Cross-sensitivity between isoflurane and diazepam: evidence from a bidirectional tolerance study in mice.
We examined in mice the effect of chronic diazepam treatment on the sensitivity to isoflurane, and that of repeated isoflurane exposure on the sensitivity to diazepam. Mice were divided into four groups: group 1, treated with diazepam, 10 mg/kg i.p. twice daily; group 2, vehicle-treated controls; group 3, exposed to 3% isoflurane for 25 min twice daily; and group 4, untreated controls. After 14 days the effect of the treatment was assessed. Twenty-four hours after the last 10 mg/kg diazepam treatment, groups 1 and 2 received diazepam, 5 mg/kg i.p., and were subjected to the horizontal wire test (HWT). All control mice but only 10% of the diazepam-treated mice failed the HWT. Groups 1 and 2 were then exposed to increasing concentrations of isoflurane. Diazepam-treated mice (group 1) lost the HWT at 0.7+/-0.7%, compared with 0.6+/-0.1% in controls (group 2) (P<0.001); the ED50 was 0.75% vs. 0.65%. Group 1 mice lost the righting reflex at 0.94+/-0.07% isoflurane vs. 0.87+/-0.06% in group 2 (P<0.01); the ED50 was 0.93% vs. 0.82%. Recovery time was 175+/-161 s in group 1 vs. 343+/-275 s in group 2 (P<0.02). Twenty-four hours after the last of the repeated exposures to isoflurane, we examined the responses of groups 3 and 4 to increasing concentrations of isoflurane. Mice in group 3 lost the righting reflex at 1.0+/-0.06% isoflurane vs. 0.9+/-0.04% in controls (group 4) (P<0.001); the ED50 was 0.96% vs. 0.85%. Recovery time was 113+/-124 s vs. 208+/-126 s in groups 3 and 4 (P<0.09). Diazepam, 3 mg/kg i.p. administered to groups 3 and 4, caused loss of the HWT reflex in 33% of group 3 mice and in 82% of controls (group 4) (P<0.001). It appears that prolonged exposure to both diazepam and isoflurane caused reduced sensitivity to each drug separately, as well as to the other drug. This finding may strengthen the theory that inhalational anesthetics may act via the same mechanism as the benzodiazepines.


Stabilization of hESCs in two distinct substates along the continuum of pluripotency.
A detailed understanding of the developmental substates of human pluripotent stem cells (hPSCs) is needed to optimize their use in cell therapy and for modeling early development. Genetic instability and risk of tumorigenicity of primed hPSCs are well documented, but a systematic isogenic comparison between substates has not been performed. We derived four hESC lines in naive human stem cell medium (NHSM) and generated isogenic pairs of NHSM and primed cultures. Through phenotypic, transcriptomic, and methylation profiling, we identified changes that arose during the transition to a primed substate. Although early NHSM cultures displayed naive characteristics, including greater proliferation and clonogenic potential compared with primed cultures, they drifted toward a more primed-like substate over time, including accumulation of genetic abnormalities. Overall, we show that transcriptomic and epigenomic profiling can be used to place human pluripotent cultures along a developmental continuum and may inform their utility for clinical and research applications.


Morbidity and mortality in patients with usual interstitial pneumonia (UIP) pattern undergoing surgery for lung biopsy.
Previous studies revealed that surgical lung biopsy in usual interstitial pneumonia (UIP) patients is accompanied with higher morbidity and mortality. The aim of this retrospective analysis was to assess morbidity and mortality of patients with suspected UIP undergoing surgical lung biopsy. We conducted a retrospective study of 45 patients with suspected UIP pattern undergoing surgical biopsy for diffuse pulmonary infiltrates in our department. Data concerning medical history, histology, and survival status were extracted from the medical database of the University Medical Center Freiburg. UIP was diagnosed by experienced pneumo-pathologists according to the criteria of American Thoracic Society/European Respiratory Society (ATS/ERS) consensus classification. Due to adhesions the surgeon decided in two patients to perform wedge resection via open surgery. In 43 patients lung biopsy was performed via Video-assisted thoracoscopy (VATS). No intraoperative complications were observed. Postoperative complications consisted of bradyarrhythmia (n = 1), gastrointestinal bleeding (n = 1), bacterial pneumonia (n = 1), candida pneumonia (n = 1) and acute exacerbation (n = 1). There was no 30-day mortality, but one patient was lost in follow-up and therefore censored. The intraoperative placed thoracic drain was removed at the first postoperative day in most cases (mean day of removal 1.9, ±2.6). The mean length of hospital stay was 8.1 days (±6.8). We conclude that surgical biopsy can be safely performed in patients with suspected UIP.


Benign acute childhood myositis in an accident and emergency setting.
Four children presented to the Accident and Emergency department of the Royal Hospital for Sick Children in Edinburgh during seven days in February 2003. They shared a strikingly similar clinical picture with debilitating muscle pain in their calves. This paper discusses their clinical course and presents a literature review of the problem.


Kinesin family member 15 promotes cancer stem cell phenotype and malignancy via reactive oxygen species imbalance in hepatocellular carcinoma.
The development and progression of hepatocellular carcinoma (HCC) is associated with the presence of cancer stem cells (CSCs). In the present study, kinesin family member 15 (KIF15) expression was shown to be overexpressed in HCC tissues, cell lines, and CSCs. Patients with HCC with high KIF15 expression had shortened overall survival (OS) and high recurrence probability. Downregulation of KIF15 in vitro as well as in HCC organoids resulted in a significant reduction in sphere formation and expression of stemness-related genes. KIF15 downregulation in human HCC xenograft models delayed tumor initiation, growth, and metastasis. KIF15 was also demonstrated to interact with phosphoglycerate dehydrogenase (PHGDH) and inhibit proteasomal degradation of PHGDH, thus promoting CSC phenotype and malignancy via PHGDH-mediated intracellular reactive oxygen species (ROS) imbalance in HCC. Moreover, AAA nuclear coregulator cancer-associated protein (ANCCA) upregulation acts as a key mediator in KIF15 expression upregulation in HCC. Conclusion: In this study, we found that KIF15 promotes the CSC phenotype and malignancy via PHGDH-mediated ROS imbalance in HCC. These findings highlight potential therapeutic targets for HCC.


The in vitro synthesis of final maturational steroids by ovaries of brook trout (Salvelinus fontinalis) and yellow perch (Perca flavescens).
The steroidogenic profile produced by ovaries of brook trout (Salvelinus fontinalis) and yellow perch (Perca flavescens) was examined using radioactive incorporation incubations. The radioactive metabolites produced were identified and were tested for their ability to induce germinal vesicle breakdown (GVBD) in oocytes in in vitro bioassays. Brook trout ovarian tissue converted [14C]progesterone to five metabolites that were effective in inducing GVBD in the bioassays: 5 beta-pregnanedione, 17 alpha-hydroxyprogesterone, deoxycorticosterone, and two more polar metabolites that were not identified. One of these two metabolites comigrated with 11-deoxycortisol and 17 alpha-hydroxy,20 beta-dihydroprogesterone (17 alpha, 20 beta prog) in thin layer chromatography. Androstenedione, testosterone, and estradiol-17 beta were also identified as metabolites of progesterone. Brook trout ovarian tissue did not extensively metabolize [14C]pregnenolone. Dehydroepiandrosterone and 17 alpha-hydroxypregnenolone were tentatively identified as metabolites of pregnenolone. Yellow perch ovarian tissue converted [14C]progesterone or [14C]pregnenolone to six metabolites that were effective in inducing GVBD in the bioassays: 5 alpha-pregnanedione, 17 alpha-hydroxyprogesterone, 20 alpha-dihydroprogesterone, 17 alpha-hydroxy, 20 alpha-dihydroprogesterone (tentatively identified), and two other unidentified metabolites. One of these two metabolites comigrated with 11-deoxycortisol and 17 alpha, 20 beta prog in thin layer chromatography. The only metabolite that induced ovulation of yellow perch oocytes in vitro was the metabolite comigrating with 11-deoxycortisol and 17 alpha, 20 beta prog. Androstenedione and testosterone were also identified as metabolites produced by yellow perch ovarian tissue. The results show that the ovaries of both species produce steroids that are active in the induction of oocyte final maturation.


Opening the window for endothelial-to-hematopoietic transition.
Definitive long-term hematopoietic stem cells (LT-HSCs) arise during embryogenesis in a process termed endothelial-to-hematopoietic transition (EHT), in which specialized hemogenic endothelial cells (HECs) transform into hematopoietic cells. The transcription factor RUNX1 marks HECs and is essential for EHT. Ectopic RUNX1 expression in non-HECs is sufficient to convert them into HECs. However, the conversion efficiency depends on the developmental timing of expression. In this issue of Genes & Development, Howell and colleagues (pp. 1475-1489) leverage this observation to further understand how RUNX1 mediates EHT. They engineered mice that ectopically express RUNX1 in endothelial cells at different developmental time points and doses. They then performed chromatin accessibility and other analyses and correlate this with hemogenic potential. They found that RUNX1 collaborates with TGFβ signaling transcription factors to drive chromatin accessibility changes that specify HECs. They also highlight interesting parallels between EHT and endothelial-to-mesenchymal transition (EndoMT), which occurs during cardiac development. The results of Howell and colleagues provide new mechanistic insights into EHT and take us one step closer to generating patient-specific LT-HSCs from induced pluripotent stem cells.


Carriage of Clostridium perfringens by benthic crabs in a sewage-polluted estuary.
The Estuary of Bahía Blanca (EBB), Argentina, is an important wetland under intense sewage pollution. We investigated the occurrence of Clostridium perfringens (CP) in populations of two benthic crabs (Neohelice granulata and Cyrtograpsus angulatus) and in sediment from the EBB. CP was found in 49.1% of the crabs and all of the isolates were identified as type A. The alpha (cpa) and enterotoxin (cpe) encoding genes were identified. Genetic analyses identified 13 novel sequence types, and found no clustering among isolates, suggesting that CP is not part of the crabs' commensal flora. CP carriage was 51 times more likely in crabs from the area nearest sewage outfalls compared with crabs from a reference site. Our in vitro experiments suggest that the carriage of CP in crabs is transient. The use of these benthic crabs as monitoring organisms of sewage pollution in coastal habitats is proposed.


A study of fundoplication disruption and deformity.
Three distinct forms of postoperative breakdown after Nissen fundoplication have been discussed. Disruption and recurrent reflux is most common, with slipping occurring infrequently. For the first time, three patients developing a proximal gastric pouch deformity causing partial obstruction of the fundus without recurrent herniation are reported on. Two patients required remedial surgery.


Dataset of food delivery app users at a public university: Insights into digital transformation.
The food delivery apps (FDAs) have facilitated the connection between food service providers and consumers, enabling online ordering through smartphones and offline delivery in Vietnam. The Covid-19 pandemic has significantly impacted the food and beverage industry, accelerating the process of digital transformation and promoting sustainability through online-to-offline service. The usage of FDAs amongst consumers has exhibited a discernible escalation, primarily attributable to its ability to expedite the delivery of food in a hassle-free and convenient manner. Given the ongoing pandemic and the swift increase in demand for online food ordering services, particularly among the younger demographic, it has become imperative to comprehend the drivers that impel consumers to adopt these applications. This article aims to present a dataset pertaining to the decision-making factors that university students in Danang, Vietnam, take into account when they use FDAs and express positive feedback about them on the internet. The survey was conducted between September 2022 and January 2023 and gathered 346 usable responses. The results provide novel perspectives on the adoption of FDAs by university students, which is an emerging technology in the food and beverage sector. This dataset could be useful to various stakeholders, such as service providers, small and medium enterprises (SMEs), and vendors operating on these platforms, as it can help them acquire valuable insights into their customers' preferences and behavior. In addition, the dataset can serve as a basis for conducting comparative research in different universities or countries.


Double burden of malnutrition amongst patients with first-episode schizophrenia in a psychiatric hospital: A 1-year follow-up study.
Despite the burgeoning data on the double burden of malnutrition (DBM) in sub-Saharan Africa, longitudinal studies to examine malnutrition amongst first-episode schizophrenia are uncommon in the modern literature. To determine the extent of nutritional variations amongst persons with schizophrenia at intervals of 1-year treatment follow-up. This study was conducted at the Federal Neuropsychiatric Hospital, Enugu, Nigeria. Consecutive incident cases that fulfilled the criteria for schizophrenia were recruited into the study. After a baseline assessment, 206 incident cases of schizophrenia were followed up at 4th, 8th, 12th weeks, 6 months and 1 year for indicators of nutritional outcome. The body mass index (BMI) was used to measure the nutritional status amongst the study participants. Changes in the BMI across intervals of follow-up were examined using repeated measures analysis of variance, whereas the socio-demographic and clinical variables were evaluated as predictors of outcome using multiple regression analysis. After 1 year of treatment with antipsychotics, the prevalence of underweight decreased from 19.9% (95% CI, 19.8% - 20.0%) at baseline to 16.0% (95% CI, 15.9% - 16.1%) at 1 year, but the prevalence of overweight/obesity increased from 29.1% (95% CI, 29.0% - 29.2%) at baseline to 43.2% (95% CI, 43.0% - 43.3%) at 1 year of follow-up. The predictors of BMI at 1 year were antipsychotic medication (32.7% variance), duration of vagrancy (24.0%) and age at onset (20.0%). The finding of coexistence of undernutrition and overnutrition across the intervals of treatment follow-up underscores the need for comprehensive interventions to address both extremes of malnutrition amongst patients with schizophrenia.


Hook-pin fixation in femoral neck fractures. A two-year follow-up study of 300 cases.
In 300 femoral neck fractures treated with hook-pin internal fixation, no perioperative mortality and no deep infection was seen. Eighty-four patients (28%) died within two years of the date of fracture. At two-year follow-up examination, 56 of 300 cases (19%) had developed radiographic healing complications, i.e., redisplacement, nonunion, or segmental femoral head collapse (26% of the survivors). Three of 85 undisplaced fractures (4%) developed segmental collapse (5% of the survivors) while among displaced fractures, radiographic evidence of malhealing was found in 53 of 215 cases (25%; 35% of survivors) at two-year follow-up examination. In the total series, secondary hip arthroplasty was performed in 34 cases (11%). Atraumatic reduction and internal fixation are recommended as primary treatment in femoral neck fractures.


Immunoglobulin expression and its biological significance in cancer cells.
It is generally believed that the expression of a gene is restricted "within the right place and at the right time". This principle has long been considered applicable as well to the expression of immunoglobulin (Ig) lymphocytes of B cell lineage. However, increasing evidence has shown Ig "paradoxically" expressed in malignant tumors of epithelial origin. We reviewed the recent progress in the study of cancer-derived Ig, and also discussed its mechanisms and possible functions, trying to arouse interest and attention to those working in the field of immunology and oncology.


The impact of personality traits on pessary treatment outcomes in patients with pelvic organ prolapse.
Personality traits can play an important role in outcomes of different chronic disorders. We hypothesize that the pessary treatment outcomes in symptomatic pelvic organ prolapse (POP) can also be influenced by personality traits. This prospective observational study included consecutive women with symptomatic POP seeking pessary treatment between December 2018 and January 2020. The personality profile was measured using the Eysenck Personality Questionnaire (EPQ-R) at baseline, and patient health-related quality of life (HRQoL) was measured using the Pelvic Floor Impact Questionnaire-7 (PFIQ-7) and the Pelvic Floor Distress Inventory (PFDI-20) at baseline and at 3 months. The correlation between HRQoL and personality traits was investigated by means of linear regression. In total, 213 patients were included, of which 163 patients (76.5%) achieved success by the 3-month follow-up. No significant differences were found in the EPQ scores between the successful and unsuccessful groups. The scores on both the PFIQ-7 and PFDI-20 correlated significantly with neuroticism and correlated inversely with extraversion at both baseline and the 3-month follow-up. The degree of improvement in PFIQ-7 and PFDI-20 scores was not associated with personality traits. Our data indicate that neurotic and introverted women were more bothered by POP-related symptoms, although the improvement in symptoms was not significantly associated with personality traits after 3 months of pessary treatment.


Increased brain uptake of copper and zinc in mice caused by diethyldithiocarbamate.
Mice given 64CuCl2 and 65ZnCl2 (10 mumol/kg) were treated with sodium diethyldithiocarbamate (0.5 mmol/kg). The treatment increased the brain level of radioactive copper five-fold and that of radioactive zinc three-fold. Such redistribution of metal ions may be explained from the formation of lipophilic metal chelates. The increased brain levels may involve neurotoxic effects.


A prognostic model based on the Augmin family genes for LGG patients.
Gliomas are the most prevalent primary tumors in the central nervous system. Despite some breakthroughs in the treatment of glioma in recent years, survival rates remain low. Although genes of the Augmin family play a key role in microtubule nucleation, the role they play in gliomas is unclear. Transcriptome data were extracted from UCSC XENA and GTEx for low-grade glioma (LGG) and normal tissues, respectively. The protein interaction network associated with Augmin family genes was established using STRING and GeneMANIA databases. Enrichment analysis of gene-related functions and pathways was used to explore potential biological pathways and TIMER to assess immune cell infiltration. Regression analysis and Kaplan-Meier analysis were used to look at the clinical characteristics of the Augmin family genes and the association with the prognosis of patients with glioma. The results showed that the mRNA expression of Augmin family genes was significantly elevated in LGG tissues, except for HAUS7. Immunoregulation, cell cycle, apoptosis and other signaling pathways may be involved in the development and progression of LGG. Except for HAUS4 and HAUS7, the expression of all genes was positively correlated with immune cell infiltration. High expression of HAUS1, HAUS3, HAUS5, HAUS7, HAUS8 and low expression of HAUS4, HAUS6 in LGG was associated with poor prognosis. The risk models constructed based on the pivotal genes HAUS2, HAUS4 and HAUS8 were validated by nomogram and confirmed to be clinically useful for predicting the prognosis of LGG.


The need for a specific risk prediction system in native valve infective endocarditis surgery.
The need for a specific risk score system for infective endocarditis (IE) surgery has been previously claimed. In a single-center pilot study, preliminary to future multicentric development and validation, bivariate and multivariate (logistic regression) analysis of early postoperative mortality predictors in 440 native valve IE patients were performed. Mathematical procedures assigned scores to the independent predictors emerged (AUC of the ROC curve: 0.88). Overall mortality was 9.1%. Six predictors were identified and assigned scores, including age (5-13 points), renal failure (5), NYHA class IV (9), critical preoperative state (11), lack of preoperative attainment of blood culture negativity (5), perivalvular involvement (5). Four risk classes were drawn ranging from "very low risk" (≤5 points, mean predicted mortality 1%), and to "very high risk" (≥20 points, 43% mortality). IE-specific risk stratification models are both needed, as disease-specific factors (e.g., cultures, abscess), beside the generic ones (e.g., age, renal impairment) affect mortality, and feasible.


Knowledge base design for decision support in respirator therapy.
A knowledge base is built for decision support applied to respirator therapy (the KUSIVAR project). The knowledge representation is object-oriented using frames to store multiple forms of knowledge: variable descriptions, transformation tables, rules and mathematical models. The system is data-driven, generating and displaying advice automatically triggered by changes in data from the respirator and the patient. The inferenceing mechanism is forward-chaining i.e. a rule is evaluated as soon as it's condition is satisfied. Temporal aspects of the reasoning are represented by a number of mechanisms, among others limited validity times for data, trend analysis and mathematical models. The knowledge base is organized according to disease groups and decision situation which simplifies knowledge acquisition and improves response times since it enables the system to focus on a limited set of rules in each situation. To test the feasibility of the system design a prototype has been built using Knowledge Engineering Environment (KEE) from Intellicorp on an Explorer workstation from Unisys. The production system, which is interfaced to a Siemens Elema Servo Ventilator 900C, is currently being implemented under the Microsoft Windows multitasking environment on a microcomputer based on an Intel 80386 processor.


Successful vaginal delivery after caesarean scar rupture: a case report.
A case of successful vaginal delivery following a previous lower segment caesarean scar rupture is presented.


Deriving folds of macromolecular complexes through electron cryomicroscopy and bioinformatics approaches.
Intermediate-resolution (7-9A) structures of large macromolecular complexes can be obtained by electron cryomicroscopy. This structural information, combined with bioinformatics data for the individual protein components or domains, can lead to a fold model for the entire complex. Such approaches have been demonstrated with the 6.8 A structure of the rice dwarf virus to derive models for the major capsid shell proteins.


[Seasonal dynamics of chrysophyte stomatocyst formation in the plankton of Southern Baikal].
The results of studies on the phytoplankton of Southern Baikal in 2004 show that siliceous stomatocysts (cysts) of chrysophyte algae make a significant contribution to this community. Their abundance reaches a peak of 46 800 cysts/l between August and October, when the concentration of biogenic elements is minimum. The D/C coefficient (the ratio of diatom cells to cysts) varies during the year, reflecting the seasonal succession of phytoplankton and changes in the concentration of biogenic elements in the photic layer. Fifty morphotypes of the cysts have been distinguished and divided into 25 groups by morphological characters. These groups differ in seasonal dynamics. The cysts of group 5 (with spines of different lengths in the equatorial and posterior areas) dominate over other morphotypes and reach the highest concentration (13,600 cysts/l) in August. The data obtained in this study may provide an additional criterion for assessing the present-day state of Lake Baikal and for paleolimnological reconstructions.


Evaluating the performance of WHO and CDC case definitions for influenza-like illness in diagnosing influenza during the 2022-2023 flu season in Mexico.
This study aimed to evaluate the performance of the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) case definitions for influenza-like illness (ILI) in diagnosing influenza during the 2022-2023 flu season in Mexico. We conducted a cross-sectional analysis of national epidemiological surveillance data in Mexico, focusing on respiratory viral pathogens. We analyzed data from 6027 non-hospitalized patients between 5 and 65 years old who underwent molecular testing for respiratory viral pathogens. The performance of both case definitions was evaluated in terms of sensitivity, specificity, and the area under the receiver operating characteristic (AUROC) curve. Overall, the diagnostic accuracy of the evaluated ILI definitions in identifying influenza patients was low, particularly among older patients. When compared to the CDC, the WHO definition had a lower sensitivity but a higher specificity, resulting in a higher AUROC (P = 0.031) for the WHO criteria. Our findings suggest that the WHO and CDC ILI case definitions have limited accuracy for diagnosing influenza in non-hospitalized patients and highlight the need for more specific diagnostic tools to improve the detection of influenza cases during the flu season.


The Effects of Pre-medical Anatomy and Clinical Experiences on Medical School Anatomy-Related Academic Performance.
The objective of this study was to examine the effects that pre-medical patient care clinical experiences and anatomical education had on undergraduate medical course grades and anatomy practical exam scores. This study provides a unique perspective to this line of inquiry in that it included data from 9 class year cohorts between academic years 2010-2011 and 2018-2019, all from a single institution. A survey to assess pre-medical clinical and anatomical experiences was completed by each new matriculate. Results were compared to each student's course grades and anatomy practical exam scores. The effects of pre-medical experiences on practical scores and final grades were evaluated using generalized linear mixed models. Several positive and negative associations were identified. The most obvious effect revealed by data analysis was the class year cohort effect, seen as variation in the academic performance of each cohort from year-to-year. Other significant results included a positive association between pre-medical comparative anatomy coursework and anatomy assessment performance over the entire year's anatomy curriculum. Counterintuitively, some pre-medical clinical experiences, such as nursing experience, had a negative effect on course grades and practical exam performance. Pre-medical students can use this information to decide whether to enroll in undergraduate anatomy courses or engage in extra pre-medical clinical work. It may also be valuable to medical school admissions departments in regard to determining the anatomy coursework and clinical experience requirements for their applicants.


FTIR spectroscopy of ZrC nanoparticles under the gamma radiation.
In the presented work, infrared spectra of nano-ZrC samples were taken in the range of 400-4000 cm-1 of the wavenumbers before and after gamma irradiation (5 Mrad, 15 Mrad, 50 Mrad and 150 Mrad). As a result of the spectral analysis, it is possible to notice that seven IR bands appear in the general approach before irradiation. The peaks explaining the vibration of the ZrC bonds before and after gamma irradiation were explained by the corresponding wavenumbers in the infrared (IR) absorption spectra. Simultaneously, the stretching vibration of the ZrOC bonds are explained by the effect of gamma radiation and the corresponding wavenumbers. Surface activity of ZrC nanoparticles increased as a result of gamma irradiation and this increasing directly affected to the intensity of infrared peaks, which is characterized the COH groups and CO asymmetric stretching vibration. At the relatively high doses, such as 50 Mrad and 150 Mrad, the state of amorphization in nanomaterials is explained by the corresponding spectra.


Topographic electroencephalographic study of transient ischemic attacks.
Twenty-five patients with TIAs in the carotid artery distribution were studied by means of computed mapping of EEG (CME) and conventional EEG. In addition, CT scan and cerebral angiography, and in 10 patients rCBF measurements were performed. The CME provided topographic maps of the average power spectra for each of 6 frequency bands from 2.0 to 29.5 Hz which were displayed two-dimensionally in a color-coded isopower format. EEG abnormalities were analyzed and the results of the two different methods of EEG interpretation were compared. Sixty-eight percent of the patients showed unilateral abnormalities on CME appropriately lateralized to the clinical symptoms even after these symptoms had cleared completely. Furthermore, 88% of those who were examined within 2 weeks of last TIA showed corresponding CME abnormalities. Only 3 out of 10 TIA patients who had rCBF studies showed reduction of blood flow on the appropriate hemisphere, whereas 7 of the 10 patients had corresponding CME abnormalities. Comparing the results of the CME and of conventional EEG reading revealed the CME to be slightly more sensitive in detecting asymmetrical voltage depression of background activity than the conventional reading of the EEG, while the latter detected low amplitude sporadic activities which were missed by CME. Both methods were equally sensitive in detecting slow wave foci and non-transient symmetrical changes. The two most significant points of this report are the following: first, 68% of the TIA patients studied had residual unilateral abnormalities in CME in their symptom-free period. In the subset of patients subjected to rCBF studies only 30% showed residual flow aberrations, whereas 70% of the same subset demonstrated unilateral abnormalities in CME. Second, though conventional EEG reading by an experienced electroencephalographer can nearly match the performance of CME the CME format makes subtle but useful EEG findings readily available to the uninitiated. The CME also quantifies the data making objective comparisons more amenable to software manipulations for further studies.


Sun-burn induced upper limb lymphedema 11 years following breast cancer surgery: A case report.
Upper arm lymphedema is a common complication one year after breast cancer surgery, which profoundly impacts patients' quality of life. We reported a case of lymphedema induced by prolonged sun exposure 11 years after breast cancer surgery. Breast screening, patient education and follow-up after hospital discharge could help to prevent upper-arm lymphedema.


Variation in the pattern of omissions and substitutions of grammatical morphemes in the spontaneous speech of so-called agrammatic patients.
We describe the patterns of omissions (and substitutions) of freestanding grammatical morphemes and the patterns of substitutions of bound grammatical morphemes in 20 so-called agrammatic patients. Extreme variation was observed in the patterns of omissions and substitutions of grammatical morphemes, both in terms of the distribution of errors for different grammatical morphemes as well as in terms of the distribution of omissions versus substitutions. Results are discussed in the context of current debates concerning the possibility of a theoretically motivated distinction between the clinical categories of agrammatism and paragrammatism and, more generally, concerning the theoretical usefulness of any clinical category. The conclusion is reached that the observed heterogeneity in the production of grammatical morphemes among putatively agrammatic patients renders the clinical category of agrammatism, and by extension all other clinical categories from the classical classification scheme (e.g., Broca's aphasia, Wernicke's aphasia, and so forth) to more recent classificatory attempts (e.g., surface dyslexia, deep dysgraphia, and so forth), theoretically useless.


Rationale, design and baseline results of the Treatment Optimisation in Primary care of Heart failure in the Utrecht region (TOPHU) study: a cluster randomised controlled trial.
Heart failure (HF) is mainly detected and managed in primary care, but the care is considered suboptimal. We present the rationale, design and baseline results of the Treatment Optimisation in Primary care of Heart failure in the Utrecht region (TOPHU) study. In this study we assess the effect of a single training of GPs in the pharmacological management of patients with HF. A cluster randomised controlled trial. Thirty primary care practices are randomly assigned to care as usual or intervention defined as a single training in the up-titration and management of HF drug therapy according to the heart failure guidelines of the European Society of Cardiology (ESC). Patients with a GP's diagnosis of HF will be re-evaluated by an expert panel of two cardiologists and a GP with expertise in HF to come to a definite diagnosis of HF according to the ESC heart failure guidelines. Those with definite HF will be analysed in this study. Drug use will be measured after six months, health status after twelve months, and heart-related hospital admissions and all-cause mortality after two years. Our cluster randomised trial will show whether a single training of GPs improves the pharmacological management of patients with HF and confers beneficial effects on health status after one year, and cardiac hospital admissions and all-cause mortality after two years of follow-up. ClinicalTrials.gov Identifier NCT01662323.


The RasGAP N-terminal fragment generated by caspase cleavage protects cells in a Ras/PI3K/Akt-dependent manner that does not rely on NFkappa B activation.
RasGAP, a regulator of Ras GTPase family members, is cleaved at low levels of caspase activity into an N-terminal fragment (fragment N) that generates potent anti-apoptotic signals. At higher levels of caspase activity, fragment N is further cleaved into two fragments that strongly potentiate apoptosis. RasGAP could thus function as a sensor of caspase activity to determine whether a cell should survive or not. Here we show that fragment N protects cells by activating the Ras-PI3K-Akt pathway. Surprisingly, even though nuclear factor kappaB (NFkappaB) can be activated by Akt, it plays no role in the anti-apoptotic functions of fragment N. This indicates that Akt effectors are differentially regulated when fragment N is generated.


Deep learning radiomics model related with genomics phenotypes for lymph node metastasis prediction in colorectal cancer.
The preoperative lymph node (LN) status is important for the treatment of colorectal cancer (CRC). Here, we established and validated a deep learning (DPL) model for predicting lymph node metastasis (LNM) in CRC. A total of 423 CRC patients were divided into cohort 1 (training set, n = 238, testing set, n = 101) and cohort 2 (validation set, n = 84). Among them, 84 patients' tumour tissues were collected for RNA sequencing. The DPL features were extracted from enhanced venous-phase computed tomography of CRC using an autoencoder. A DPL model was constructed with the least absolute shrinkage and selection operator algorithm. Carcinoembryonic antigen and carbohydrate antigen 19-9 were incorporated into the DPL model to construct a combined model. The model performance was assessed by receiver operating characteristic curves, calibration curves and decision curves. The correlations between DPL features, which have been selected, and genes were analysed by Spearman' correlation, and the genes correlated with DPL features were used to transcriptomic analysis. The DPL model, integrated with 20 DPL features, showed a good discrimination performance in predicting the LNM, with areas under the curves (AUCs) of 0.79, 0.73 and 0.70 in the training set, testing set and validation set, respectively. The combined model had a better performance, with AUCs of 0.81, 0.77 and 0.73 in the three sets, respectively. Decision curve analysis confirmed the clinical application value of the DPL model and combined model. Furthermore, catabolic processes and immune-related pathways were identified and related with the selected DPL features. This study presented a DPL model and a combined model for LNM prediction. We explored the potential genomic phenotypes related with DPL features. In addition, the model could potentially be utilized to facilitate the individualized prediction of LNM in CRC.


A randomized trial of amorolfine 5% solution nail lacquer in association with itraconazole pulse therapy compared with itraconazole alone in the treatment of Candida fingernail onychomycosis.
Treatment failures and relapses are not uncommon in onychomycosis. Therefore, it is worthwhile to consider the combination of systemic and topical antifungals to improve the cure rates further and to reduce the duration of systemic treatment. To evaluate and compare itraconazole pulse therapy combined with amorolfine with itraconazole alone in the treatment of Candida fingernail onychomycosis. Ninety patients with moderate to severe Candida fingernail onychomycosis were randomized into two treatment groups of 45 subjects each. Group 1 received itraconazole pulse therapy for 2 months and applied amorolfine 5% solution nail lacquer for 6 months, while group 2 received monotherapy with three pulses of itraconazole. The primary efficacy criterion was the result of mycological examination at 3 months. The secondary criterion was the combined mycological and clinical response at 9 months. A pharmacoeconomic analysis was also performed to compare the cost-effectiveness of combined therapy vs. monotherapy. Eighty-five patients were analysed (73 women and 12 men, mean +/- SD age 44.2 +/- 12.9 years). Patients had a mean +/- SD of 3.64 +/- 2.0 nails involved and 228.6 +/- 148.0 mm2 of their nail surface diseased. The mean duration of onychomycosis was 11 months. Paronychial involvement was evident in 71 patients. C. albicans was isolated in 85 cases, C. parapsilosis in three and other Candida species in two cases. Side-effects were uncommon and in only one case led to withdrawal. At the 3-month visit, mycological cure was seen in 32 (74%) of 43 patients in group 1 and in 25 (60%) of 42 patients in group 2. At the 9-month visit, a global cure was seen in 40 patients (93%) in group 1 and in 34 patients (81%) in group 2. Statistical analysis showed no statistically significant difference (P > 0.1) between the two treatment groups. The cost per cure ratio was 1.63 and 1.70euro for groups 1 and 2, respectively. The combination of amorolfine and oral itraconazole, which interfere with different steps of ergosterol synthesis, exhibited substantial synergy. Compared with oral itraconazole alone, the combination achieved greater mycological cure and increased total cure rate. However, no statistically significant difference was documented for this number of observations. Combination treatment with amorolfine and two pulses of itraconazole is at least as safe and effective as three pulses of itraconazole, with a lower cost per patient. In our opinion, the addition of amorolfine to oral itraconazole pulse therapy is of value in the treatment of moderate to severe Candida fingernail onychomycosis.


[Clinical and hemodynamic characteristics of ischemic heart disease in patients with deficient body mass].
To elucidate clinical and hemodynamic characteristics of patients with ischemic heart disease and low body mass. Patients with stable angina (n=162) divided into 3 groups according to body mass index (below 25, 25-27 kg/m2 and above 27 kg/m2). Patients with low body mass index compared with those with intermediate values had worse clinical (arrhythmias, derangements of conduction, recurrent myocardial infarctions, cases with heart failure), hemodynamic (lower stroke volume and cardiac index, higher total peripheral resistance), and cardiometric (lower ejection fraction, larger diastolic volumes, greater relative myocardial mass) characteristics. These findings constitute a pathophysiological substrate for increased risk of death in patients with ischemic heart disease and deficient body mass.


Retrievable inferior vena cava filters in patients with cancer are safe but are they beneficial?
The availability and insertion of permanent and retrievable inferior vena cava filter devices have increased substantially over the past decade. Our retrospective study provides the first detailed assessment of the safety and efficacy of retrievable inferior vena cava filters in a large cohort of cancer patients with predominantly advanced malignancies. We retrospectively reviewed the medical records of consecutive patients with the diagnosis of cancer who underwent inferior vena cava filter placement at a single academic medical center from 2007 to 2012 with special attention to safety, recurrent venous thromboembolism, and survival data. Three hundred thirty-seven cancer patients were included in the analysis. Gastrointestinal, lung, and genitourinary malignancies were the most commonly represented malignancies [94 (27.8 %), 70 (20.8 %), and 37 (10.9 %) patients, respectively]. Immediate complications were diagnosed in one of 258 (1 %) evaluable patients following placement of a retrievable filter. Delayed complications occurred in 23 of 258 (8 %) patients. The 7, 14, 30, 90, and 365 day post-filter survival rates for patients with stage IV cancer were 0.91, 0.86, 0.71, 0.52, and 0.29, respectively. Patients with lung and gastrointestinal tumors demonstrated a significantly reduced post-filter survival rate compared with those with genitourinary, brain, and breast cancers. Retrievable and non-retrievable inferior vena cava filters are associated with an overall low rate of complications in patients with cancer. However, survival rates following filter placement are poor in this patient population.


Tyr2105Cys mutation in exon 22 of FVIII gene is a risk factor for the development of inhibitors in patients with mild/moderate haemophilia A.
We report the case of a patient with mild haemophilia A, due to a Tyr2105Cys mutation in exon 22 of the C1 domain, who developed a high-titre factor VIII inhibitor (maximum titre 1600 BU) with recurrent severe haemorrhages and fatal intracranial bleeding. Based on published data, it appears that although this mutation occurs rarely in patients with mild or moderate haemophilia A, it is frequently associated with the development of high-titre inhibitors.


Classico-molecular targeting of oligopeptidase B, cysteine protease and variable surface glycoprotein (VSG) genes of Trypanosoma evansi.
Trypanosomosis or Surra can rightly be attributed as the most economically important vector-borne haemoprotozoan disease encountering India. Surra infected chronic cases show almost similar types of signs and symptoms often confusing it with other haemoprotozoan infections, thereby, making it prerequisite for the development of aspecific and sensitive technique for its detection in susceptible animals. Blood microscopy and serology suffers from the hands of lack of sensitivity and specificity thereby leaving molecular detection techniques as one of the promising alternative. Alongside, there is utmost need for exploring of new molecular gene targets for the development of a putative alternative for diagnosis and immunoprophylaxsis. The present communication describes the identification and amplification of oligopeptidase B, cysteine protease and variable surface glycoprotein genes of T. evansi so as to exploit them in future as potential candidates for immune protection and/or molecular detection.


Degradation of biochemical activity in soil sterilized by dry heat and gamma radiation.
The activities of three enzymes present in soil, phosphatases, urease, and decarboxylase, were monitered as indicators of the loss of biochemical information occurring when soil was sterilized by dry heat (0.08% relative humidity), gamma radiation, or a combination of both. More enzymatic activity was retained in soil sterilized by a long exposure to dry heat at relatively low temperature (8 weeks at 100.5 degrees C) than by a shorter exposure to a higher temperature (2 weeks at 124.5 degrees C). No enzymatic activity was detectable in soil sterilized by an even higher temperature (4 days at 148.5 degrees C). Soil sterilized with 7.5 Mrads of radiation retained much higher enzymatic activity than with heat sterilization. Combining sublethal doses of heat radiation effectively sterilized the soil and yielded enzymatic activities higher than those of soil sterilized by dry heat alone but lower than those of soil sterilized by radiation.


Precision and accuracy of stereotactic convergent beam irradiations from a linear accelerator.
The accuracy and the precision for radiosurgery procedures at linear accelerator facilities were investigated. The technique of convergent beam irradiation, that is a series of successive isocentric arc irradiations, is specifically considered in this paper. Accuracy and precision depend on a sequence of methods and equipment among which localization of the target, patient alignment, and the dose delivery are the most critical steps. The purpose of the investigation was to quantitatively assess their contribution to the overall accuracy. The definitions and methods used to quantify and control accuracy are described. Measurements were carried out at a phantom to analyze the localization and positioning errors. Errors which may occur with the dose delivery technique were studied by a computer simulation. The calculations showed that these errors are not the main contributors to the overall accuracy as long as the linac inaccuracies are in the order or less than 1 mm. The accuracy found in the localization and positioning methods was less than 1 mm. It was concluded that an overall accuracy in the order of 1 mm can be obtained also under routine conditions. The great importance of adequate quality control is emphasized.


Synthesis and antibacterial activity of new 2-substituted penems. I.
A new type of penem derivative (3-6) having a cyclic amidine moiety or a quaternary heterocycle moiety at the C-2 position was prepared. The susceptibility to renal dehydropeptidase-1 (DHP-1) and the antimicrobial activity of these compounds were determined. Some of these compounds (5,6) showed a broad spectrum of antibacterial activity, including activity against Pseudomonas aeruginosa.


Virtual reality for pain reduction during intravenous injection in pediatrics: a systematic review and meta-analysis of controlled clinical trials.
Intravenous (IV) injections often cause pain, fear, and anxiety in pediatric patients. Virtual reality (VR) is a relatively new intervention that can be used to provide a distraction during or prepare patients for IV injections. To date, no meta-analysis has examined the evidence regarding the effectiveness of VR at reducing pain in pediatric IV injections. The PubMed, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials databases were searched for articles published through August 7, 2022. The methodological quality of the studies was measured using the Delphi checklist. The chi-square test and the I2 statistic were used to assess heterogeneity across studies. A summary measure of the mean difference in pain scores between the VR and control groups was obtained using a random effects model. All statistical analyses were set at a significance level of 0.05 using Stata 14. Nine studies were included in this meta-analysis of VR interventions used during IV injections in pediatric patients. The difference in mean pain score between the intervention and control groups showed significant reductions in the VR group (mean difference, 0.47; 95% confidence interval, 0.3-0.65; I2=9.1%). No interstudy heterogeneity was observed. Our results suggest that VR effectively reduces pain associated with IV injections in pediatric patients. No interstudy heterogeneity was noted among the analyzed studies. The Delphi checklist was used to assess methodological quality.


The extent of the stimulated electrical potential decay under phosphorylating conditions and the H+/ATP ratio in Rhodopseudomonas sphaeroides chromatophores following short flash excitation.
1. In chromatophores from Rps. sphaeroides, the stimulation by ADP and Pi of the electric potential decay indicated by the carotenoid shift is greater than the stimulation of the decay of pH change indicated by the colour change of added cresol red under similar conditions. This difference is attributed to H+ consumption during the synthesis of ATP. The ratio of H+ translocated across the membrane to ATP synthesized was estimated to be approximately 1.7 H+/ATP. 2. The stimulation of the electrical potential decay by ADP and Pi was found to be a constant fraction (10%) of the total decay when the flash intensity was varied. No 'critical' or 'threshold' potential was observed. 3. The stimulated electrical potential decay after a second flash, given within a few seconds of the first, was related to the amplitude of the electrical potential produced by the second flash (10%) but neither to the dark time between the flashes, nor to the total extent of the electrical potential above the dark level. These results are consistent with two hypotheses (a) the chromatophores are a mixed population of vesicles, only a small fraction (10%) of which possess an active ATP synthesizing system (b) the activity of the ATP synthesizing system, though driven by a proton motive force, is controlled by electron transport processess. If alternative (a) is correct then the overall single turnover flash yield of 1 ATP per 1470 bacteriochlorophyll measured in (1) would mean that the yield of the active vesicles is approximately 10 ATP per 1470 bacteriochlorophyll or 30 ATP per vesicle. 4. The stimulation of the electrical potential decay by ADP and Pi is approximately 40% less in antimycin-treated chromatophores. It is shown that this is probably a consequence of antimycin-inhibited H+-release on the inside of the chromatophore vesicles following a flash.


Acute Pancreatitis: A Rare Complication After Percutaneous Mechanical Thrombectomy of Portal Vein Thrombosis.
Acute pancreatitis caused by Percutaneous Mechanical Thrombectomy treatment is extremely rare, and so far, no clinical report involving portal veins has been reported. In the article, we summarize this unusual case and share our experience. Percutaneous mechanical thrombectomy was performed for the patient who was diagnosed with portal vein thrombosis. Postoperatively, the patient was complicated by acute pancreatitis and received a series of medical treatments. During the first month of follow-up, the patient was free of any clinical symptoms or signs. When performing percutaneous mechanical thrombectomy therapy, it is crucial to grasp the time limit strictly, strengthen perioperative rehydration and urine alkalinization to prevent massive hemolysis and subsequent complications. Early detection and the early administration of therapy for this potentially severe complication are essential for obtaining a good prognosis.


DNA ligase I is not essential for mammalian cell viability.
Of the three DNA ligases present in all vertebrates, DNA ligase I (Lig1) has been considered essential for ligating Okazaki fragments during DNA replication and thereby essential for cell viability. Here, we report the striking finding that a Lig1-null murine B cell line is viable. Surprisingly, the Lig1-null cells exhibit normal proliferation and normal immunoglobulin heavy chain class switch recombination and are not hypersensitive to a wide variety of DNA damaging agents. These findings demonstrate that Lig1 is not absolutely required for cellular DNA replication and repair and that either Lig3 or Lig4 can substitute for the role of Lig1 in joining Okazaki fragments. The establishment of a Lig1-null cell line will greatly facilitate the characterization of DNA ligase function in mammalian cells, but the finding alone profoundly reprioritizes the role of ligase I in DNA replication, repair, and recombination.


[Spontaneous pneumomediastinum as a cause of chest pain].
Two patients, both 16 years old, presented because of chest pain after extended sports activity. The thoracal X-ray showed trapped air in the mediastinum especially around the cervical vessels in one patient. In the thoracal X-ray of the other patient a vertical lucent streak along the left side of the heart, showing the pleura as a fine opaque line, was found. Both developed subcutaneous emphysema after a few hours, which led to the diagnosis spontaneous pneumomediastinum. The chest pain resolved under analgetic medication, and after resorption of the subcutaneous emphysema both patients recovered completely. The main differential diagnosis of the spontaneous pneumomediastinum is besides pericarditis and myocarditis, the spontaneous esophageal perforation (also called Boerhaave syndrome), with the high morbidity, it has to be ruled out consequently.


Wounds inflicted by survival-knives.
A homicidal fatality is presented to demonstrate that the pattern of injuries may suggest the use of an unusual sharp force, a survival-knife, the characteristics of which are in any case well defined. This knife has saw teeth along the back that can leave characteristic scrape marks on the skin.


Nitrification and denitrification processes for biologic treatment of industrial effluents.
Nitrification process performance was evaluated using a three-phase fluidized-bed bioreactor. A synthetic effluent was used for this experiment containing 180-230 mg/L of chemical oxygen demand (COD), 25-30 mg/L of N-NH4+, 12 to 13 mg/L of total phosphorous, and micronutrients. The bioreactor used for denitrification behaved as completely mixed. The results indicate that the nitrification process was efficient, reaching efficiencies of about 98%. The best results related to the efficiency of the denitrification process were obtained when the processes were supplemented with the carbon source. The results indicated an efficiency of 86-98% COD removal.


Profiling of differential gene expression in the hypothalamus of broiler-type Taiwan country chickens in response to acute heat stress.
Acute heat stress severely impacts poultry production. The hypothalamus acts as a crucial center to regulate body temperature, detect temperature changes, and modulate the autonomic nervous system and endocrine loop for heat retention and dissipation. The purpose of this study was to investigate global gene expression in the hypothalamus of broiler-type B strain Taiwan country chickens after acute heat stress. Twelve 30-week-old hens were allocated to four groups. Three heat-stressed groups were subjected to acute heat stress at 38 °C for 2 hours without recovery (H2R0), with 2 hours of recovery (H2R2), and with 6 hours of recovery (H2R6). The control hens were maintained at 25 °C. At the end, hypothalamus samples were collected for gene expression analysis. The results showed that 24, 11, and 25 genes were upregulated and 41, 15, and 42 genes were downregulated in H2R0, H2R2, and H2R6 treatments, respectively. The expressions of gonadotropin-releasing hormone 1 (GNRH1), heat shock 27-kDa protein 1 (HSPB1), neuropeptide Y (NPY), and heat shock protein 25 (HSP25) were upregulated at all recovery times after heat exposure. Conversely, the expression of TPH2 was downregulated at all recovery times. A gene ontology analysis showed that most of the differentially expressed genes were involved in biological processes including cellular processes, metabolic processes, localization, multicellular organismal processes, developmental processes, and biological regulation. A functional annotation analysis showed that the differentially expressed genes were related to the gene networks of responses to stress and reproductive functions. These differentially expressed genes might be essential and unique key factors in the heat stress response of the hypothalamus in chickens.


Drooling disrupts the brain functional connectivity network in Parkinson's disease.
This study aimed to investigate the causal interaction between significant sensorimotor network (SMN) regions and other brain regions in Parkinson's disease patients with drooling (droolers). Twenty-one droolers, 22 PD patients without drooling (non-droolers), and 22 matched healthy controls underwent 3T-MRI resting-state scans. We performed independent component analysis and Granger causality analysis to determine whether significant SMN regions help predict other brain areas. Pearson's correlation was computed between imaging characteristics and clinical characteristics. ROC curves were plotted to assess the diagnostic performance of effective connectivity (EC). Compared with non-droolers and healthy controls, droolers showed abnormal EC of the right caudate nucleus (CAU.R) and right postcentral gyrus to extensive brain regions. In droolers, increased EC from the CAU.R to the right middle temporal gyrus was positively correlated with MDS-UPDRS, MDS-UPDRS II, NMSS, and HAMD scores; increased EC from the right inferior parietal lobe to CAU.R was positively correlated with MDS-UPDRS score. ROC curve analysis showed that these abnormal ECs are of great significance in diagnosing drooling in PD. This study identified that PD patients with drooling have abnormal EC in the cortico-limbic-striatal-cerebellar and cortio-cortical networks, which could be potential biomarkers for drooling in PD.


Differentiating the associations between alcohol use, cigarette smoking, and conditional suicidal behaviors among adolescents.
Both alcohol use and cigarette smoking have been identified as risk factors for suicidal behaviors. However, suicide is a process from ideation to action, and some evidence have implied us that alcohol use and cigarette smoking may play different roles in the different process of suicidal behaviors. Data was derived from the 2019 Youth Risk Behavior Survey (YRBS), and a total of 12, 487 valid samples were analyzed in the study. To distinguish the different situation of suicidal behaviors, participants were divided into general people without any suicidal behavior (GNS), suicidal ideators without plan or attempt (SINPA), suicide planners without attempt (SPNA), and suicide attempters (SA).1 RESULTS: The prevalence of suicidal ideation, plan, and attempt were 19.4 %, 15.9 %, and 7.7 %, respectively. Comparing to GNS, alcohol use and cigarette smoking were associated with SINPA (OR = 1.27, P < 0.05; OR = 1.47, P < 0.001), SPNA (OR = 1.29, P < 0.01; OR = 1.26, P < 0.01), and SA (OR = 1.31, P < 0.01; OR = 2.11, P < 0.001). However, alcohol use was not associated with SA comparing to SINPA (OR = 1.05, P > 0.05) and SPNA (OR = 1.03, P > 0.05), while cigarette smoking was associated with SA (OR = 1.40, P < 0.01; OR = 1.74, P < 0.001). Firstly, using the secondary data was possibly limited. Next, this was a cross-sectional study, the casual relationship was unsure. Lastly, the amount of alcohol consumption and cigarette smoking status were not considered. Both alcohol use and cigarette smoking are risk factors for any suicidal behaviors. However, controlling alcohol use may be a limited method to prevent the further suicidal behaviors for ideators and planners. Managing cigarette smoking should be considered.


Long-term physical and mental health outcomes of pediatric firearm-injured victims: A prospective cohort study.
Firearms are a leading cause of injury among US youth. There is little research describing outcomes after pediatric firearm injuries, particularly past 1 year. This study aimed to assess long-term physical and mental health outcomes among nonfatal firearm versus motor vehicle collision (MVC)-injured victims and versus a standard population. We retrospectively identified firearm and MVC-injured pediatric patients seen at one of our four trauma centers (January 2008 to October 2020) and prospectively assessed outcomes using validated patient-reported outcome measures. Eligible patients were English speaking, injured ≥5 months before study start, younger than 18 years at time of injury, and 8 years or older at study start. All firearm patients were included; MVC patients were matched 1:1 with firearm patients for Injury Severity Score (dichotomized <15 or ≥15), age range (±1 year), and year of injury. We conducted structured interviews of patients and parents using validated tools (Patient-Reported Outcomes Measurement Information System tools, Children's Impact of Event Scale for younger than 18 years and parent proxies). Patient-Reported Outcomes Measurement Information System scores are reported on a T score metric (mean [SD], 50 [10]); higher scores indicate more of the measured domain. We used paired t tests, Wilcoxon signed-rank tests, and McNemar's test to compare demographics, clinical characteristics, and outcomes. There were 24 participants in each of the MVC and firearm-injured groups. Compared with MVC-injured patients, firearm-injured patients younger than 18 years had similar scores, and firearm-injured patients 18 years or older had higher anxiety scores (59.4 [8.3] vs. 51.2 [9.4]). Compared with a standard population, patients younger than 18 years had worse global health scores (mean [SD], 43.4 [9.7]), and participants 18 years or older reported increased fatigue (mean [SD], 61.1 [3.3]) and anxiety (mean [SD], 59.4 [8.3]). Long-term effects of firearm-injured patients were poorer than matched MVC and the standard population in few domains. Further study in a larger, prospectively recruited cohort is warranted to better characterize physical and mental health outcomes.


Erratum: A total EQD2 greater than 85 Gy for trachea and main bronchus D2cc being associated with severe late complications after definitive endobronchial brachytherapy.
[This corrects the article DOI: 10.5114/jcb.2015.54968.].


Induced membrane technique using an equal portion of autologous cancellous bone and β-tricalcium phosphate provided a successful outcome for osteomyelitis in large part of the femoral diaphysis - Case report.
No report has yet described good prognosis following the induced membrane technique (IMT) for bone defects over 200 mm. A 46-year-old male developed osteomyelitis over a large portion of the right femoral diaphysis, which had an unknown infection route, and subtrochanteric fracture during the waiting period of the planed IMT. Around 3 days after the pathological fracture, the first stage was performed. Aggressive debridement resulted in large segmental bone defect, which was treated with internal fixation using intramedullary nailing and insertion of an antibiotic-impregnated polymethylmethacrylate (PMMA) spacer. Postoperative radiographs showed a radiographic apparent bone gap of 221 mm. A subsequent culture of the debrided bone test identified Corynebacterium as the causative organism, with blood examination indicating normal C-reactive protein, white blood cell count, and erythrocyte sedimentation rate following 4 weeks of intravenous antibiotic administration. Around 7 weeks after the first stage, the second stage was initiated. After removing the PMMA spacer, grafting was performed by filling the bone defect with a combination of autologous cancellous bone harvested from the posterior iliac crest and β-tricalcium phosphate (β-TCP), which were mixed in approximately equal proportions. Routine postoperative radiographs confirmed a sequential healing process and callus formation in three out of four cortices 3 years after surgery. In the present case, IMT was able to successfully treat the osteomyelitis-induced large segmental bone defect of the femoral shaft exceeding 200 mm. Had autologous cancellous bone alone been applied during the second stage, the possible amount of bone defect covered by the IMT would have been limited. However, this limitation can be addressed by applying β-TCP. Further expansion of IMT indications may help address challenges in the treatment of extensive bone defects.


Factors influencing transfusion requirement in patients undergoing first-time, elective coronary artery bypass graft surgery.
Coronary artery bypass graft (CABG) operation is associated with high frequency of allogeneic blood transfusion due to the acquired hemostatic challenges in patients undergoing CABG. However, allogeneic blood transfusion carries risks of infection, adverse reaction, and mortality as well as prolonged hospital stay and increased hospital cost. It is important to identify patients who require blood transfusion to mitigate their risk factors and reduce the chance of exposure to allogeneic blood. This study was conducted to evaluate factors that influence the decision to transfuse red cell in first-time elective CABG patients. This was a cross-sectional study based on a retrospective record review. The study was done in the National Heart Institute. All patients who underwent first-time elective CABG were included in this study. Variables analyzed include age, gender, body weight, preoperative hemoglobin (Hb) level, patients' comorbidities, and other clinical parameters. Data were analyzed using SPSS software version 20. A total of 463 patients underwent first-time elective CABG during the period of the study. Three hundred and eighty-six (83.4%) patients received red cell transfusion. From multiple logistic regression analysis, only age (odds ratio [OR] = 1.040, 95% confidence interval [CI]: 1.003, 1.077, P = 0.032), body weight (OR = 0.951, 95% CI: 0.928, 0.974, P < 0.001), Hb level (OR = 0.500, 95% CI: 0.387, 0.644, P < 0.001), and cardiopulmonary bypass time (OR = 1.013, 95% CI: 1.004, 1.023, P < 0.001) were the significant independent predictors of red cell transfusion. By stratifying patients according to their risk factor for red cell transfusion, the high-risk patients could be recognized and should be enrolled into effective patient blood management program to minimize their risk of exposure to allogeneic blood transfusion.


Noninvasive localization of urinary tract infection: clinical investigations and experience.
Previously we evaluated new methods to localize the source of bacteriuria in monkeys with experimental urinary tract infection. A high level of diagnostic accuracy was obtained with studies of antibody coating of urinary bacteria by immunofluorescence, 131iodine hippuran quantitative scintillation camera studies with the patient in the hydropenic state and 67gallium citrate scintiphotos. We identified unique patterns that differentiated cystitis, ureteritis, pyelonephritis and renal or perinephric abscess. Herein we review our clinical experience with these combined techniques in 40 patients and correlate the degree of accuracy of these studies with that of standard radiographic examinations. In 20 patients diagnostic studies also were compared to the findings of split ureteral urine cultures or bacteriologic culture of renal tissue obtained from surgical specimens or autopsy. The use of the quantitative scintillation camera studies done with the patient in a state of controlled hydropenia increased clearly the level of diagnostic sensitivity in demonstrating the source of a urinary tract infection compared to urine culture and excretory urography alone. In patients with an abnormal 131iodine hippuran study the performance of 67gallium renal imaging on the same day usually provided information that allowed specific localization of the source and extent of an infection. Both studies must be performed with a high degree of resolution over the renal areas and then must be interpreted carefully to ensure accuracy. Study of antibody coating of urinary bacteria was helpful in suggesting the presence or absence of upper urinary tract disease but was less sensitive and accurate than the combined radionuclide studies.


Clinical characteristics and outcome of morbidly obese bariatric patients with concurrent hepatitis B viral infection.
Bariatric surgery is the only effective and long-lasting treatment of morbidly obese patients. However, the safety and efficacy of bariatric surgery in patients with hepatitis B viral (HBV) infection is not clear. The aim of the present study is to investigate whether HBV infection influences clinic features and outcomes of bariatric surgery. The preoperative seropositivity of HBV surface antigen (HBsAg) using radioimmunoassay was determined in 592 patients (481 female, 111 male: mean age 30.5 +/- 8.1 years; mean body mass index [BMI] 43.1 +/- 6.0) who had undergone bariatric surgery (209 banding and 383 gastric bypass) for their morbid obesity in the past 5 years. All the clinical data were prospectively collected and stored. The overall seroprevalence of HbsAg was 18.8%. Morbidly obese patients positive for HBV infection were associated with older age and higher diastolic blood pressure, but not with sex, BMI, liver enzyme, blood lipid, and glucose levels. Although minigastric bypass (MGB) had a better weight reduction than gastric banding, there was no difference in weight reduction between patients who were positive and negative for HBV infection. The weight loss curves and resolution of obesity-related comorbidities were similar between the two groups except the postoperative aspartate transaminase (AST) and alanine transaminase (ALT) were significantly higher in patients who were positive for HBV infection. During follow-up, two patients developed fulminating hepatitis after MGB with one mortality. Morbidly obese patients with the existence of HBV infection do not influence the outcome of bariatric surgery, but continuing monitor of the liver function is indicated.


Bats (Mammalia: Chiroptera) in urban-rural interfaces: community structure associated with pathogen screening in São Paulo-the largest metropolitan region in Brazil.
Little is known about the influence of the urban environments on bat species 'ecology. The urbanization process potentially lead to critical ecological changes in bat communities' intra and interspecific pathogenic transmissions dynamics. To date, the monitoring of pathogens in bats in Brazil has only been done with bats found dead or alive in households, from rabies surveillance systems. The present work aimed to investigate how urbanization influenced bat richness, relative abundance and pathogen occurrence. Most captured bats were Phyllostomidae, especially Sturnira lilium, Artibeus lituratus, A. fimbriatus, Glossophaga soricina, and Platyrrhinus lineatus, among others. From preserved-rural towards urban areas the lesser the bat richness, the higher the relative abundance of the captured bats. Noise level, luminosity and relative humidity correlated with bat abundance. The proportion of genders, sexually active bats and their size (weight, right forearm length, and body condition index) were stable throughout the investigation. Still, the proportion of pregnant females was higher in Spring and the number of juveniles in Summer, evidencing the seasonality of reproduction. Several Enterobacteria were isolated, evidencing a significant role of bats in the circulation of pathogens of medical and veterinary interest. These results are crucial in the pursuit of a harmonious coexistence between humans, bats and domestic animals in areas with different levels of anthropization.


Fuzzy modeling and parameters optimization for the enhancement of biodiesel production from waste frying oil over montmorillonite clay K-30.
Transesterification is a promising technology for the biodiesel production to provide an alternative fuel that considers the environmental concerns. From the economic and environmental protection points of view, utilization of waste frying oil for the production of biodiesel addresses very beneficial impacts. Production of higher yield of biodiesel is a challenging process in order to commercialize it with a lower cost. The current study focuses on the influence of different parameters such as reaction temperature (°C), reaction period (min), oil to methanol ratio and amount of catalyst (wt%) on the production of biodiesel. The main objective of this work is to develop a model via fuzzy logic approach in order to maximize the biodiesel produced from waste frying oil using montmorillonite Clay K-30 as a catalyst. The optimization for the operating parameters has been performed via particle swarm optimization (PSO) approach. During the optimization process, the decision variables were represented by four different operating parameters: temperature (40-140 °C), reaction period (60-300 min), oil/methanol ratio (1:6-1:18) and amount of catalyst (1-5 wt%). The model has been validated with the experimental data and compared with the optimal results reported based on other optimization techniques. Results showed the increment of biodiesel production by 15% using the proposed strategy compared to the earlier study. The obtained biodiesel production yield reached 93.70% with the optimal parameters for a temperature at 69.66 °C, a reaction period of 300 min, oil/methanol ratio of 1:9 and an amount of catalyst of 5 wt%.


Systems biology informed deep learning for inferring parameters and hidden dynamics.
Mathematical models of biological reactions at the system-level lead to a set of ordinary differential equations with many unknown parameters that need to be inferred using relatively few experimental measurements. Having a reliable and robust algorithm for parameter inference and prediction of the hidden dynamics has been one of the core subjects in systems biology, and is the focus of this study. We have developed a new systems-biology-informed deep learning algorithm that incorporates the system of ordinary differential equations into the neural networks. Enforcing these equations effectively adds constraints to the optimization procedure that manifests itself as an imposed structure on the observational data. Using few scattered and noisy measurements, we are able to infer the dynamics of unobserved species, external forcing, and the unknown model parameters. We have successfully tested the algorithm for three different benchmark problems.


Co-contraction recruitment and spinal load during isometric trunk flexion and extension.
Pushing and pulling tasks account for 20% of occupational low-back injury claims. Primary torso muscle groups recruited during pushing tasks include rectus abdominis and the external obliques. However, analyses suggest that antagonistic co-contraction of the paraspinal muscles is necessary to stabilize the spine during flexion exertions. The study quantified co-contraction and spinal load differences during isometric flexion and extension exertions. The goal was to provide insight into the mechanisms requiring greater co-contraction during trunk flexion exertions compared to extension exertions. Electromyographic (EMG) signals were recorded from the trunk muscles of healthy volunteers during isometric trunk flexion and extension exertions. A biomechanical model was implemented to estimate total muscle force from the measured EMG and trunk moment data. A similar model estimated the muscle forces necessary to achieve equilibrium while minimizing the sum of squared muscle forces. The difference in these forces represented co-contraction. Spinal load attributed to co-contraction was computed. Average co-contraction during flexion exertions was approximately twice the value of co-contraction during extension, i.e. 28% and 13% of total muscle forces respectively. Co-contraction accounted for up to 47% of the total spinal load during flexion exertions. Consequently, spinal compression during the flexion tasks was nearly 50% greater than during extension exertions despite similar levels of trunk moment. Co-contraction must be considered when evaluating spinal load during pushing exertions. Results underscore the need to consider neuromuscular control of spinal stability when evaluating the biomechanical risks.


Loss of tumor suppressor Merlin in advanced breast cancer is due to post-translational regulation.
Unlike malignancies of the nervous system, there have been no mutations identified in Merlin in breast cancer. As such, the role of the tumor suppressor, Merlin, has not been investigated in breast cancer. We assessed Merlin expression in breast cancer tissues by immunohistochemistry and by real-time PCR. The expression of Merlin protein (assessed immunohistochemically) was significantly decreased in breast cancer tissues (although the transcript levels were comparable) simultaneous with increased expression of the tumor-promoting protein, osteopontin (OPN). We further demonstrate that the loss of Merlin in breast cancer is brought about, in part, due to OPN-initiated Akt-mediated phosphorylation of Merlin leading to its proteasomal degradation. Restoring expression of Merlin resulted in reduced malignant attributes of breast cancer, characterized by reduced invasion, migration, motility, and impeded tumor (xenograft) growth in immunocompromised mice. The possibility of developing a model using the relationship between OPN and Merlin was tested with a logistic regression model applied to immunohistochemistry data. This identified consistent loss of immunohistochemical expression of Merlin in breast tumor tissues. Thus, we demonstrate for the first time a role for Merlin in impeding breast malignancy, identify a novel mechanism for the loss of Merlin protein in breast cancer, and have developed a discriminatory model using Merlin and OPN expression in breast tumor tissues.


The structural relation between intermediate filament proteins in living cells and the alpha-keratins of sheep wool.
Although not complete, the available sequence data on smooth muscle desmin, a prototype of 10 nm filaments present in living vertebrate cells, and two wool alpha-keratin components indicate a common structural motif . A similarly sized rod-like middle domain based mainly on alpha-helices probably able to form coiled-coils is flanked by differently sized terminal domains of non-alpha-helical nature. Within the middle domain there seem to be at least two regions where wool keratins and 10 nm filament proteins show a noticeable degree of sequence homology. In general, however, the proteins have diverged to an astonishing degree. Although the analysis seems to support, in general terms, a separation of the rod into two nearly equally long coiled-coils it raises doubts about additional aspects of current models of 10 nm filament organization. We propose that the terminal domains are directly involved in filament assembly making this process permanent in wool alpha-keratins because of the many disulfide bonds present in these regions. The 10 nm filaments of most living cells seem to avoid this frozen state and lack a similar wealth of cysteine residues.


Anti-obesity effects of yuja (Citrus junos Sieb ex Tanaka) pomace extract fermented with lactic acid bacteria on the hepatocytes and epididymal fat tissue of rats.
This study investigated the anti-obesity effects of yuja pomace extract fermented with lactic acid bacteria in rats with high-fat diet-induced obesity over a period of eight weeks. Epididymal fat cell size was significantly smaller, by about 33%, in the treatment groups given yuja pomace extract fermented with lactic acid bacteria compared to the CON group. Electron microscopic observation of hepatocyte microstructure showed that the number of lipid droplets was lower in hepatocytes, the number of mitochondria was higher, along with distinct cristae, and the rough endoplasmic reticula were well developed with stacks of cisternae and ribosomes. Thus, it is believed that yuja pomace extract fermented with lactic acid bacteria, by influencing body weight and lipid accumulation, is effective in the prevention and treatment of obesity.


A descriptive study of early nonspecific chest pain after PTCA: important area for the acute health care personnel.
Many patients report chest pain of varying intensity at various locations during the first hours after percutaneous transluminal coronary angioplasty (PTCA). The aim of the study was to increase knowledge regarding differentiating between harmless chest pain versus ischemic chest pain, focusing on patients description of their pain. A total of 192 patients after elective PTCA were interviewed twice. In addition patients experiencing chest pain within 6 hours after the procedure completed the McGill Pain Questionnaire (MPQ). Nonspecific chest pain occurred in 34 patients (18%) and ischemic chest pain in 6 (3%), whereas 152 (79%) did not report early chest pain after PTCA. The nonspecific pain group reported statistically significant less pain intensity (VAS P =.001), used fewer (P =.006) and qualitatively weaker (P =.008) words compared to the ischemic pain group. No predisposing factors that could predict chest pain were identified. Discriminators appear to be the pain intensity and the word descriptors. MPQ combined with a VAS could be valuable clinical tools with regard to patients' description of pain.


Effect of Lysinibacillus isolated from environment on probiotic properties and gut microbiota in mice.
Soil microorganisms (SM) are primarily involved in organism degradation, plant nitrogen nutrient immobilization, host microorganisms and oxidation. However, research on the effect of soil-derived Lysinibacillus on the intestinal microbiota spatial disparity of mice is lacking. To test the probiotic properties of Lysinibacillus and the spatial disparity on mice intestinal microorganisms, hemolysis test, molecular phylogenetic analysis, antibiotic sensitivity testing, serum biochemical assays and 16S rRNA profiling were applied. The results showed that Lysinibacillus (LZS1 and LZS2) was resistant to two common antibiotics, Tetracyclines and Rifampin, and sensitive to other antibiotics among the 12 antibiotics tested and negative for hemolysis. In addition, the body weight of group L (treatment of Lysinibacillus, 1.0 × 108 CFU/d for 21days) mice was significantly greater than that of the control group; serum biochemical tests showed that the TG and UREA were significantly lower in group L. The spatial disparity of intestinal microorganisms in mice was significant, treatment of Lysinibacillus (1.0 × 108 CFU/d for 21days) reduced the intestinal microbial diversity and decreased the richness of Proteobacteria, Cyanobacteria and Bacteroidetes in mice. Furthermore, Lysinibacillus treatment enhanced Lactobacillus and Lachnospiraceae richness and significantly reduced 6 bacterial genera in jejunum community, reduced 8 bacterial genera, but increased bacteria at the 4 genera level in cecum microorganisms. In conclusion, this study demonstrated spatial disparity of intestinal microorganisms in mice and probiotic potential of Lysinibacillus isolated from soil.


Robotic-arm assisted medial unicondylar knee arthroplasty versus jig-based unicompartmental knee arthroplasty with navigation control: study protocol for a prospective randomised controlled trial.
There remains a paucity of clinical studies assessing how any differences in accuracy of implant positioning between robotic-arm assisted unicompartmental knee arthroplasty (RO UKA) and conventional jig-based unicompartmental knee arthroplasty (CO UKA) translate to patient satisfaction, functional outcomes, and implant survivorship. The objectives of this study are to compare accuracy of implant positioning, limb alignment, patient satisfaction, functional outcomes, implant survivorship, cost-effectiveness, and complications in CO UKA versus RO UKA. Computer navigation will be used to assess intraoperative knee kinematics in all patients undergoing CO UKA. This prospective randomised controlled trial will include 140 patients with symptomatic medial compartment knee arthritis undergoing primary UKA. Following informed consent, patients will be randomised to CO UKA (control group) or RO UKA (investigation group) at a ratio of 1:1 using an online random number generator. The primary objective of this study is to compare accuracy of implant positioning in CO UKA versus RO UKA. The secondary objectives are to compare the following outcomes between the two treatment groups: limb alignment, surgical efficiency, postoperative functional rehabilitation, functional outcomes, quality of life, range of motion, resource use, cost effectivness, and complications. Observers will review patients at regular intervals for 2 years after surgery to record predefined study outcomes pertaining to these objectives. Ethical approval was obtained from the London-Bloomsbury Research Ethics Committee, UK. The study is sponsored by University College London, UK. This study compares a comprehensive and robust range of clinical, functional, and radiological outcomes in CO UKA versus RO UKA. The findings of this study will provide an improved understanding of the differences in CO UKA versus RO UKA with respect to accuracy of implant positioning, patient satisfaction, functional outcomes, implant survivorship, cost-effectiveness, and complications. ClinicalTrials.gov NCT04095637 . Registered on 19 September 2019.


Overlapping Urological Surgeries at a Tertiary Academic Center.
To evaluate whether the practice of procedure-time overlapping surgery (OS) is associated with inferior outcomes compared to nonoverlapping surgery (NOS) in urology, to address the paucity of data surrounding urologic surgeries to support or refute this practice. We performed a retrospective review of all urological surgeries at a single tertiary-level academic center, Emory University Hospital, from July 2016 to July 2018. Patients who received OS were matched 1:2 to patients who had NOS. The primary outcomes were perioperative and postoperative complications and mortality. We reviewed 8535 urological surgeries. In-room time overlap was seen in 50.5% of cases and procedure-time overlap in 7.4%. Eleven out of the 13 attending urologists performed OS. The average time in the operating room was greater for OS by an average of 14 minutes. The average operative time was greater for OS than NOS by 11 minutes, but this did not reach statistical significance. There was no significant difference between the cohorts for rate of blood transfusions, ICU stay, need for postoperative invasive procedures, length of postoperative hospital stay, discharge location, Emergency Room visits, hospital readmission rate, 30 and 90-day rates of postoperative complications, and mortality. Procedure-time overlapping surgeries constituted a minority of urological cases. OS were associated with greater in-room time. We found no increased risk of perioperative or postoperative adverse outcomes in OS compared to matched NOS.


Transmembrane potential measurement with carbocyanine dye diS-C3-(5): fast fluorescence decay studies.
The mechanism of carbocyanine dye diS-C3-(5) fluorescence intensity variations with transmembrane potential changes has been studied using time-resolved fluorescence spectroscopy. Clear evidence is given of the transmembrane-potential-dependent partition of the dye among various sites with different fluorescence lifetimes. It was found that fluorescence decay profiles reflect the transmembrane potential changes.


In patients with lung cancer is combined endobronchial ultrasound and endoscopic ultrasound superior to conventional mediastinoscopy in staging the mediastinum?
A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'In patients with lung cancer, is combined endobronchial ultrasound and endoscopic ultrasound (EBUS + EUS) superior to cervical mediastinoscopy (CM) in staging the mediastinum?' Altogether more than 110 papers were found, of which one meta-analysis, two RCTs, and two cohort studies represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Studies directly comparing EBUS + EUS and CM are limited in number and quality, with the majority of studies focusing on comparing endosonographic techniques or a single technique with surgical staging. Moreover, in four out of five studies, surgical staging of the mediastinum was undertaken following a negative EBUS + EUS result, limiting the utility of comparing endosonography alone. Regardless of this, the initial EBUS + EUS approach followed by surgical staging if negative resulted in greater sensitivity and detection of N2/3 metastases as well as greater sampling in the majority of studies, resulting in higher likelihood of upstaging and treatment alterations for patients. There was also improved quality of life demonstrated in the EBUS + EUS group with significant reductions in futile thoracotomies and less complications when compared with exclusive CM staging. We conclude that a combined approach of combined endosonography in the first instance, followed by CM staging of the mediastinum results in greater sensitivity of nodal disease and subsequent greater accuracy in upstaging and determining treatment plans with a concurrent reduction in complication rates and futile procedures.


Lymphotonic activity of Ruscus extract, hesperidin methyl chalcone and vitamin C in human lymphatic smooth muscle cells.
Besides actions including their venotonic, anti-inflammatory, and anti-oxidant effects, venoactive drugs are expected to act on edema via their action on lymphatics. The objective of this study was to evaluate the effect of the combination of Ruscus, hesperidin methyl chalcone and Vitamin C (Ruscus/HMC/Vit C) on intracellular calcium mobilization and contraction of human lymphatic smooth muscle cells (LSMCs) to better characterize the mechanism of its lymphotonic activity. Calcium mobilization was evidenced by videomicroscopy analysis of the fluorescence emitted by a specific Ca2+ sensitive dye and measured after injection of Ruscus/HMC/Vit C at 0.1, 0.3, 1.0, and 3.0 mg/mL into LSMCs. Ruscus/HMC/Vit C induced a strong and reproducible concentration-dependent calcium mobilization in LSMCs. On the contrary, another venoactive drug used as comparator, micronized purified flavonoid fraction (MPFF), did not induce calcium mobilization whatever the tested concentration. Although alternative mechanisms of action may result in potential lymphotonic effects, the efficacy of lymphotonic products is nonetheless related to their stimulating effect on the contractile activity of the smooth muscle cells surrounding lymphatic vessels. In the light of the results obtained in this study, the direct effect of Ruscus/HMC/Vit C on LSMC contraction may partially explain its clinical efficacy on lymphotonic activity, as has been observed in terms of objective signs of edema as reported in the recent guidelines on chronic venous disease.


Implementation of the scientific evidence into daily practice--example from fast-track colonic cancer surgery.
To report the implementation and results of fast-track surgery for colonic cancer in the daily routine. A total of 131 consecutive patients scheduled for elective colonic cancer resections entered a fast-track perioperative course after thorough information. The regimen contained: no preoperative bowel cleansing, transverse and small abdominal incisions, no drains nor tubes, mobilization and normal meal the evening on the day of surgery, epidural analgesia, oral laxatives, and a planned discharge on postoperative day 3. Median number of days postoperative in hospital were 4 days (range 1-46). Eighty-nine per cent experienced an uncomplicated course, 3% were readmitted within 30 days, and the 30-day mortality was 3.8%. Fast-track surgery is feasible in an unselected patient population scheduled for elective colon cancer resections without compromising quality.


A comprehensive review on potential therapeutics interventions for COVID-19.
COVID-19 is an infectious respiratory disease caused by SARS-CoV-2, a new beta coronavirus that emerged in Wuhan, China. Being primarily a respiratory disease, it is highly transmissible through both direct and indirect contacts. It displays a range of symptoms in different individuals and thus has been grouped into mild, moderate, and severe diseases. The virus utilizes spike proteins present on its surface to recognize ACE-2 receptors present on the host cells to enter the cell cytoplasm and replicate. The viral invasion of cells induces damage response, pyroptosis, infiltration of immune cells, expression of pro-inflammatory cytokines (cytokine storm), and activation of the adaptive immune system. Depending on viral load and host factors like age and underlying medical conditions, the immune responses mounted against SARS-CoV-2 may cause acute respiratory distress syndrome (ARDS), multiple organ failure, and death. In this review, we specify and justify both viral and host therapeutic targets that can be modulated to relieve the symptoms and treat the disease. Furthermore, we discuss vaccine development in the time of pandemic and the most promising vaccine candidates by far, according to WHO database. Finally, we discuss the conventional re-purposed drugs and potential alternative treatments as adjuvants.


Genetic variability at the LXR gene (NR1H2) may contribute to the risk of Alzheimer's disease.
We have initiated a systematic analysis of the role of cholesterol metabolizing genes as risk factors for Alzheimer's disease pathogenesis. As part of this analysis, we have assessed the NR1H2 gene on chromosome 19 and report here a modest association with the locus in sibpairs with late onset disease.


Structure-based discovery of glycolipids for CD1d-mediated NKT cell activation: tuning the adjuvant versus immunosuppression activity.
Introduction of an aromatic group into the fatty acyl chain of alpha-GalCer modulates the activity and selectivity of IFN-gamma/IL-4 secretion through CD1d-mediated activation of NKT cells. Compound 14-16 are more potent than alpha-Galcer and biased for IFN-gamma than for IL-4. These new glycolipids may find use as adjuvants or as antimetastatic agents.


Counter hegemony, popular education, and resistances: A systematic literature review on the squatters' movement.
The squatting movement is a social movement that seeks to use unoccupied land or temporarily or permanently abandoned buildings as farmland, housing, meeting places, or centers for social and cultural purposes. Its main motivation is to denounce and at the same time respond to the economic difficulties that activists believe exist to realize the right to housing. Much of what we know about this movement comes from the informational and journalistic literature generated by actors that are close or even belong to the movement. However, there is also a significant diversity of knowledge and scientific evidence on the squatters' movement that is being produced by academia and that is worth knowing and grouping together. With the aim of defining and understanding how the squatters' movement is constituted and organized, and how it acts, this research analyzes what the scientific literature affirms about it. Through qualitative research based on the systematic literature review (SLR) method, information was sought in the Web of Science (WOS) and Scopus databases. The initial universe of 262 articles was finally reduced to a sample of 32 articles. These have been analyzed by means of a categorized classification content analysis. The results obtained allow us to establish the state of the art on the squatting movement, placing special emphasis on its dynamics of resistance, its process of political subjectivation and its mechanisms of action and self-management. The study suggests that the movement is understood based on collective actions with a political role of resistance to neoliberalism and the inequalities it generates, and of response to the basic and social needs of the communities through self-management. [doi: 10.5281/zenodo.7179670], identifier [7179670].


Periodic activity in electroencephalography.
We report ana analysis of 12 cases in which periodic activity was observed in more than one EEG recording in patients with subacute sclerosing panencephalitis (4 cases), encephalitis of unknown etiology (1 case) and vascular disease (7 cases). In the patients with infective disease periodic high voltage potentials were elicited from all over the brain and the background rhythm was markedly impaired. In the patients with vascular disease the bursts were localized, reversible and sometimes recurrent. The impression gained is that a periodic EEG pattern denotes a pathological modification of behavior of the cerebral cortex rather than any particular disease.


Comparison of hemodynamic data before and after corrective surgery for Down's syndrome and ventricular septal defect.
Left ventricular function and the extent of pulmonary vascular disease were studied in 18 children with Down's syndrome and 20 children without Down's syndrome who underwent corrective surgery for ventricular septal defect (VSD) and severe pulmonary hypertension. This study was conducted between 1985 and 1993. All patients underwent routine cardiac catheterization preoperatively and postoperatively (mean, 11.4 months after surgery). Left ventricular function was estimated using cineangiographic levograms. In both groups, the pulmonary-to-systemic arterial pressure ratio (Pp/Ps) and pulmonary vascular resistance (PVR) were significantly lower after surgery (P < 0.05). Postoperative improvement was more remarkable in the non-Down group (P < 0.05). Left ventricular end-diastolic volume (percent of normal) (LVEDV%N) was significantly lower after surgery in both groups (P < 0.01). The left ventricular stroke work-to-end-diastolic volume ratio (LVSW/EDV) was significantly higher after surgery in the non-Down group only (P < 0.01). Postoperative left ventricular ejection fraction (LVEF) was significantly lower in the Down group than in the non-Down group (P < 0.01). Some degree of irreversible pulmonary vascular disease was present after repair of VSD in patients with Down's syndrome. In the Down group, there were no significant changes in left ventricular function after surgery, despite the relief of volume overload. These results suggest that early diagnosis and surgical repair are key elements in the management of patients with Down's syndrome and VSD.