Zeolitic imidazolate framework (ZIF-8)/polyacrylonitrile derived millimeter-sized hierarchical porous carbon beads for peroxymonosulfate catalysis.
Well dispersed nanocatalysts on porous substrate with macroscopic morphology are highly desired for the application of heterogeneous catalysis. Traditional fabrication process suffers from multiple steps for controlling the structure on nanocatalysts and matrix or both. Herein, we report a facile strategy for the synthesis of millimeter-sized hierarchical porous carbon beads (HPCBs) which containing well dispersed hollow-nano carbon boxes for peroxymonosulfate catalysis. Specially, the precursors of HPCBs were prepared by phase inversion method, which involving introduction of zeolitic imidazolate framework (ZIF-8) nanocubes into polyacrylonitrile (PAN) solutions followed by solidification of the mixture. After pyrolysis, nitrogen doped and hierarchical porous HPCBs with diameter of about 1.2 mm were obtained. The merits of our synthesis strategy lie in that synchronizes the hollow microstructure evolution with the shaping of ZIF-8 nanocubes into millimeter scale beads. Attribute to its special structure feature and the appropriate chemical composition, the resultant millimeter-sized HPCBs exhibit enhanced catalytic performance by activation of peroxymonosulfate (PMS) for tetracycline degradation. The degradation efficiency of TC is up to 85.1% within 120 min, which is 18% higher than that of ZIF8-Solid/PAN carbon bead (SPCBs). In addition, the possible decomposition pathways, main reactive oxygen species, and reasonable enhanced mechanism for the HPCBs/PMS system are systematically investigated by quenching experiments, electron paramagnetic resonance (EPR) and liquid chromatography-mass spectrometry (LC-MS). This work addresses the issue of easy aggregation and recycling of carbon materials in industrial productions and extends the prospects of carbon materials in engineering applications.


Lipofuscin can be eliminated from the retinal pigment epithelium of monkeys.
Lipofuscin is a cytologic hallmark of aging in metabolically active postmitotic cells including neurons, cardiac muscle cells, and the retinal pigment epithelium (RPE). High levels of lipofuscin are involved in the pathogenesis of age-related macular degeneration (AMD), the main cause of blindness in the elderly population in the western world. Degradation and exocytosis of lipofuscin by RPE cells have not been observed in vivo until now, and no drug is known to eliminate the intracellular amount of lipofuscin. Here, we show that in monkeys treated with a small molecule belonging to the tetrahydropyridoethers class (n = 36 of 48 monkeys), RPE cells significantly release lipofuscin. In 4 eyes, macrophages were detected which had taken up lipofuscin. They were located between the Bruch's membrane and the RPE, and in the choroid. The quantification of pigment granules was performed by transmission electron microscopy. Our findings open the way to develop therapeutic strategies to remove lipofuscin from RPE cells, which may have implications for the treatment of age-related macular degeneration in which lipofuscin accumulation in cells is a causative factor.


Enhancement of kainate-gated currents in retinal horizontal cells by cyclic AMP-dependent protein kinase.
Dopamine, acting via cyclic adenosine 3':5'-monophosphate (cAMP), has been shown to enhance a kainate-gated ionic conductance in white perch retinal horizontal cells in vitro. To determine whether this effect involves stimulation of a protein kinase, kainate-gated currents were observed in cultured horizontal cells that were dialyzed with the catalytic subunit of cAMP-dependent protein kinase. Intracellular application of catalytic subunit or cAMP, but not heat-inactivated catalytic subunit, caused significant enhancement of the kainate-evoked currents. These results suggest that kainate-gated channels in horizontal cells may be modified by a phosphorylation event.


The LptA protein of Escherichia coli is a periplasmic lipid A-binding protein involved in the lipopolysaccharide export pathway.
The LptA protein of Escherichia coli has been implicated in the transport of lipopolysaccharide (LPS) from the inner membrane to the outer membrane. Here we provide evidence that LptA binds structurally diverse LPS substrates in vitro and demonstrate that it interacts specifically with the lipid A domain of LPS. These results are consistent with LptA playing a chaperone role in the transport of LPS across the periplasm and have implications for possible assembly models.


Hyaluronic acid as a potential marker for assessment of fibrosis regression after direct acting antiviral drugs in chronic hepatitis C patients.
Fibrosis is an inevitable complication of chronic hepatitis C virus (HCV) infection. Direct acting antivirals (DAAs) radically treated HCV and were suggested to ameliorate fibrosis. Silymarin (a natural herbal remedy) was proposed to further decrease hepatic inflammation and fibrosis. Consequently, serial monitoring of liver fibrosis status by different biomarkers is needed. To assess hyaluronic acid (HA) as a potential marker of fibrosis regression after DAAs in chronic HCV patients; in addition, to evaluate silymarin as an agent that, beside DAAs, could further improve fibrosis. Two groups were included (150 patients each). Group 1 received DAAs only, while group 2 received DAAs followed by silymarin. Hyaluronic acid and FIB4 score were assessed at baseline before treatment and 1 year after inclusion in the study. We found that DAA therapy alone or in combination with silymarin resulted in a significant reduction in serum HA level. However, the latter case showed a statistically significantly greater reduction (p = 0.034). Mean ±SD of serum HA level was 211.8 ±179.9 and 143.3 ±123.9 µg/l before and one year after inclusion respectively in group 1 (p = 0.001) and also, its level decreased significantly in group 2 from 188.3 ±211.8 µg/l before receiving DAAs to 126.4 ±136.9 µg/l at one year after inclusion (p = 0.001). There was no significant difference between the 2 studied groups as regards FIB-4 at 1 year after inclusion (p = 0.103). Hyaluronic acid might be a sensitive marker for monitoring fibrosis regression in treated chronic HCV patients. Adding silymarin to treatment protocols could ameliorate the fibrosis status.


The Decapentaplegic morphogen gradient: a precise definition.
Two key processes are in the basis of morphogenesis: the spatial allocation of cell types in fields of naïve cells and the regulation of growth. Both are controlled by morphogens, which activate target genes in the growing tissue in a concentration-dependent manner. Thus the morphogen model is an intrinsically quantitative concept. However, quantitative studies were performed only in recent years on two morphogens: Bicoid and Decapentaplegic. This review covers quantitative aspects of the formation and precision of the Decapentaplegic morphogen gradient. The morphogen gradient concept is transitioning from a soft definition to a precise idea of what the gradient could really do.


The effect of topical CS-088, an angiotensin AT1 receptor antagonist, on intraocular pressure and aqueous humor dynamics in rabbits.
To evaluate the ocular hypotensive effect of topical CS-088, an angiotensin AT1 receptor antagonist, and the effect of CS-088 on aqueous humor dynamics. The effects of CS-088 on intraocular pressure (IOP) were studied in 2 models of rabbit ocular hypertension. Experimental ocular hypertension was induced in albino rabbits by injecting alpha-chymotrypsin into the anterior chamber (alpha-chymotrypsin rabbit). The effects of the single application of CS-088 were examined. Additionally, CS-088 was repeatedly administered over a period of 3 weeks to hereditary ocular hypertensive rabbits (buphthalmic rabbits, JWHR bu/bu) and the IOPs were monitored throughout the experiment. The effects of CS-088 on aqueous humor dynamics were also examined in normal rabbits. In this study, the methods of IOP recovery rate, two-level constant pressure perfusion and fluorescein-dextran perfusion were used respectively to determine the aqueous inflow, outflow facility and uveoscleral outflow (USF). CS-088 at 1% and 2% significantly lowered the IOP in the alpha-chymotrypsin rabbits with a maximum IOP reduction of 10.1 mmHg. The maximum effect obtained with 2% CS-088 was no greater than that with 1% CS-088. In the buphthalmic rabbits, 2% CS-088 also lowered IOP significantly. Timolol was effective in both models. In the study on aqueous humor dynamics, a slight increase in USF (17%) was seen after a topical application of CS-088 whereas changes in aqueous inflow or outflow facility were not observed. Topical CS-088 can decrease IOP in rabbits. Despite the USF change, the ocular hypotensive mechanism by CS-088 was not fully determined.


Arabic translation and cultural adaptation of the stigma-devaluation scale in Jordan.
A review of the literature on measuring the concept of stigma related to caring for a relative with mental illness yielded no instrument appropriate for use in Jordan. To translate and culturally modify the stigma-devaluation scale (SDS) into Arabic, and to test the reliability, content and construct validity of the Arabic version of the SDS. The SDS was translated into the Arabic language, modified and culturally adapted by a translation model. Estimation of internal consistency was used to assess the reliability of the SDS. Construct validity was determined by confirmatory factor analysis (CFA). Measurements of content validity and reading level of the Arabic SDS were included. The Arabic SDS was evaluated in a sample of 164 family caregivers in Jordan. Content validity index was determined to be 1.0. Reading level of the Arabic SDS was deemed to be at a sixth grade level or higher. Cronbach's alpha coefficient of the Arabic SDS total scale was 0.87. The results of the CFA revealed that the factor structure of the SDS had a satisfactory fit. This study provided psychometric evidence that the modified Arabic SDS is valid and conceptually consistent with the content of the original English SDS.


Sarcoidlike granulomas as an early manifestation of Whipple's disease.
Whipple's disease is often accompanied by a long, preintestinal phase of vague symptoms, such as weight loss, fever, and migratory arthralgia, which may delay diagnosis and proper treatment. We report a patient who presented with sarcoidlike granulomas in the lung 1.5 yr before the development of gastrointestinal symptoms. He was treated with prednisone and his lung lesions improved dramatically. However, steroids could not be discontinued until the diagnosis of Whipple's disease was made and he was started on antibiotic treatment. Whipple's disease was diagnosed from a small intestinal biopsy specimen by electron microscopic demonstration of characteristic bacillary bodies. Liver biopsy specimens also demonstrated a few Kupffer cells containing degenerative bacillary bodies. Based on this case and other reported cases of Whipple's disease with sarcoidlike lesions in various organs, we suggest that sarcoidlike tissue reaction can be an early manifestation of Whipple's disease, recognition of which may have practical value in facilitating an early diagnosis and treatment.


Correlation between the Epworth Sleepiness Scale and the Maintenance of Wakefulness Test in Obstructive Sleep Apnea Patients Treated with Positive Airway Pressure.
The Epworth sleepiness scale (ESS) is often used to evaluate the impact of treatment in patients with obstructive sleep apnea hypopnea syndrome (OSA). We aimed to evaluate the correlation between ESS and the Maintenance of Wakefulness Test (MWT) in a population of OSA patients treated with positive airway pressure (PAP). We retrospectively included all patients during a 2-year period who were diagnosed with OSA in our sleep clinic and required PAP therapy. ESS was evaluated at baseline and after PAP therapy for all patients, and all had a concomitant MWT. Correlation between final ESS, change in ESS, and MWT were evaluated using Spearman's correlation. Given that MWT is considered as the gold standard, the diagnostic performance of ESS was evaluated against MWT. Hundred thirty-four OSA patients were included. At the time of MWT, 89.6% of the patients were compliant (PAP use ≥4hours/night), and only 9 (6.7%) had persistent sleepiness despite PAP treatment (mean sleep latency at MWT<19.4min). Moderate correlation was observed between final ESS and MWT (Spearman's correlation coefficient=-0.42), but no correlation was found between change in ESS and MWT. Diagnostic performance was as follows for final ESS: sensitivity=55.6%, specificity=84.8%, PPV=20.8%, and NPV=96.4%. ESS was moderately correlated with MWT in a population of OSA patients compliant with PAP therapy. In this population, ESS showed poor diagnostic performance in identifying patients with persistent excessive daytime sleepiness. CLINICALTRIALS. NCT03629834.


Evaluation of the predictive value of different dietary antioxidant capacity assessment methods on healthy and unhealthy phenotype in overweight and obese women.
Predictive value of different dietary antioxidant capacity assessment methods on healthy and unhealthy phenotypes in overweight and obese women is still unclear. This study aimed to evaluate the predictive value of different dietary antioxidant capacity assessment methods on healthy and unhealthy phenotypes in overweight and obese women. A total of 290 overweight and obese women were included in this cross-sectional study. Food intake was assessed using a semi-quantitative food frequency questionnaire (FFQ). Dietary antioxidant capacity was calculated using valid databases of antioxidant value. The receiver operating characteristic (ROC) curve method was used to evaluate the predictive value of antioxidant capacity indices, including dietary antioxidant quality score (DAQS), ferric reducing ability of plasma (FRAP), total reactive antioxidant potential (TRAP), and trolox equivalent antioxidant capacity (TEAC). The results showed that the highest area under the ROC curve for predicting metabolically healthy obesity (MHO) belongs to the TRAP method (area under the curve (AUC) = 0.53). In addition, this method had the highest AUC for predicting inflammatory marker of C-reactive protein (hs-CRP) (AUC = 0.54) and the index of the homeostatic model assessment for insulin resistance (HOMA-IR) (AUC = 0.59). The highest AUC for triglyceride prediction was related to the DAQS method (AUC = 0.56). Moreover, a significant correlation of FRAP (r = -0.15, P = 0.02), TRAP (r = -0.19, P < 0.001), TEAC (r = -0.18, P< 0.001) with HOMA-IR was reached. The findings of this study show that the best way to predict the status of MHO is TRAP method. This method is also the best predictor of hs-CRP and HOMA-IR. DAQS method is the best predictor for TG.


Examination of a Stillbirth Workup: A Rural Statewide Experience.
The objective of our study was to determine whether recommended assessments were conducted on stillbirths delivered in our predominantly rural state. This was a descriptive study of stillbirths delivered in a rural state and included in one site of the Birth Defects Study to Evaluate Pregnancy Exposures stillbirth study. Hospital and fetal death records were examined to determine whether the following areas were evaluated: genetic testing (noninvasive perinatal testing, quad screen, amniocentesis/chorionic villus sampling with karyotype, microarrays, fetal tissue specimen), placenta/membrane/cord sent for pathologic examination, examination of the stillbirth after delivery by the healthcare provider, and fetal autopsy was performed. From July 1, 2015 to June 30, 2020, there were 1108 stillbirths delivered in Arkansas. The most frequent assessments undertaken were placental pathology (72%), genetic testing (67%), fetal inspection (31%), and autopsy (13%). All four assessments were done in 2% of stillbirth cases, three assessments in 27%, two assessments in 47%, one assessment in 14%, and no assessment in 15%. There was no association between stillbirth assessment evaluation by gestational age (<28 weeks and > 28 weeks; P = 0.221); however, there was an overall association between hospital delivery volume with number of components completed (P < 0.0001). Hospitals with >2000 deliveries had a higher proportion of three or four completions compared with those hospitals with <1000 deliveries or 1000 to 2000 deliveries (P = 0.021 and P < 0.0001). Fetal stillbirth assessment is suboptimal in our rural state, with 15% of stillbirths having no assessment and only 2% having all four assessments. There is no association between stillbirth assessment and gestational age (<28 weeks vs >28 weeks), but there is a correlation between delivery volume and stillbirth assessment.


Immobilization of viral and mycoplasma antigens and of immunoglobulins on polystyrene surface for immunoassays.
The immobilization of purified influenza virus, rubella virus, crude nuclear cytomegalovirus antigen and of mycoplasma on polystyrene tubes was studied using radio-iodinated preparations. The antigen activities on tube surfaces were determined using sequentially specific human antibodies and alkaline phosphatase-conjugated anti-human IgG in an enzyme-immunoassay (EIA) reaction. In addition, immobilization of radio-iodinated human IgG, IgM, and IgA, serving as model proteins, was studied using the respective anti-immunoglobulin conjugates in EIA directly. Pretreatment of the surface with albumin and glutaraldehyde inhibited the adsorption and antigenicity of IgG. Increase of temperature and thus of speed of adsorption did not affect the fraction of antigen eluted during the test procedure. Only with IgG and IgA was it necessary to saturate the polystyrene surface in order to achieve maximal reactivity in EIA. With other antigens, maximal reactivity in EIA was obtained with amounts of protein much lower than the maximal amount that could be adsorbed per tube. IgM was found to have an exceptionally high affinity to polystyrene.


Empathy, emotional intelligence, and communication in Nursing: The moderating effect of the organizational factors.
to evaluate the relation and the moderating effect of the organizational factors on the attitudes towards communication, empathy, and emotional intelligence in the nurses. a cross-sectional study was conducted with a convenience sample of 268 nurses from Valencia, Spain. The attitudes towards communication were evaluated by means of the specifically designed instrument, those towards empathy with the Jefferson's Scale of Empathy for Nursing Students, and those towards emotional intelligence by means of the Trait Meta-Mood Scale, consisting of 24 items. The effect of the studied variables was assessed by means of ANOVA, multiple linear regression models were applied, and the moderating effect was analyzed using PROCESS. there are statistically significant differences based on the type on contract (permanent); and statistically significant differences were found in the cognitive dimension of the attitudes towards communication. Regarding the regression models, the perspective taking dimension of empathy was the main predictive variable tn the dimensions of the attitudes towards communication. Finally, a moderating effect of the type of contract was evidenced in the effect of emotional reparation over the cognitive dimension of the attitudes towards communication. the organizational factors exert an influence on the attitudes towards communication, empathy, and emotional intelligence.


NLRP3 associated with chronic kidney disease progression after ischemia/reperfusion-induced acute kidney injury.
Nod-like receptor protein 3 (NLRP3), as an inflammatory regulator, has been implicated in acute kidney injury (AKI). Failed recovery after AKI can lead to chronic kidney disease (CKD). However, the role of NLRP3 in the AKI-CKD transition is still unknown. A mild or severe AKI mouse model was performed by using ischemia-reperfusion injury (IRI). We evaluated the renal NLRP3 expression in acute and chronic phases of ischemic AKI, respectively. Although serum creatinine (Cr) and blood urea nitrogen (BUN) levels in AKI chronic phase were equivalent to normal baseline, histological analysis and fibrotic markers revealed that severe AKI-induced maladaptive tubular repair with immune cell infiltration and fibrosis. Tubular damage was restored completely in mild AKI rather than in severe AKI. Of note, persistent overexpression of NLRP3 was also found in severe AKI but not in mild AKI. In the severe AKI-induced chronic phase, there was a long-term high level of NLRP3 in serum or urine. Overt NLRP3 was mainly distributed in the abnormal tubules surrounded by inflammatory infiltrates and fibrosis, which indicated the maladaptive repair. Renal Nlrp3 overexpression was correlated with infiltrating macrophages and fibrosis. Renal NLRP3 signaling-associated genes were upregulated after severe AKI by RNA-sequencing. Furthermore, NLRP3 was found increased in renal tubular epitheliums from CKD biopsies. Together, persistent NLRP3 overexpression was associated with chronic pathological changes following AKI, which might be a new biomarker for evaluating the possibility of AKI-CKD transition.


Synthesis of 9-substituted 2,3,4,9-tetrahydro-1H-carbazole derivatives and evaluation of their anti-prion activity in TSE-infected cells.
2,3,4,9-Tetrahydro-9-[2-hydroxy-3-(1-piperidinyl)propyl]-6-methyl-1H-carbazol-1-one (GJP14) is a novel anti-prion compound that we previously discovered by in silico screening and cellular assay. In this study, a variety of GJP14 derivatives were prepared using pyrrole derivatives, (haloalkyl)oxiranes, and amines, and their anti-prion activity was evaluated in TSE-infected cells. It was found that the tricyclic aromatic ring, a hydroxy group at the 2-position and an amino group at the 3-position of the N-propyl group were the basic requirements for anti-prion activity. The derivatives bearing an N-ortho-halobenzyl group exhibited an improved activity, and the most potent derivative was 8 times as effective as the original lead compound, GJP14.


Digital anthropometry via three-dimensional optical scanning: evaluation of four commercially available systems.
Digital anthropometry is increasingly accessible due to commercial availability of three-dimensional optical scanners (3DO). One hundred and seventy-nine participants were assessed by four 3DO systems (FIT3D®, Size Stream®, Styku®, and Naked Labs®) in duplicate, air displacement plethysmography (ADP), and dual-energy x-ray absorptiometry (DXA). Test-retest precision was evaluated, and validity of total and regional volumes was established. All scanners produced precise estimates, with root mean square coefficient of variation (RMS-%CV) of 1.1-1.3% when averaged across circumferences and 1.9-2.3% when averaged across volumes. Precision for circumferences generally decreased in the order of: hip, waist and thigh, chest, neck, and arms. Precision for volumes generally decreased in the order of: total body volume (BV), torso, legs, and arms. Total BV was significantly underestimated by Styku® (constant error [CE]: -10.1 L; root mean square error [RMSE]: 10.5 L) and overestimated by Size Stream® (CE: 8.0 L; RMSE: 8.3 L). Total BV did not differ between ADP and FIT3D® (CE: -3.9 L; RMSE: 4.2 L) or DXA BV equations (CE: 0-1.4 L; RMSE: 0.7-1.5 L). Torso volume was overestimated and leg and arm volumes were underestimated by all 3DO. No total or regional 3DO volume estimates exhibited equivalence with reference methods using 5% equivalence regions, and proportional bias of varying magnitudes was observed. All 3DO produced precise anthropometric estimates, although variability in specific precision estimates was observed. 3DO BV estimates did not exhibit equivalence with reference methods. Conversely, DXA-derived total BV exhibited superior validity and equivalence with ADP.


Conjoined lumbosacral nerve roots. Diagnosis with metrizamide myelography.
The most common anomaly of the lumbosacral nerve roots consists of a composite root sleeve containing the roots for two spinal nerves. Before the advent of water-soluble myelography, this anomaly was rarely diagnosed except at operation. Metrizamide myelography readily demonstrates the anomaly because of improved filling of the root sleeves and greater definition of the nerve roots within the subarachnoid space. However, an underlying disk herniation may not be evident on the myelogram because of the unique anatomic configuration.


Safety footwear: A survey of end-users.
This paper presents the results of an extensive survey concerning the experience of safety footwear end-users. Safety footwear has been in widespread use across many industries worldwide since the 1970s, and has become an essential part of industrial Personal Protective Equipment. The number of women entering predominantly male industrial environments, and requiring safety footwear is rising, and this is accompanied by anecdotal reports of ill-fitting and uncomfortable footwear. This research proactively compares the opinions of women and men regarding their experience of safety footwear. A systematically designed survey aims to substantiate previously anecdotal knowledge around safety footwear, including key drivers for end-user purchases, wear habits and comfort issues (establishing any differences between women and men). Chi-squared testing was used to assess statistical significance and ensure robustness of findings. The responses and resulting analysis confirmed that comfort and fit were key drivers for all end users; women and men have different wear habits (women wear their safety footwear less frequently and for shorter periods of time than men - likely due to the reported comfort issues); a significant proportion of women (60%) found their safety footwear less comfortable than their regular footwear, however, 45% of men also reported the same, which has not been reported anecdotally. In general, the users of safety footwear accepted a level of discomfort in at least one area of the foot before deeming footwear 'uncomfortable'. The significant analysis performed on the captured data has, to the authors knowledge, never before been undertaken for this breadth of industry, age and gender with 632 responses received. This makes it the largest study of this field to date.


The inverted terminal repetition of the DNA of weakly oncogenic adenovirus type 7.
By use of the chemical modification technique of Maxam and Gilbert (1977), the first 180 base pairs at both termini of the human adenovirus 7 genome have been determined. The results show that adenovirus 7 DNA contains a perfect inverted terminal repetition of 136 base pairs.


Magnetic Resonance of the Small Bowel: How to Do It.
Small bowel magnetic resonance (MR) imaging has been clinically implemented for many years, albeit with variation in study technique. Considerable research has been performed during this time regarding optimum patient preparation, choice of enteric contrast medium, and MR imaging sequence protocol but findings have not been universally implemented. However, evidence-based consensus statements have recently been published from the United States and Europe. This article summarizes key findings from this guidance and presents practice examples from the authors' own institution.


Tube growth stimulation of pine pollen by low doses of irradiation. Dose rate, reproducibility and comparison between UV-light and ionizing rays.
Stimulation of the tube growth of pine pollen by low doses of UV-light or X-rays is a reproducible process, but it depends strongly of the dose rate applied. It can be proved that the observed effect is more determined by dose rate and irradiation time than by the dose itself which can vary by nearly one order of magnitude for achieving the same increase in tube elongation. The range of absorbed energy at which the stimulation effect can be observed is rather broad and overlapping between UV and X-rays. In the average the UV-energy needed is 5 times higher than X-ray energy.


Finite element analysis in brace treatment on adolescent idiopathic scoliosis.
Adolescent idiopathic scoliosis (AIS) is a musculoskeletal disorder characterized as three-dimensional (3D) deformity, and bracing is a common conservative treatment for AIS. Finite element analysis (FEA) is a technique for numerically solving the differential equations arising in engineering and mathematical modeling and has been widely used in biomechanical studies. Recently, FEA has been under intensive focus to improve the clinical outcomes of brace treatment. This review focuses on using FEA to assist brace treatment for AIS and technique choices that may be encountered during the construction of the finite element model (FEM). The construction of geometric models, the mechanical property, element type, the boundary condition, and the observation items of FEA have been summarized while establishing FEM. In each technical aspect, different fields and limitations of FEA are discussed. The observation items based on FEA are collected in addition to the biomechanical value in clinical research. We also summarized the technical aspects of brace treatment by FEA and observation items and provided guidance and directions to improve the brace treatment.


Tuberculosis, hepatitis B, rubella, rubeola, and varicella infection and immunity among medical school employees.
To assess baseline health status of a medical school employee population and to assess this population's acceptance of vaccination and other interventions to reduce risk of disease transmission. A retrospective review of an employee health records database for a 4-year period. A large, urban university hospital. 5,007 employees screened by employee health for immunity to vaccine-preventable illnesses and tuberculosis. 9.4% of the employees had positive tuberculin skin tests, with a conversion rate of 6.4% for those who had negative tests within the previous 2 years. Two individuals were identified who had active pulmonary tuberculosis. Fewer than 10% of the individuals for whom isoniazid chemoprophylaxis was recommended completed the 6 months of therapy. Most clinical employees (96.1%) did not have a history of prior hepatitis B virus (HBV) infection or immunization, but 77% of them subsequently completed the vaccination series. Most employees with a negative history for infection with or immunization against rubella, rubeola, and varicella had serological evidence of immunity (90.2%, 97.9%, and 87.2%, respectively). Review of aggregate employee health databases may assist individuals who must establish strategies for prevention of occupational illness and disease transmission in this specialized setting. While many employees at risk for HBV complete the vaccination series, strategies for improving this rate could be helpful. Substantial work is needed to analyze reasons why so few individuals for whom isoniazid chemoprophylaxis is recommended complete the therapy, and strategies tailored to the impediments identified should be implemented.


Immune-related disorders in families of children with inflammatory bowel disease--a prospective cohort study.
The aim of this paper was to examine the prevalence of immune-related disorders in families of children with inflammatory bowel disease (IBD) compared to those without IBD. Children ≤18 years of age presenting to the IBD clinic between September 2007 and August 2009 with an established diagnosis of IBD were recruited. Age and sex matched controls without IBD were recruited. The study was a single-centre prospective cohort study. Outcome measures were prevalence of immune-based/inflammatory diseases in families of both patients and controls. One hundred and eight children in each group were recruited. Asthma was the most frequently reported disease in families of the IBD patients (52.8%) and controls (46.3%). The prevalence of IBD in families of IBD patients was significantly higher than in those without IBD (OR 2.03, 95% CI 1.04-3.95). The prevalence of immune-based disorders, as a group, in families of children with IBD was not significantly higher when compared to children without IBD.


[New technique of renal plication for the treatment of severe hydronephrosis].
We present the case of an eleven-year old boy affected of giant hydronephrosis on a unique right pelvic kidney, treated according to an original technique consisting in the use of a free peritoneal flap for the completion of a renal banding to complement Mollard's (1973) and Stewart Hamilton's (1957) nephroplasty procedures.


Hepatic enhancement during helical CT: a comparison of moderate rate uniphasic and biphasic contrast injection protocols.
The purpose of this study was to compare the degree and timing of peak hepatic enhancement, optimal scanning intervals, and optimal delay times of moderate-rate uniphasic and biphasic contrast material injection protocols for hepatic helical CT. One hundred fifty patients were randomized into three injection protocols, receiving 42.3 g iodine (150 ml iothalamate meglumine) delivered using 3 ml/sec uniphasic, 2 ml/sec uniphasic, or biphasic (3 ml/sec [50 ml], 1 ml/sec [100 ml]) technique. Statistically fitted aortic and hepatic enhancement curves were generated from dynamic incremental CT data for each patient. Protocols were compared by maximum hepatic enhancement, and contrast enhancement indices were modeled for a 38-sec helical acquisition. The 3 ml/sec and 2 ml/sec uniphasic protocols produced higher peak hepatic enhancement (64 +/- 15 H and 62 +/- 15 H [mean +/- 1 SD]) than the 3 ml/sec biphasic protocol (52 +/- 10 H; p < .001). Contrast enhancement indices for the 3 ml/sec uniphasic and 2 ml/sec uniphasic protocols (385 +/- 398 H/sec and 397 +/- 412 H/sec) were significantly greater than the index for the 3 ml/sec biphasic protocol (123 +/- 194 H/sec; p < .0001) at a 50-H threshold. Optimal scan delay times were 50 +/- 8, 75 +/- 7, and 119 +/- 8 sec, respectively, for the 3 ml/sec uniphasic, 2 ml/sec uniphasic, and 3 ml/sec biphasic techniques. The moderate-rate uniphasic injections studied provided greater hepatic enhancement throughout the helical acquisition without requiring the prohibitively long delay time necessitated by the moderate-rate biphasic injection. These findings differ from prior results that showed that a uniphasic injection may provide comparable levels of hepatic enhancement when compared with a high-flow-rate biphasic injection.


Clinical Pharmacokinetics of the Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitor Doravirine: An Assessment of the Effect of Patient Characteristics and Drug-Drug Interactions.
Doravirine (MK-1439) is a novel non-nucleoside reverse transcriptase inhibitor indicated for the combination treatment of human immunodeficiency virus type-1 (HIV-1) infection. The recommended dose is 100 mg once daily. This review summarizes the pharmacokinetics of doravirine, the influence of intrinsic factors, and its drug-drug interaction (DDI) profile. Following oral administration, doravirine is rapidly absorbed (median time to maximum plasma concentration, 1-4 h) and undergoes cytochrome P450 (CYP)3A-mediated oxidative metabolism. Steady-state geometric means for AUC0-24, C24, and Cmax in individuals with HIV-1 following administration of doravirine 100 mg once daily are 37.8 μM·h, 930 nM, and 2260 nM, respectively. Age, gender, severe renal impairment, and moderate hepatic impairment have no clinically meaningful effect on doravirine pharmacokinetics, and there is limited potential for DDIs. No dose adjustment is necessary when doravirine is co-administered with strong CYP3A inhibitors. However, doravirine is contraindicated with strong CYP3A inducers (e.g., rifampin), and dose adjustment of doravirine is recommended for co-administration with the moderate CYP3A inducer, rifabutin. Included in this review are clinical trial data from phase I pharmacokinetic trials, including DDI trials and trials in participants with renal and hepatic disease but without HIV-1 infection (N = 326), as well as phase I, II, and III safety and efficacy trials in participants living with HIV-1 (N = 991). Based on these data, the pharmacokinetic profile of doravirine supports its use in diverse populations living with HIV-1 and allows co-administration with various antiretroviral agents and treatments for commonly occurring co-morbidities.


Droplets in underlying chemical communication recreate cell interaction behaviors.
The sensory-motor interaction is a hallmark of living systems. However, developing inanimate systems with "recognize and attack" abilities remains challenging. On the other hand, controlling the inter-droplet dynamics on surfaces is key in microengineering and biomedical applications. We show here that a pair of droplets can become intelligently interactive (chemospecific stimulus-response inter-droplet autonomous operation) when placed on a nanoporous thin film surface. We find an attacker-victim-like non-reciprocal interaction between spatially separated droplets leading to an only-in-one shape instability that triggers a drop projection to selectively couple, resembling cellular phenomenologies such as pseudopod emission and phagocytic-like functions. The nanopore-driven underlying communication and associated chemical activity are the main physical ingredients behind the observed behavior. Our results reveal that basic features found in many living cell types can emerge from a simple two-droplet framework. This work is a promising step towards the design of microfluidic smart robotics and for origin-of-life protocell models.


Iatrogenic gastrocolic fistula associated with non-steroidal anti-inflammatory drug administration.
An unusual case is presented of a benign gastrocolic fistula occurring in a 70-year-old man treated with piroxicam for arthritis for a period of only two months. This report illustrates that significant upper gastrointestinal complications can occur, even with short-term treatment, with non-steroidal anti-inflammatory drugs (NSAIDs).


[Radiosensitivity of stem cells in the spermatogenic epithelium of mice of different strains and different ages].
In experiments on CBA and BALB/c male mice (3 months of age) and F1(CBA X C57BL/6) hybrids (at the age of 3, 12, and 24 months) a difference was noted in the radiosensitivity of spermatogenic epithelium stem cells displayed by the changes in their colony-forming ability in testicular tubules 42 days following local 60Co-gamma-irradiation. The older the hybrid mice the smaller was the number of spermatogenic epithelium stem cells.


Influence of pleurotomy on pulmonary function after off-pump coronary artery bypass grafting.
This study evaluated the influence of pleurotomy on pulmonary function after off-pump coronary artery bypass grafting (CABG) using the left internal thoracic artery (LITA). Thirty patients were prospectively allocated into two groups: 15 patients with an opened left pleural cavity (OP group) and 15 patients with an intact pleural cavity (IP group). Bedside pulmonary function tests were recorded preoperatively and on postoperative days 1, 3, and 5. Arterial blood gas analyses and ratio of partial pressure of arterial oxygen (PaO2/fraction of inspired oxygen (FiO2) ratio were evaluated preoperatively and on postoperative day 1. A significant decrease of pulmonary function was observed in both groups until postoperative day 5. When compared with the percentage of the preoperative value, the forced vital capacity was significantly lower in the OP group than in the IP group on postoperative days 1 (33.3% +/- 8.3% versus 49.1% +/- 8.4%, p < 0.001), 3 (45.4% +/- 7.0% versus 62.1% +/- 8.6%, p < 0.001), and 5 (56.1% +/- 8.7% versus 77.5% +/- 11.6%, p < 0.001). Similar results were found for forced expiratory volume in 1 second on postoperative days 1 (35.7% +/- 8.6% versus 50.0% +/- 9.8%, p < 0.001), 3 (48.4% +/- 7.0% versus 61.5% +/- 9.02%, p < 0.001) and 5 (58.8% +/- 8.5% versus 75.9% +/- 10.2%, p < 0.001). The PaO2 value and the PaO2/FiO2 ratio dropped on postoperative day 1 in both groups (p < 0.05), with a higher fall in the OP group (p < 0.05). Orotracheal intubation time (p = 0.012) and hospital stay (p = 0.002) were lower in the IP group. Off-pump CABG using the LITA, independently of pleural opening, induced a significant reduction in early postoperative pulmonary function. However, the patients undergoing pleurotomy demonstrated more pronounced pulmonary dysfunction.


[Sustainability in intensive and emergency care : A nationwide survey by the German Society of Medical Intensive Care and Emergency Medicine].
The impact of climate change on humans is well known. However, the health care system is also a relevant contributor, accounting for up to 5-7% of global greenhouse gas emissions, and work should be adapted to be more sustainable. The survey investigated whether sustainability plays a role in hospitals and specifically in the field of emergency and intensive care. Concrete measures and which hurdles are already recognized were also inquired. The "AG Nachhaltigkeit" (working group on sustainability) of the "Deutschen Gesellschaft für Internistische Intensivmedizin und Notfallmedizin" (DGIIN) conducted an electronic survey among the staff of intensive care units, emergency rooms, and ambulance services in Germany. In all, 218 survey results were included in the analysis: 108 (50%) participants were from the nursing sector and 98 (45%) belonged to the medical staff. The majority of participants work in an intensive care unit (181 [83%]) followed by intermediate care unit (52 [24%]). A total of 104 (47%) participants indicated that their workplace had already implemented sustainability measures. However, when asked whether decision-makers in the workplaces incorporate sustainability into their decisions, management scored highest with only 20%. Potential for improvement is seen in energy and waste management, among others. The survey results show that (1) employees are highly motivated to address the issue of sustainability and to implement measures, (2) the potential to establish a resource-saving and environmentally friendly hospital is far from being exhausted, and (3) it must become a priority that decision-makers in the hospital propagate sustainability, make processes transparent, and support the motivation of employees on the subject of sustainability. In addition, this process must be supported by politicians and health insurance companies.


Yokukansan, a Kampo medicine, enhances the level of neuronal lineage markers in differentiated P19 embryonic carcinoma cells.
Yokukansan (YKS), a traditional Japanese Kampo medicine, affects neurological and psychiatric disorders. It ameliorates hippocampal neurogenesis in animals. However, its effect on neuronal cell differentiation remains unclear. Therefore, we investigated the effects of YKS on pluripotent P19 embryonic carcinoma cells as neuronal differentiation model cells. Western blotting and immunocytochemistry revealed that 10 μg/mL YKS treatment during embryoid body formation or neuronal differentiation increased the expression of the neuronal stem cell marker, Nestin, by 1.9-fold and 1.7-fold, respectively, and of the mature neuron marker, NeuN, by 1.5-fold and 1.4-fold, respectively. We examined the effect of YKS on intracellular signaling pathways in P19 cells and found significant elevation in phospho-PDK1 and phospho-mTOR expression (1.1-fold and 1.2-fold, respectively). Therefore, we investigated the effect of PDK1 and mTOR inhibitors on the level of neuronal lineage markers. We found that the mTOR inhibitor significantly abolished the YKS effect on the level of neuronal lineage markers. Moreover, to identify the target(s) of YKS, antibody array analysis that simultaneously detects 16 phosphorylated proteins was performed. YKS significantly upregulated 10 phosphorylated proteins including PDK1, Akt, AMPK, PRAS40, mTOR, p70 S6 kinase, GSK-3α, Bad and ERK1/2 under cell proliferation conditions. These results suggest that YKS simultaneously activates multiple signaling pathways. Thus, we concluded that YKS enhances the level of neuronal lineage markers in differentiated P19 cells, however it does not induce neuronal differentiation. Furthermore, mTOR is the predominant mediator of the YKS effect on these cells.


How best to manage late preterm pre-eclampsia?
Review of: Chappell LC, Brocklehurst P, Green MF, et al Planned early delivery or expectant management for later preterm pre-eclampsia (PHOENIX): a randomised controlled trial. Lancet 2019;394:1181-90.


The comparative effects of a synthetic and a 'natural' oestrogen on the haemostatic mechanism in patients with primary amenorrhoea.
A synthetic and a natural oestrogen were administered alternately for three months to nine women with primary amenorrhoea using a randomized cross-over schedule. Measurements of haemostatic function were performed before and at the end of each treatment period. No significant change in haemostatic function was observed after treatment with the 'natural' oestrogen, oestriol succinate. In contrast, treatment with a synthetic oestrogen, ethinyloestradiol, caused shortening of the prothrombin time and an increase in plasma concentration of factor VII and plasminogen. These data support other observations in suggesting that natural oestrogens may have fewer potentially adverse effects on haemostatic function than synthetic oestrogen.


Endothelin-1: expression and role in human corpus luteum.
Several recent data suggest an involvement of endothelin (ET)-1, a powerful vasoconstrictor peptide, in reproductive function. This study was designed to investigate the presence and role of ET-1 in human corpus luteum. Purified luteal cells were incubated for different times with ET-1 or ET-3 alone or associated with human chorionic gonadotropin. In another set of experiments cells were treated with ET-1 and BQ485, an ET-A receptor antagonist, or with phorbol 12-myristate-13 acetate (PMA), an activator of protein kinase C. ET-1 reduced both basal and human chorionic gonadotropin-induced progesterone production at all examined times, similarly PMA inhibited basal progesterone synthesis. BQ485 prevented the inhibitory effect of ET-1, while no effect was observed with ET-3. Finally, ET-1 mRNA was detected in the luteal cells. ET-1 is expressed by human luteal cells and reduces basal and human chorionic gonadotropin-induced progesterone synthesis through the ET-A receptors and the protein kinase C pathway. Conversely, ET-3 does not affect luteal steroidogenesis.


Supplementation of pooled human milk with casein hydrolysate: energy and nitrogen balance and weight gain composition in very low birth weight infants.
Growth and nitrogen and energy balances were studied with a combined technique of nutrient balance and indirect calorimetry measurement in two groups of eight very low birth weight infants fed pooled pasteurized human milk (HM) or cow's milk casein hydrolysate supplemented HM (HM-Pr). There was no difference in the amount of energy absorbed (91 +/- 17 kcal/kg/day with HM-Pr versus 95 +/- 8 with HM-P) or in the growth rate. The infants fed HM-Pr had a higher nitrogen intake (602 +/- 80 versus 395 +/- 64 mg/kg/day; p less than 0.001), urinary nitrogen excretion (160 +/- 64 versus 78 +/- 16 mg/kg/day; p less than 0.005) and nitrogen retention (326 +/- 32 versus 252 +/- 48 mg/kg/day; p less than 0.01). They also had increased plasma concentrations of essential amino acids, urea nitrogen, and total protein without metabolic imbalance. Energy expenditure was higher (58 versus 49 kcal/kg/day; p less than 0.005) and energy storage lower (33 versus 47 kcal/kg/day; p less than 0.05) with HM-Pr. In percent of weight gain, protein and fat accretion represented 12 and 14% in HM-Pr group versus 10 and 27% in HM group. Very low birth weight infants fed casein hydrolysate supplemented pooled HM achieved a growth rate and a weight gain composition similar to the fetus.


[Video-assisted thoracoscopic removal of esophageal leiomyomas with intraoperative tumor location by endoscopy].
To summarize our experience with video-assisted thoracoscopic (VATS) removal of esophageal leiomyoma located with endoscopy during operation. Between January 2006 and December 2010, 55 patients with esophageal leiomyoma underwent VATS enucleation. The surgical procedure was similar to that of open thoracotomy with intraoperative endoscopic location of the tumor and examination of the mucosal integrity especially for tumors less than 1 cm in diameter. Of the 55 patients undergoing VATS tumor removal, 54 patients completed the procedures smoothly, and 1 patient experienced ventricular fibrillation during the operation to require an open thoracotomy. Endoscopy was used in 38 patients during the operation. VATS enucleation differed significantly from open thoracotomy in the volume of bleeding, postoperative fasting days and postoperative hospital stay (P<0.05). The symptoms were completely relieved after the operation without postoperative complications. The patients were followed up for 8 to 59 months (mean 23.0 months) and no recurrence was found. VATS removal of esophageal leiomyomas is minimally invasive, safe and effective and can serve as the primary option for surgical removal of esophageal leiomyomas.


Health-related quality of life and metabolic control in adolescents with diabetes: the role of parental care, control, and involvement.
This questionnaire-based study explored the role of parenting in health-related quality of life in a population of 115 adolescents with type 1 diabetes (aged 11-18 years, 48% girls). Healthy adolescents (n = 9,345) and physically disabled adolescents (n = 291) were included as controls. The adolescents with diabetes reported their parents as being more controlling and involved than did adolescents in the 2 other groups. In multiple regression analyses, age, gender, and a higher degree of parental care and involvement explained 46% of the variation in mental health. Age, gender, a higher degree of parental care and involvement, and a lower perception of parental control explained 52% of the variation in diabetes life-satisfaction. Neither glycosylated hemoglobin nor the other clinical variables studied were significantly related to the perception of health-related quality of life. Family support should be provided to facilitate coping with everyday management and demands of diabetes.


Bioavailability of cinnarizine in dogs: effect of SNEDDS loading level and correlation with cinnarizine solubilization during in vitro lipolysis.
To investigate the effect of increasing the loading level of the poorly soluble drug cinnarizine in a self-nanoemulsifying drug delivery system (SNEDDS) both in vitro and in vivo. A fixed dose of cinnarizine was administered orally to dogs in solution in different amounts of SNEDDS vehicle. Furthermore, the SNEDDSs were characterised using the dynamic in vitro lipolysis model. Statistical differences in bioavailability were not obtained between the different amounts of SNEDDS vehicle, in spite of differences in the tendency of cinnarizine to precipitate during in vitro lipolysis of the treatments. Use of the SNEDDS concept decreased the variation in cinnarizine exposure observed between dogs as compared to administering cinnarizine in an aqueous suspension. Optimization of SNEDDSs towards keeping the drug compound in solution upon in vitro lipolysis of the SNEDDSs may not be as important as previously suggested.


High False Positives and False Negatives in Yeast Parameter in an Automated Urine Sediment Analyzer.
Automated urine sediment analyzers have proven their feasibility in medical laboratories. However, editing manual microscopic review of some specimens severely limits the usefulness of such systems. This study aims to give feedback on the practical experience on »Yeast«, which is one of the parameters that compel frequent manual reviews. 5448 freshly collected urine specimens submitted from various departments of our hospital for diagnostic urinalysis were studied by the UriSed® (77 Elektronika, Hungary). A specialist medical doctor inspected every image on-board, and reviewed the ones with a »Yeast« alarm by traditional manual microscopy. UriSed alarmed in 491 samples (9%) for yeast. In 59 samples (1%) the number of particles exceeded the cut-off and a »positive for yeast« was set. A false positive report of yeast +1 to 3+/HPF was found in 51 samples (0.9%). There were 8 cases with positive for yeast from both microscopic methods. Thirty-three »negative for yeast« samples were corrected as positive after the manual microscopic review. We report a high percentage of false positives and negatives in the yeast parameter, in line with other studies on UriSed as well as on other instruments in the market. As an important feedback, our observations showed that the major concern in false results was »the focusing problem«. We believe in the necessity of a focus check and comparison of alarms between images on board.


Pyrimidinylimidazole inhibitors of CSBP/p38 kinase demonstrating decreased inhibition of hepatic cytochrome P450 enzymes.
Pyrimidine analogs of the pyrimidinylimidazole class of CSBP/p38 kinase inhibitors were prepared in an effort to reduce the potent inhibition of hepatic cytochrome P450 observed for the pyridinyl compounds. The substitution of pyrimidin-4-yl, 2-methoxypyrimidin-4-yl, or 2-methylaminopyrimidin-4-yl for pyridin-4-yl effectively dissociates CSBP/p38 kinase from P450 inhibition for this series and furthermore achieves an increase in oral activity.


Creatine-enhanced diet alters levels of lactate and free fatty acids after experimental brain injury.
Free fatty acids (FFA) and lactic acid are markers of secondary cellular injury following traumatic brain injury (TBI). We previously showed that animals fed a creatine (Cr)-enriched diet are afforded neuroprotection following TBI. To further characterize the neuroprotective Cr diet, we studied neurochemical changes in cortex and hippocampus following a moderate injury. Adult rats were fed either a control or Cr-supplemented diet (0.5%, 1%) for 2 weeks before TBI. At 30 min or 6 h after injury, tissue was processed for quantitative analysis of neurochemical changes. Both lactate and FFA were significantly increased in all tissues ipsilateral to the injury. Cr-fed animals had significantly lower levels, although the levels were elevated compared to sham controls. Animals fed a 1% Cr-diet were afforded greater neuroprotection than animals fed a 0.5% Cr diet. These results support the idea that a Cr-enriched diet can provide substantial neuroprotection in part by suppressing secondary brain injury.


Synthesis, X-ray crystal structure, and biological activity of FR186054, a novel, potent, orally active inhibitor of acyl-CoA:cholesterol O-acyltransferase (ACAT) bearing a pyrazole ring.
The synthesis, single crystal X-ray structural analysis, and biological activity of FR186054 (2c), a new, potent, orally efficacious inhibitor of acyl-CoA:cholesterol O-acyltransferase (ACAT), containing a pyrazole ring are described. This compound displayed excellent in vitro efficacy, irrespective of dosing method, indicating superior characteristics compared to other ACAT inhibitors.


Using Deprescribing Practices and the Screening Tool of Older Persons' Potentially Inappropriate Prescriptions Criteria to Reduce Harm and Preventable Adverse Drug Events in Older Adults.
Approximately 98% of older Americans are simultaneously taking 5-or more-medications to manage at least 2 chronic conditions. Polypharmacy and the use of potentially inappropriate medications (PIMs) are a concern for older adults because they pose a risk for adverse drug events (ADEs), which are associated with emergency department visits and hospitalizations and are an important patient safety priority. We sought to review the evidence of patient safety practices aimed at reducing preventable ADEs in older adults, specifically (i) deprescribing interventions to reduce polypharmacy and (ii) use of the Screening Tool of Older Persons' Potentially Inappropriate Prescriptions (STOPP) to reduce PIMs. We conducted a systematic review of literature published between 2008 and 2018 that studied examined the effect of these interventions to reduce preventable ADEs in older adults. Twenty-six studies and 1 systematic review were included (14 for deprescribing and 12 for STOPP and the systematic review). The deprescribing interventions involved decision support tools, educational interventions, and medication reviews by pharmacists and/or providers. Deprescribing studies primarily examined the effect of interventions on process outcomes and observed reductions in polypharmacy, often significantly. A few studies also examined clinical and economic outcomes. Studies of the use of the STOPP screening criteria most commonly reported changes in PIMs, as well as some economic outcomes. Deprescribing interventions and interventions using the STOPP criteria seem effective in reducing polypharmacy and PIMs in older adults, respectively. Future research on the effectiveness of these approaches on clinical outcomes, the comparative effectiveness of different multicomponent interventions using these approaches, and how to most effectively implement them to improve uptake and evidence-based care is needed.


Chromosomal aberrations in bone marrow and peripheral blood cells from the same rats.
Spontaneous cytogenetic aberrations were analyzed in bone-marrow cells and cultured peripheral lymphocytes from the same animals. No significant differences in the total number of cells with aberrations or total aberrations were detected between the bone-marrow cells and cultured lymphocytes. It was concluded that short-term culture does not contribute significantly to in vivo aberration yield within the experimental conditions used.


Production and characterization of monoclonal antibodies to the major protein of boar outer dense fibers.
Outer dense fibers (ODF) are structural elements in the mammalian sperm tail which surround the axoneme in the midpiece and principal piece and probably may help to maintain the elastic structures and elastic recoil of the sperm tail. In the present study, we have generated and characterized and describe a series of monoclonal antibodies (mAbs) against the 30 kDa major protein from boar ODF. For antibody screening an ELISA was developed using a newly developed method to fix the ODF proteins to the solid phase. A total of seven mAbs were selected and characterized by ELISA, Western blot and immunofluorescence. The mAbs recognize the major protein component of boar ODF on preparative Western blot and mark the mid- and principal piece of demembranated flagella. These mAbs also recognize the mid- and principal piece of demembranated human spermatozoa from normozoospermic patients, but not from those with asthenozoospermia. For the first time, we succeeded in obtaining hybridoma cell lines that secrete mAbs of class IgM, which react with the 30 kDa protein of boar ODF.


Induction of chicken avidin and related mRNAs after bacterial infection.
Inflammation-mediated avidin gene expression in the chicken was studied using hybridization analysis, polymerase chain reaction (RT-PCR) and sequencing. The results indicate the presence of avidin mRNA in the oviduct and intestine after Escherichia coli infection. The mRNA for the inflammation-induced avidin was mainly encoded by the avidin gene, but the avidin-related genes, avr2 and avr3, were also transcribed at a low level in the oviduct and intestine, respectively. Because avidin is also induced in the chicken oviduct by progesterone, our results indicate a multifactorial regulation of avidin gene expression.


Effects of ethanol on pancreatic beta-cell death: interaction with glucose and fatty acids.
Western lifestyle plays an important role in the prevalence of type 2 diabetes by causing insulin resistance and pancreatic beta-cell dysfunction, a prerequisite for the development of diabetes. High fat diet and alcohol are major components of the western diet. The aim of the present study was to investigate the effects of ethanol and fatty acids on beta-cell survival and metabolism. We treated the rat beta-cell line RINm5F with ethanol, a mixture of palmitic and oleic acids, or both. Reactive oxygen species (ROS) were determined by (5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate) (CM-H2DCFDA) fluorescence assay, and mitochondrial activity was assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) reduction assay and by determining ATP production. Cell viability was assessed with a cell counter and trypan blue exclusion, and the mode of cell death by Hoechst33342 and propidium iodide staining. With both ethanol and fatty acid treatments, MTT reduction and ATP production decreased, whereas ROS production increased. Ethanol treatment had no effect on cell number, whereas fatty acid treatment reduced the cell number. Cell incubation with ethanol, fatty acids, or both increased the number of Hoechst 33342-positive nuclei. However, the majority of nuclei from fatty acid-treated cells were stained with propidium iodide, indicating a loss of plasma membrane integrity. We conclude that both ethanol and fatty acids generate cellular oxidative stress, and affect mitochondrial function in RINm5F beta-cells. However, ethanol causes beta-cell death by apoptosis, whereas fatty acids cause cell death predominantly by necrosis. It is not known whether these results are applicable to human beta-cells.


Assessment of renal circulation in small for gestational age and appropriate for gestational age term newborns: a prospective study.
To compare selected parameters of renal circulation between small for gestational age (SGA) and appropriate for gestational age (AGA) newborns. Fifty-two SGA and 100 AGA term newborns were examined. The size of the kidneys were measured, and renal blood flow in the central and intraparenchymal renal arteries were assessed via Doppler sonography. Peak systolic velocity (PSV), end diastolic velocity (EDV), mean blood flow velocity (V mean), resistance index (RI), and pulsatility index (PI) were determined and compared between the groups. No statistically significant differences in the velocity parameters were found between SGA and AGA infants in central renal arteries. Slightly higher RIs and PIs were seen in AGA newborns (RI, 0.76 +/- 0.13 versus 0.78 +/- 0.06 [p < 0.05]; PI, 1.65 +/- 0.54 versus 1.84 +/- 0.46 [p < 0.05]). There were statistically significant differences between the groups in all measured parameters in intraparenchymal arteries (RI, 0.57 +/- 0.11 versus 0.63 +/- 0.05 [p < 0.001]; PI, 0.89 +/- 0.26 versus 1.09 +/- 0.16 [p < 0.001]) except PSV (7.11 +/- 1.55 versus 7.14 +/- 0.81 cm/s [p > 0.05]). Based on our findings, we suggest that renal circulation is not negatively influenced by intrauterine growth restriction in SGA neonates compared with AGA newborns.


A meta-analysis of human papillomavirus type-distribution in women from South Asia: implications for vaccination.
To determine human papillomavirus (HPV) prevalence and type-distribution in women from South Asia, with and without cervical lesions, in order to estimate the impact of an HPV 16/18 prophylactic vaccine in this region and to assess additional types that should be incorporated in new vaccines. A meta-analysis was conducted that included studies using polymerase chain reaction to detect HPV-16, -18, -6, -11 and at least one other HPV type, with a minimum of 20 cases in each grade of lesion. Total as well as type-specific prevalence of various HPV types were estimated, stratified by cervical lesion grade, using Stata 9.0 software package. Nine studies from India fulfilled the inclusion criteria. A total of 558, 52, 52 and 3061 women, respectively with invasive cervical cancer (ICC), high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL) and normal cytology/histology were included. Overall HPV prevalence was 94.6%, 86.5%, 65.4% and 12.0% in women with ICC, HSIL, LSIL and normal cytology/histology, respectively. In ICC, HPV-16 was the predominant type (64.8%), followed by HPV-18, -45, -33, -35, -58, -59 and -31. The estimated HPV-16/18 positive fraction was 78.9% in women with ICC (87.7% in North and 77.2% in South India), 61.5% with HSIL, 30.8% with LSIL and 3.9% in women with normal cytology/histology. There was no difference in overall HPV prevalence in cervical cancer between North and South India (P=0.063). However, HPV-16 and -45 appeared to be more prevalent in North India (P=0.018 and 0.013, respectively), while HPV-35 appeared to be more prevalent in South India (P=0.033). It is estimated that HPV-16/18 vaccines will provide over 75% protection against ICC in South Asia. HPV-45, -33, -35 and -58 account for an additional 20% of cervical cancer in this region. The addition of these additional HPV types in a second-generation vaccine could provide optimal cervical cancer prevention in this region.


Carbamazepine.
This chapter includes the aspects of carbamazepine. The drug is synthesized by the use of 5H-dibenz[b,f]azepine and phosgene followed by subsequent reaction with ammonia. Carbamazepine is generally used for the treatment of seizure disorders and neuropathic pain, it is also important as off-label for a second-line treatment for bipolar disorder and in combination with an antipsychotic in some cases of schizophrenia when treatment with a conventional antipsychotic alone has failed. Other uses may include attention deficit hyperactivity disorder, schizophrenia, phantom limb syndrome, complex regional pain syndrome, borderline personality disorder, and posttraumatic stress disorder. The chapter discusses the drug metabolism and pharmacokinetics and presents various methods of analysis of this drug such electrochemical analysis, spectroscopic analysis, and chromatographic techniques of separation. It also discusses its physical properties such as solubility characteristics, X-ray powder diffraction pattern, and thermal methods of analysis. The chapter is concluded with a discussion on its biological properties such as activity, toxicity, and safety.


Can transthoracic echocardiography with subcostal view predict abdominal aortic atherosclerosis?
Prompt detection of atherosclerosis (ATH) may profoundly impact therapy and patient outcome. During transthoracic echocardiography (TTE), subcostal views may suggest abdominal (ABD) aortic (AO) ATH, but this diagnosis may be inaccurate due to suboptimal images, which may in part relate to use of nonlinear probes. Therefore, we investigated the accuracy of TTE assessment of ABD AO ATH relative to transesophageal (TEE) AO images. Routine clinical TTE and TEE studies of 100 patients (44 men), aged 30-92 years old, were reviewed retrospectively and blindly. ABD AO ATH by TTE was graded qualitatively as grade (GR) 0 = smooth wall surface; GR 1, 2, and 3 = mild, moderate, and severe irregularities, respectively; and GR 4 = mobile/complex plaque. TEE images were graded quantitatively as the maximal intimal-medial, or plaque thickness, imaged in the AO arch or descending AO, as: GR 0 <or= 1.5 mm, GR 1 = 1.5-2.4 mm, GR 2 = 2.5-4 mm, GR 3 = >4 mm, or GR 4 = mobile/complex plaque >4 mm. TTE ability to detect the presence (>GR 0) of ABD AO ATH on TEE was measured in terms of sensitivity (SN), specificity (SP), positive (PPV) and negative (NPV) predictive accuracy-in patients with adequate and suboptimal images-compared to TEE. TTE image quality was adequate in 75 patients and suboptimal in 25. SP and PPV of grading ATH by TTE were directly related to grading by TEE; however, SN and NPV demonstrated an inverse relationship with increasing grading of ATH. TTE correlated with TEE grading with an r = 0.42 (P = 0.0001) for patients (n = 75) with adequate TTE and r = 0.32 (P = 0.001) for all patients (n = 100), including those with suboptimal TTE images. Routine TTE imaging is usually correct in predicting ATH on TEE, but with modest error, it should generally not be relied on as a definitive test for ATH. Adequate image quality improves the correlation of TEE and TTE grading of ABD ATH, and more severe ATH on TTE is more predictive of ATH on TEE.


Ultrasensitive and rapid detection of miRNA with three-way junction structure-based trigger-assisted exponential enzymatic amplification.
Aberrant expression of micro RNA (miRNA) is associated with development of cancers and diseases, so miRNA has become a tissue-based biomarker for cancer prognosis and diagnosis. Herein, a novel trigger-assisted exponential enzymatic amplification (T-EXPEA) method for ultrasensitive miRNA detection based on three-way junction (3-WJ) structure driven has been reported, which can be used in potential applications in cancer prognosis and diagnoses. In this assay, target miRNA can unfold hairpin probe and start the reaction, and thus specifically form stable 3-WJ structure with helper. Then it can produce triggers under the synergetic polymerase and restriction endonucleases amplification. The produced triggers could be used to unfold molecular beacon (MB) and initiate T-EXPEA process. In the EXPEA part, the exponential triggers were generated to initiate new T-EXPEA and high enhancement fluorescence amplification efficiency was obtained. The feature of our strategy lies in the T-EXPEA combining with 3-WJ structure has been utilized for fluorescence miRNA detection. It is worth noting that the sequence of the triggers in T-EXPEA part is the same to that of triggers generated from the 3-WJ part. In addition, the design of restriction enzyme cutting sites using the same restriction enzyme (Nt.BbvCI) in hairpin probe and MB respectively, improved reaction efficiency cost-efficiently. This method can quantitatively detect sequence-specific miRNA in a dynamic range from 10 aM to 10 pM with a detection limit as low as 7.8 aM.


Transcriptomics and machine learning to advance schizophrenia genetics: A case-control study using post-mortem brain data.
Alterations of the expression of a variety of genes have been reported in patients with schizophrenia (SCZ). Moreover, machine learning (ML) analysis of gene expression microarray data has shown promising preliminary results in the study of SCZ. Our objective was to evaluate the performance of ML in classifying SCZ cases and controls based on gene expression microarray data from the dorsolateral prefrontal cortex. We apply a state-of-the-art ML algorithm (XGBoost) to train and evaluate a classification model using 201 SCZ cases and 278 controls. We utilized 10-fold cross-validation for model selection, and a held-out testing set to evaluate the model. The performance metric utilizes to evaluate classification performance was the area under the receiver-operator characteristics curve (AUC). We report an average AUC on 10-fold cross-validation of 0.76 and an AUC of 0.76 on testing data, not used during training. Analysis of the rolling balanced classification accuracy from high to low prediction confidence levels showed that the most certain subset of predictions ranged between 80-90%. The ML model utilized 182 gene expression probes. Further improvement to classification performance was observed when applying an automated ML strategy on the 182 features, which achieved an AUC of 0.79 on the same testing data. We found literature evidence linking all of the top ten ML ranked genes to SCZ. Furthermore, we leveraged information from the full set of microarray gene expressions available via univariate differential gene expression analysis. We then prioritized differentially expressed gene sets using the piano gene set analysis package. We augmented the ranking of the prioritized gene sets with genes from the complex multivariate ML model using hypergeometric tests to identify more robust gene sets. We identified two significant Gene Ontology molecular function gene sets: "oxidoreductase activity, acting on the CH-NH2 group of donors" and "integrin binding." Lastly, we present candidate treatments for SCZ based on findings from our study CONCLUSIONS: Overall, we observed above-chance performance from ML classification of SCZ cases and controls based on brain gene expression microarray data, and found that ML analysis of gene expressions could further our understanding of the pathophysiology of SCZ and help identify novel treatments.


Social cognition and adjustment in adult survivors of pediatric central nervous system tumors.
Survivors of pediatric central nervous system (CNS) tumors are at risk for neurocognitive and social difficulties throughout childhood. This study characterized social cognition (perception and reasoning from social cues) and adjustment in adulthood. A total of 81 adult survivors of pediatric CNS tumors (51% female; mean [SD] age, 28.0 [5.8] years), were recruited across four groups: (1) no radiation therapy (RT) [n = 21], (2) infratentorial (IT) tumors + focal RT [n = 20], (3) IT tumors + craniospinal irradiation [n = 20], and (4) supratentorial tumors + focal RT [n = 20]. Prevalence of social cognitive and adjustment impairments was compared to test norms. Multivariable models examined clinical and neurocognitive predictors of social cognition and its impact on functional outcomes. Survivors demonstrated elevated risk of severe social cognitive impairments (social perception Morbidity Ratio [95% CI] 5.70 [3.46-9.20]), but self-reported few social adjustment problems. Survivors of IT tumors treated with craniospinal irradiation performed nearly 1 SD worse than survivors treated without RT on multiple measures of social cognition (e.g., social perception: β = -0.89, p = .004). Impaired executive functioning and nonverbal reasoning were associated with worse social cognitive performance (e.g., social perception: β = -0.75, p < .001; β = -0.84, p < .001, respectively). Better social perception was associated with higher odds of attaining full-time employment (odds ratio, 1.52 [1.17-1.97]) and at least some college education (odds ratio, 1.39 [1.11-1.74]). Adult survivors of CNS tumors are at elevated risk of severely impaired social cognition, but do not perceive social adjustment difficulties. Better understanding of potential mechanisms underlying social cognitive deficits may inform intervention targets to promote better functional outcomes for at-risk survivors.


No estrogen-like effects of an isopropanolic extract of Rhizoma Cimicifugae racemosae on uterus and vena cava of rats after 17 day treatment.
The effects of black cohosh extracts (Rhizoma Cimicifugae racemosae) on primary estrogen target organs, like mammary gland and endometrium are better described then those on other estrogen-sensitive systems e.g. the vasculature. We therefore treated ovariectomized DA/Han rats for 17 days with an isopropanolic Cimicifuga racemosa rhizoma extract (iCR) alone and in combination with the pure antiestrogen fulvestrant. As control groups vehicle, estradiol, fulvestrant, and estradiol fulvestrant cotreatment were used. Effects of all substances were investigated by vena cava and uterine gene expression analysis using real-time-PCR. Uterus wet weight was increased after estradiol treatment compared to the negative controls but none of the other treatments including the treatment with iCR had a uterotrophic effect. While estradiol-induced changes in uterine gene expression were mainly analogous to those detectable in shorter term experiments, iCR showed no or slightly antiestrogenic effects on gene expression in the uterus. This is mirrored in the vena cava where iCR had a very minor impact on the expression of the genes analyzed. While C. racemosa is effectively used for treatment of peri- and post-menopausal symptoms for a long time its mechanism of action remains unresolved. Contrary to earlier suggestions C. racemosa does not seem to act as an estrogen agonist, but possibly as a weak antiestrogen.


Major histocompatibility complex and strong human leukocyte antigen-DRB1 and gender association with Vogt-Koyanagi-Harada syndrome in Mexican Mestizos.
Vogt-Koyanagi-Harada syndrome (VKH) is a multisystem autoimmune disorder mediated by cytotoxic T cells targeting melanocytes antigen(s). A strong major histocompatibility complex (MHC) association with HLA-DRB1*04:05 has been demonstrated in different populations. We investigated the contribution of HLA-A*, -B*, -C*, -DRB1*, and -DQB1* genes, belonging to the human leukocyte antigen (HLA), to the expression of VKH and we analyzed the influence of gender on the HLA association. A total of 76 patients and 256 healthy Mexican Mestizo individuals were included. HLA-A, B, C, and DQB1 typing was performed using the polymerase chain reaction, and hybridization was done using sequence specific probes. DRB1 alleles were defined by means of sequence base typing. The frequency of DRB1*04:05 (odds ratio=2.95) and DRB1*04:04 (odds ratio=2.79) were found to be significantly increased in the patients, conferring a similar risk. Gender stratification analysis showed that these alleles were associated with female gender only. No HLA class I or class II alleles were significantly deviated in males. The frequency of DRB1*04:07 was increased in the whole group, upon withdrawal from analysis the DRB1*04:04 and *04:05 positive patients. A trend of DRB1 alleles contributing to the expression of VKH is suggested: DRB1*04:05=*04:04>*04:07>*01:01>*01:02. Although none of the results were significant after the p value was corrected, the data are consistent with those in numerous other studies, suggesting that several different DRB1* alleles may be involved in the etiopathogenesis of the disease by presenting an overlapping set of ocular peptides to the T cells, which in turn may trigger the autoimmune response that is present in the patients.


Characterization of multiple fumarase proteins in Escherichia coli.
Two different types of fumarase were found in sonic extracts of Escherichia coli; one required Fe-S for the enzyme activity, and the other did not. When the cells were grown without aeration, the Fe-S-independent enzyme occupied over 80% of the overall fumarase activity. Highly purified Fe-S-independent enzyme was suggested to be composed of four subunits (Mr = 48 kDa) by SDS-polyacrylamide gel electrophoresis and gel filtration. Amino acid and N-terminal sequence analyses supported the possibility that the enzyme is a product of fumC gene (FUMC). In aerobically grown cells, however, the content of FUMC was low and the Fe-S-dependent fumarase occupied over 80% of the overall activity. The Fe-S-dependent enzyme appeared to be labile and the activity was rapidly lost during purification. Although the spontaneous inactivation was previously ascribed to thermal lability (S.A. Woods & J.R. Guest (1987) FEMS Microbiol. Lett. 48, 219), the activity could be restored by anaerobic incubation with ferrous ions and SH-compounds.


Amelioration in Ankle Pain and Improvement in Function After Total Knee Arthroplasty for Ipsilateral Knee and Ankle Osteoarthritis: A Report of Two Cases.
We report 2 cases of ipsilateral ankle and knee osteoarthritis (OA), with the chief complaint being chronic ankle and knee pain. In the first patient, the ankle pain was more severe than the knee pain, whereas the second patient had more severe pain in the knee than in the ankle. In both cases, varus malalignment of the knee and varus tilt of the ankle joint were detected on standing radiographs. The severity of OA was found to be grade 4 in the knee, according to the Kellgren-Lawrence grading system, and stage IIIa in the ankle, according to the modified Takakura ankle OA classification system. Navigation-assisted total knee arthroplasty was performed in both cases, leading to a decreased degree of varus malalignment in the knee and ankle, as well as a significantly improved patient-based outcome in both joints. Correction of malalignment of the ankle by total knee arthroplasty relieved the severe pain and restored optimal function in the ankle without surgical intervention.


Prevalence of odontogenic cysts in a group of Libyan population: A retrospective study.
Odontogenic cysts (OCs) are commonly encountered lesions affecting the human jaws having special clinical and radiographic features depending on cyst type. The aim of this study was to determine the prevalence of odontogenic jaw cysts in a Libyan population in Benghazi and to compare these data with previously published reports from Libyan and other geographic areas. This is a descriptive study where screening of 2189 biopsies (retrieved from the archives of The Department of Oral Pathology/University of Benghazi, Libya) was performed for the sake of recognizing the three cysts chosen for the purpose of this study. : Out of the screened lesions, 276 cases (12.6%) were diagnosed as odontogenic cysts in the period from 2006 to 2019. Of those, 67.39% were inflammatory and 32.61% were developmental in nature. Radicular cysts (60.5%) were the most frequent cysts followed by dentigerous cysts (14.8%) and keratocysts (14.5%). The mean ages of the patients were 32.3, 29.7, and 33.2 years, respectively. Occurrence of the cysts was noticed more in the maxilla than in the mandible (1.3:1). The overall male-to-female ratio was 1.1:1. The prevalence of odontogenic cysts was similar to that reported in a previous study in Libya and other countries irrespective to WHO (2017) classification of odontogenic cysts.


Neural circuit dynamics of drug-context associative learning in the mouse hippocampus.
The environmental context associated with previous drug consumption is a potent trigger for drug relapse. However, the mechanism by which neural representations of context are modified to incorporate information associated with drugs of abuse remains unknown. Using longitudinal calcium imaging in freely behaving mice, we find that unlike the associative learning of natural reward, drug-context associations for psychostimulants and opioids are encoded in a specific subset of hippocampal neurons. After drug conditioning, these neurons weakened their spatial coding for the non-drug paired context, resulting in an orthogonal representation for the drug versus non-drug context that was predictive of drug-seeking behavior. Furthermore, these neurons were selected based on drug-spatial experience and were exclusively tuned to animals' allocentric position. Together, this work reveals how drugs of abuse alter the hippocampal circuit to encode drug-context associations and points to the possibility of targeting drug-associated memory in the hippocampus.


Assessment of adult cancer pain: shortcomings of current methods.
The evaluation of cancer pain remains a problematic clinical problem, not only due to the subjective and multidimensional nature of pain per se, but also because of its specific characteristics. Cancer pain has an insidious onset, often involves many sites, and is frequently multicausal. Tools have been developed to quantify pain, the most commonly used being the verbal rating scale (VRS), the visual analogue scale (VAS), and the McGill Pain Questionnaire (MPO). The first 2 scales are short, easy to administer and to score, but only measure pain intensity. The VRS is assumed to be an ordinal scale although unequal differences between pain descriptors have been demonstrated; it offers a restrictive choice of words that may not represent pain experience with sufficient precision, and is not sensitive to change especially for mild pain. The VAS on the other hand, represents pain as a continuum and is sensitive to change. The MPQ has the advantage of evaluating the sensory, affective and evaluative dimensions of pain. However, it is lengthy to administer and some words are not readily understandable. In addition, the words within a given category are considered to be equidistant, the number of words in each category are unequal, and the number of categories evaluating a given dimension are not taken into account when calculating the total pain rating index. A further issue in assessing pain, other than the choice of a valid and reliable tool, is the frequency with which pain evaluations should be repeated. To date no studies have addressed this problem.(ABSTRACT TRUNCATED AT 250 WORDS)


Synthesis, molecular structure and antioxidant activity of bis [L(μ2-chloro)copper(II)] supported by phenoxy/naphthoxy-imine ligands.
A new series of Cu(II) complexes [bis[{(μ2-chloro)-2-MeO-Ph-CH2-(N=CH)-2,4-tert-butyl-2-OC6H2)}Cu(II)] (Cu1); bis[{(μ2-chloro)-2-MeS-Ph-CH2-(N=CH)-2,4-tert-butyl-2-(OC6H2)}Cu(II)] (Cu2); bis[{(μ2-chloro)-2-MeO-Ph-CH2-(N=CH)-2-(OC10H6)} Cu(II)] (Cu3); bis[{(μ2-chloro)-2-MeS-Ph-CH2-(N=CH)-2-(OC10H6)}Cu(II)] complex (Cu4); bis[{2-MeS-Ph-CH2-(N=CH)-2,4-tert-butyl-2-(OC6H2)}Cu(II)] (Cu5)] have been synthesized and characterized by elemental analysis, IR, UV-Visible and by X-ray crystallography for Cu1, Cu4 and Cu5. In the solid state, Cu1 features of a chloro-bridged dimer complex with κ2 coordination of the monoanionic phenoxy-imine ligand onto the copper center. On the other hand, the molecular structure of Cu4 reveals the naphthoxy-imine ligand with pendant S-group coordinated to the copper atom in tridentate meridional fashion. Treatment of [Cu(OAc)2·H2O] with two equiv. of [2-MeS-Ph-CH2-(N=CH)-2,4-tert-butyl-2-(HOC6H2)] led to a monomeric complex Cu5, with the ONS-donor Schiff base acting as a bidentate ligand. The redox behavior was explored by cyclic voltammetry. The reduction/oxidation potential of Cu(II) complexes depends on the structure and conformation of the central atom in the coordination compounds. Antioxidant activities of the complexes, Cu1 - Cu5, were determined by in vitro assays such as 1,1-diphenyl-2-picryl-hydrazyl free radicals (DPPH) and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radicals (ABTS+). The dinuclear compounds Cu1-Cu4, from the concentration of 5 μM, presented a good activity in scavenging DPPH radical. In addition, most of the Cu(II) complexes showed ABTS.+ radical-scavenging activity. The monomeric complex Cu5 at all concentrations tested showed antioxidant inability. The cytotoxicity of the Cu1 and Cu3 was determined in V79 cell line by reduction of 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay.


Dopamine, noradrenaline and 3,4-dihydroxyphenylacetic acid (DOPAC) levels of individual brain nuclei, effects of haloperidol and pargyline.
Noradrenaline (NA), dopamine (DA) and DOPAC were determined with a newly developed radioenzymatic method simultaneously in the striatum, limbic system, hypothalamus and in catecholamine-containing cell groups of the rat brain. Only a loose relationship could be established between DOPAC and DA contents in the various brain areas. The lowest relative DOPAC level (DOPAC/DA ratio) was found in the median emience, while it was the highest in the periventricular nucleus of the hypothalamus. Haloperidol increased the DOPAC level in only part of the nuclei examined (striatum, olfactory tubercle, central amygdaloid nucleus), while in other limbic regions as well as in the hypothalamic dorsomedial, arcuate and paraventricular nuclei it proved to be ineffective. The DOPAC level in the locus coeruleus was decreased by haloperidol. Pargyline caused an appr. 50% decrease of DOPAC content of most of the nuclei in 10 min; the effectivity of the drug did not show parallelism with that of haloperidol. The monoamine oxidase inhibition caused no change in the DOPAC level in the hypothalamic periventricular and paraventricular nuclei. Results are discussed as a consequence of different reactivity of various DA-ergic terminals and catecholamine cell bodies to haloperidol and pargyline.


Patients with an Open Abdomen in Asian, American and European Continents: A Comparative Analysis from the International Register of Open Abdomen (IROA).
International register of open abdomen (IROA) enrolls patients from several centers in American, European, and Asiatic continent. The aim of our study is to compare the characteristics, management and clinical outcome of adult patients treated with OA in the three continents. A prospective analysis of adult patients enrolled in the international register of open abdomen (IROA). NCT02382770. 1183 patients were enrolled from American, European and Asiatic Continent. Median age was 63 years (IQR 49-74) and was higher in the European continent (65 years, p < 0.001); 57% were male. The main indication for OA was peritonitis (50.6%) followed by trauma (15.4%) and vascular emergency (13.5%) with differences among the continents (p < 0.001). Commercial NPWT was preferred in America and Europe (77.4% and 52.3% of cases) while Barker vacuum pack (48.2%) was the preferred temporary abdominal closure technique in Asia (p < 0.001). Definitive abdominal closure was achieved in 82.3% of cases in America (fascial closure in 90.2% of cases) and in 56.4% of cases in Asia (p < 0.001). Prosthesis were mostly used in Europe (17.3%, p < 0.001). The overall entero-atmospheric fistula rate 2.5%. Median open abdomen duration was 4 days (IQR 2-7). The overall intensive care unit and hospital length-of-stay were, respectively, 8 and 11 days (no differences between continents). The overall morbidity and mortality rates for America, Europe, and Asia were, respectively, 75.8%, 75.3%, 91.8% (p = 0.001) and 31.9%, 51.6%, 56.9% (p < 0.001). There is no uniformity in OA management in the different continents. Heterogeneous adherence to international guidelines application is evident. Different temporary abdominal closure techniques in relation to indications led to different outcomes across the continents. Adherence to guidelines, combined with more consistent data, will ultimately allow to improving knowledge and outcome.


[Electronic-conformational interactions of molecular-biological systems. II. Study of the enzyme-substrate complex with the help of qualitative methods of quantum chemistry].
The electronic-conformational interactions (ECI) of enzyme-substrate complexes are treated with the help of the method of intermolecular orbitals. The applicability of this approach is shown concerning some problems, related to ECI. The activation of N2 in the active site of nitrogenase, the proton transfer in the system, containing hydrogen bonds, and the modelling of the initial state of the reaction of lysozyme with oligosaccharides were examined.


Causative Organisms and Associated Antimicrobial Resistance in Healthcare-Associated, Central Line-Associated Bloodstream Infections From Oncology Settings, 2009-2012.
Recent antimicrobial resistance data are lacking from inpatient oncology settings to guide infection prophylaxis and treatment recommendations. We describe central line-associated bloodstream infection (CLABSI) pathogens and antimicrobial resistance patterns reported from oncology locations to the Centers for Disease Control and Prevention's National Healthcare Safety Network (NHSN). CLABSI data reported to NHSN from 2009 to 2012 from adult inpatient oncology locations were compared to data from nononcology adult locations within the same hospitals. Pathogen profile, antimicrobial resistance rates, and CLABSI incidence rates per 1000 central line-days were calculated. CLABSI incidence rates were compared using Poisson regression. During 2009-2012, 4654 CLABSIs were reported to NHSN from 299 adult oncology units. The most common organisms causing CLABSI in oncology locations were coagulase-negative staphylococci (16.9%), Escherichia coli (11.8%), and Enterococcus faecium (11.4%). Fluoroquinolone resistance was more common among E. coli CLABSI in oncology than nononcology locations (56.5% vs 41.5% of isolates tested; P < .0001) and increased significantly from 2009-2010 to 2011-2012 (49.5% vs 60.4%; P = .01). Furthermore, rates of CLABSI were significantly higher in oncology compared to nononcology locations for fluoroquinolone-resistant E. coli (rate ratio, 7.37; 95% confidence interval [CI], 6.20-8.76) and vancomycin-resistant E. faecium (rate ratio, 2.27, 95% CI, 2.03-2.53). However, resistance rates for some organisms, such as Klebsiella species and Pseudomonas aeruginosa, were lower in oncology than in nononcology locations. Antimicrobial-resistant E. coli and E. faecium have become significant pathogens in oncology. Practices for antimicrobial prophylaxis and empiric antimicrobial therapy should be regularly assessed in conjunction with contemporary antimicrobial resistance data.


Brain nicotine cholinoceptor binding in spontaneous hypertension.
To study the role of central cholinergic mechanisms in hypertension, we have determined nicotinic and muscarinic agonist binding sites in the brain regions of stroke-prone spontaneously hypertensive rats (SHRSP), using [3H]nicotine and [3H]cismethyldioxolane (CD). There was a significant decrease in specific [3H]nicotine binding in the cerebral cortex, thalamus, midbrain, cerebellum and medulla oblongata of SHRSP at 16-24 weeks of age compared to that of age-matched Wistar Kyoto rats (WKY). Scatchard analysis revealed 35% decrease in the Bmax value for [3H]nicotine binding in the SHRSP medulla oblongata without a change in the Kd value, suggesting a change in the receptor density. Similar reduction of nicotinic cholinoceptor binding sites was also observed in the discrete brain regions of young (5-week-old) SHRSP. In contrast, there was no alteration in specific [3H]CD binding in the SHRSP brains regions, except the hypothalamus which showed a significant increase. The SHRSP medulla oblongata showed no change in the ChAT activity. Thus, the present study suggests an important role for medullary nicotinic cholinoceptors in the pathogenesis of spontaneous hypertension.


Comorbid Sleep Disturbance in Adolescents with Functional Abdominal Pain.
Sleep disturbances have been commonly reported as comorbid in youth with pain conditions, but prior research specific to functional abdominal pain (FAP) is limited. This study describes individual factors associated with increased risk for sleep disturbance and characterizes the relationship between sleep disturbance and pain-related variables. Participants included 278 adolescents (age 11 to 17 years, M age = 15 years; 89% Caucasian; 65% female) with FAP. Participants reported on sleep disturbances, abdominal pain severity, functional disability, somatic symptoms, and healthcare utilization. Female adolescents reported greater sleep disturbance than male adolescents (t(276) = 5.52, p < .001, Cohen's d = 0.70) and increased age was associated with greater sleep disturbance (r =.20, p =.001). In hierarchical regressions controlling for age, sex, and abdominal pain, greater sleep disturbance was significantly associated with greater functional disability (β =.32), non-gastrointestinal somatic symptoms (β =.35), and emergency department visits (β =.29). Results suggest that sleep disturbance is common and should be assessed in youth presenting with FAP and may be a potential target for intervention.


Changes in air pollution due to COVID-19 lockdowns in 2020: Limited effect on NO2, PM2.5, and PM10 annual means compared to the new WHO Air Quality Guidelines.
Lockdowns have been fundamental to decreasing disease transmission during the COVID-19 pandemic even after vaccines were available. We aimed to evaluate and compare changes in air quality during the first year of the pandemic in different cities around the world, investigate how these changes correlate with changes in mobility, and analyse how lockdowns affected air pollutants' annual means. We compared the concentrations of NO2, PM2.5, and PM10 in 42 cities around the world in the first months of the pandemic in 2020 to data from 2016-2019 and correlated them with changes in mobility using Human Development Indexes (HDIs). Cities with the highest decreases in air pollutants during this period were evaluated for the whole year 2020. We calculated the annual means for these cities and compared them to the new World Health Organization (WHO) Air Quality Guidelines. A Student's t-test (95% confidence interval) was used to evaluate significant changes. Highest decreases in NO2, PM2.5, and PM10 were between -50 and -70%. Cities evaluated for the whole year 2020 generally showed a recovery in air pollution levels after the initial months of the pandemic, except for London. These changes positively correlated with year-long mobility indexes for NO2 and PM2.5 for some cities. The highest reductions in air pollutants' annual means were from -20 to -35%. In general, decreases were higher for NO2, compared to PM2.5 and PM10. All analysed cities showed annual means incompliant with the new WHO Air Quality Guidelines for NO2 of 10 μg/m3, with values 1.7 and 4.3 times higher. For PM2.5, all cities showed values 1.3 to 7.6 times higher than the WHO Guidelines of 5 μg/m3, except for New Delhi, with a value 18 times higher. For PM10, only New York complied with the new guidelines of 15 μg/m3 and all the other cities were 1.1 to 4.2 times higher, except for New Delhi, which was 11 times higher. These data show that even during a pandemic that highly affected mobility and economic activities and decreased air pollution around the world, complying with the new WHO Guidelines will demand a global strategical effort in the way we generate energy, move in and around the cities, and manufacture products.


Conceptualizations of clinical decision-making: a scoping review in geriatric emergency medicine.
Clinical decision-making (CDM) is an important competency for young doctors especially under complex and uncertain conditions in geriatric emergency medicine (GEM). However, research in this field is characterized by vague conceptualizations of CDM. To evolve and evaluate evidence-based knowledge of CDM, it is important to identify different definitions and their operationalizations in studies on GEM. A scoping review of empirical articles was conducted to provide an overview of the documented evidence of findings and conceptualizations of CDM in GEM. A detailed search for empirical studies focusing on CDM in a GEM setting was conducted in PubMed, ProQuest, Scopus, EMBASE and Web of Science. In total, 52 publications were included in the analysis, utilizing a data extraction sheet, following the PRISMA guidelines. Reported outcomes were summarized. Four themes of operationalization of CDM emerged: CDM as dispositional decisions, CDM as cognition, CDM as a model, and CDM as clinical judgement. Study results and conclusions naturally differed according to how CDM was conceptualized. Thus, frailty-heuristics lead to biases in treatment of geriatric patients and the complexity of this patient group was seen as a challenge for young physicians engaging in CDM. This scoping review summarizes how different studies in GEM use the term CDM. It provides an analysis of findings in GEM and call for more stringent definitions of CDM in future research, so that it might lead to better clinical practice.