completed. The postoperative recovery was uneventful.


Associations between parental food choice motives, health-promoting feeding practices, and infants' fruit and vegetable intakes: the Food4toddlers study.
Parents influence their infants' diets and are the providers of healthy foods such as fruit and vegetables. Parental motives can influence infant's diets directly or through parental feeding practices. This study aimed to assess the associations between parental food choice motives and infants' fruit and vegetable intakes and to examine whether parental feeding practices mediated these associations. A total of 298 parents participated in the Norwegian Food4toddlers study. Before the child's first birthday (mean age = 10.9 months), the parents completed an online baseline questionnaire. Five parental food choice motives were assessed: health, convenience, sensory appeal, price, and familiarity. Infants' fruit and vegetable intakes and three health-promoting feeding practices were also assessed. For each food choice motive and its relation to fruit or vegetable intake, three single mediation models were conducted. Mediation effects were examined using MacKinnon's product of coefficients procedure, and bootstrap confidence intervals (CIs) were used for inferential testing. Higher scores on the motive of health were positively associated with infants' vegetable intake (τ = 0.394, P < 0.001). No other significant associations were found between food choice motives and fruit or vegetable intake. The feeding practice of shaping a healthy environment mediated the relationships between health motive and both fruit (αβ = 0.067, CI: 0.001-0.146) and vegetable (αβ = 0.105, CI: 0.042-0.186) intakes. The feeding practice of encouraging balance and variety mediated the relationships between health motive and vegetable (αβ = 0.085, CI: 0.030-0.150) intake and between sensory appeal motive and vegetable intake (αβ = 0.047, CI: 0.005-0.103). High levels of parental health motive are associated with higher infant vegetable intake. Our study contributes to understand the structure of parental feeding behaviors that may have implication for nutrition interventions targeting parents.


Geostatistical linkage of national demographic and health survey data: a case study of Tanzania.
When Service Provision Assessment (SPA) surveys on primary health service delivery are combined with the nationally representative household survey-Demographic and Health Survey (DHS), they can provide key information on the access, utilization, and equity of health service availability in low- and middle-income countries. However, existing linkage methods have been established only at aggregate levels due to known limitations of the survey datasets. For the linkage of two data sets at a disaggregated level, we developed a geostatistical approach where SPA limitations are explicitly accounted for by identifying the sites where health facilities might be present but not included in SPA surveys. Using the knowledge gained from SPA surveys related to the contextual information around facilities and their spatial structure, we made an inference on the service environment of unsampled health facilities. The geostatistical linkage results on the availability of health service were validated using two criteria-prediction accuracy and classification error. We also assessed the effect of displacement of DHS clusters on the linkage results using simulation. The performance evaluation of the geostatistical linkage method, demonstrated using information on the general service readiness of sampled health facilities in Tanzania, showed that the proposed methods exceeded the performance of the existing methods in terms of both prediction accuracy and classification error. We also found that the geostatistical linkage methods are more robust than existing methods with respect to the displacement of DHS clusters. The proposed geospatial approach minimizes the methodological issues and has potential to be used in various public health research applications where facility and population-based data need to be combined at fine spatial scale.


Maternal Western-style diet remodels the transcriptional landscape of fetal hematopoietic stem and progenitor cells in rhesus macaques.
Maternal obesity adversely impacts the in utero metabolic environment, but its effect on fetal hematopoiesis remains incompletely understood. During late development, the fetal bone marrow (FBM) becomes the major site where macrophages and B lymphocytes are produced via differentiation of hematopoietic stem and progenitor cells (HSPCs). Here, we analyzed the transcriptional landscape of FBM HSPCs at single-cell resolution in fetal macaques exposed to a maternal high-fat Western-style diet (WSD) or a low-fat control diet. We demonstrate that maternal WSD induces a proinflammatory response in FBM HSPCs and fetal macrophages. In addition, maternal WSD consumption suppresses the expression of B cell development genes and decreases the frequency of FBM B cells. Finally, maternal WSD leads to poor engraftment of fetal HSPCs in nonlethally irradiated immunodeficient NOD/SCID/IL2rγ-/- mice. Collectively, these data demonstrate for the first time that maternal WSD impairs fetal HSPC differentiation and function in a translationally relevant nonhuman primate model.


Polarcardiographic criteria for infarction evaluated by angiocardiography.
Out of a series of 1000 consecutive patients studied by angiocardiography, two groups were selected on the basis of the probability of having suffered myocardial infarction: an infarction group of 324 cases, and a non-infarction group of 112 cases. Members of the infarction group had complete occlusion of at least one major coronary artery; members of the non-infarction group had less than 50% occlusion in all coronary arteries, normal hemodynamics, and negative histories of infarction. The diagnostic performances of the independently-read 12-lead electrocardiograms (ECGs) and the polarcardiograms (PCGs) were evaluated in terms of sensitivity, specificity, validity and risk ratio. The performance of the ECG was significantly lower than the PCG. Corresponding figures were 56%, 99%, 67%, and 1.67 for the ECG, and 75%, 91%, 80%, and 2.23 for the PCG. There is a 99.9% probability that the PCG can detect at least 21% more cases of infarction than the ECG can.


The C. elegans lethal gut-obstructed gob-1 gene is trehalose-6-phosphate phosphatase.
We identified the gob-1 (gut-obstructed) gene in a forward genetic screen for intestinal defects in the nematode Caenorhabditis elegans. gob-1 loss of function results in early larval lethality, at least in part because of a blocked intestinal lumen and consequent starvation. The gob-1 gene is first expressed in the 8E cell stage of the embryonic intestine, and the GATA factor ELT-2 is sufficient but not necessary for this early phase of gob-1 expression; gob-1 expression later becomes widespread in embryos, larvae, and adults. GOB-1 is a member of the HAD-like hydrolase superfamily and shows a robust and specific phosphatase activity for the substrate trehalose-6-phosphate. Trehalose is a glucose disaccharide found in bacteria, fungi, plants, insects, and nematodes but not in mammals. Trehalose plays a number of critical roles such as providing flexible energy reserves and contributing to thermal and osmotic stress resistance. In budding yeast and in plants, the intermediate in trehalose synthesis, trehalose-6-phosphate, has additional critical but less well-defined roles in controlling glycolysis and carbohydrate metabolism. Strong loss-of-function mutants in the C. elegans tps-1 and tps-2 genes (which encode the two trehalose phosphate synthases responsible for trehalose-6-phosphate synthesis) completely suppress the lethality associated with gob-1 loss of function. The suppression of gob-1 lethality by ablation of TPS-1 and TPS-2, the upstream enzymes in the trehalose synthesis pathway, suggests that gob-1 lethality results from a toxic build-up of the intermediate trehalose-6-phosphate, not from an absence of trehalose. GOB-1 is the first trehalose-6-phosphate phosphatase to be identified in nematodes and, because of its associated lethality and distinctive sequence properties, provides a new and attractive target for anti-parasitic drugs.


A Bayesian approach to generating tutorial hints in a collaborative medical problem-based learning system.
Today a great many medical schools have turned to a problem-based learning (PBL) approach to teaching. While PBL has many strengths, effective PBL requires the tutor to provide a high degree of personal attention to the students, which is difficult in the current academic environment of increasing demands on faculty time. This paper describes intelligent tutoring in a collaborative medical tutor for PBL. The main contribution of our work is the development of representational techniques and algorithms for generating tutoring hints in PBL group problem solving, as well as the implementation of these techniques in a collaborative intelligent tutoring system, COMET. The system combines concepts from computer-supported collaborative learning with those from intelligent tutoring systems. The system uses Bayesian networks to model individual student clinical reasoning, as well as that of the group. The prototype system incorporates substantial domain knowledge in the areas of head injury, stroke and heart attack. Tutoring in PBL is particularly challenging since the tutor should provide as little guidance as possible while at the same time not allowing the students to get lost. From studies of PBL sessions at a local medical school, we have identified and implemented eight commonly used hinting strategies. In order to evaluate the appropriateness and quality of the hints generated by our system, we compared the tutoring hints generated by COMET with those of experienced human tutors. We also compared the focus of group activity chosen by COMET with that chosen by human tutors. On average, 74.17% of the human tutors used the same hint as COMET. The most similar human tutor agreed with COMET 83% of the time and the least similar tutor agreed 62% of the time. Our results show that COMET's hints agree with the hints of the majority of the human tutors with a high degree of statistical agreement (McNemar test, p=0.652, kappa=0.773). The focus of group activity chosen by COMET agrees with that chosen by the majority of the human tutors with a high degree of statistical agreement (McNemar test, p=0.774, kappa=0.823). Bayesian network clinical reasoning models can be combined with generic tutoring strategies to successfully emulate human tutor hints in group medical PBL.


Identification of four functionally important microRNA families with contrasting differential expression profiles between drought-tolerant and susceptible rice leaf at vegetative stage.
Developing drought-tolerant rice varieties with higher yield under water stressed conditions provides a viable solution to serious yield-reduction impact of drought. Understanding the molecular regulation of this polygenic trait is crucial for the eventual success of rice molecular breeding programmes. microRNAs have received tremendous attention recently due to its importance in negative regulation. In plants, apart from regulating developmental and physiological processes, microRNAs have also been associated with different biotic and abiotic stresses. Hence here we chose to analyze the differential expression profiles of microRNAs in three drought treated rice varieties: Vandana (drought-tolerant), Aday Sel (drought-tolerant) and IR64 (drought-susceptible) in greenhouse conditions via high-throughput sequencing. Twenty-six novel microRNA candidates involved in the regulation of diverse biological processes were identified based on the detection of miRNA*. Out of their 110 predicted targets, we confirmed 16 targets from 5 novel microRNA candidates. In the differential expression analysis, mature microRNA members from 49 families of known Oryza sativa microRNA were differentially expressed in leaf and stem respectively with over 28 families having at least a similar mature microRNA member commonly found to be differentially expressed between both tissues. Via the sequence profiling data of leaf samples, we identified osa-miR397a/b, osa-miR398b, osa-miR408-5p and osa-miR528-5p as being down-regulated in two drought-tolerant rice varieties and up-regulated in the drought-susceptible variety. These microRNAs are known to be involved in regulating starch metabolism, antioxidant defence, respiration and photosynthesis. A wide range of biological processes were found to be regulated by the target genes of all the identified differentially expressed microRNAs between both tissues, namely root development (5.3-5.7 %), cell transport (13.2-18.4 %), response to stress (10.5-11.3 %), lignin catabolic process (3.8-5.3 %), metabolic processes (32.1-39.5 %), oxidation-reduction process (9.4-13.2 %) and DNA replication (5.7-7.9 %). The predicted target genes of osa-miR166e-3p, osa-miR166h-5p*, osa-miR169r-3p* and osa-miR397a/b were found to be annotated to several of the aforementioned biological processes. The experimental design of this study, which features rice varieties with different drought tolerance and tissue specificity (leaf and stem), has provided new microRNA profiling information. The potentially regulatory importance of the microRNA genes mentioned above and their target genes would require further functional analyses.


Effects of chlordecone and its structural analogs on p-nitrophenyl phosphatase.
The effects of chlordecone, mirex, and four photoderivatives of mirex on K+-stimulated p-nitrophenyl phosphatase (KPNPPase) in rat brain synaptosomes were determined. Additionally, the effect of chlordecone on the substrate and K+ activation kinetics and the inhibition of KPNPPase at 17, 27, and 37 degrees C were determined. The sensitivity of KPNPPase to various chemicals was highly variable. Chlordecone was the most effective inhibitor with an IC50 of 6.2 X 10(-6)M. All other chemicals showed a maximum inhibition of 20% at 20 muM concentration. The order of inhibition at 20 muM concentration was chlordecone (100%) greater than 8-monohydro mirex (20%) greater than 2,8-dihydromirex (10%) greater than mirex (10%) greater than 10-monohydro mirex (9%) greater than 5,10-dihydro mirex (2%). Double reciprocal plots of the data obtained on the effect of chlordecone on the substrate and K+ activation kinetics showed that the Vmax and Km were decreased with respect to paranitrophenyl phosphate, while it was competitive inhibition with respect to K+ activation. Chlordecone inhibited KPNPPase more at 37 degrees C than at 27 degrees C and 17 degrees C suggesting a positive temperature effect. These results suggest that chlordecone is the most effective inhibitor among its structural analogs tested on KPNPPase in rat brain synaptosomes.


Eukaryotic DNA methylation.
Eukaryotic genomes contain 5-methylcytosine (5mC) as a rare base.5mC arises by postsynthetic modification of cytosine and occurs, at least in animals, predominantly in the dinucleotide CpG. The base is not distributed randomly in these genomes but conforms to a pattern. This pattern varies between taxa but appears to be inherited in a semi-conservative fashion. At the level of the genome, gross changes in the level of DNA methylation have been noted. This has encouraged speculation that the modification may play a role in cellular differentiation. Tissue-specific patterns of DNA methylation, predicted by various models of differentiation, have been found for most vertebrate genes so far examined. A correlation has emerged between the undermethylation of these regions and their transcription, but this is not always the case. While data for eukaryotic viral sequences are less equivocal, studies of this kind cannot in isolation distinguish between undermethylation being a cause or a consequence of gene activity. If it were a cause, it is probable that the demethylation of specific CpG sites would be a necessary yet not a sufficient condition for transcription to occur. The introduction of artificially methylated DNA sequences into individual eukaryotic cells by microinjection or transformation may provide the means to elucidate these questions in the future. In the meantime, the study of eukaryotic DNA methylation promises to contribute much to our understanding of the regulation of gene expression in these organisms.


High levels of soluble RAGE are associated with a greater risk of mortality in COVID-19 patients treated with dexamethasone.
Blood levels of the soluble receptor for advanced glycation end-products (sRAGE) are acutely elevated during the host inflammatory response to infection and predict mortality in COVID-19. However, the prognostic performance of this biomarker in the context of treatments to reduce inflammation is unclear. In this study we investigated the association between sRAGE and mortality in dexamethasone-treated COVID-19 patients. We studied 89 SARS-CoV-2 positive subjects and 22 controls attending the emergency department of a University Teaching Hospital during the second wave of COVID-19 and measured sRAGE at admission. In positive individuals sRAGE increased with disease severity and correlated with the National Early Warning Score 2 (Pearson's r = 0.56, p < 0.001). Fourteen out of 72 patients treated with dexamethasone died during 28 days of follow-up. Survival rates were significantly lower in patients with high sRAGE (> 3532 pg/mL) than in those with low sRAGE (p = 0.01). Higher sRAGE levels were associated with an increased risk of death after adjustment for relevant covariates. In contrast, IL-6 did not predict mortality in these patients. These results demonstrate that sRAGE remains an independent predictor of mortality among COVID-19 patients treated with dexamethasone. Determination of sRAGE could be useful for the clinical management of this patient population.


Metal contaminant accumulation in the hive: Consequences for whole-colony health and brood production in the honey bee (Apis mellifera L.).
Metal pollution has been increasing rapidly over the past century, and at the same time, the human population has continued to rise and produce contaminants that may negatively impact pollinators. Honey bees (Apis mellifera L.) forage over large areas and can collect contaminants from the environment. The primary objective of the present study was to determine whether the metal contaminants cadmium (Cd), copper (Cu), lead (Pb), and selenium (Se) can have a detrimental effect on whole-colony health in the managed pollinator A. mellifera. The authors isolated small nucleus colonies under large cages and fed them an exclusive diet of sugar syrup and pollen patty spiked with Cd, Cu, Pb, and Se or a control (no additional metal). Treatment levels were based on concentrations in honey and pollen from contaminated hives around the world. They measured whole-colony health including wax, honey, and brood production; colony weight; brood survival; and metal accumulation in various life stages. Colonies treated with Cd or Cu contained more dead pupae within capped cells compared with control, and Se-treated colonies had lower total worker weights compared to control. Lead had a minimal effect on colony performance, although many members of the hive accumulated significant quantities of the metal. By examining the honey bee as a social organism through whole-colony assessments of toxicity, the authors found that the distribution of toxicants throughout the colony varied from metal to metal, some caste members were more susceptible to certain metals, and the colony's ability to grow over time may have been reduced in the presence of Se. Apiaries residing near metal-contaminated areas may be at risk and can suffer changes in colony dynamics and survival.


Providing support and care through a hospital at home.
The greater emphasis on community care and consumer choice lead to the introduction of a hospital-at-home scheme in Kingston and District Community NHS Trust. The rationale for the scheme, its structure and the way in which it works are discussed in this paper.


Body mass index and employment-based health insurance.
Obese workers incur greater health care costs than normal weight workers. Possibly viewed by employers as an increased financial risk, they may be at a disadvantage in procuring employment that provides health insurance. This study aims to evaluate the association between body mass index [BMI, weight in kilograms divided by the square of height in meters] of employees and their likelihood of holding jobs that include employment-based health insurance [EBHI]. We used the 2004 Household Components of the nationally representative Medical Expenditure Panel Survey. We utilized logistic regression models with provision of EBHI as the dependent variable in this descriptive analysis. The key independent variable was BMI, with adjustments for the domains of demographics, social-economic status, workplace/job characteristics, and health behavior/status. BMI was classified as normal weight (18.5-24.9), overweight (25.0-29.9), or obese (> or = 30.0). There were 11,833 eligible respondents in the analysis. Among employed adults, obese workers [adjusted probability (AP) = 0.62, (0.60, 0.65)] (P = 0.005) were more likely to be employed in jobs with EBHI than their normal weight counterparts [AP = 0.57, (0.55, 0.60)]. Overweight workers were also more likely to hold jobs with EBHI than normal weight workers, but the difference did not reach statistical significance [AP = 0.61 (0.58, 0.63)] (P = 0.052). There were no interaction effects between BMI and gender or age. In this nationally representative sample, we detected an association between workers' increasing BMI and their likelihood of being employed in positions that include EBHI. These findings suggest that obese workers are more likely to have EBHI than other workers.


Site specificities of three transfer RNA methyltransferases from yeast.
The site specificities of two distinct tRNA(m1G)methyltransferases and one tRNA(m2G)methyltransferase from yeast have been investigated by heterologous methylation and analysis of purified Escherichia coli tRNAs. The two tRNA(m1G)methyltransferases were found to be specific for sites 9 and 37, respectively. The tRNA(m2G)methyltransferase was specific for site 10. Two of the enzymes were purified by affinity chromatography on tRNA-Sepharose.


Hint1 is a haplo-insufficient tumor suppressor in mice.
The HINT1 protein, a member of the histidine triad (HIT) family, is highly conserved in diverse species and ubiquitously expressed in mammalian tissues. However, its precise function in mammalian cells is not known. As a result of its structural similarity to the tumor-suppressor protein FHIT, we used homozygous-deleted Hint1 mice to study its role in tumorigenesis. We discovered that after 2 to 3 years of age the spontaneous tumor incidence in Hint1 -/- mice was significantly greater than that in wild-type Hint1 +/+ mice (P < 0.05). Using a well-established mouse model of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis we found a marked and significant (P < 0.05) increase in the incidence of mammary and ovarian tumors in both, Hint1 -/- and +/- mice versus +/+ mice. The Hint1 -/- and +/- mice had similar tumor incidence and similar tumor histologies. Therefore, deletion of Hint1 in mice enhances both spontaneous tumor development and susceptibility to tumor induction by DMBA. In addition, since the Hint1 +/- tumors retained expression of the unmutated wild-type allele, Hint1 is haplo-insufficient with respect to tumor suppression in this model system.


Left main coronary artery-to-pulmonary artery fistula with severe aneurysmal dilatation.
Coronary artery fistulas (CAF) are rare abnormalities that can be symptomatic or asymptomatic. Most drain into the right ventricle or pulmonary artery, though a variety of other drainage sites have been reported. We report the results of the surgical closure of a symptomatic left coronary-to-pulmonary artery fistula associated with a giant 10-cm aneurysm and discuss the management of coronary artery fistulas.


Continuous alendronate treatment throughout growth, maturation, and aging in the rat results in increases in bone mass and mechanical properties.
Alendronate (4-amino-1-hydroxybutylidene bisphosphonate) is a novel amino bisphosphonate that is being developed for the treatment of osteolytic bone disorders such as osteoporosis. As part of a 2-year carcinogenicity study, we investigated the morphologic and biomechanical effects of long-term alendronate (ALN) therapy, given throughout skeletal growth, maturation, and aging, on rat vertebrae and femora. Three treatment groups, receiving either deionized water, low- (1.00 mg/kg), or high-dose (3.75 mg/kg) ALN, were given daily oral treatment for 105 weeks. Results from mechanical tests indicate that ALN therapy (in males) increased the vertebral ultimate compressive load by 96% in the high- and 51% in the low-dose groups when compared with controls. ALN similarly increased the male ultimate femoral bending load by 59% in the high- and 31% in the low-dose groups. Vertebrae and femora from female rats treated with both high- and low-dose ALN also failed at significantly higher loads than controls, but no differences were seen between low- and high-dose groups. Morphologic analysis of both male and female vertebrae revealed a dose-dependent increase in area fraction of bone. Rats receiving high-dose ALN had a greater area fraction of bone than those receiving low doses. Both groups were greater than controls. Thus, the administration of ALN resulted in increased femoral cortical bending load when compared with control animals, as well as increased vertebral ultimate compressive load commensurate with a dose-related preservation of vertebral bone.(ABSTRACT TRUNCATED AT 250 WORDS)


Autocitrullination confers monocyte chemotactic properties to peptidylarginine deiminase 4.
Peptidylarginine deiminase 4 (PAD4) contributes to the production of citrullinated proteins as autoantigens for anti-citrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA). PAD4 can also self-deiminate via autocitrullination. However, the role of this process in RA pathogenesis has not been elucidated. This study aimed to clarify PAD4 function before and after autocitrullination and identify citrullinated PAD4 in the synovial fluid of patients with RA. The autocitrullination of recombinant human PAD4 (rhPAD4) was catalyzed in vitro and determined using anti-modified citrulline immunoblotting. Monocyte chemotaxis was evaluated using Boyden chambers, and citrullinated rhPAD4's ability to induce arthritis was assessed in a C57BL/6J mouse model. Citrullinated PAD4 levels were measured in the synovial fluid of patients with RA and osteoarthritis using a novel enzyme-linked immunosorbent assay. Chemotactic findings showed that citrullinated rhPAD4 recruited monocytes in vitro, whereas unmodified rhPAD4 did not. Compared to unmodified rhPAD4, citrullinated rhPAD4 induced greater inflammation in mouse joints through monocyte migration. More citrullinated PAD4 was found in the synovial fluid of patients with RA than in those with osteoarthritis. Citrullinated PAD4 was even detected in ACPA-negative patients with RA. The autocitrullination of PAD4 amplified inflammatory arthritis through monocyte recruitment, suggesting an ACPA-independent role of PAD4 in RA pathogenesis.


Children with chronic conditions in the 21st century.
The care of children who have chronic conditions should focus on improving the lives of the children and their families. This is accomplished most effectively through community-based, family-centered care. Critical issues for these children and families in entering the next century include the level of insurance, content of benefits package, level of evidence required for health insurance reimbursement, preparation of and incentives for health care professionals, roles being demanded of families. As the richest country in the world, we should be able to (1) provide universal coverage, (2) guarantee a comprehensive benefits package that applies a child-specific standard of medical necessity, (3) establish criteria for requiring insurers to reimburse for new effective therapies, (4) develop strategies for overcoming professional barriers, and (5) create mechanisms for compensating family caretakers for their care.


Corrigendum: Analysis of Anxiety and Depression Status in Patients Undergoing Radiotherapy During the COVID-19 Epidemic.
[This corrects the article DOI: 10.3389/fpsyt.2021.771621.].


Protein 4.1 G localizes in rodent microglia.
Although it was reported that protein 4.1 G, a cytoskeletal protein characterized by its general expression in the body, interacts with some signal transduction molecules in the central nervous system (CNS), its distribution and significance in vivo remained to be elucidated. In the present study, we have identified 4.1 G-positive cells in the rodent CNS, and demonstrated its immunolocalization in the developing mouse CNS. In the rodent CNS, 4.1 G was colocalized with markers for microglia, such as CD45, OX-42 and ionized calcium-binding adapter molecule 1 (Iba1), but not with markers for neuronal or other glial cells. Additionally, colocalization of 4.1 G and A1 adenosine receptor was observed in the mouse cerebrum. In a mixed glial culture, most OX-42-positive microglia were positive for 4.1 G, and 4.1 G isoforms of the same molecular weight as in the rat brain were expressed in cultured microglia, where 4.1 G mRNA was detected by RT-PCR. In the developing mouse cerebral cortex, 4.1 G was detected in immature microglia, which were positive for Iba1. These results indicate that 4.1 G in the CNS is mainly distributed in microglia in vivo. Considering the interactions between 4.1 G and the signal transduction molecules, putative roles have been proposed for 4.1 G in microglial functions in the CNS.


Interleukin-1 induces c-fos and c-jun gene expression in T helper type II cells through different signal transmission pathways.
Interleukin (IL)-1 induces proliferation and expression of several protooncogenes in the T helper 2 cell line D10A. We have analyzed the signal transmission pathways activated by IL-1 in these cells, leading to the expression of c-jun and c-fos. IL-1 induced c-jun gene transcription and mRNA expression by means of a pathway dependent on protein tyrosine kinase activity since tyrphostin, a specific inhibitor of tyrosine kinase, inhibited this induction. This mechanism of transmission signaling was independent of protein kinase C (PKC) and was linked to the 80-kDa IL-1 receptor (IL-1R). In addition, phorbol esters did not induce c-jun mRNA expression, whereas c-fos mRNA expression mediated by IL-1 dependent on PKC; this pathway was linked to a different, still unidentified IL-1R that was functional in the D10A cell line. Accumulation of intracellular cAMP generated by IL-1 through the 80-kDa IL-1R negatively regulated c-fos expression which was induced by IL-1 through PKC activation. We conclude that IL-1 modulates the expression of c-fos in D10A cells by occupying of two independent IL-1R that are linked to different signal transduction pathways.


Regioselective glycosylation method using partially protected arabino- and galactofuranosyl thioglycosides as key glycosylating substrates and its application to one-pot synthesis of oligofuranoses.
We describe in this paper the development of a novel regioselective furanosylation methodology using partially protected furanosyl thioglycosides as central glycosylating building blocks and its application in the efficient one-pot synthesis of a series of linear and branched-type arabino- and galactofuranoside fragments structurally related to the cell wall polysaccharides of Mycobacterium tuberculosis , Streptococcus pneumoniae serostype 35A, and sugar beet.


Antimuscarinic and noncompetitive antagonist properties of dicyclomine hydrochloride in isolated human and rabbit bladder muscle.
In isolated strips of bladder neck (prostatic capsule) and detrusor of rabbit and man, dicyclomine had minimal effect on the resting tension. Competitive antimuscarinic activity against carbachol could be demonstrated at doses of dicyclomine less than or equal to 1 X 10(-6) M, whereas at higher doses a noncompetitive action against both carbachol and potassium was observed. The ratio of dissociation constants relating to the noncompetitive and competitive actions, respectively, was about 1200, approximately 100 times higher than that previously reported in ileum. Dicyclomine was only about 1/30 as potent as atropine in competitive antimuscarinic activity. Dicyclomine hydrochloride may be useful in the clinical management of "uninhibited bladder."


BTX in urban areas of eastern Spain: a focus on time variations and sources.
Seasonal and daily cycles of BTX were studied in a non-industrialized city (Alicante) and an urban area near an oil refinery plant (Castellón) in order to evaluate the influence of different sources on time variations. Lower levels were observed in summer than in winter at both locations due to higher dispersion conditions and photochemical removal of BTX during the summer season. Daily patterns showed seasonal differences and were controlled by traffic emissions and the evolution of the mixing layer height, with no influence of the petroleum refinery plant in the city of Castellón. The results of the conditional bivariate probability function suggest that the influence of this source on BTX concentrations was limited to point impacts. At both sites, benzene exhibited a different behavior from toluene and xylenes, most likely due to its significantly lower chemical reactivity.


Evaluation of combined B cell specific N-terminal immunogenic domains of LipL21 for diagnosis of leptospirosis.
Leptospiral outer membrane protein LipL21 and its truncated N-terminal immunogenic region (I-LipL21) were evaluated for diagnosis of leptospirosis. The complete coding sequence of LipL21 nucleotide sequence was subjected to BCPred and VaxiJen analysis for determination of B cell specific immunogenic epitopes. Epitope1 ACS STD TGQ KDA TTV GDG (1.8837), Epitope2 WGG PPE QRN DGK TPR DTN (0.9483), Epitope3 VKG VGV YEC KAT GSG SDP (1.4077) and Epitope4 NEW ECQ CVI YAK FPG GKD (0.4462) were predicted. LipL21 and N-terminal fragment having B-cell specific epitopes with higher VaxiJen score >0.9 as truncated I-LipL21 were cloned independently in pET15b and expressed in Escherichia coli. IgM ELISA and dot blot assay was performed for sera samples collected from Delhi-NCR for leptospiral whole cell lysate (WCL), recombinant LipL21 and I-LipL21. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were found to be 92.5%, 92.8%, 83.3%, and 97% respectively for recombinant I-LipL21 by IgM-ELISA. 11-14.8% increased sensitivity was observed over LipL21 and WCL. The I-LipL21 dot blot assay showed a further increased sensitivity of 3.8% over the IgM-ELISA. Therefore I-LipL21 may be the ideal candidate protein for diagnosis of leptospirosis.


Prospective assessment of cytokine IL-15 activity in patients with refractory atrial fibrillation episodes.
Inflammatory state is considered a risk factor of atrial fibrillation (AF) occurrence. The aim of this study was a prospective evaluation of the inflammation parameters in patients with different forms of AF without structural heart disease. One hundred fifty-eight patients with paroxysmal/persistent AF (87; 55.1% men, mean age 65.8±9.6 years) without structural heart disease were enrolled in the study. Inflammatory parameters: WBC, ESR, hs-CRP, IL-6, IL-15 and TNF-alpha were measured at baseline and after one year follow-up. Despite frequent AF episodes median values of WBC, ESR and C-reactive protein at baseline and after follow up were within normal ranges. There were no significant differences between WBC, ESR and hs-CRP regarding AF types. In patients who developed permanent AF form (n=14) hs-CRP concentrations were higher at baseline: 0.35 (IQR1: 0.09 IQR: 0.61) vs 0.15 (IQR1: 0.07 IQR: 0.29), p<0.01. Nevertheless, after one year's observation these differences were not significant. Among all cytokines were studied only IL-15 was significantly correlated with the number of AF episodes (r=0.26), mean (IQ1-IQ3): 10 (3-30) vs 60 (50-100), p=0.00681. Basic inflammatory markers were not changed in patients with refractory atrial fibrillation episodes in prospective one year's observation. Only cytokine IL-15 was correlated to numbers of AF episodes. It's potential role as a marker of arrhythmia deserves further evaluation.


Thermo-reversible gelation of atactic poly(methyl methacrylate) in poly(ethylene glycol) oligomers.
The temperature-concentration behavior of physical gel by atactic poly(methyl methacrylate) (aPMMA) in poly(ethylene glycol) oligomer (PEG400) was investigated. A liquid-liquid demixing interferes with a glass transition during cooling. The combination of demixing and T g leads to the formation of amorphous gels at low temperature. We suggest that the gelation of aPMMA/PEG400 is a glassy gel, in which short-range attractive depletion interaction in the polymer/oligomer system was the driving force at molecular level.


Personal History and Physical Examination in Judgment of Urinary Tract Infection in Children Aged 3 Months to 2 Years.
Pediatricians ubiquitously rely on urine analysis for diagnosing urinary tract infection (UTI) in young febrile children due to discrepancies in symptom presentation. This study aimed to identify the determinants of physical examination and personal history for diagnosing UTI. Four hundred and ten patients aged between 3 months and 2 years presenting with a tympanic temperature of >38°C for >24 hours were requested to undergo urinary tests. Pediatricians completed patient record charts before the test results were generated, examined the final results of the tests, and compared the results with those reported in the medical records. Multivariate logistic regression analysis was performed to detect potential confounding factors. An age of <1 year [odds ratio (OR): 5.05; p < 0.01], female sex (OR: 2.117; p < 0.05), and the absence of throat redness (OR: 1.907; p < 0.05) were risk factors for UTI. Patients defecating ≤3 times/day (OR: 8.80; p < 0.05) were more likely to have pyuria than those who defecated >3 times/day. For febrile patients in the age group examined, the absence of throat redness and female sex were independent predictors of UTI. Moreover, the risk of UTI was higher in younger patients.


Absolute and relative quantification of placenta-specific micrornas in maternal circulation with placental insufficiency-related complications.
Placental insufficiency-related complications are one of the leading causes of maternal and perinatal morbidity and mortality. This study investigated the quantification of placenta-specific microRNAs (miRNAs) in the maternal circulation during gestation in a cohort of women with normally progressing pregnancies, the differentiation between placental insufficiency-related complications and normally progressing pregnancies, and the differentiation between placental insufficiency and normally progressing pregnancies during the early stages of gestation. Both absolute and relative quantification of placenta-specific miRNAs (ie, miR-516-5p, miR-517*, miR-518b, miR-520a*, miR-520h, miR-525, and miR-526a) was determined in 50 women with normally progressing pregnancies, 32 with complicated pregnancies [21 with preeclampsia with or without intrauterine growth retardation (IUGR) and 11 with IUGR], and 7 women with pregnancies at various gestational stages who later developed preeclampsia and/or IUGR using real-time PCR and a comparative C(T) method relative to normalization factor (ie, geometric mean of ubiquitous miR-16 and let-7d). Both quantification approaches revealed significant increases in extracellular placenta-specific miRNA levels over time in women with normally progressing pregnancies; however, they were not able to differentiate between normally progressing and complicated pregnancies at the time of preeclampsia and/or IUGR onset. Nevertheless, significant elevation of extracellular miRNA levels was observed during early gestation (ie, within the 12th to 16th weeks) in pregnancies with later onset of preeclampsia and/or IUGR. Early gestation extracellular miRNA screening can differentiate between women with normally progressing pregnancies and those who may later develop placental insufficiency-related complications.


Capacitive coupling of atomic systems to mesoscopic conductors.
We describe a technique that enables a strong, coherent coupling between isolated neutral atoms and mesoscopic conductors. The coupling is achieved by exciting atoms trapped above the surface of a superconducting transmission line into Rydberg states with large electric dipole moments that induce voltage fluctuations in the transmission line. Using a mechanism analogous to cavity quantum electrodynamics, an atomic state can be transferred to a long-lived mode of the fluctuating voltage, atoms separated by millimeters can be entangled, or the quantum state of a solid-state device can be mapped onto atomic or photonic states.


The structure of (xylose)2glucose-O-serine 53 found in the first epidermal growth factor-like domain of bovine blood clotting factor IX.
We reported the presence of a new trisaccharide composed of two xylose and reducing terminal glucose residues linked to serine residues of bovine blood clotting factors VII and IX (Hase, S., Kawabata, S., Nishimura, H., Takeya, H., Sueyoshi, T., Miyata, T., Iwanaga, S., Takao, T., Shimonishi, Y., and Ikenaka, T. (1988) J. Biochem. (Tokyo) 104, 867-868). The present paper describes the detailed structural analysis of the trisaccharide. Glycopeptides were prepared from bovine factor IX by digestion with Pronase followed by purification by column chromatography. The trisaccharide was released from the protein by the beta-elimination reaction with hydrazine, and the reducing end of the sugar chain was tagged with 2-aminopyridine. The fluorescent pyridylamino derivative of the trisaccharide was purified by gel filtration and reversed-phase high performance liquid chromatography. The glycopeptides and pyridylamino-trisaccharide thus obtained were subjected to methylation study, 500-MHz 1H nuclear magnetic resonance spectroscopy, and periodate oxidation. Glucose and xylose belong to the D series by high performance liquid chromatography on a chiral column. From the results, the structure of the trisaccharide is proposed as: D-Xyl p alpha 1-3-D-Xyl p alpha 1-3-D-Glcp beta 1-O-Ser-53.


Inhibition of TNF-alpha promoter activity and synthesis by A11-99-1, a new cyclopentenone from the ascomycete Mollisia melaleuca.
In a search for inhibitors of the inducible tumor necrosis factor-a (TNF-a) promoter activity and synthesis, a new chlorinated cyclopentenone was isolated from fermentations of the ascomycete Mollisia melaleuca. The structure was determined by a combination of spectroscopic techniques The compound blocked the inducible human TNF-alpha promoter activity and synthesis with IC50-values of 2.5-5 microg/ml (8.1-16.1 microM). Studies on the mode of action of the compound revealed that the inhibition of TNF-a promoter activity is caused by an inhibition of the phosphorylation of the IkappaB protein which prevents the activation of the transcription factor NF-xB. No cytotoxic, antibacterial and antifungal activities could be observed up to 100 microg/ml (323 microM) of the compound.


Neuroprotection of low-molecular-weight galactan obtained from Cantharellus cibarius Fr. against Alzheimer's disease.
The large molecular weight of polysaccharides limits their absorption and utilization by organisms, affecting their biological activities. In this study, we purified α-1,6-galactan from Cantharellus cibarius Fr. (chanterelle) and reduced its molecular weight from approximately 20 kDa to 5 kDa (named CCP) to increase its solubility and absorption. In APP/PS1 mice, CCP improved both spatial and non-spatial memory loss in Alzheimer's disease (AD) mice, as confirmed by the Morris water maze, step-down, step-through, and novel object recognition tests, and dampened the deposition of amyloid-β plaques, as assessed by immunohistochemical analysis. Proteomic analysis suggested that the neuroprotective effects of CCP are related to anti-neuroinflammation. Immunofluorescence analysis and western blotting confirmed that CCP attenuated AD-like symptoms partly by inhibiting neuroinflammation, which was related to the blocking of complement component 3. Our study provides theoretical support and experimental evidence for the future application of chanterelle-extracted polysaccharides in AD treatment, promoting the modern development of traditional medicines originating from natural polysaccharides.


Unveiling the genomic potential of a novel thermostable glycoside hydrolases producing Neobacillus sedimentimangrovi UE25.
Genetic and enzymatic potential of Neobacillus sedimentimangrovi has not been assembled to date. Here, we report a high-quality genome assembly of thermophilic bacterium Neobacillus sedimentimangrovi UE25 using Illumina Hi-seq 2500. The strain was isolated from a crocodile pond Manghopir, Karachi, Pakistan. QUAST quality parameters showed 37.75% GC content and exhibited the genome into 110 contigs, with a total size of 3,230,777 bases. Genome of N. sedimentimangrovi UE25 harbors phage mediated DNA through horizontal gene exchange from the phages, symbiotic and pathogenic bacteria. Most of the phage genome encodes for hypothetical proteins, protease, and phage assembly proteins. Gene clusters encoding the intrinsic resistance to glycopeptides, isoniazid, rifamycin, elfamycin, macrolide, aminoglycosides, tetracycline and fluoroquinolone were identified into the genome. Since, the strain has been reported for the production of many industrially important thermostable enzymes, therefore, the genomic data of thermostable enzymes might be helpful to employ this species in commercial sectors. Probing genes of multiple thermostable glycoside hydrolase enzymes especially xylanases of N. sedimentimangrovi UE25 showed genetic diversity among the genes and confer the industrial importance of this microorganism. Furthermore, the genome of N. sedimentimangrovi will greatly improve our understanding of its genetics and evolution.


Infrared optical absorption loss of antireflection coatings on germanium and potassium chloride substrates at the 10-µm wavelength by the photothermal deflection technique.
The photothermal deflection technique is used to study the infrared absorption of antireflection coatings on Ge and KCl substrates. The thin films deposited by the thermal resistance evaporation technique, both with and without ion-assisted deposition, are investigated. The experimental results show that Ar-ion bombardment with low energy can evidently reduce the absorption of the coatings.


Null cell adenomas of the pituitary gland. An immunohistochemical study.
Fourteen null cell adenomas of the pituitary gland were examined immunohistochemically with antisera against three general neuroendocrine markers and 22 hormones. All cases showed positive immunostaining for neuron-specific enolase, ten cases for synaptophysin, and six cases expressed chromogranin immunoreactivity. Hormone immunoreactivity was detected in a few cells in ten of the 14 cases studied and the number of hormones demonstrated in each case was one or two. Thyroid-stimulating hormone was detected in five of the 14 cases, gastrin in four, beta-endorphin in two, calcitonin gene related peptide in one, prolactin in one, and follicle-stimulating hormone in one.


Clinical outcome following reinjection of Ranibizumab for reactivation of retinopathy of prematurity.
To assess reactivation after initial intravitreal injection of ranibizumab (IVR) for type 1 retinopathy of prematurity (ROP) or worse and the outcome following reinjection of ranibizumab for this reactivation. This retrospective study was performed on infants screened for ROP between March 2013 and February 2020 in Mansoura University Children Hospital, Mansoura, Egypt. Infants treated with ranibizumab 0.25 mg/0.025 mL were identified for review of their clinical outcomes. Data of infants with reactivation and IVR re-injection were analysed. A total of 2318 infants were screened for ROP, 115 (5%) infants (216 eyes) with a mean gestational age of 30 ± 2.5 weeks and mean birth weight of 1290 ± 355.2 g received IVR at mean postmenstrual age (PMA) of 38 ± 3.1 weeks. All treated eyes demonstrated initial regression of ROP. However, ROP reactivation occurred in 5 (2.3%) eyes of 3 patients, at an average of 9.6 ± 2.9 weeks after treatment. None of these eyes had retinal detachment. A second dose IVR was administered and all five eyes showed regression with complete retinal vascularisation, at a mean PMA of 60 ± 5.1 weeks. IVR is beneficial as an initial and subsequent treatment for type 1 ROP or APROP. A long-term follow-up until complete retinal vascularisation is recommended to avoid disease reactivation.


Route of admission and hospital costs for urologic patients.
This study of 2,549 urology patients examined resource consumption by route of admission into the hospital. Almost all urologic admissions were more expensive as emergencies. These more expensive emergency urologic admissions had higher diagnostic costs, a longer hospital length of stay, and a greater severity of illness than their less expensive non-emergency counterpart. The more expensive emergency admission had a high referral rate to urology from non-urologic clinical services. These findings suggest that efficiency might be improved in the emergency urologic patients by increasing the speed of diagnosis and admission of patients to the appropriate clinical service (urology).


An alternative synthesis of 4-deoxy-4-fluoro-D-glucose and its transport in the human erythrocyte.
Treatment of methyl 4-O-mesy-alpha-D-galactopyranoside with benzyl bromide in N,N-dimethylformamide in the presence of silver oxide yielded methyl 2,3,6-tri-O-benzyl-4-O-mesyl-alpha-D-galactopyranoside which with tert-butylammonium fluoride at reflux underwent nucleophilic displacement to give methyl 2,3,6-tri-O-benzyl-4-deoxy-4-fluoro-alpha-D-glucopyranoside. This compound on hydrogenolysis provided crystalline methyl 4-deoxy-4-fluoro-alpha-D-glucopyranoside (9). The structure of 9 was established by its conversion to the 2,3,6-tri-O-acetyl derivative and by n.m.r. and m.s. analysis. Acid hydrolysis of 9 gave 4-deoxy-4-fluoro-D-glucose (1). A modification of an established synthesis of 4-deoxy-D-xylo-hexose (2) from methyl 2,3,6-tri-O-benzoyl-alpha-D-galactopyranoside is described. A systematic comparison was made of the transport parameters (Kx and Vmax) of D-glucose, 2, and 1 in human erythrocytes. The Kx values observed for the above sugars are: 4.0mM, 4.5mM, and 4.6mM, respectively. These results indicate that O-4 in beta-D-glucopyranose is not involved in hydrogen bonding to the carrier protein associated with the transport of D-glucose in the erythrocyte.


Lipocalin-2 induces mitochondrial dysfunction in renal tubular cells via mTOR pathway activation.
Mitochondrial dysfunction is a critical process in renal epithelial cells upon kidney injury. While its implication in kidney disease progression is established, the mechanisms modulating it remain unclear. Here, we describe the role of Lipocalin-2 (LCN2), a protein expressed in injured tubular cells, in mitochondrial dysfunction. We show that LCN2 expression decreases mitochondrial mass and function and induces mitochondrial fragmentation. Importantly, while LCN2 expression favors DRP1 mitochondrial recruitment, DRP1 inhibition antagonizes LCN2's effect on mitochondrial shape. Remarkably, LCN2 promotes mitochondrial fragmentation independently of its secretion or transport iron activity. Mechanistically, intracellular LCN2 expression increases mTOR activity, and rapamycin inhibits LCN2's effect on mitochondrial shape. In vivo, Lcn2 gene inactivation prevents mTOR activation and mitochondrial length decrease observed upon ischemia-reperfusion-induced kidney injury (IRI) in Lcn2+/+ mice. Our data identify LCN2 as a key regulator of mitochondrial dynamics and further elucidate the mechanisms leading to mitochondrial dysfunction.


Modest catalysis of the decarboxylation of orotate by hydrogen bonding: a theoretical model for orotidine- 5' -monophosphate decarboxylase.
As a model for interactions present in the active site of orotidine-5'-monophosphate decarboxylase (ODCase), the effect of hydrogen bonds to the carbonyl groups (O-2 and O-4) of orotic acid and its decarboxylation product was probed with ab initio calculations. We have found that the transition state/carbanion intermediate is a better proton receptor and therefore, the hydrogen bonds can be a modest source of catalysis. Comparison of the calculated data with results from site-directed mutagenesis provides some insights into the polarity of the active site.


Health status, anxiety, and depressive symptoms following complicated and uncomplicated colorectal surgeries.
The purpose of this study was to evaluate the impact of complications following colorectal surgery on anxiety, depressive symptoms, and health status. Previously, very few studies examined the psychological impact of complications following colorectal surgery. Also, in clinical practice, little attention is paid to the psychological impact of complications. Patients undergoing colorectal surgery were evaluated prospectively preoperatively and postoperatively at 3 days, 6 weeks, and 1 year, using the Center for Epidemiological Studies-Depression (CES-D), State-Trait Anxiety Inventory (STAI), and Short Form 36 (SF-36) questionnaires. Patient data and complications were prospectively recorded. Postoperative CES-D, STAI, and SF-36 scores in patients with minor and severe complications were compared to scores of patients without complications using a general linear model. Of 218 patients, 130 (59.6%) had complications. Colorectal surgery significantly increased depressive symptoms and anxiety levels in the same amount in all patient subgroups. Furthermore, it also lowered all domains of health status in all patient subgroups, but not equally. Patients with a severely complicated postoperative course had a larger postoperative decrease in health status, most notably at 6 weeks postoperatively with the largest effects in the physical-, mental-, social-, and vitality domains compared with the other subgroups. Colorectal surgery has a profound effect on depressive and anxiety symptoms, as well as nearly all domains of health status. Occurrence of severe complications increases the negative effect of colorectal surgery on most domains of health status but do not specifically increase depressive symptoms or anxiety levels. At 6 weeks, these effects are most notable, but at 1 year, they have faded.