Early Weight Loss during Chemoradiotherapy Has a Detrimental Impact on Outcome in NSCLC.
The aim of this study was to assess the effect of early weight loss before the onset of radiation esophagitis on overall survival (OS) in patients with non-small cell lung cancer treated with concurrent chemoradiotherapy. Characteristics (e.g., patient weight, radiation esophagitis score, sex, World Health Organization performance status, chemotherapy dose, nodal status, and gross tumor volume) of 151 patients who received concurrent chemoradiotherapy (in 2006-2013) were retrospectively correlated with OS. Early weight loss was defined as weight loss of more than 5% between the start and third week of radiotherapy in patients whose weight was stable before treatment initiation. In 17% of the patients early weight loss was observed. Median OS (95% confidence interval [CI]) was significantly shorter in the early weight loss group (OS = 13.0 months, 95% CI: 2.0-24.0) versus in the non-early weight loss group (OS = 23.0 months, 95% CI: 14.7-31.3) (hazard ratio [HR] = 1.8, 95% CI: 1.12-2.96, p = 0.017). On multivariate analysis sex (HR = 2.1, 95% CI: 1.33-3.29, p = 0.001), World Health Organization performance status (HR = 1.9, 95% CI: 1.20-2.97, p = 0.006), nodal status (HR = 2.9, 95% CI: 1.38-6.01, p = 0.005), and early weight loss (HR = 1.9, 95% CI: 1.10-3.19, p = 0.022) were associated with OS. Early weight loss in patients with non-small cell lung cancer was found to be associated with worse prognosis. These data warrant further investigation into the efficacy of tailored intervention to prevent early weight loss.


Pharmacies Wrestle With Drug-Tracing Rule: Confusion as Deadline Passes: Paper, Digital, or Web Portal?
Pharmacies wrestle with the FDA's new drug-tracing rule.


Biosynthesis of cobalamin in Salmonella typhimurium: transformation of riboflavin into the 5,6-dimethylbenzimidazole moiety.
In order to elucidate the biosynthesis of the base moiety of cobalamin in Salmonella typhimurium LT2, this organism was grown in the presence of [1'-14C]riboflavin. The vitamin B12 isolated was 14C-labeled. It was shown by chemical degradation that the 14C-label was exclusively localized in carbon atom 2 of the 5,6-dimethylbenzimidazole moiety. This demonstrated the precursor function of riboflavin in the biosynthesis of 5,6-dimethylbenzimidazole in S. typhimurium.


Image Quality Control in Lumbar Spine Radiography Using Enhanced U-Net Neural Networks.
To standardize the radiography imaging procedure, an image quality control framework using the deep learning technique was developed to segment and evaluate lumbar spine x-ray images according to a defined quality control standard. A dataset comprising anteroposterior, lateral, and oblique position lumbar spine x-ray images from 1,389 patients was analyzed in this study. The training set consisted of digital radiography images of 1,070 patients (800, 798, and 623 images of the anteroposterior, lateral, and oblique position, respectively) and the validation set included 319 patients (200, 205, and 156 images of the anteroposterior, lateral, and oblique position, respectively). The quality control standard for lumbar spine x-ray radiography in this study was defined using textbook guidelines of as a reference. An enhanced encoder-decoder fully convolutional network with U-net as the backbone was implemented to segment the anatomical structures in the x-ray images. The segmentations were used to build an automatic assessment method to detect unqualified images. The dice similarity coefficient was used to evaluate segmentation performance. The dice similarity coefficient of the anteroposterior position images ranged from 0.82 to 0.96 (mean 0.91 ± 0.06); the dice similarity coefficient of the lateral position images ranged from 0.71 to 0.95 (mean 0.87 ± 0.10); the dice similarity coefficient of the oblique position images ranged from 0.66 to 0.93 (mean 0.80 ± 0.14). The accuracy, sensitivity, and specificity of the assessment method on the validation set were 0.971-0.990 (mean 0.98 ± 0.10), 0.714-0.933 (mean 0.86 ± 0.13), and 0.995-1.000 (mean 0.99 ± 0.12) for the three positions, respectively. This deep learning-based algorithm achieves accurate segmentation of lumbar spine x-ray images. It provides a reliable and efficient method to identify the shape of the lumbar spine while automatically determining the radiographic image quality.


Effectiveness of internet-based guided self-help for binge-eating disorder and characteristics of completers versus noncompleters.
Binge-eating disorder (BED) is characterized by recurrent episodes of binge eating, accompanied by a lack of control and feelings of shame. Online intervention is a promising, accessible treatment approach for BED. In the current study, we compared completers with noncompleters in a 10-session guided internet-based treatment program (iBED) based on cognitive behavioral therapy. Adults (N = 75) with mild to moderate BED participated in iBED with weekly written support from psychologists. Participants were compared on the Eating Disorder Examination Questionnaire (EDE-Q), diagnostic criteria for BED (BED-Q), major depression inventory (MDI), quality of life (EQ-5D-5L), body mass index (BMI) and sociodemographic variables. Minor differences were observed between completers and noncompleters on depression. No differences were found in BED-symptoms, BMI, and sociodemographic variables. Participants who completed treatment showed large reductions in eating disorder pathology. More research is needed to determine risk factors for attrition or treatment outcome in internet-based interventions for BED. It is suggested that iBED is an efficient intervention for BED. However, more studies of internet-interventions are needed.


Effect of Chemistry on Osteogenesis and Angiogenesis Towards Bone Tissue Engineering Using 3D Printed Scaffolds.
The functionality or survival of tissue engineering constructs depends on the adequate vascularization through oxygen transport and metabolic waste removal at the core. This study reports the presence of magnesium and silicon in direct three dimensional printed (3DP) tricalcium phosphate (TCP) scaffolds promotes in vivo osteogenesis and angiogenesis when tested in rat distal femoral defect model. Scaffolds with three different interconnected macro pore sizes were fabricated using direct three dimensional printing. In vitro ion release in phosphate buffer for 30 days showed sustained Mg2+ and Si4+ release from these scaffolds. Histolomorphology and histomorphometric analysis from the histology tissue sections revealed a significantly higher bone formation, between 14 and 20% for 4-16 weeks, and blood vessel formation, between 3 and 6% for 4-12 weeks, due to the presence of magnesium and silicon in TCP scaffolds compared to bare TCP scaffolds. The presence of magnesium in these 3DP TCP scaffolds also caused delayed TRAP activity. These results show that magnesium and silicon incorporated 3DP TCP scaffolds with multiscale porosity have huge potential for bone tissue repair and regeneration.


Comparison of cerebrospinal fluid dynamics studied by computed tomography (CT) and radioisotope (RI) cisternography.
CT and RI cisternography were done on 55 cases with normal and abnormal CSF circulation. Of 19 cases in which both studies were done, 14 case disclosed a good correspondence. The remaining five cases showed no correspondence because of technical failure. Analyzing the results, CT cisternography demonstrates pathology of the CSF dynamics in a more precise and quantitative manner than RI cisternography does. Metrizamide CT cisternography will soon be the most reliable method of investigation for the evaluation of the CSF kinetics.


Epidemiology of obesity and its link to heart disease.
Univariate analyses of many prospective studies have demonstrated that obesity increases the likelihood of developing cardiovascular disease. However, multivariate analyses have yielded more inconsistent results. Some studies have indicated that lean individuals have a greater total mortality than normal-weight individuals, but this may be attributable to the higher proportion of smokers in the lean population. Mexican Americans, a population with a high incidence of obesity, have the same mortality rate as non-Hispanic white Americans, suggesting that obesity does not increase their death rate. In the United States, the percentage of the population that is overweight has increased sharply since the 1970s, but the mortality rate has actually decreased. The increase in body weight has had little effect on mortality, possibly because factors associated with obesity, like hypertension, are treated more effectively. Large-scale clinical trials are required to determine the true effects of obesity on cardiovascular disease, diabetes and total mortality rate.


Fibrin glue sealing for the prevention of pancreatic fistulas following distal pancreatectomy.
To evaluate the use of fibrin glue sealing of the pancreatic stump for the prevention of postoperative pancreatic fistulas. A prospective, randomized clinical trial. Fibrin glue is a biologic adhesive consisting of highly concentrated human fibrinogen, thrombin, and factor VIII. Twenty-six of 56 patients who underwent distal pancreatectomy for gastric cancer or pancreatic disease were randomly assigned to the fibrin glue group. Fibrin glue was applied to the suture line of the pancreatic stump with the ligated main pancreatic duct. Pancreatic fistula was defined as a pancreatic fluid discharge for over 7 post-operative days diagnosed by local findings, with amylase concentration in the discharge fluid more than three times the serum amylase concentration, a level low enough that even a small pancreatic leakage could be diagnosed. The overall incidence of pancreatic fistula was 28.6%. Postoperative pancreatic fistulas occurred in four patients (15.4%) in the fibrin glue group and 12 (40.0%) in the control group (P = .04). The lower pancreatic fistula rate was seen in the fibrin glue group also when analyzing patients with gastric cancer or pancreatic disease only, although there was no statistically significant difference. Intraoperative use of fibrin glue following distal pancreatectomy could prevent pancreatic fistula formation. This method was feasible, safe, and reliable and will complement other prophylactic methods.


Neuropathological abnormalities of astrocytes, GABAergic neurons, and pyramidal neurons in the dorsolateral prefrontal cortices of patients with major depressive disorder.
Human post-mortem brain studies have revealed reduced density and size of neurons and glial cells in the dorsolateral prefrontal cortex (dlPFC) in major depressive disorder (MDD). However, the basis of these cytoarchitectural abnormalities and the relationship between them are not understood. We hypothesized that the reduced density of GABAergic neurons and glial cells was associated with altered glutamate neurotransmission in the dlPFC. In order to test this hypothesis, we examined a specific marker type (i.e., calretinin, CR: as a marker of GABAergic neurons) and also attempted to identify the neuropathological markers that correlate with the density of CR-immunoreactive (IR) GABAergic neurons in the dlPFC, using the Stanley Neuropathology Consortium Integrative Database (SNCID, http://sncid.stanleyresearch.org/), which is a web-based tool used to integrate Stanley Medical Research Institute (SMRI) data sets. We found that the density of CR-IR GABAergic neurons was significantly lower in layer I of the dlPFC of MDD patients (n=15) than in that of unaffected controls (n=15) (p=0.021). CR-IR GABAergic neuronal changes were positively correlated with changes in several markers for glial cells and pyramidal neurons in the dlPFC of all SNC subjects (n=60). We also found that the glutamate changes negatively correlated with glial fibrillary acidic protein (GFAP) expression levels and CR-IR GABAergic neuronal density in the prefrontal cortex of all SNC subjects (P<0.05). These findings yield some insight into the mechanism by which increased glutamatergic neurotransmission leads to excitotoxic damage both in neurons and glial cells in the dlPFC of MDD patients.


The role of N-methyl-D-aspartate receptors and nitric oxide in cochlear dopamine release.
Dopamine (DA) released from lateral olivocochlear (LOC) terminals may have a neuroprotective effect in the cochlea. To explore the role of N-methyl-d-aspartate (NMDA) receptors and nitric oxide (NO) in the modulation of a cochlear DA release, we measured the release of [3H]DA from isolated mouse cochlea in response to the application of NMDA. NMDA at 100 muM significantly increased the electrical-field stimulation-evoked and resting release of DA from the cochlea. The NO donor sodium nitroprusside enhanced the basal outflow of DA but failed to influence the evoked release. The administration of the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) alone was ineffective, but it significantly inhibited the initial phase of the NMDA-induced elevation of DA outflow, which suggested the role of NO in the NMDA-induced DA release. The DA uptake inhibitor nomifensine increased the electrically evoked release of DA. Nomifensine failed to change the effect of NMDA on the resting or electrically-evoked DA release, which suggested that the uptake mechanism does not play a role in NMDA-evoked and NO-mediated DA release. In summary, we provide evidence that NO can modulate the release of DA from the cochlea following NMDA receptor activation, but does not affect the uptake of DA.


Effects of wear time recording on the patient's compliance.
To assess the effect of wear-time recording on subjective and objective wear time. This study retrospectively examined a group of 18 patients and a control group of 14 patients at four appointments over 168 days. The patients were treated with removable appliances with embedded TheraMon-microsensors to be worn for 15 hours per day. The study group was not told about the microsensor until the first appointment after fitting of the appliance. At each appointment patients were asked about their subjective wear time and afterward were told about the objective wear time. The existence of the microsensor was revealed to the control group when the appliance was fitted. Objective wear time was also announced at every appointment. Mean wear times did not significantly differ between groups at any appointment or regarding overall wear time. Highly significant differences between subjective and objective wear time were found when patients did not know that their wear time had been monitored. Mean wear times assessed in this study concur with data of previous studies. Patients tend to overestimate their wear times but become more realistic once they know wear time is being monitored. Objective measurement of wear time allows a more realistic view of compliance by patient and orthodontist. Knowing that wear time is recorded does not necessarily increase the amount of time removable appliances are worn by the patient.


Reduced folate carrier (RFC-1) gene expression in normal and psoriatic skin.
Methotrexate is widely used in the treatment of severe psoriasis. However, little is currently known about the mechanisms underlying its therapeutic activity in the skin. Methotrexate has been shown to be carried into cells through the reduced folate carrier (RFC-1). The recent cloning and characterization of the human gene encoding this transmembranal carrier enabled us to investigate RFC-1 gene expression in human skin. Biopsies were obtained from the skin of healthy and psoriatic volunteers. RNA extracted from these biopsies was analyzed by the reverse transcriptase-polymerase chain reaction technique. While RFC-1 gene expression was barely detectable in the uninvolved skin of psoriatic patients and in the skin of healthy volunteers, high levels of RFC-1 transcripts were found in biopsies obtained from psoriatic plaques. To further investigate this pattern of gene expression, we studied skin biopsies by in situ hybridization with a labeled antisense riboprobe specific for the RFC-1 gene. The RFC-1 gene was found to be weakly expressed in the epidermis, in biopsies obtained from the skin of healthy subjects as well as in those from the uninvolved skin of psoriatic patients. In contrast, in biopsies obtained from psoriatic plaques, high levels of RFC-1 gene transcripts were found mostly in the spinous layer of the epidermis. These results suggest the existence of a specific methotrexate carrier in the human epidermis, and may bear relevance to the cutaneous manifestations of methotrexate toxicity.


Triple therapy for anti-vascular endothelial growth factor nonresponders in neovascular age-related macular degeneration: impact of different photodynamic therapy parameters.
To evaluate the safety and exploratory efficacy of triple therapy (TT) with single-session intravitreal ranibizumab, modified juxtascleral triamcinolone, and photodynamic therapy (PDT) in exudative age-related macular degeneration non-responder to anti-vascular endothelial growth factor. Thirty consecutive eyes were included. The first 10 eyes (cohort 1) enrolled received same-day TT with reduced-fluence/reduced-irradiance PDT, 10 eyes (cohort 2) received same-day TT with reduced-fluence/standard irradiance PDT, the last 10 eyes (cohort 3) received same-day TT with standard fluence/standard irradiance PDT. All patients completed the 6-month follow-up. Mean best corrected visual acuity (BCVA) at baseline was 1.1 (cohort 1), 0.9 (cohort 2) and 1.1 (cohort 3) logMAR. After 6 months, mean BCVA change was -0.15 (not significant), -0.13 (not significant) and 0.29 (p < 0.05) logMAR, respectively. Among eyes treated with standard fluence/standard irradiance PDT, 2 showed choroidal ischemia. The combination of modified juxtascleral triamcinolone, reduced-fluence PDT, and ranibizumab appears as a safe treatment option.


The dynamics analysis of Gompertz virus disease model under impulsive control.
The pandemic of Gompertz virus disease remains a pressing issue in agricultural production. Moreover, the dynamics of various infectious diseases is usually investigated by the method of mathematical modelling. A new mathematical model for dynamics on Gompertz virus disease impulsive system is proposed and analyzed in this paper. We prove the dynamic characteristics about the permanence and globally exponential stability of Gompertz virus disease model. Moreover, we also give the sufficient condition that one positive solution which satisfies [Formula: see text] if [Formula: see text] exists. Eventually, numerical simulations are utilized to validate the validity of the theoretically analyzed conclusion in this paper.


The role of biological processes in reducing both odor impact and pathogen content during mesophilic anaerobic digestion.
Mesophilic anaerobic digestion (MAD) produces renewable energy, but it also plays a role in reducing the impact of digestates, both by reducing odor and pathogen content. Ten full-scale biogas plants characterized by different plant designs (e.g. single digesters, parallel or serial digesters), plant powers (ranging from 180 to 999 kWe), hydraulic retention time (HRT) (ranging between 20 to 70 days) and feed mixes were monitored and odors and pathogens were observed in both ingestates and digestates. Results obtained indicated that MAD reduced odors (OU) from, on average, OUingestate=99,106±149,173 OU m(-2) h(-1) (n=15) to OU digestate=1106±771 OU m(-2) h(-1) (n=15). Pathogens were also reduced during MAD both because of ammonia production during the process and competition for substrate between pathogens and indigenous microflora, i.e. Enterobacteriaceae from 6.85∗10(3)±1.8∗10(1) to 1.82∗10(1)±3.82∗10(1); fecal Coliform from 1.82∗10(4)±9.09 to 2.45∗10(1)±3.8∗10(1); Escherichia coli from 8.72∗10(3)±2.4∗10(1) to 1.8∗10(1)±2.94∗10(1); Clostridium perfringens from 6.4∗10(4)±7.7 to 5.2∗10(3)±8.1 (all data are expressed as CFU g(-1) ww). Plants showed different abilities to reduce pathogen indicators, depending on the pH value and toxic ammonia content.


[Effectiveness of preoxygenation using the head-up position and noninvasive ventilation to reduce hypoxaemia during intubation].
The purpose of this article was to present an update of the preoxygenation management in morbidly obese adults, parturient women and hypoxemic critically-ill patients. All references obtained from the medical database Medline related to the area and more specifically during the last five years were reviewed. Preoxygenation decreases the risk of hypoxia and should be optimized when the standard technique appears to be less effective as in morbidly obese adults, parturient women and critically-ill patients. The head-up position and noninvasive ventilation may be useful during preoxygenation probably because of the increase of ventilation and alveolar recruitment. The effectiveness of preoxygenation (when defined as the duration of the desaturation safety period) is enhanced in the head-up position as compared to supine position in the obese patient but not in parturient women. Noninvasive ventilation improves preoxygenation in the hypoxemic critically-ill patient but not in the obese patient. Neither the head-up position nor the noninvasive ventilation improve preoxygenation in parturient women. Further studies are required to investigate other methods attempting to improve preoxygenation and prevent hypoxemia during intubation.


Incisional endometriomas: CT findings.
We report a woman with two painful abdominal-wall masses within the scar of a previous cesarian section. The CT findings and the differential diagnosis are presented.


The Role of No. 10 Lymphadenectomy for Advanced Proximal Gastric Cancer Patients Without Metastasis to No. 4sa and No. 4sb Lymph Nodes.
There is no consensus in the impact of No. 10 lymph node dissection (LND) for advanced proximal gastric cancer (APGC) and the status of negative No. 4sa and No. 4sb lymph nodes (No. 4s LNs) is reportedly associated with no metastasis to No. 10 LN. We aimed to evaluate the role of No. 10 LND in APGC patients with negative No. 4s LNs and the diagnostic accuracy of intraoperative pathologic examination. We analyzed data on 727 patients with APGC who had undergone D2 lymphadenectomy with No. 10 LND (n = 380) or without No. 10 LND (n = 347) between January 2005 and December 2010. Additionally, from January to July 2014, we prospectively enrolled 48 patients with APGC and examined their No. 4s LNs intraoperatively. The negative predictive efficacy of No. 4s LN status for no metastasis to No. 10 LN was 98.09 %. Operation time, blood loss, time to first solid diet, hospital stay, and postoperative complication rate differed significantly between patients with negative No. 4s LNs who underwent No. 10 LND (n = 260) and those who did not undergo No. 10 LND (n = 243). Differences between the two groups in 5-year overall and disease-free survival were not statistically significant. The sensitivity, specificity, and accuracy of intraoperative pathological examination of LNs were 93.42, 96.56, and 95.86 %, respectively. The No. 10 lymphadenectomy may not be recommended in patients with APGC who are found by intraoperative pathological examination to have negative No. 4s LNs.


Induction of tumors in the small intestine and mammary gland of female Donryu rats by continuous oral administration of N-carboxymethyl-N-nitrosourea.
The carcinogenicity of N-carboxymethyl-N-nitrosourea (CMNU), a naturally occurring N-nitroso compound, was tested in female Donryu rats. Four groups of female Donryu rats were given 400, 200, 100, or 0 ppm of CMNU solution continuously as drinking water. The incidence of tumors was highest and the mean survival time shortest in the 400 ppm group. A dose-effect relationship was observed in the tumor incidence and the mean survival time and the incidences of tumors in all experimental groups were significantly different from those in the control group. In the 400 ppm group, tumors were detected most frequently in the small intestine, followed by the mammary gland. In contrast, most tumors were observed in the mammary gland in the other two experimental groups, although dose-dependent induction of tumors of the small intestine was also detected in these two groups. The organ specificity of CMNU is compared with that of other N-alkyl-N-nitrosourea derivatives.


[The microflora of sour dough. IV. Communication: bacterial composition of sourdough starters genus Lactobacillus beijerinck (author's transl)].
The bacterial composition of three so called pure culture sourdough starters of varying origin was investigated. 245 isolates were obtained all belonging to the genus Beijerinck. According to their morphological, physiological and biochemical characteristics they were classified into the subgroups: Thermobacterium (L. acidophilus), Streptobacterium (L. casei, L. plantarum, L. farciminis, L. alimentarius) and Betabacterium (L. brevis, L. brevis var. lindneri, L buchneri, L. fermentum, L. fructi vorans). In the three sourdough starters the identified lactic organisms varied in number and proportion. In starter preparation "A" only the varieties L. fructi vorans and L. fermentum were present. Preparation "B" contained a great variety of microorganisms with L. brevis and L. brevis L. lindneri predominating. In starter "C" L. brevis, L. plantarum and L. alimentarius predominated.


Copeptin is a predictive biomarker of severity in acute pancreatitis.
Acute pancreatitis remains a common intraabdominal disease with a complex pathophysiology. The overall outcome has improved, but specific treatment remains elusive. The challenge is the early identification and treatment of patients who will develop severe acute pancreatitis. Therefore, the aim of the present study is to investigate plasma levels of copeptin in the initial phase of predicted severe acute pancreatitis. Between August 2008 and December 2011, 57 patients with acute pancreatitis and 30 healthy individuals were included in the study. Four blood samples, for serum copeptin measurement, were taken from each individual in each group. The first measurement was taken from the admission blood sample. The subsequent 3 samples were taken at 12, 24, and 48 hours after the onset of pain. Copeptin plasma concentrations were significantly higher in patients with acute pancreatitis when compared with healthy controls. Copeptin plasma concentrations in severe pancreatitis patients were significantly higher than in mild pancreatitis patients. Copeptin plasma concentrations were significantly higher in patients with acute pancreatitis when compared with healthy controls. Copeptin plasma concentrations in severe pancreatitis patients were significantly higher than in mild pancreatitis patients.


Opsonic activity of the alternative complement pathway in infected human intra-abdominal fluid.
The complement-mediated opsonic activity (CMOA) in intra-abdominal exudates collected during laparotomy from peritonitis patients was examined by an in vitro phagocytic bactericidal assay. It was found that infected intra-abdominal exudates barely promoted detectable killing of Escherichia coli 01 by polymorphonuclear leukocytes. Only the minority of bacteria recovered by differential centrifugation from the infected exudates had C3 on their surfaces. Such bacteria were not optimally opsonized in vivo, whereas they became fully coated with C3 during a brief incubation in vitro in normal human serum. The low level of CMOA in the peritoneal fluid paralleled a depletion of complement in the peripheral blood. Thus, in cases complicated by sepsis with gram-negative bacteria, the CMOA in the blood was extremely low. These data suggest that the high susceptibility of the peritoneum to infection by gut flora, despite the normal phagocytic response, may be partly explained by the low local level of functional complement which is inadequate for optimal opsonization of the bacteria.


COVID-19 infection in patients with late-onset Pompe disease.
Severe acute respiratory syndrome coronavirus-2 2019 (SARS-CoV2/COVID-19) is frequently more severe in individuals with pre-existing respiratory and cardiovascular conditions. The impact on patients with neuromuscular disorders is of concern, but remains largely unknown. Late-onset Pompe disease (LOPD) is a lysosomal-storage disorder characterized by progressive skeletal and respiratory muscle degeneration. Mortality is typically caused by respiratory failure. We examined the impact of COVID-19 on these patients. This is a case series of four patients with LOPD who contracted COVID-19. All patients had a mild/moderate illness from COVID-19 and did not require hospitalization. Neurological worsening occurred in one, with no change in physical ability in the other three, and respiratory symptoms remained stable in all four. COVID-19 infection can result in a benign course in some patients with LOPD. However, individuals with LOPD remain at high risk and should receive COVID-19 vaccinations and exercise precautions to avoid exposure to COVID-19 infection.


[Spontaneous regression of pulmonary metastasis of cancer of the kidney. Apropos of a case occurring after the irradiation of a pelvic metastasis. Review of the literature].
Spontaneous regression of metastases from cancer of kidney is an exceptional event, original but non-specific to this neoplasm. Observed principally in secondary pulmonary localizations this phenomenon occurs most frequently after nephrectomy. A personal case is presented of regression of pulmonary images considered as being metastatic after irradiation of a pelvic metastasis from renal adenocarcinoma, and a literature review carried out. The various pathogenic hypotheses are discussed and the place of nephrectomy for metastatic renal cancer (Robson's stage IV) debated.


A multi-site evaluation of innovative approaches to increase tuberculosis case notification: summary results.
Globally, TB notifications have stagnated since 2007, and sputum smear positive notifications have been declining despite policies to improve case detection. We evaluate results of 28 interventions focused on improving TB case detection. We measured additional sputum smear positive cases treated, defined as the intervention area's increase in case notification during the project compared to the previous year. Projects were encouraged to select control areas and collect historical notification data. We used time series negative binomial regression for over-dispersed cross-sectional data accounting for fixed and random effects to test the individual projects' effects on TB notification while controlling for trend and control populations. Twenty-eight projects, 19 with control populations, completed at least four quarters of case finding activities, covering a population of 89.2 million. Among all projects sputum smear positive (SS+) TB notifications increased 24.9% and annualized notification rates increased from 69.1 to 86.2/100,000 (p = 0.0209) during interventions. Among the 19 projects with control populations, SS+TB case notifications increased 36.9% increase while in the control populations a 3.6% decrease was observed. Fourteen (74%) of the 19 projects' SS+TB notification rates in intervention areas increased from the baseline to intervention period when controlling for historical trends and notifications in control areas. Interventions were associated with large increases in TB notifications across many settings, using an array of interventions. Many people with TB are not reached using current approaches. Different methods and interventions tailored to local realities are urgently needed.


CRISPR/Cas9-based precision tagging of essential genes in bloodstream form African trypanosomes.
Proteins of interest are frequently expressed with a fusion-tag to facilitate experimental analysis. In trypanosomatids, which are typically diploid, a tag-encoding DNA fragment is typically fused to one native allele. However, since recombinant cells represent ≪0.1% of the population following transfection, these DNA fragments also incorporate a marker cassette for positive selection. Consequently, native mRNA untranslated regions (UTRs) are replaced, potentially perturbing gene expression; in trypanosomatids, UTRs often impact gene expression in the context of widespread and constitutive polycistronic transcription. We sought to develop a tagging strategy that preserves native UTRs in bloodstream-form African trypanosomes, and here we describe a CRISPR/Cas9-based knock-in approach to drive precise and marker-free tagging of essential genes. Using simple tag-encoding amplicons, we tagged four proteins: a histone acetyltransferase, HAT2; a histone deacetylase, HDAC3; a cleavage and polyadenylation specificity factor, CPSF3; and a variant surface glycoprotein exclusion factor, VEX2. The approach maintained the native UTRs and yielded clonal strains expressing functional recombinant proteins, typically with both alleles tagged. We demonstrate utility for both immunofluorescence-based localisation and for enriching protein complexes; GFPHAT2 or GFPHDAC3 complexes in this case. This precision tagging approach facilitates the assembly of strains expressing essential recombinant genes with their native UTRs preserved.


Mobile technology features and technostress in mandatory online teaching during the COVID-19 crisis.
Technostress is defined as any unhealthy condition caused by dealing with modern technology in various harmful ways; examples of technostress include addiction and stress. Even though technostress has been extensively studied in the literature, little attention has been paid to investigating technostress among academics who work in exceptional circumstances, such as crises, and who might be experiencing different psychological states due to those circumstances. To fill the gap, this study aims to explore the factors influencing technostress among school teachers. The study examined technostress's level and factor graphics structure among 692 academics from different Arab countries during COVID-19. The technostress factors and their stories were explored and measured using sequential mixed methods and confirmatory and exploratory factor analysis. The study discusses various factors' direct and indirect effects on mobile technology integration in education and the theoretical and practical implications of managing technostress in online classes. A model of techno-stressors among Arab academics was found to include: schedule overload, complexity, uncertainty, uselessness, invasion, and compulsion. The direct effect of various factors on mobile technology integration in education is mainly positive, while indirect effects are more varied. The theoretical and practical implications of managing technostress in online classes include: considering the psychological and physiological impact of technostress on students' learning performance, decreasing overall satisfaction with the learning experience, and improving the overall quality of online courses. As a result of this study's findings, a new perspective is provided on how academics in particular circumstances (in this study, the occupation of Palestine) may behave and feel toward technology in teaching.


(1)H, (15)N, and (13)C chemical shift assignments of the calflagin Tb24 flagellar calcium binding protein of Trypanosoma brucei.
Flagellar calcium binding proteins are expressed in a variety of trypanosomes and are potential drug targets for Chagas disease and African sleeping sickness. We report complete NMR chemical shift assignments of the flagellar calcium binding protein calflagin Tb24 of Trypanosoma brucei. (BMRB no. 18011).


Possible mechanism of rubidium-induced hyperactivity in the rat.
This study suggests that replacement of intracellular potassium by rubidium ions might lower the resting membrane potential. Thus rubidium-treated rats were more responsive to depolarizing influences and generated more cyclic AMP in the brainstem and consequently the behavioral changes.


Prevalence of Bordetella bronchiseptica in cats attended by a veterinary practice in the Manawatu region.
To determine the prevalence by isolation of Bordetella bronchiseptica infection in healthy cats and in cats showing signs of upper respiratory tract (URT) disease attended by a veterinary practice in the Manawatu region. The nasal cavity and oropharynx of 100 cats of mixed sex and age were swabbed and the swabs cultured for B. bronchiseptica. The population of cats surveyed was that attended by the Massey University Veterinary Teaching Hospital, and included healthy cats, cats with clinical signs of URT disease, cats with a recent history of URT disease, cats from single cat households, cats from multiple-cat households, and cats from a colony. Bordetella bronchiseptica was recovered from 7 cats (5 from pharyngeal samples and 2 from nasal samples). Five of the 7 cats appeared to be healthy at the time of sampling, whilst 2 showed clinical signs of URT disease. Six of the 7 culture-positive cats were from a cat colony. The prevalence of B. bronchiseptica in healthy cats sampled was 7% and in cats with URT disease was 8%. This study confirms that B. bronchiseptica infection is present, but the prevalence of infection is low, in both healthy cats and in cats with URT disease attended by the Massey University Veterinary Teaching Hospital. It is unlikely that B. bronchiseptica infection is a frequent cause of feline URT disease of cats in this region.


A novel homozygous RTEL1 variant in a consanguineous Lebanese family: phenotypic heterogeneity and disease anticipation.
Phenotypic heterogeneity is often observed in patients with telomeropathies caused by pathogenic variants in telomere biology genes. However, the roles of recessive variants in these different phenotypes are not fully characterized. Our goal is to describe the biological roles of a novel homozygous RTEL1 variant identified in a consanguineous Lebanese family with unusual presentation of telomeropathies. A proband was screened for germline variants in telomere biology genes by whole exome sequencing. Leukocytes' telomere length was measured in the proband and eight relatives. We identified a novel homozygous p.E665K RTEL1 variant in the proband, his mother, and seven siblings that associated with telomere shortening and a broad spectrum of clinical manifestations, ranging from mild unspecific findings to severe phenotypes. Consanguinity in at least three family generations led to increased frequency of the homozygous p.E665K variant in the youngest generation and progressive telomere shortening. The increased frequency of the homozygous RTEL1 variant due to consanguinity in this Lebanese family allowed us to infer novel behaviors of recessive RTEL1 variants, as the expressivity and penetrance of this gene are very heterogenous between inter- and intra-generations. Progressive telomere shortening was associated with disease anticipation, first reported in recessive autosomal telomeropathies. Both genetic testing and telomere length measurement were critical for the clinical diagnosis of this family with telomere diseases marked by phenotypic heterogeneity.


"Nothing is absolute in life": understanding uncertainty in the context of psychiatric genetic counseling from the perspective of those with serious mental illness.
No genetic tests are currently clinically available for serious mental illnesses such as schizophrenia and bipolar disorder. Rather, the full spectrum of genetic variants that confer susceptibility remain unknown, and estimates of probability of condition recurrence typically have the form of ranges rather than single absolute numbers. Genetic counselors have been shown to feel that the information that can be provided for patients with serious mental illness could be more confusing than helpful. However, how those with serious mental illness perceive this uncertainty remains unknown. So, to investigate this, individuals with serious mental illness participated in a psychiatric genetic counseling (GC) session and responded to a single open ended question about their reactions towards the uncertainty that they encountered in their GC session immediately and one month post-counseling (from which themes were identified), and completed the Genetic Counseling Satisfaction Scale immediately post-session (descriptive statistics applied). While some of the 37 participants were disappointed with the uncertainty, twice as many were unconcerned. Overall, responses from immediately and one month after GC were very similar; participants were very satisfied with, and found value in GC despite uncertainty, and four approaches to coping with uncertainty emerged. Ultimately, these findings offer insight into providing GC for those with serious mental illness, and potentially could be applied to other areas of GC where uncertainty lies, with downstream impact on GC practice and future research.


miR-155 mediates suppressive effect of progesterone on TLR3, TLR4-triggered immune response.
It has been demonstrated that progesterone has immune suppressive properties and can inhibit Toll-like receptor 4 (TLR4)-triggered immune response. Multiple microRNAs are induced in innate immune cells, among them miR-155, miR-146a and miR-21 are particularly ubiquitous. In this study, we investigated the potential roles of miR-155 in progesterone-mediated regulation of innate immune responses. We found that progesterone pre-treatment suppressed LPS- and poly(I:C)-induced miR-155 expression in macrophages. Increasing the activity of miR-155, significantly attenuated the progesterone's inhibition on LPS-induced IL-6 as well as LPS- and poly(I:C)-induced IFN-β expression in macrophages. Furthermore, we demonstrated that progesterone up-regulated LPS-induced SOCS1 expression while overexpression of miR-155 inhibited SOCS1 expression. In conclusion, the present study has demonstrated that progesterone suppresses TLRs-triggered immune response by regulating miR-155, and the decreased miR-155 contributes to inhibit TLR-induced IL-6 and IFN-β via increased SOCS1 expression.


Prostacyclin for ischemic ulcers in peripheral arterial disease. A random assignment, placebo controlled study.
A 72 h infusion of prostacyclin or placebo was given into femoral artery as a treatment for ischemic ulcers in 30 patients with peripheral arterial disease. Patients were well matched for age, sex, type and localization of disease, rest pain, number and area of ulcers, calf blood flow and previous sympathectomies. They had no diabetes mellitus, gangrene or marked aorto-iliac involvement. Six weeks after the infusion there was a significant difference in ulcer area between the two groups (p less than 0.02, t unpaired test): mean ulcer area decreased (p less than 0.02, t paired test) in the prostacyclin-treated group, but not in the placebo group (p greater than 0.05, t paired test). Thus, intra-arterial infusion of prostacyclin promotes healing of ischemic ulcers in non-diabetic patients with peripheral arterial disease without gangrene.


Mycobacteria in the light of modern genetics development.
It is generally assumed that genetic research of mycobacteria is delayed as compared with other, more commonly used, bacterial models, particularly in the field of genetic transfers. In the field of mutagenesis the problems have been studied to such an extent that replication maps of the chromosome of M. phlei and M. tuberculosis H37 Rv have already been constructed and a new model of the cell cycle of bacteria exhibiting a slow growth rate has been worked out. When the problems of mycobacterial genetics are looked upon in the light of gene manipulations it may be concluded that mycobacteria belong to a few models whose genes are used for cloning and that problems of practical significance will be studied by means of the most modern approaches.


Studies on the etiology and pathogenesis of motor neuron diseases. II. Clinical and electrophysiologic features of pyramidal dysfunction in macaques fed Lathyrus sativus and IDPN.
A primate model of lathyrism has been produced in well-nourished male cynomolgus monkeys chronically fed a fortified diet composed of Lathyrus sativus (chickling or grass pea) and given daily per os an alcoholic extract of this legume. Animals given a diet of non-neurotoxic Cicer arietinum (chick pea) cross-matched with the nutritional properties of the experimental diet served as controls. Another group of animals received the same diet and oral doses of beta, beta'-iminodipropionitrile (IDPN), a reference compound that has been termed an "experimental neurolathyrogen." Monkeys fed Lathyrus developed clinical and electrophysiologic evidence of corticospinal deficits after 3 to 10 months of feeding. Animals administered IDPN showed clinical and/or electrophysiologic changes in the PNS and CNS motor and sensory pathways, and signs of cerebellar dysfunction. Since the two primate disorders are separable on clinical and electrophysiologic grounds, further use of the term "experimental neurolathyrogen" to describe the neurotoxic properties of IDPN seems inappropriate. These findings demonstrate the feasibility of developing a model of early human lathyrism in adequately nourished nonhuman primates.


Impact of an advanced image-based monoenergetic reconstruction algorithm on coronary stent visualization using third generation dual-source dual-energy CT: a phantom study.
To evaluate the impact of an advanced monoenergetic (ME) reconstruction algorithm on CT coronary stent imaging in a phantom model. Three stents with lumen diameters of 2.25, 3.0 and 3.5 mm were examined with a third-generation dual-source dual-energy CT (DECT). Tube potential was set at 90/Sn150 kV for DE and 70, 90 or 120 kV for single-energy (SE) acquisitions and advanced modelled iterative reconstruction was used. Overall, 23 reconstructions were evaluated for each stent including three SE acquisitions and ten advanced and standard ME images with virtual photon energies from 40 to 130 keV, respectively. In-stent luminal diameter was measured and compared to nominal lumen diameter to determine stent lumen visibility. Contrast-to-noise ratio was calculated. Advanced ME reconstructions substantially increased lumen visibility in comparison to SE for stents ≤3 mm. 130 keV images produced the best mean lumen visibility: 86 % for the 2.25 mm stent (82 % for standard ME and 64 % for SE) and 82 % for the 3.0 mm stent (77 % for standard ME and 69 % for SE). Mean DLP for SE 120 kV and DE acquisitions were 114.4 ± 9.8 and 58.9 ± 2.2 mGy × cm, respectively. DECT with advanced ME reconstructions improves the in-lumen visibility of small stents in comparison with standard ME and SE imaging. • An advanced image-based monoenergetic reconstruction algorithm improves lumen visualization in stents ≤3.0 mm. • Application of high keV reconstructions significantly improves in-stent lumen visualization. • DECT acquisition resulted in 49 % radiation dose reduction compared with 120 kV SE.


Intraoperative posture and workload assessment in vascular surgery.
Quantifying the workload and postural demand on vascular surgeons provides valuable information on the physical and cognitive factors that predispose vascular surgeons to musculoskeletal pain and disorders. The aim of this study was to quantify the postural demand, workload, and discomfort experienced by vascular surgeons and to identify procedural factors that influence surgical workload. Both objective (wearable posture sensors) and subjective (surveys) assessment tools were used to evaluate intraoperative workload during 47 vascular surgery procedures. Results demonstrate unfavorable neck and low back postures as well as high pain scores for those body segments. Additionally, workload from subjective surveys increased significantly as a function of operative duration, and mental workload was high across all procedure types. Neck postural risk exposure and physical demand were among the variables that increased with surgical duration, procedure type, and loupes used by the surgeons. Correlations among postural angles and pain scores showed consistency between the objective assessment and the subjective surveys for neck and trunk. The authors believe that the results of this study highlight the need for developing mitigating measures such as ergonomic interventions for vascular surgery.


Engineered carbon (biochar) prepared by direct pyrolysis of Mg-accumulated tomato tissues: characterization and phosphate removal potential.
An innovative method was developed to produce engineered biochar from magnesium (Mg) enriched tomato tissues through slow pyrolysis in a N2 environment. Tomato plants treated with 25mM Mg accumulated much higher level of Mg in tissue, indicating Mg can be substantially enriched in tomato plants, and pyrolysis process further concentrated Mg in the engineered biochar (8.8% Mg). The resulting Mg-biochar composites (MgEC) showed better sorption ability to phosphate (P) in aqueous solutions compared to the other four tomato leaves biochars. Statistical analysis showed a strong and significant correlation between P removal rate and biochar Mg content (R(2)=0.78, and p<0.001), indicating the enriched Mg in the engineered biochar is the main factor controlling its P removal ability. SEM-EDX, XRD and XPS analyses showed that nanoscale Mg(OH)2 and MgO particles were presented on the surface of MgEC, which serve as the main adsorption sites for aqueous P.


In vitro effects of thirty-eight cardiac drugs on human serum paraoxonase.
In this study, the effects of 38 commonly used cardiac drugs on the human paraoxonase (PON1) were investigated. PON1 was purified from human serum blood by ammonium sulfate precipitation (60%-80%) and hydrophobic interaction chromatography (Sepharose-4B~L-tyrosine~1-napthylamine gel). All of the cardiac drugs inhibited PON1 at the micro molar level. IC50 and Ki values were determined for each drug. The tested drugs displayed potent PON1 inhibitory activity. It was found that the weakest PON1 inhibitors are Irbesartan (Ki : 421.73 µM), Glyceryl Trinitrate (Ki : 351.48 µM), and Apixaban (Ki : 333.27 µM). Bisoprolol hemifumarate (Ki : 269.31 µM) is also other weak PON1 inhibitor. Therefore, these drugs, having weak PON1 inhibitory activity, may be preferred primarily in patients with atheroclerotic heart disease compared to other drugs due to the protective effect of PON1 on atherosclerosis. Conversely, the most potent inhibitors against PON1 were propafenone (Ki : 0.35 µM), Lacidipine (Ki : 0.78 µM), Lidocaine HCl (Ki : 1.78 µM), and Propranolol (Ki : 1.86 µM). Molecular docking was also applied to confirm the activity of some cardiac drugs on PON1.


Anti-Receptor-Binding Domain Immunoglobulin G Antibody as a Predictor of Seropositivity for Anti-SARS-CoV-2 Neutralizing Antibody.
Neutralizing antibody detection can assess the incidence of COVID-19 and the effectiveness of vaccines. However, commercial reagents for neutralizing antibodies were developed after the anti-SARS-CoV-2 immunoglobulin (Ig) G and IgM antibodies. Therefore, some laboratories did not perform neutralizing antibody testing services because of multiple factors. To find a fast, accurate, and economic alternative for the detection of neutralizing antibodies for the development of COVID-19 screening programs. The response and correlation of 3 antibodies (anti-spike protein neutralizing antibody, total anti-receptor-binding domain [RBD] antibody, and anti-RBD IgG) were determined by observing the dynamics in 61 participants for 160 days after vaccination. The levels of neutralizing and anti-RBD IgG antibodies reached their peak values on day 42 after vaccination (120.75 IU/mL and 14.38 signal-to-cutoff ratio [S/CO], respectively). The total antibody levels peaked at 138.47 S/CO on day 35 after vaccination. The strongest correlation was found between neutralizing and anti-RBD IgG antibody levels (r = 0.894, P < .001). The area under the receiver operating characteristic curve for total antibody levels for the prediction of seropositivity for neutralizing antibodies was 0.881 (P < .001), and that for anti-RBD IgG antibody levels was 0.937 (P < .001). Neutralizing and anti-RBD IgG antibody levels were strongly correlated, and thus anti-RBD IgG antibody levels can be used for the accurate assessment of immunity following SARS-CoV-2 infection or vaccination.


Functional importance of myocardial relaxation in patients with congestive heart failure.
The factors that determine left ventricular end-diastolic pressure (LVEDP) are not completely understood. While many investigators measure relaxation in patients with heart failure, its relative functional importance remains unclear. The authors studied 22 patients with cardiomyopathy before and after 3 months of therapy with metoprolol or placebo. At catheterization, LVEDP, isovolumic relaxation rates not normalized for load (tau), the slope of the tau-end-systolic pressure relation (R), the constant of chamber stiffness (k), left ventricular ejection fraction, stroke volume, and coronary sinus norepinephrine levels were measured using micromanometer pressure measurements and digital ventriculography. The myocardial respiratory quotient was measured using blood gas analysis of the coronary sinus and left ventricular blood. Univariate analysis demonstrated that changes in LVEDP correlated with changes in relaxation rates, R, and the myocardial respiratory quotient. However, multivariate stepwise regression analysis demonstrated that only changes in R independently correlated with changes in LVEDP. These data suggest that relaxation may play some role in the determination of LVEDP in patients with heart failure. Changes in glycolytic activity may also play a role in the determination of LVEDP in patients with congestive heart failure.


Routine vocal cord mobility assessment post cardiac surgery via median sternotomy approach.
Surgery of the aortic arch carries a risk of injury to the vagus and recurrent laryngeal nerves, particularly in a young child, as these structures lie in close proximity to aortic arch. This study aimed to determine the incidence, symptomatology and natural history of vocal cord dysfunction (VCD) following aortic arch reconstructive surgery through a median sternotomy approach. Prospective assessment was performed of all consecutive newborns who underwent cardiac surgery for aortic arch surgery via median sternotomy between January 2016 and May 2017 at a tertiary paediatric hospital. All patients underwent post-operative flexible fibreoptic nasolaryngoscopy (FNL) after extubation to assess for the presence of vocal cord dysfunction (VCD). Those with VCD were re-examined at followup. A feeding assessment performed by speech pathologists (SPs) and a video fluoroscopic swallow study (VFSS) were also performed in those with VCD or feeding difficulties. A total of 35 newborns were included in the study. At initial review, left sided VCD was demonstrated in 65.7% of patients (n=23). Significant associations with VCD were younger age (3.0 versus 6.5 days, p=0.041) and a weak or absent cry (Relative Risk=16.4, 95%CI 3.8-47.8, p<0.001). 52.5% (n=11) of patients with VCD had evidence of aspiration on VFSS. There was no significant difference in intensive care unit stay or overall hospital stay between patients with VCD compared to those without (33.0 days vs 28.8 days, p=0.73; 52.5 vs 45.9, p=0.72.) Infants with either proven VCD or a weak cry were more likely to be discharged home with a nasogastric (NG) tube (RR=4.67, p= 0.048; RR=7.00 p=0.022 respectively). At followup after 106 days, complete resolution was seen in 100% patients with partial VCD and 61.5% with complete VCD. VCD is a common complication following neonatal aortic arch surgery, although most experience resolution of symptoms over time. The authors recommend post-operative laryngoscopy in all patients should be routine, and particularly those with a weak cry.


Protocol for the postoperative radiotherapy in N1 breast cancer patients (PORT-N1) trial, a prospective multicenter, randomized, controlled, non-inferiority trial of patients receiving breast-conserving surgery or mastectomy.
Postoperative radiotherapy (PORT) could be useful for pN1 breast cancer patients who have undergone breast-conserving surgery (BCS) or mastectomy. However, the value of regional nodal irradiation (RNI) for BCS patients, and the indications for post-mastectomy radiotherapy (PMRT) for pN1 breast cancer mastectomy patients, have recently been challenged due to the absence of relevant trials in the era of modern systemic therapy. "PORT de-escalation" should be assessed in patients with pN1 breast cancer. The PORT-N1 trial is a multicenter, randomized, phase 3 clinical trial for patients with pN1 breast cancer that compares the outcomes of control [whole-breast irradiation (WBI) and RNI/PMRT] and experimental (WBI alone/no PMRT) groups. PORT-N1 aims to demonstrate non-inferiority of the experimental group by comparing 7-year disease-free survival rates with the control group. Female breast cancer patients with pT1-3 N1 status after BCS or mastectomy are eligible. Participants will be randomly assigned to the two groups in a 1:1 ratio. Randomization will be stratified by surgery type (BCS vs. mastectomy) and histologic subtype (triple-negative vs. non-triple-negative). In patients who receive mastectomy, dissection of ≥5 nodes is required when there is one positive node, and axillary lymph node dissection when there are two or three positive nodes. Patients receiving neoadjuvant chemotherapy are not eligible. RNI includes a "high-tangent" or wider irradiation field. This study will aim to recruit 1106 patients. The PORT-N1 trial aims to verify that PORT de-escalation after BCS or mastectomy is safe for pN1 breast cancer patients in terms of oncologic outcomes and capable of reducing toxicity rates. This trial will provide information crucial for designing PORT de-escalation strategies for patients with pN1 breast cancer. This trial was registered at ClinicalTrials.gov (NCT05440149) on June 30, 2022.


Statistical methods in epidemiology. VIII. On the use of likelihood ratios for diagnostic testing with an application to general practice.
An array of statistical methods is available for 2 x 2 contingency table analysis. These include odds ratios, reliability coefficients and the Chi-squared test. This paper continues the '2 x 2' theme but extends it to look at diagnostic testing. The setting is primary care, the disease is urological cancer. Several statistical indices are discussed to measure diagnostic efficiency; these include sensitivity, specificity and the likelihood ratio. The latter can be converted into a flexible 'weight of evidence', which is equivalent to the naive Bayes' discriminant. The utility of the naive Bayes' discriminant is illustrated in a primary care setting. The naive Bayes' discriminant has proved to be the most durable of statistical discriminants in medical diagnosis. The reason for its durability is ease of use. Despite a concern about independence, it remains a popular choice as a diagnostic aid.


In vivo synthesis of phosphatidylcholine in rat brain via the phospholipid methylation pathway.
We examined the in vivo synthesis of brain phosphatidylcholine (PC) by the methylation of phosphatidylethanolamine (PE). [3H-methyl]methionine was infused i.c.v., by indwelling cannula, and brain samples were taken 0.5-18 h thereafter and assayed for [3H]PC, as well as for its biosynthetic intermediates [3H]phosphatidylmonomethylethanolamine ([3H]PMME) and [3H]phosphatidyldimethylethanolamine ([3H]PDME), and for [3H]lysophosphatidylcholine ([3H]LPC) and S-[3H]adenosylmethionine ([3H]SAM). Most of the [3H]PC (79-94%) was present ipsilateral to the infusion site, indicating that the radioactivity in the [3H]PC was primarily of intracerebral origin, and not taken up from the blood. Moreover, only very low levels of [3H]PC were attained in brains of animals receiving [3H]methionine i.p. and these levels were symmetrically distributed. [3H]PMME and [3H]PDME turned over with apparent half-lives of 2.2 h and 2.4 h. In contrast, the accumulation of brain [3H]PC was biphasic, suggesting the existence of two pools, the more labile of which turned over rapidly (t1/2 = 5 h) and was formed for as long as [3H]PMME and [3H]PDME are present in the brain, and another, which was distinguishable only at 18 h after the [3H]methionine infusion. (The latter pool may have been synthesized from [3H]choline that was released via the hydrolysis of some of the brain [3H]PC previously formed by the methylation of PE.) Subcellular fractionation of brain tissue obtained after in vivo labelling with [3H]methionine revealed that mitochondrial PC had the highest specific radioactivity (dpm per mumol total lipid phosphorus), and myelin the least. These observations affirm that rat brain does synthesize PC in vivo by methylating PE, and the technique provides an experimental system which may be useful for examining the physiological regulation of this process.


Survey of a pelvic health physiotherapy community of practice: a pilot study to gain member input to help sustain and advance the group.
To gather input and perspectives from members of the Calgary Pelvic Health Physiotherapists' Community of Practice (PHPT CoP) to ensure common goals that help sustain and advance the group. An online survey grounded in CoP theory was used to elicit feedback from 23 PHPTs. Descriptive statistics summarized survey results. The response rate was 96%; all respondents worked in women's pelvic health. Respondents expressed interest in continuing regular face-to-face meetings, a speaker series, case studies, and connecting with other PHPTs. The findings suggest continuation of regular meetings, with a focus on clinical skill development, and an annual Alberta PHPT conference. Members of this community of practice seek a strategy to promote PHPT to the public and develop referral sources.


Purity determination by a combination of spectrophotometric and liquid chromatographic methods: application to 13-cis-retinoic acid.
A method is described to determine the purity of 13-cis-retinoic acid. Spectrophotometry is used to determine the non-UV-absorbing impurities, and HPLC is used to determine the UV-absorbing impurities. In combination, these methods permit determination of the purity. An authentic standard is used in developing this method, but it is not needed in the application of the method.


Oxidative damages and antioxidant defences after feeding a single meal in rainbow trout.
Feeding and digestion are metabolically demanding causing a rise on metabolic rate called Specific Dynamic Action (SDA). Although SDA has been vastly reported in fish, its potential consequences on the oxidative-antioxidant balance has not been evaluated to date in fish, a model with a long alkaline tide associated with feeding as well. Using rainbow trout (Oncorhynchus mykiss) as a model species, the aims of the present study were to: (1) assess potential oxidative damages and changes in oxidative defences after feeding on a single meal, and (2) identify the timescale of such changes over a 96 h post-feeding period. Oxidative damage in proteins and lipids and the activities of four enzymatic antioxidant defences: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) were measured in gill, stomach, intestine and liver. DNA damage was measured in red blood cells. Fish were sampled before and after 1.5, 6, 24, 48, 72 and 96 h of ingestion of a 3% body mass ration. Trends of post-prandial damage were present in all tissues, but only protein oxidation varied significatively during digestion in the stomach. The intestine and stomach presented the highest enzymatic activities, likely due to the high metabolic action that these tissues have during digestion, with peaks during post-feeding: at 24 h of SOD in stomach and at 48 h of CAT in intestine. Observed GPx peaks during post-feeding in gills are likely due to the exacerbated demands for ion fluxes and/or oxygen during feeding. The differential response of the antioxidant system observed in tissues of rainbow trout during digestion indicates a coordinated and tissue-specific antioxidant defence.


Would physicians override a do-not-resuscitate order when a cardiac arrest is iatrogenic?
To assess whether physicians would be more likely to override a do-not-resuscitate (DNR) order when a hypothetical cardiac arrest is iatrogenic. Mailed survey of 358 practicing physicians. A university-affiliated community teaching hospital. Of 358 physicians surveyed, 285 (80%) responded. Each survey included three case descriptions in which a patient negotiates a DNR order, and then suffers a cardiac arrest. The arrests were caused by the patient's underlying disease, by an unexpected complication of treatment, and by the physician's error. Physicians were asked to rate the likelihood that they would attempt cardiopulmonary resuscitation for each case description. Physicians indicated that they would be unlikely to override a DNR order when the arrest was caused by the patient's underlying disease (mean score 2.55 on a scale from 1 "certainly would not" to 7 "certainly would"). Physicians reported they would be much more likely to resuscitate when the arrest was due to a complication of treatment (5.24 vs 2. 55; difference 95% confidence interval [CI] 2.44, 2.91; p <.001), and that they would be even more likely to resuscitate when the arrest was due to physician error (6.32 vs 5.24; difference 95% CI 0. 88, 1.20; p <.001). Eight percent, 29%, and 69% of physicians, respectively, said that they "certainly would" resuscitate in these three vignettes (p <.001). Physicians may believe that DNR orders do not apply to iatrogenic cardiac arrests and that patients do not consider the possibility of an iatrogenic arrest when they negotiate a DNR order. Physicians may also believe that there is a greater obligation to treat when an illness is iatrogenic, and particularly when an illness results from the physician's error. This response to iatrogenic cardiac arrests, and its possible generalization to other iatrogenic complications, deserves further consideration and discussion.


Insulin signaling in the central nervous system, a possible pathophysiological mechanism of anesthesia-induced delayed neurocognitive recovery/postoperative neurocognitive disorder: a narrative review.
Impairment in neurocognitive functions ranges between delayed neurocognitive recovery (DNR) and postoperative neurocognitive disorders (pNCD). Incidence varies from 11% after noncardiac surgery to 60% after cardiac surgery. Insulin receptors (IRs) signaling pathway in the central nervous system (CNS) could be a possible pathophysiological mechanism of anesthesia-induced DNR/pNCD and perioperative intranasal insulin administration could be a preventive approach. This hypothesis is supported by the following evidence: effects of IRs-CNS signaling pathway on neuromodulation; higher incidence of DNR/pNCD in patients with insulin resistance; neurotoxicity of IRs signaling pathways after anesthetic exposure; improvement of neurocognitive impairment after insulin exposure. This narrative review was conducted after a literature search of PubMed, EMBASE and SCOPUS online medical data performed in May 2022. Perioperative intranasal insulin is shown to be protective and future studies should address: the role of insulin as a neuromodulator; its integration into neuroprotection approaches; patient populations that might benefit from this approach; a well-defined protocol of intranasal insulin administration in a perioperative background and other disciplines; and possible collateral effects.


The deciding factors.
Nurses constantly make choices about the care they give - some decisions are quick and intuitive, others require evidence and analysis.


Postpartum acute myocardial infarction: a rare occurrence of uncertain etiology.
Two women who had an acute myocardial infarction during the early postpartum period are described, and the findings in nine other women previously reported on are summarized. Attention is called to the atypical nature of ischemic heart disease and myocardial infarction in these patients when compared with myocardial infarction during pregnancy and with ischemic heart disease in men. Postpartum infarcts most often occur in women in their 20s during their first pregnancy, frequently a pregnancy complicated by the preeclampsia-eclampsia syndrome, and are associated with a high mortality rate. In one of our patients and one patient previously reported on, the results of coronary arteriography were normal, suggesting that coronary arterial thromboembolism or spasm was a cause of the infarction. Because postpartum myocardial infarction may be unrelated to atherosclerotic narrowing, detailed angiographic studies in such patients appear warranted. These cases indicate the variety and complexity of ischemic heart disease in women.


Loss of autophagy in hypothalamic POMC neurons impairs lipolysis.
Autophagy degrades cytoplasmic contents to achieve cellular homeostasis. We show that selective loss of autophagy in hypothalamic proopiomelanocortin (POMC) neurons decreases α-melanocyte-stimulating hormone (MSH) levels, promoting adiposity, impairing lipolysis and altering glucose homeostasis. Ageing reduces hypothalamic autophagy and α-MSH levels, and aged-mice phenocopy, the adiposity and lipolytic defect observed in POMC neuron autophagy-null mice. Intraperitoneal isoproterenol restores lipolysis in both models, demonstrating normal adipocyte catecholamine responsiveness. We propose that an unconventional, autophagosome-mediated form of secretion in POMC neurons controls energy balance by regulating α-MSH production. Modulating hypothalamic autophagy might have implications for preventing obesity and metabolic syndrome of ageing.


Platelet MAO activity and psychosis proneness in college students.
A population of individuals potentially at risk for psychiatric disorders was identified by screening 633 college students using the Wisconsin Scales for psychosis proneness. Platelet monoamine oxidase (MAO) activity was measured in high-scoring individuals and controls using 14C-benzylamine. Males with deviant scores on the Perceptual Aberration-Magical Ideation Scale showed a bimodal distribution of platelet MAO activity. Kinetic analysis of platelets from probands with the highest and lowest levels of MAO activity in this group revealed differences in Vmax but not in Km. Since abnormal platelet MAO activity has been linked to psychiatric vulnerability, the results provide further support for the validity of the Wisconsin Scales as predictors of psychopathology.


Ultrasound fetal anthropometry to identify large-for-gestational-age: a meta-analysis.
Large-for-gestational-age (LGA) has been suggested to show high rates of mortality and morbidity in pregnant women and their neonates. This study was based on data from 2015 or later to determine whether ultrasound fetal anthropometry is helpful for identifying LGA. Sensitivity, specificity, positive and negative likelihood ratios (LRs), and diagnostic odds ratio (DOR) of studies published in English were summarized using bivariate diagnostic meta-analysis. Study quality was assessed using the revised Quality Assessment of Diagnostic Accuracy Studies tool. Deeks' funnel plot asymmetry test was assessed to identify publication bias. The findings of abdominal circumference were based on a single article. Despite high specificity (0.92), anthropometric formulas showed moderate sensitivity (0.71) and DOR (26) and were categorized as providing "neither exclusion (positive LR<10) nor confirmation (negative LR>0.1)" strategy based on 28 good-quality studies in five articles. However, they were more promising than previous meta-analytic findings not limited to 2015 or later. No publication bias was identified with respect to assessment of anthropometric formulas (P=0.286). Current ultrasound fetal anthropometry is not strongly helpful, but the values of anthropometric formulas provided by future ultrasound are expected especially as the secondary screening of LGA.


Accurate Triage of Oncological Patients for Safely Continuing Cancer Therapy During the SARS-CoV-2 Pandemic.
To evaluate the efficacy of clinical triage of oncological patients for safe continuation of cancer therapy implemented during the first SARS-CoV-2 outbreak. Between 25 February and 21 April 2020, patients attending the Medical Oncology Unit, Spedali Civili Hospital, Brescia (Italy) for cancer therapy underwent triage to identify those with no signs and symptoms suspicious for SARS-CoV-2 infection in which antineoplastic treatment could be continued as scheduled. Triage questions investigated common symptoms (e.g., fever, cough, dyspnea, anosmia, dysgeusia, headache, nasal congestion, conjunctival congestion, sore throat, diarrhea, nausea and vomiting); body temperature and pulse oximetry were also recorded. All patients were followed-up for overt SARS-CoV-2 through to 18th May 2020. Overall, 1180 patients (median age 65 years) underwent triage during the study period. The most frequent primary malignances were breast (32%), gastrointestinal (18%), and lung (16.5%) cancer. Thirty-one (2.5%) presented with clinically evident SARS-CoV-2 infection and tested positive on nasopharyngeal swab testing and/or radiological imaging. Triage identified 69 (6%) grey zone patients with symptoms suspicious for SARS-CoV-2; 5 (7.2%) subsequently developed symptomatic disease. Neither the symptomatic nor the grey zone patients received their scheduled treatment; instead, they were referred for hospitalization or home quarantine. Triage of oncological patients at our Unit provided for safe continuation of scheduled cancer treatment in 91.5% of patients during the initial SARS-CoV-2 outbreak.


Cognitive and behavioral risk factors for low quality of life in survivors of childhood acute lymphoblastic leukemia.
With high survival rates for pediatric acute lymphoblastic leukemia (ALL), long-term quality of life is a prominent consideration in treatment. We concurrently evaluated cognition, behavior, and quality of life in child and adolescent ALL survivors and determined associations between them. The sample included 83 controls (mean age: 12.5 years) and 71 ALL survivors (mean age: 11.9 years, mean age at diagnosis: 3.8 years). Participants completed measures of general intellectual abilities, math achievement, and fine motor skills. Parents and teachers completed a survey assessing child participants' cognitive, behavioral, and emotional function. Parents additionally completed a survey about their child's quality of life. Survivors had lower scores on measures of working memory, processing speed, timed math, and fine motor skills (effect size 0.5-1, p < 0.001). Parents identified more problems with executive function and learning in survivors than controls (effect size > 0.7, p < 0.001), and indicated a lower quality of life in all categories evaluated (effect size > 0.7, p < 10-4). Reduced quality of life was associated with lower math achievement scores and with inattention and executive function problems. ALL survivors experience diffuse cognitive, behavioral, and motor impairments, which are associated with reduced quality of life. These findings underscore the need to address these challenges in ALL survivors. Compared with cancer-free peers, parents of childhood acute lymphoblastic leukemia survivors treated with chemotherapy only reported reduced quality of life. Math difficulties and behavioral problems increased the risk for reduced quality of life. Reduced quality of life is associated with mild cognitive and behavioral difficulties, suggesting that even relatively mild impairments have broad implications for ALL survivors. Screening and early intervention targeting cognitive and behavioral function may enhance quality of life for ALL survivors.


Transposition of Tn5096 and related transposons in Streptomyces species.
IS493 is an insertion sequence isolated from Streptomyces lividans by a method designed to 'trap' transposable elements. IS493 was converted to functional transposons by cloning antibiotic-resistance-encoding genes between ORF-A and ORF-B of IS493 or near the left-end inverted repeat of the element. Tn5096 transposed relatively randomly in several Streptomyces species. Tn5096 can be introduced into streptomycetes on temperature-sensitive vectors by protoplast transformation, FP43-mediated transduction, or by conjugation from Escherichia coli. We have shown that additional genes can be inserted in Tn5096 without disrupting transposition, and that Tn5096 insertions in a tylosin (Ty)-producing strain of Streptomyces fradiae frequently cause no deleterious effects on Ty production. A promoter probe transposon, Tn5099, containing a promoterless xylE gene, transposed in Streptomyces griseofuscus and S. fradiae, and transcriptional fusions were readily identified.


[A diffusion tensor magnetic resonance imaging study of age-related cerebral white matter diffusion anisotropy in normal human adult].
To investigate the correlation between cerebral white matter fraction anisotropy (FA) in normal human adults using the diffusion tensor magnetic resonance (MR) imaging (DTI). Forty-five adults with normal cerebral white matter MRI findings in 3 age groups (n=15), namely 25 approximately 35 years (young), 45 approximately 55 years (middle-aged) and 65 years or above (elderly), underwent conventional MRI and diffusion tensor MR imaging. FA was measured in different regions of interest (ROIs) including the genu and splenium of the corpus callosum, posterior limb and anterior limb of the internal capsule, centrum semiovale, frontal white matter, thalamus and head of the caudate nucleus. The FA values of the corresponding regions were similar between the left and right hemispheres. The FA value in the genu of the corpus callosum, centrum semiovale and the frontal white matter decreased with age, showing significant differences between the 3 age groups (P<0.05). The FA value in the splenium of the corpus callosum decreased significantly with age, with significant differences between the elderly and young groups and between the elderly and middle-aged groups (P<0.05). The values in the posterior limb and anterior limb of the internal capsule also decreased significantly with age as shown by comparison between the elderly and young groups (P<0.05). No significant difference was found in the FA value of the thalamus and head of the caudate nucleus between the three groups (P>0.05). The FA values decrease with age, especially in the genu of corpus callosum, centrum semiovale and frontal white matter. The patient's age and age-related white matter degradation must be considered in DTI-based diagnosis of cerebral diseases.


NEK2 induces drug resistance mainly through activation of efflux drug pumps and is associated with poor prognosis in myeloma and other cancers.
Using sequential gene expression profiling (GEP) samples, we defined a major functional group related to drug resistance that contains chromosomal instability (CIN) genes. One CIN gene in particular, NEK2, was highly correlated with drug resistance, rapid relapse, and poor outcome in multiple cancers. Overexpressing NEK2 in cancer cells resulted in enhanced CIN, cell proliferation and drug resistance, while targeting NEK2 by NEK2 shRNA overcame cancer cell drug resistance and induced apoptosis in vitro and in a xenograft myeloma mouse model. High expression of NEK2 induced drug resistance mainly through activation of the efflux pumps. Thus, NEK2 represents a strong predictor for drug resistance and poor prognosis in cancer and could be an important target for cancer therapy.


Intracellular pH regulation and the acid delusion.
The hydrogen ion concentration ([H+]) in intracellular cytoplasmic fluid (ICF) must be maintained in a narrow range in all species for normal protein functions. Thus, mechanisms regulating ICF are of fundamental biological importance. Studies on the regulation of ICF [H+] have been hampered by use of pH notation, failure to consider the roles played by differences in the concentration of strong ions (strong ion difference, SID), the conservation of mass, the principle of electrical neutrality, and that [H+] and bicarbonate ions [HCO3-] are dependent variables. This argument is based on the late Peter Stewart's physical-chemical analysis of [H+] regulation reported in this journal nearly forty years ago (Stewart. 1983. Can. J. Physiol. Pharmacol. 61: 1444-1461. Doi:10.1139/y83-207). We start by outlining the principles of Stewart's analysis and then provide a general understanding of its significance for regulation of ICF [H+]. The system may initially appear complex, but it becomes evident that changes in SID dominate regulation of [H+]. The primary strong ions are Na+, K+, and Cl-, and a few organic strong anions. The second independent variable, partial pressure of carbon dioxide (PCO2), can easily be assessed. The third independent variable, the activity of intracellular weak acids ([Atot]), is much more complex but largely plays a modifying role. Attention to these principles will potentially provide new insights into ICF pH regulation.


Real-Life Experience on Dolutegravir and Lamivudine as Initial or Switch Therapy in a Silver Population Living with HIV.
Clinical trials and real-life studies have granted the efficacy and safety of dolutegravir and lamivudine (DTG/3TC) in naïve and experienced people living with HIV (PLWH), but there are no long-term data in elderly people. We herein describe our real-life cohort of PLWH who were ≥65 years of age (PLWH ≥ 65) who started or were switched to DTG/3TC, single-tablet regimen, or DTG plus 3TC. We considered laboratory/clinical parameter changes from the baseline to the last follow-up time point available for each person by the paired Wilcoxon test and analyzed factors associated with virological failure (VF) and discontinuation. We included 112 PLWH with a median age of 66 (IQR: 65-70) years, 77.6% males; 84.8% of people had multimorbidity, 34.8% were on polypharmacy, and only 5.4% were naïve to treatment. Reasons to be switched to DTG/3TC were: abacavir removal (38.7%), treatment simplification (33.1%), and PI discontinuation (28.2%). The median treatment durability was 6 (IQR: 5.4-7) years. No significant changes were detected in metabolic, renal, immunological, or cardiovascular biomarkers during follow-up. HIV RNA undetectability was maintained in 104 (92.8%) individuals for whom follow-up evaluation was available. We observed eight discontinuations (two deaths, two VFs, two early intolerances, one significant weight gain, and one switch to long-acting therapy). No factors were significantly associated with VF or discontinuation. This is the first study on DTG/3TC in PLWH ≥ 65 with a follow-up longer than 5 years. DTG/3TC was found to be safe and effective, neutral on metabolic parameters, and with a low discontinuation rate for toxicity or VF.


The impact of calcium peroxide on groundwater bacterial diversity during naphthalene removal by permeable reactive barrier (PRB).
Oxygen-releasing compounds (ORCs) have recently gained much attention in contaminated groundwater remediation. We investigated the impact of calcium peroxide nanoparticles on the groundwater indigenous bacteria in a bioremediation process by permeable reactive barrier (PRB). Three sand-packed columns were applied, including (1) control column (fresh groundwater), (2) natural remediation column (contaminated groundwater), and (3) biostimulation column (contaminated groundwater amended with CaO2). Actinobacteria and Proteobacteria constituted the main phyla among the identified isolates. According to the results of next-generation sequencing, Proteobacteria was the dominant phylum (81% relative abundance) in the natural remediation condition. But, it was declined to 38.1% in the biostimulation column. Meanwhile, the abundance of Actinobacteria and Bacteroidetes were increased to 25.9% and 15.4%, respectively, by exposing the groundwater microbial structure to CaO2 nanoparticles. Furthermore, orders Chlamydiales, Nitrospirales, and Oceanospirillales existing in the control column were detected in the presence of naphthalene. Shannon index was 4.32 for the control column samples, while it was reduced to 2.73 and 2.00 in the natural and biostimulation columns, respectively. Therefore, the present study provides a considerable insight into the impact of ORCs on the groundwater microbial community during the bioremediation process.


The equilibrium constant of beta-cyclodextrin-phenolphtalein complex; influence of temperature and tetrahydrofuran addition.
The temperature influence on creation of a supramolecular complex in which beta-cyclodextrin (beta-CD) is the host molecule and phenolphtalein (PP) is the guest has been studied in aqueous solution by UV-visible absorption spectroscopy. The decrease of temperature of beta-cyclodextrin-phenolphtalein system resulted in a decrease in absorbance of the UV-vis spectrum. Under favourable conditions (0.1 mM beta-CD, 30 microM PP) the termochromic effect is very significant (approximately =0.1 U of absorbance/10 degrees C). The formation constant of inclusion complex was determined at various temperatures (from 10 to 70 degrees C) using Scott's equation. The association constants (K11) for the binding in 0.02 M sodium carbonate (pH 10.5) at 10 and 70 degrees C are 7.44 and 0.26 x 10(4) M(-1) respectively. The stoichiometric ratio of investigated complex was found to be 1:1 on wide range of beta-cyclodextrin:phenolphtalein concentration ratio (from 0.8:1 to 427:1). Additionally, strong interaction between cyclodextrin and tetrahydrofuran (THF) was observed and the inhibitory effect of tetrahydrofurane on the association of beta-CD PP complex was studied. From linear Van't Hoff plots thermodynamic parameters such as: the change of enthalpy (deltaH(o)) and change of entropy (deltaS(o)) were estimated and interpreted.


Regulation of the pulmonary circulation in the perinatal period and in children.
In the fetus, the pulmonary circulation is actively maintained in a constricted state due to low oxygen environment and perhaps leukotrienes. Pulmonary blood flow represents about 8% of fetal cardiac output. Shortly after birth, pulmonary vascular resistance (PVR) and pulmonary arterial pressure fall rapidly, whereas pulmonary blood flow reaches systemic levels. The exact mechanisms by which the dramatic changes in PVR occur with the onset of ventilation at birth are extensively reviewed. They include: oxygen environment and release of vasoactive substances such as bradykinin, PGI2 or PGD2. Thus, regulation of the fetal and immediate postnatal pulmonary circulation reflects a balance between factors producing active pulmonary vasoconstriction and those producing vasodilatation.


Clinical conundrums involving statin drug-drug interactions.
Statins are the cornerstone of pharmacologic therapy for the prevention and treatment of atherosclerotic cardiovascular disease. While they are generally considered safe, statins can be affected by drug-drug interactions (DDIs) that increase their systemic exposure increasing the risk for statin-associated muscle symptoms. These interactions are primarily mediated through metabolizing enzymes such as cytochrome P450 isoenzymes and membrane-bound drug transporting proteins including P-glycoprotein and organic ion transporting polypeptide. Recognition and avoidance of clinically significant statin DDIs is important to ensure their safe use. Conversely, concern over statin DDIs that are not clinically significant may lead to inappropriate underutilization or avoidance of statins in patients who would benefit from them. While many statin DDIs are well-characterized, we present several others that are less-well-established which may warrant clinical attention.


T cell activation and T cell receptor variable region gene usage in measles.
T cell activation and T cell receptor variable (V) regions were studied with monoclonal antibodies in peripheral blood lymphocytes from 22 patients with measles. Increased (greater than 5%) activated T cells (HLA-DR+ CD3+ cells) were noted in 14 of the 22 patients. Elevations of V beta 5+ and V beta 8+ T cells were observed in two and four patients, respectively, and appeared to be associated with T cell activation. The duration of fever was significantly prolonged in those with increased (greater than 10%) activated T cells (p less than 0.01). These results suggest that T cell activation and the preferential expansion of V beta 8+ and V beta 5+ T cells are associated with the pathogenic process of measles.


Dropout in youth and adult education: a multilevel analysis of students and schools in Chile.
School dropout is an increasing worldwide phenomenon, marked by inequality and educational exclusion. In Chile, many students who have dropped out of regular schools attempt to reenter youth and adult education (YAE). However, some of them drop out again from YAE. The aim of this study was to identify and jointly analyze school and individual factors that influence dropout in YAE. This secondary multilevel analysis of official datasets from Chile's Ministry of Education focused on students enrolled in YAE (N = 10,130). According to the findings, YAE dropout can be explained by the individual risk factors of age (19-24 years), low academic achievement, and school-level factors such as number of teachers (raw and student-to-teacher ratio), economic resources, and school management quality. We discuss the need to develop school-level protective factors that build connections, foster student engagement, and ultimately, promote students' permanence and progress in YAE.


Absence of mutation in the putative tumor-suppressor gene KLF6 in colorectal cancers.
The KLF6 gene encodes the Krüppel-like factor 6, a transcription factor that has been individualized as a tumor-suppressor gene involved in the regulation of cell proliferation and differentiation. Recently, high frequency (42%) of KLF6 mutations have been reported in colorectal cancers (CRC) as in prostate cancers, astrocytic gliomas and hepatocellular carcinomas. The aims of the study was to confirm the frequency of KLF6 mutations in a larger series of CRC than that previously published by using DNA extracted from frozen tissue samples, which have been proved to generate less mutational artefact than that extracted from formalin-fixed paraffin-embedded tissue samples, in order to compare KLF6 mutation frequency with that of other common genetic alterations and to determine genotype-phenotype correlations. Amplification and direct sequencing of KLF6 exon 2 of 76 CRC and matched normal frozen tissues was performed. Polymorphisms were observed in 14 cases, among which two (T35T and S116S) had not already been reported. No KLF6 somatic mutation was observed. Our data suggest a minor role of KLF6 mutation in colorectal carcinogenesis and underline the fact that the validity of sequence informations obtained from DNA extracted from formalin-fixed tissues may be limited.


Yoga meets positive psychology: examining the integration of hedonic (gratitude) and eudaimonic (meaning) wellbeing in relation to the extent of yoga practice.
The present study aims to explore the existence of a relationship between the extent of yoga practice and two dimensions of psychological wellbeing: meaning in life and gratitude. Both of the variables are positive psychology constructs; there is theoretical affinity and empirical evidence that they are related to overall psychological wellbeing. One hundred and twenty four participants aged 18 years and above, with yoga experience ranging from none to over six years, responded to a number of scales. The extent of yoga practice was measured by the number of years during which individuals practiced yoga at least two times a week. Participants responded to the following scales: MLQ (Meaning in Life Questionnaire) and GQ-6 (Gratitude Questionnaire). This study hypothesised that the number of years practicing yoga would be positively correlated to the score obtained on the aforementioned scales. Positive correlations were identified between the extent of yoga practice and meaning in life and gratitude. Important implications regarding the contribution of yoga to both hedonic and Eudaimonic happiness are discussed.


Utility of SARS-CoV-2 rapid antigen testing for patient triage in the emergency department: A clinical implementation study in Melbourne, Australia.
Early, rapid detection of SARS-CoV-2 is essential in healthcare settings in order to implement appropriate infection control precautions and rapidly assign patients to care pathways. Rapid testing methods, such as SARS-CoV-2 rapid antigen testing (RAT) may improve patient care, despite a lower sensitivity than real-time PCR (RT-PCR) testing. Patients presenting to an Emergency Department (ED) in Melbourne, Australia, were risk-stratified for their likelihood of active COVID-19 infection, and a non-randomised cohort of patients were tested by both Abbott Panbio™ COVID-19 Ag test (RAT) and SARS-CoV-2 RT-PCR. Patients with a positive RAT in the 'At or High Risk' COVID-19 group were moved immediately to a COVID-19 ward rather than waiting for a RT-PCR result. Clinical and laboratory data were assessed to determine test performance characteristics; and length of stay in the ED was compared for the different patient cohorts. Analysis of 1762 paired RAT/RT-PCR samples demonstrated an overall sensitivity of 75.5% (206/273; 95% CI: 69·9-80·4) for the Abbott Panbio™ COVID-12 Ag test, with specificity of 100% (1489/1489; 95% CI: 99·8-100). Sensitivity improved with increasing risk for COVID-19 infection, from 72·4% (95% CI: 52·8-87·3) in the 'No Risk' cohort to 100% (95% CI: 29·2-100) in the 'High Risk' group. Time in the ED for the 'At/High Risk' group decreased from 421 minutes (IQR: 281, 525) for those with a positive RAT result to 274 minutes (IQR:140, 425) for those with a negative RAT result, p = 0.02. The positive predictive value of a positive RAT in this setting was high, allowing more rapid instigation of COVID-19 care pathways and an improvement in patient flow within the ED. Royal Melbourne Hospital, Melbourne, Australia.


Evidence emerges for early metastasis and parallel evolution of primary and metastatic tumors.
Tumor progression to metastasis usually is assumed to occur through clonal genomic and epigenetic evolution. However, present evidence that challenges this paradigm. They show that genomic aberrations in tumor cells disseminated in the bone marrows of patients with no clinical evidence of metastasis generally do not resemble the aberrations in the primary tumors from which they arose. They interpret this to mean that tumor cells disseminate very early and evolve to metastatic disease independent from the primary tumor. Their model suggests that adjuvant therapies should be targeted to lesions in the disseminated cells rather than lesions found in primary tumors.


Effects of external pelvic compression on form closure, force closure, and neuromotor control of the lumbopelvic spine--a systematic review.
Optimal lumbopelvic stability is a function of form closure (joint anatomy), force closure (additional compressive forces acting across the joints) and neuromotor control. Impairment of any of these mechanisms can result in pain, instability, altered lumbopelvic kinematics, and changes in muscle strength and motor control. External pelvic compression (EPC) has been hypothesised to have an effect on force closure and neuromotor control. However, the specific application parameters (type, location and force) and hypothesized effects of EPC are unclear. Thus, a systematic review was conducted to summarize the in vivo and in vitro effects of EPC. Eighteen articles met the eligibility criteria, with quality ranging from 33% to 72% based on a modified Downs and Black index. A modified van Tulder's rating system was used to ascertain the level of evidence synthesised from this review. There is moderate evidence to support the role of EPC in decreasing laxity of the sacroiliac joint, changing lumbopelvic kinematics, altering selective recruitment of stabilizing musculature, and reducing pain. There is limited evidence for effects of EPC on decreasing sacral mobility, and affecting strength of muscles surrounding the SIJ, factors which require further investigation.


CD4+CD25+ Tregs as dependent factor in the course of bleomycin-induced pulmonary fibrosis in mice.
The immune system is felt to play an essential role in pulmonary fibrosis (PF). CD4+CD25+ regulatory T cells (Tregs) are crucial in maintaining immune tolerance and immune homeostasis, but their role in the pathogenesis of PF is controversial and still unclear. We here explored the relationship between peripheral blood CD4+CD25+ Tregs and the course of bleomycin-induced PF in mice. Mouse PF models were established by intratracheal instillation of bleomycin. Lung histology, hydroxyproline, Th1/Th2 balanc, CD4+CD25+ Tregse were analyzed at the 3rd,7th,14th,21st and 28th days after instillation. CD4+CD25+ Tregs were also transferred into mice with or without PF by tail vein injection. The trend of CD4+CD25+ Tregs changes was increased firstly, decreased, increased again from 7th to 28th days after bleomycin instillation, which had great relevance with alveolitis and fibrosis scores. There also were high Th1 polarization index from 3rd to 14th days and high Th2 polarization index at 21st and 28th days after bleomycin treatment. CD4+CD25+ Tregs could promote the secretion of Th2 cytokines and inhibit the secretion of Th1 cytokines, allow the Th1/Th2 balance to Th2 direction in PF. Moreover, preventive adoptive transfer of CD4+CD25+ Tregs may ameliorate the process of PF, while acute adoptive transfer of CD4+CD25+ Tregs may aggravate the process of PF. These findings suggested that the dynamic changes of CD4+CD25+ Tregs as dependent factor might designate a different course of PF induced by bleomycin in mice, and might be a selected drug use indicator for therapy of PF.