A triphasic curve characterizes the retention of lever-pressing behavior rewarded by lateral hypothalamic stimulation during the immediate-post-trial period in rats: implications for a transient-intermediate stage between short- and long-term memory.
We investigated the retention of lever-pressing behavior in rats rewarded by lateral hypothalamic (LHT) stimulation. Rats with electrodes implanted into the lateral hypothalamus were trained to press a lever to receive LHT stimulation. More than 90% of rats which had self-stimulated for longer than 30 min retained this behavior when tested 1 or 7 days later, indicating that intracranial self-stimulation (ICSS) produced a stable long-term memory lasting for at least 7 days. Subsequently, we examined retention at shorter ICSS-test intervals. Retention rates were measured 15, 30, 60, 90, 120, 180 or 360 min after the end of a 90-min period of ICSS, using a different group of 15 rats for each interval. Unexpectedly, retention rates in shorter interval tests were lower than those observed after 1 or 7 days. We observed a characteristic fluctuation in retention rates with lower rates at 30 and 180 min, giving a triphasic form to the retention curve with peaks at 15, 90 and 360 min. When a group of rats that had been previously stimulated and shown to have retained the lever-pressing behavior was allowed to re-stimulate a second time, no fluctuations were observed in short-term interval tests. This indicates that the fluctuations in the retention curve immediately after initial ICSS are closely related to the initial acquisition of the memory. Our results support a three-phase model of memory formation that includes a transient-intermediate stage between short- and long-term memory.


Distribution of lead in lactating mice and suckling offspring with special emphasis on the mammary gland.
The distribution of lead in lactating mice and suckling offspring was studied with whole body autoradiography at 4 and 24 h after a single intravenous injection of 203Pb (50 nmol Pb/kg) to the dams. In the lactating mice on day 14 of lactation, the highest uptake of radioactivity at 4 h after administration was recorded in renal cortex, skeleton and liver. A high uptake was also evident in the mammary gland. At 24 h after administration, the radioactivity had decreased in most organs except in the skeleton. In the suckling pups, exposed to lead only via dams' milk for 24 h, the highest level of radioactivity was present in the intestinal mucosa and a much lower level of radioactivity was present in the skeleton. The mammary glands from mice given three daily intravenous injections of 240 mumol Pb/kg were examined with X-ray microanalysis. At 4 h after the last injection, lead was found associated with casein micelles both inside the alveolar cell and in the milk lumen, indicating that lead is excreted into the milk, bound to casein, via the Golgi secretory system.


Geographic location and mental health services utilization among the chronically mentally ill.
This study examined the relationship between geographic location and use of mental health services using data collected on 1053 Community Support Program (CSP) clients. Multiple regression analyses revealed that geographic location (i.e., urban, suburban, rural) influences mental health services utilization even when service availability and accessibility, socio-demographic and need factors are controlled. The results do not support the assumption that rural residence has uniformly negative effects on service use. Rural CSP clients, for example, were more likely to use crisis and supportive housing services than their urban counterparts. The findings suggest that models of service utilization must be carefully specified with regard to residential location.


The effect of zinc supplements in cystic fibrosis patients.
To study the effect of Zn supplements in cystic fibrosis (CF) on disease evolution. A retrospective study of all CF patients treated with Zn supplements (January 2002 to December 2004). Data from patient files for the year before and the first year of supplementation were compared. The controls were CF patients with normal serum Zn and without Zn supplementation. 21 patients (7 females), median age 8.9 (interquartile range 13.1) years, received 5 mg/kg Zn sulfate/day (maximum 150 mg). The number of infections decreased from 3 (1.25) to 2 (2.0) (tied p < 0.02) and the forced expiratory volume in 1 s (FEV(1)) increased from 72.0 (38.4) to 76.5 (52)% (p < 0.02). Energy intake improved (92.3 (14.5) to 117.0 (28.5)%; tied p < 0.02), as did weight for height (W/H; 90 (9.4) to 94 (8.5)%; tied p = 0.043). In the CF control patients the number of infections (2.0 (2.0)), energy intake (116 (43.3)%) and nutritional status remained stable (W/H 99 (17.2)%), but pulmonary function decreased significantly (DeltaFEV(1) loss of 2.0 (8.0)%). There was a significantly different evolution for the change in forced vital capacity (p < 0.004) and DeltaFEV(1) (p < 0.001) between supplemented and control patients. Analysis of the clinical data on Zn supplementation in CF showed beneficial effects in Zn-deficient CF patients. These results must be confirmed in a prospective double-blind randomized control trial.


Correction of aberrations in the human eye using computational methods.
Phase-sensitive imaging and computational correction of patient-specific optical aberrations enable high-resolution imaging of the human retina to aid diagnosis and treatment of eye diseases.


Phase separation propensity of the intrinsically disordered AB region of human RXRβ.
RXRβ is one of three subtypes of human retinoid X receptor (RXR), a transcription factor that belongs to the nuclear receptor superfamily. Its expression can be detected in almost all tissues. In contrast to other subtypes - RXRα and RXRγ - RXRβ has the longest and unique N-terminal sequence called the AB region, which harbors a ligand-independent activation function. In contrast to the functional properties of this sequence, the molecular properties of the AB region of human RXRβ (AB_hRXRB) have not yet been characterized. Here, we present a systematic biochemical and biophysical analysis of recombinant AB_hRXRB, along with in silico examinations, which demonstrate that AB_hRXRB exhibits properties of a coil-like intrinsically disordered region. AB_hRXRB possesses a flexible structure that is able to adopt a more ordered conformation under the influence of different environmental factors. Interestingly, AB_hRXRB promotes the formation of liquid-liquid phase separation (LLPS), a phenomenon previously observed for the AB region of another human subtype of RXR - RXRγ (AB_hRXRG). Although both AB regions seem to be similar in terms of their ability to induce phase separation, they clearly differ in the sensitivity to factors driving and regulating LLPS. This distinct LLPS response to environmental factors driven by the unique amino acid compositions of AB_hRXRB and AB_hRXRG can be significant for the specific modulation of the transcriptional activation of target genes by different subtypes of RXR. Video Abstract.


Investigation of PEG directed Sb2WO6 for dyes removal from wastewater.
Pristine and polyethylene glycol assisted antimony tungstate (Sb2WO6) was developed via hydrothermal route. The pristine and surfactant assisted Sb2WO6 were further exemplified to reveal the properties of the samples. The bandgap calculated for Sb2WO6, 5 ml PEG- Sb2WO6, 10 ml PEG- Sb2WO6 was 2.78 eV, 2.66 eV and 2.21 eV. The 10 ml PEG assisted sample exhibited narrow bandgap. The Fourier transform infrared spectroscopy (FTIR) spectra of the samples showed metal vibrations and stretching of the water molecules adsorbed. The Raman spectra showed the vibrational modes present in Sb2WO6. The morphology was analyzed employing transmission electron microscope (TEM) for all samples. Pristine Sb2WO6 showed growth of nanorods with higher dimensions with high agglomeration. 5 ml PEG- Sb2WO6 showed the growth of nanorods with lesser agglomeration. 10 ml PEG assisted Sb2WO6 exhibited distinct growth of nanorods with no agglomeration on the surface. The elemental composition was examined employing X-ray Photoelectron Spectroscopy. Prepared product photocatalytic behaviour was tested employing Rhodamine B dye degrading. Different catalyst loading were investigated for degrading the toxic pollutants. 0.2 g 10 ml PEG-Sb2WO6 showed 81% efficiency on degrading the toxic pollutant from wastewater. The OH radicals are accountable for photocatalytic behaviour of prepared photocatalyst. The 10 ml PEG-Sb2WO6 has the good reusability behavior and stable properties after three cycles. The prepared 10 ml PEG- Sb2WO6 photocatalyst will be the potential candidate for the remediation of the water treatment.


Severity of depression risk predicts health outcomes and recovery following surgery for hip-fractured elders.
This study examined how depression risk interfaces with health outcomes of hip-fractured patients during the first year after hospital discharge. Physical function recovery and health outcome trajectories were much poorer for hip-fractured elders with persistent depression risk than for those with transitory and no risk for depression. This study examined how depression risk interfaces with the trajectories of physical activities and health-related quality of life (HRQoL) among hip-fractured elderly patients during the first 12 months after hospital discharge. Based on 12-month scores for the Chinese version of Geriatric Depression Scale, patients over age 60 years (N = 147) were classified as (a) at persistent risk for depression, (b) at transitory risk for depression, and (c) at no risk for depression. Outcomes were measured by the Chinese Barthel Index and Medical Outcomes Study Short Form, Taiwan version, and analyzed by the generalized estimating equations approach. Patients who were at persistent risk for depression (n = 46, 31.3%) had much less chance of recovering activities of daily living (OR = 0.16, CI = 0.06-0.42) and walking ability (OR = 0.09, CI = 0.04-0.21) than patients at no risk for depression (n = 36, 24.5%). The trajectories of SF-36 scores for the physical and mental health summary scales were significantly different among the three depression groups; those "at persistent risk for depression" were the poorest and those "at no risk for depression" were the best. These results may provide a reference for developing timely assessments and interventions for hip-fractured elders at risk of depression.


Time delay during intra-base proton tunneling in the guanine base of the single stranded DNA.
Spontaneous point mutations are one of the main actors in evolution, and the tautomerization of organic bases in the DNA is hypothesized to be the underlying mechanism of this crucial process. Tautomerization can be induced by proton tunneling, and if it occurs in single-stranded DNA (ssDNA) during the replication process, tautomerized bases might give rise to a mismatch, which will eventually defect the genetic code. In the present work, we report on the tautomerization time in the guanine base of the ssDNA. The model we use includes an intra-base tunneling mechanism such that time tunneling (delay time) is estimated to be around a few pico-seconds. The time delay is found to be biologically relevant which indicates that it is long enough to induce point mutations. Our results close a gap in the literature and sheds light on the importance of point mutations originating from quantum effects in the ssDNA.


Influence of endothelial nitric oxide synthase gene polymorphisms (-786T>C, 4a4b, 894G>T) in Korean patients with coronary artery disease.
Endothelium-derived nitric oxide (NO) is synthesized from l-arginine by endothelial nitric oxide synthase (eNOS) encoded by the eNOS3 gene on chromosome 7. The effects of the eNOS polymorphisms with the risk of coronary artery disease are conflicting. In this study, we investigated the association of the eNOS genotypes with coronary artery disease in Koreans. A case-control study was performed to evaluate the association between the eNOS -786T>C, 4a4b, or 894G>T polymorphism and coronary artery disease. 147 consecutive patients with coronary artery disease and 222 healthy controls were recruited. The genotypes of eNOS -786T>C and 894G>T polymorphisms were determined by the polymerase chain reaction-restriction fragment length polymorphism analysis. The genotypes of a 27 bp insertion/deletion in intron 4 (eNOS 4a4b) were determined by the banding pattern on gel electrophoresis. The eNOS -786T>C (odds ratio [OR]; 1.61, 95% confidence interval [CI]; 0.97-2.69), 894G>T (OR; 1.12, 95% CI; 0.65-1.92) and 4a4b (OR; 1.44, 95% CI; 0.87-2.39) polymorphisms were not an independent predisposition factor to coronary artery disease. However, a subgroup analysis adjusted with various cardiovascular risk factors confirmed positive association of the -786T>C polymorphism in CAD patients with hypertension and a smoking history and also a significant association of the intron 4 genotypes with a smoking history, but no significance has been found in the eNOS polymorphisms of 894G>T upon any risk adjustment. In this study we also found that the distribution of heterozygotes (-786TC, 894GT, and 4a4b) and variant homozygotes for the -786C, 894T, and intron 4a alleles of eNOS in Koreans were significantly lower than in Caucasian populations. The present study demonstrates that polymorphisms of the eNOS -786T>C and 4a4b are associated with coronary artery disease with adjustments for cardiovascular risk factors in the Koreans.


Statin treatment improves cerebral more than systemic endothelial dysfunction in patients with arterial hypertension.
The pleiotropic effects of statins on the endothelial function are well recognized. However, the effect of statins might not be equally pronounced in the cerebral and systemic circulation. We compared cerebral and systemic endothelial function by L-arginine cerebrovascular reactivity and flow-mediated dilatation (FMD), respectively, in patients with arterial hypertension (AH) and healthy controls before and after atorvastatin treatment. L-arginine reactivity and FMD were measured in patients with AH (29 patients, aged 61.1 +/- 6.2 years) and 21 healthy controls. The mean arterial velocity (v(m)) in both middle cerebral arteries was measured by transcranial Doppler sonography before, during, and after a 30-min intravenous infusion of L-arginine. FMD of the brachial artery after hyperemia was determined. The measurements were repeated after 3 months of treatment with atorvastatin. L-arginine reactivity and FMD were decreased in patients with AH (12.5 +/- 8.7%; 2.7 +/- 5.0 %) compared with controls (21.3 +/- 10.9%; 8.5 +/- 5.9%) (P < 0.01). After atorvastatin treatment, L-arginine reactivity and FMD improved in patients with AH (19.5 +/- 10.6%; 4.6 +/- 4.1%) compared with the controls (20.2 +/- 10.2%; 9.7 +/- 3.9%). The use of statin restored the cerebral circulation reactivity, while there was little change in the systemic circulation measured by FMD. The decreased L-arginine reactivity and FMD were found to improve after atorvastatin treatment in patients with AH, but the results suggest that statin therapy improved cerebral more than systemic endothelial function.


Early and Midterm Results of No-Touch Aorta Multivessel Small Thoracotomy Coronary Artery Bypass Grafting: A Propensity Score-Matched Study.
To carry out the comparative analysis of early and midterm results of no-touch aorta multivessel small thoracotomy coronary artery bypass grafting (MVST CABG), conventional off-pump (OPCABG) and on-pump CABG (ONCABG). From 2007 to 2014, 537 consecutive patients underwent CABG by the same surgeon. Propensity score computer matching was performed, and a total of 453 patients were successfully matched in 3 groups of 151 patients. Significant differences were found in the intraoperative blood loss: 220 (180; 300) mL in MVST CABG versus 400 (300; 550) mL in OPCABG vs 350 (250; 435) mL in ONCABG group; first 24-hour postoperative blood loss: 170 (100; 280), 320 (200; 470), and 380 (200; 500) mL, respectively; operation time: 352.4 ± 74.4, 289.3 ± 55.0, and 280.4 ± 56.4 minutes, respectively; median time to return to full physical activity: 14, 56, and 56 days, respectively (P < 0.05); rate of deep wound infection: 0.0%, 2.0%, and 2.0%, respectively; and postoperative length of stay (surgical department): 4.5, 7.0, and 7.5 days, respectively (P < 0.1). No significant differences were observed in rates of severe in-hospital events (P > 0.05), cumulative midterm survival, and freedom from major adverse cardiac and cerebrovascular events (P > 0.05). The MVST CABG seems as safe as OPCABG and ONCABG and is associated with less wound infections, perioperative blood loss, shorter hospital length of stay and time to return to full physical activity. Multivessel small thoracotomy CABG can be applied to most patients with coronary heart disease saving the effectiveness during midterm follow-up. The MVST CABG can be introduced avoiding a prolonged learning curve.


Solid-phase control on lead bioaccessibility in smelter-impacted soils.
The goal of this work was to identify the solid-phase control on lead (Pb) bioaccessibility in soils impacted by smelter activities in the city of San Luis Potosi, in north-central Mexico. Total Pb concentrations in 30 ha of soil terrain from a residential area adjacent to the smelter showed levels above the 400-mg/kg intervention guideline dictated by Mexican Environmental regulations. These concentrations, although raising human health and environmental concerns, showed low water-soluble lead (<0.1 mg/L) and relatively low lead bioaccessibility (2.4-20.5%). X-ray diffraction and electron microscopy techniques showed, in addition to common Pb phases reported in similar contaminated environments [galena (PbS) and anglesite (PbSO(4))], the presence of a solid lead arsenate phase. The Pb solubility measured in soils agrees very well with the low solubility reported for the Pb minerals identified and explains the relatively low Pb bioaccessibility values measured, presumably from their low dissolution during passage through the gastrointestinal tract. The results reported are highly relevant for smelter-originated environmental contamination scenarios in general.


Effectiveness of group visits for elderly patients with type 2 diabetes in an urban community in China.
The purpose of this study is to evaluate the effectiveness of a group visit intervention in comparison with the usual care for elderly patients with type 2 diabetes in a community. We randomized 109 community elderly patients with type 2 diabetes to the intervention group (n = 55) of monthly group visits sessions or to a control group (n = 54) of usual care. Repeated measures analysis of variance was used to compare the changes in HbA1C, diabetes knowledge, self-efficacy, and self-management behavior in both groups. At the 6-month follow-up, although no significant difference was observed between the groups regarding HbA1C (p = 0.272). Diabetes knowledge, self-efficacy and self-management scores were higher in patients in the intervention group than that in the control group (p < 0.05). The group visits model increased diabetes knowledge and self-efficacy and improved patients' self-management behavior. The model was found suitable for helping these elderly patients with type 2 diabetes achieve effective self-management.


Quantitative and molecular aspects of water intake in meat-type chickens.
Even though water is the most essential nutrient for poultry production, adequate data on individual water intake in broiler chickens and its relationship with other traits of economic importance is scant. Water is provided to chickens in an unrestricted manner in spite of being a finite resource. Climate change continues to affect water sources and efficient bird use of water is long overdue. Understanding the biological basis of water intake is essential for sustainability of the poultry industry. Individual water and feed intake, and growth data was collected on 520 commercial broilers aged 14 to 42 days. We introduced the concepts of water conversion ratio (WCR) and residual water intake (RWI) as parameters that can be used to assess water intake efficiency. Water conversion ratio was defined as the amount of water consumed per unit of body weight gain, and RWI was defined as the difference between the actual water intake (WI) of a given bird and the expected WI by an average bird from the population with the same metabolic body weight, feed intake (FI) and body weight gain (BWG). The correlation between WI and FI was positive (r=0.77; P<0.0001), and the correlation between WI and BWG was positive (r=0.80; P<0.0001). Based on the distribution of RWI, the bottom 5 birds (LRWI) and the top 5 birds (HRWI) for RWI were selected for mRNA expression differences. The average broiler consumed about 7.8 L (± 1L) of water from 14 to 42 days of age. The mRNA expression of arginine vasopressin (AVP) antidiuretic hormone, calcium sensing receptor (CasR), sodium channel epithelial 1 subunit alpha (SCNN1A) and SCNN1D in the hypothalamus was upregulated in the LRWI group compared to the HRWI group. Similarly, kidney aquaporins (AQP) 2, 3, and 4 were upregulated in the LRWI group compared with the HRWI group. Given that water was provided ad libitum, the up-regulation of AVP and AQP gene mRNA expressions seem to indicate that the LRWI birds were more efficient in water reabsorption in the kidney compared to their HRWI counterparts. Increased water reabsorption will reduce the amount of water consumed to attain hydration. The water reabsorption potential was reflected in the excreta moisture levels as the LRWI birds had significantly lower excreta moisture than the HRWI birds. Excreta moisture level require further studies and could be considered as a potential proxy trait for water intake.


Interactive effect of different salinity sources and their formulations on plant growth, ionic homeostasis and seed quality of maize.
Soil salinity is one of the most pernicious environmental hazards affecting crop growth and productivity in arid and semi-arid climates. In saline soils, the crop plants encounter nutrients deficient conditions mainly due to antagonistic affinity of sodium (Na+) and chloride (Cl-). The accumulation of salts in the rhizosphere restricts plant growth, the severity of which depends on the source and concentration of the salt. Therefore, we hypothesized that sodium containing salts could have toxic effects on maize plants either in a single or in combined form. To evaluate the interactive effect of sodium salts on plant growth, ionic homeostasis, and seed quality attributes, a pot study was performed using maize as a test plant at the research area of the College of Agriculture, University of Sargodha. Selected salts including, NaCl, Na2SO4 and their combination (NaCl + Na2SO4), were applied in equal ratio for different salinity levels (7, 10, 13 and 16 dS m-1) and the untreated control. The results show that all the measured growth, yield, biochemical and quality attributes of maize were negatively affected with increasing concentration of all the salt sources; however, severity of these effects were more intense when NaCl was applied at all salinity levels. It is concluded that all salts (NaCl, Na2SO4 and NaCl + Na2SO4) had negative effects on biochemical, qualitative, growth and yield characteristics of maize plant. Most importantly, NaCl was found to be more harmful compared to Na2SO4 and mixtures of both salts due to the dominance of Na+ and Cl-ions. Among all salinity levels, the more detrimental effects of NaCl occurred at salinity level of 16 dS m-1.


Use of medications and lifestyles of hypertensive patients with high risk of cardiovascular disease in rural China.
Hypertension, with a global prevalence of 40%, is a risk factor for cardiovascular diseases (CVD). We conducted an exploratory study in Zhejiang China to understand the prevention of CVD among hypertensive patients with a 10 year CVD risk of 20% or higher. We assessed current practices in a rural 'township hospital' (a primary care facility), and compared them with international evidence-based practice. A questionnaire survey was conducted to examine the use of modern drugs (antihypertensive drugs, statins and aspirin) and traditional drugs, compliance to medications and lifestyle among 274 hypertensive patients aged 40-74, with a CVD risk of 20% or higher (using the Asian Equation). The majority (72%) were diagnosed with hypertension at township hospitals. Only 15% of study participants used two anti-hypertensive drugs, 0.7% took statin and 2.9% aspirin. Only 2.9% combined two types of modern drugs, while 0.4% combined three types (antihypertensives, statins and aspirin). Herbal compounds, sometimes with internationally rarely recommended drugs such as Reserpine were taken by 44%. Analysis of drug adherence showed that 9.8% had discontinued their drug therapy by themselves. 16% had missed doses and these were on less anti-hypertensive drugs than those who did not (t=-5.217, P=0.003). Of all participants, 28% currently smoked, 39% drank regularly and only 21% exercised frequently. The average salt intake per day was 7.1 (±3.8) g, while the national recommended level is 6g. The study revealed outdated and inadequate treatment and health education for hypertensive patients, especially for those who have high risk scores for CVD. There is a need to review the community-based guidelines for hypertension management. Health providers and patients should make a transition from solely treating hypertension, towards prevention of CVD. Health system issues need addressing including improving rural health insurance cover and primary care doctors' capacity to manage chronic disease patients.


The impact of follow-up physician visits on emergency readmissions for patients with asthma and chronic obstructive pulmonary disease: a population-based study.
To examine the relation between follow-up office visits after emergency discharge and the risk of emergency readmissions in patients with asthma or chronic obstructive pulmonary disease (COPD). We used population-based data to identify all patients in Alberta, Canada, who had at least one emergency visit for asthma or COPD between April 1, 1996, and March 31, 1997 (N = 25 256). A Cox proportional hazards model was used to estimate the adjusted relative risk (RR) of a repeat visit to an emergency department within 90 days of an initial emergency visit in patients who did or did not have an office follow-up within the first 30 days. There were 7829 patients (31%) who had an office visit during the 30 days after their initial emergency encounter. Follow-up visits were associated with a significant reduction in the 90-day risk of an emergency readmission (RR = 0.79; 95% confidence interval [CI]: 0.73 to 0.86). Sensitivity analyses showed that a follow-up visit was inversely associated with a repeat emergency visit after adjusting for age, sex, area of residence, and income. Although these data should be interpreted with caution because of missing information on factors such as quality of care, they suggest that follow-up office visits are effective in reducing early relapses in patients who have been recently treated in emergency departments for asthma or COPD.


Integrating metabolic expenditure information from wearable fitness sensors into an AI-augmented automated insulin delivery system: a randomised clinical trial.
Exercise can rapidly drop glucose in people with type 1 diabetes. Ubiquitous wearable fitness sensors are not integrated into automated insulin delivery (AID) systems. We hypothesised that an AID can automate insulin adjustments using real-time wearable fitness data to reduce hypoglycaemia during exercise and free-living conditions compared with an AID not automating use of fitness data. Our study population comprised of individuals (aged 21-50 years) with type 1 diabetes from from the Harold Schnitzer Diabetes Health Center clinic at Oregon Health and Science University, OR, USA, who were enrolled into a 76 h single-centre, two-arm randomised (4-block randomisation), non-blinded crossover study to use (1) an AID that detects exercise, prompts the user, and shuts off insulin during exercise using an exercise-aware adaptive proportional derivative (exAPD) algorithm or (2) an AID that automates insulin adjustments using fitness data in real-time through an exercise-aware model predictive control (exMPC) algorithm. Both algorithms ran on iPancreas comprising commercial glucose sensors, insulin pumps, and smartwatches. Participants executed 1 week run-in on usual therapy followed by exAPD or exMPC for one 12 h primary in-clinic session involving meals, exercise, and activities of daily living, and 2 free-living out-patient days. Primary outcome was time below range (<3·9 mmol/L) during the primary in-clinic session. Secondary outcome measures included mean glucose and time in range (3·9-10 mmol/L). This trial is registered with ClinicalTrials.gov, NCT04771403. Between April 13, 2021, and Oct 3, 2022, 27 participants (18 females) were enrolled into the study. There was no significant difference between exMPC (n=24) versus exAPD (n=22) in time below range (mean [SD] 1·3% [2·9] vs 2·5% [7·0]) or time in range (63·2% [23·9] vs 59·4% [23·1]) during the primary in-clinic session. In the 2 h period after start of in-clinic exercise, exMPC had significantly lower mean glucose (7·3 [1·6] vs 8·0 [1·7] mmol/L, p=0·023) and comparable time below range (1·4% [4·2] vs 4·9% [14·4]). Across the 76 h study, both algorithms achieved clinical time in range targets (71·2% [16] and 75·5% [11]) and time below range (1·0% [1·2] and 1·3% [2·2]), significantly lower than run-in period (2·4% [2·4], p=0·0004 vs exMPC; p=0·012 vs exAPD). No adverse events occurred. AIDs can integrate exercise data from smartwatches to inform insulin dosing and limit hypoglycaemia while improving glucose outcomes. Future AID systems that integrate exercise metrics from wearable fitness sensors may help people living with type 1 diabetes exercise safely by limiting hypoglycaemia. JDRF Foundation and the Leona M and Harry B Helmsley Charitable Trust, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases.


Production, Optimization, and Characterization of Organic Solvent Tolerant Cellulases from a Lignocellulosic Waste-Degrading Actinobacterium, Promicromonospora sp. VP111.
High costs of natural cellulose utilization and cellulase production are an industrial challenge. In view of this, an isolated soil actinobacterium identified as Promicromonospora sp. VP111 showed potential for production of major cellulases (CMCase, FPase, and β-glucosidase) utilizing untreated agricultural lignocellulosic wastes. Extensive disintegration of microcrystalline cellulose and adherence on it during fermentation divulged true cellulolytic efficiency of the strain. Conventional optimization resulted in increased cellulase yield in a cost-effective medium, and the central composite design (CCD) analysis revealed cellulase production to be limited by cellulose and ammonium sulfate. Cellulase activities were enhanced by Co(+2) (1 mM) and retained up to 60 °C and pH 9.0, indicating thermo-alkaline tolerance. Cellulases showed stability in organic solvents (25 % v/v) with log P ow ≥ 1.24. Untreated wheat straw during submerged fermentation was particularly degraded and yielded about twofold higher levels of cellulases than with commercial cellulose (Na-CMC and avicel) which is especially economical. Thus, this is the first detailed report on cellulases from an efficient strain of Promicromonospora that was non-hemolytic, alkali-halotolerant, antibiotic (erythromycin, kanamycin, rifampicin, cefaclor, ceftazidime) resistant, multiple heavy metal (Mo(+6) = W(+6) > Pb(+2) > Mn(+2) > Cr(+3) > Sn(+2)), and organic solvent (n-hexane, isooctane) tolerant, which is industrially and environmentally valuable.


Diaphragmatic endometriosis and thoracic endometriosis syndrome: a review on diagnosis and treatment.
Endometriosis of the diaphragm has been gaining more attention in the practice of gynecologists and thoracic surgeons in recent years. Understanding related symptoms and developing imaging methods have improved their approach. A review of the literature was performed with the aim to report on incidence, diagnosis, treatment and prognosis of diaphragmatic endometriosis. We also cover the issue of the Thoracic Endometriosis Syndrome (TES). Complaints of cyclic chest pain in patients of childbearing age should have as differential diagnosis the presence of thoracic endometriosis. Catamenial pneumothorax is the main manifestation of diaphragmatic endometriosis and Thoracic Endometriosis Syndrome. Other possible manifestations are hemothorax, pulmonary nodules, and diaphragmatic hernia. Despite the possibility of drug treatment, many patients will be submitted to surgical treatment. The minimally invasive approach should be the one of choice. The robotic pathway allows for an easier approach due to its ability to articulate robotic arms, allowing the treatment of lesions in hard-to-reach locations, such as the posterior part of the diaphragm. Multidisciplinary treatment should be used in most cases, as only abdominal approach is not sufficient for the diagnosis and treatment of lesions in the thoracic cavity. The approach of endometriosis of the diaphragm and Thoracic Endometriosis Syndrome should be multidisciplinary, allowing the improvement of quality of life in most patients.


The association between serum lipid levels and histological type of breast cancer.
Studies have investigated the association between serum lipids level or apolipoprotein levels and breast cancer (BC) risk. However, the relationship between serum lipids level and apolipoprotein levels and histological type of breast cancer remains unclear. This study was aimed to explore the association between serum lipids level and the histological type of BC, particularly to estrogen receptor (ER) and progesterone receptor (PR) positive BC. 220 cases of pathology-confirmed BC were retrospectively collected in this study. Patients' demographic information, clinical data, and pathological features were obtained from medical records. Serum levels including high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), total cholesterol (TC), triglyceride (TG), apolipoprotein A (ApoA), ApoB, ApoE and lipoprotein a(LP(a)) were collected before treatment. Logistic regression analyses were used to show the association between serum lipids and subtypes of BC. Receiver operating characteristic (ROC) curves were generated to analyze the predictive performance. There were 70 ER-negative and 73 PR-negative BC. Patients with ER-negative BC had higher HDL-c, higher LDL-c, and higher LP(a) than those in ER-positive one (p < 0.05). Patients with PR-negative BC were more likely to have high LDL-c and high LP(a) levels than patients with PR-positive one (p < 0.05). Multivariate logistic regression analysis showed that serum HDL-c (odds ratio (OR): 0.27, 95% confidence interval (CI) 0.10-0.76), LDL-c (OR: 0.19, 95%CI 0.04-0.93) and LP(a) (OR: 0.23,95%CI 0.07-0.80) levels were negatively associated with ER-positive BC, and serum HDL-c and LDL-c levels were significantly negatively associated with PR-positive BC (OR: 0.32, 95%CI 0.12-0.82; OR: 0.14, 95%CI 0.03-0.77). In addition, ER and PR positive BC was negatively associated with serum HDL-c and LDL-c levels (OR = 0.39, 95% CI 0.17-0.91; OR = 0.22, 95% CI 0.06-0.85) after adjusting with confounders. Serum HDL-c level (OR = 0.13, 95% CI 0.02-0.87) was still independently associated with ER and PR positive BC in postmenopausal women. The area under the curves (AUCs) of HDL-c to identify ER-positive BC, PR-positive BC, and ER and PR positive BC were 0.65 (95%CI 0.58-0.73, P < 0.01), 0.62 (95%CI 0.54-0.69, P < 0.01) and 0.64 (95%CI 0.56-0.72, P < 0.01), respectively. Serum HDL-c and LDL-c levels were related to ER or PR positive BC. Lipid levels may also have acceptable performance in identifying BC histological type.


A multi-parameter study of the etiological diagnosis of hyponatremia after hypothalamic tumor surgery.
This study aimed to analyze the difference between cerebral salt-wasting syndrome (CSWS) and syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in patients with hyponatremia after hypothalamic tumor surgery, and to explore a convenient and effective way to identify CSWS and SIADH. Patients undergoing craniotomy of hypothalamic tumor admitted to the Department of The Affiliated Hospital of Qingdao University from December 2018 to May 2020 were enrolled in this study. Plasma brain natriuretic peptide (BNP), 24-h urine sodium, 24-h urine volume, and the diameter of the inferior vena cava (IVCD) were measured daily before operation and 1-7 days after operation, to analyze differences in plasma BNP, 24-h urinary sodium excretion, 24-h urine volume, and IVCD between the CSWS and SIADH. The medical data of 31 patients with hypothalamic tumors were collected. Fifteen of these patients (48%) had postoperative hyponatremia, nine patients (29%) had CSWS, and six patients (19%) had SIADH. Plasma BNP, 24-h urinary sodium excretion, and 24-h urine volume in the CSWS group were significantly higher than those in the SIADH group. IVCD decreased in the CSWS group and increased in the SIADH group. When hyponatremia occurs after hypothalamic tumor surgery, plasma BNP, 24-h urinary sodium excretion, 24-h urine volume, and IVCD are of great help in identifying CSWS and SIADH.


Treatment of chitin-producing wastewater by micro-electrolysis-contact oxidization.
The technique of micro-electrolysis-contact oxidization was exploited to treat chitin-producing wastewater. Results showed that Fe-C micro-electrolysis can remove about 30% COD(cr), raise pH from 0.7 to 5.5. The COD(cr) removal efficiency by biochemical process can be more than 80%. During a half year's operation, the whole system worked very stably and had good results, as proved by the fact that every quality indicator of effluent met the expected discharge standards; which means that chitin wastewater can be treated by the technique of micro-electrolysis, contact oxidization.


Power Amplifier Linearizer for High Frequency Medical Ultrasound Applications.
Power amplifiers (PAs) are used to produce high-voltage excitation signals to drive ultrasonic transducers. A larger dynamic range of linear PAs allows higher contrast resolution, a highly desirable characteristic in ultrasonic imaging. The linearity of PAs can be improved by reducing the nonlinear harmonic distortion components of high-voltage output signals. In this paper, a linearizer circuit is proposed to reduce output signal harmonics when working in conjunction with a PA. The PA performance with and without the linearizer was measured by comparing the output power 1-dB compression point (OP1dB), and the second- and third-order harmonic distortions (HD2 and HD3, respectively). The results show that the PA with the linearizer circuit had higher OP1dB (31.7 dB) and lower HD2 (-61.0 dB) and HD3 (-42.7 dB) compared to those of the PA alone (OP1dB (27.1 dB), HD2 (-38.2 dB), and HD3 (-36.8 dB)) at 140 MHz. A pulse-echo measurement was also performed to further evaluate the capability of the linearizer circuit. The HD2 of the echo signal received by the transducer using a PA with the linearizer (-24.8 dB) was lower than that obtained for the PA alone (-16.6 dB). The linearizer circuit is capable of improving the linearity performance of PA by lowering harmonic distortions.


Modulation of tetrodotoxin-resistant sodium channels by dihydropyrazole insecticide RH-3421 in rat dorsal root ganglion neurons.
The effects of the dihydropyrazole insecticide RH-3421 on the retrodotoxin-resistant (TTX-R) voltage-gated sodium channels in rat dorsal root ganglion (DRG) neurons were studied using the whole-cell patch clamp technique. RH-3421 at 10 nM to 1 microM completely blocked action potentials. The sodium currents were irreversibly suppressed by 1 microM RH-3421 in a time- and a dose-dependent manner and the IC50 value of RH-3421 was estimated to be 0.7 microM after 10 min of application. RH-3421 blocked the sodium currents to the same extent over the entire range of test potentials. The sodium conductance-voltage curve was not shifted along the voltage axis by 1 microM RH-3421 application In contrast, both fast and slow steady-state sodium channel inactivation curves were shifted in the hyperpolarizing direction in the presence of 1 microM RH-3421. It was concluded that RH-3421 bound to the resting and inactivated sodium channels to cause block with a higher affinity for the latter state.


5-(Adamantan-1-yl)-3-anilinomethyl-2,3-di-hydro-1,3,4-oxa-diazole-2-thione.
In the title compound, C19H23N3OS, the oxa-diazole and benzene rings are inclined at a dihedral angle of 50.30 (11)°, with the major twist between them occurring at the ring-methyl-ene N-C bond [N-N-C-N torsion angle = -101.2 (2)°]. In the crystal, helical supra-molecular chains along [010] are sustained by N-H⋯S hydrogen bonds. These are linked into layers lying parallel to (-101) by methyl-ene-phenyl C-H⋯π inter-actions.


Melanoma inhibitor of apoptosis protein is expressed differentially in melanoma and melanocytic naevus, but similarly in primary and metastatic melanomas.
Malignant melanoma is highly resistant to current treatments. The inhibitor of apoptosis protein (IAP) family member, melanoma IAP (ML-IAP), is overexpressed in some melanoma cell lines, rendering them resistant to apoptotic signals. Targeting ML-IAP is a promising approach to treating melanoma. However, the status of ML-IAP expression in human melanoma tissues and the difference in expression between melanoma and melanocytic naevus are not known. To investigate these issues. ML-IAP expression in 48 archived patient samples (34 melanomas and 14 dermal naevi) was assessed by immunohistochemistry and by in situ hybridisation and reverse transcription polymerase chain reaction (RT-PCR) assays developed for the study. Expression of ML-IAP was detected in 47.6-70.6% (10 of 21 to 24 of 34) of the melanomas, varying with detection methods. The expression rate in melanoma was much higher than that in melanocytic naevus (10.0-21.4%; one of 10 to three of 14). No significant difference was seen between primary and secondary melanomas. ML-IAP expression rates assessed by the three methods were in agreement. The ML-IAP expression rate in archived melanoma tissues is around 50-70%, with no difference between primary and secondary melanomas. A small number of dermal naevi ( approximately 20%) also expressed ML-IAP.


Fighting COVID-19 with Artificial Intelligence.
The development of vaccines for the treatment of COVID-19 is paving the way for new hope. Despite this, the risk of the virus mutating into a vaccine-resistant variant still persists. As a result, the demand of efficacious drugs to treat COVID-19 is still pertinent. To this end, scientists continue to identify and repurpose marketed drugs for this new disease. Many of these drugs are currently undergoing clinical trials and, so far, only one has been officially approved by FDA. Drug repurposing is a much faster route to the clinic than standard drug development of novel molecules, nevertheless in a pandemic this process is still not fast enough to halt the spread of the virus. Artificial intelligence has already played a large part in hastening the drug discovery process, not only by facilitating the selection of potential drug candidates but also in monitoring the pandemic and enabling faster diagnosis of patients. In this chapter, we focus on the impact and challenges that artificial intelligence has demonstrated thus far with respect to drug repurposing of therapeutics for the treatment of COVID-19.


Role of psychrotrophic bacteria and cold-active enzymes in composting methods adopted in cold regions.
Temperature-dependent composting is a challenging task but is worthy if it is done in the right manner. Cold composting has been known to be practiced since ancient times but there were not enough advancements to overcome the long mesophilic phase and bring the compost maturation to a short period. The composting processes that have been well practiced are discussed and the role of psychrotrophic bacteria that produce cold tolerant hydrolytic enzymes has been highlighted. In this chapter, the mechanism of substrate degradation has been elaborated to better understand the need of specific bacteria for a specific kind of substrate allowing fast and efficient decomposition. This chapter attempts to pave an appropriate way and suggest the best-suited method of composting for efficient production of compost by the conservation of heat in cold regions.


Distribution and Appearance of Ki-67, IL-1α, IL-10, and PGP 9.5 in Reinke's Oedema-Affected Larynx Tissue Compared with Control Tissue.
Smoking, laryngopharyngeal reflux, and vocal fold abuse can promote the development of Reinke's oedema, leading to vocal fold dysfunction and injury. The aim of the work was to investigate the appearance and distribution of proliferation marker Ki-67 (Ki-67), interleukin 10 (IL-10), interleukin 1 alpha (IL-1α), and protein gene peptide 9.5 (PGP 9.5) in Reinke's oedema-affected larynx tissue. A routine histological and immunohistochemical Reinke's oedema and control group patient analysis was conducted. We used the biotin-streptavidin biochemical method to detect Ki-67, IL-10, IL-1α, and PGP 9.5 The semiquantitative grading method was used to evaluate immunoreactive cells' appearance and local distribution. A Mann-Whitney U test and Spearman's rank coefficient were performed. A low positive correlation between IL-1α epithelial and subepithelial immunoreactive cells in the patient group was found. Mann-Whitney U tests revealed significant patient and control group immunoreactive marker differences. All examined markers showed a higher number of immunoreactive structures in the patient group. Intensive proliferation of the surface epithelium was observed in patient tissues. The notable increase in IL-10 positive structures indicates the dominant anti-inflammatory tissue response. An increased number of IL-1α structures in the larynx epithelium and subepithelium in the patient group is linked to inflammation, proliferation, and tissue remodelling. The PGP 9.5 expression increase is involved in the morphopathogenesis of Reinke's oedema.


RIP kinases as modulators of inflammation and immunity.
Receptor-interacting protein (RIP) kinases, in particular RIPK1, RIPK2 and RIPK3, have emerged as pleiotropic modulators of inflammatory responses that act either by directly regulating intracellular inflammatory signaling pathways or by causing apoptotic or necrotic cell death. In this Review, we discuss the signaling pathways and immunological functions of these RIP kinases in the inflammatory response to microbial infection and tissue injury, as well as their potential roles in the pathogenesis of inflammatory disease and aging.


Effectiveness and cost-effectiveness of blood pressure screening in adolescents in the United States.
To compare the long-term effectiveness and cost-effectiveness of 3 approaches to managing elevated blood pressure (BP) in adolescents in the United States: no intervention, "screen-and-treat," and population-wide strategies to lower the entire BP distribution. We used a simulation model to combine several data sources to project the lifetime costs and cardiovascular outcomes for a cohort of 15-year-old U.S. adolescents under different BP approaches and conducted cost-effectiveness analysis. We obtained BP distributions from the National Health and Nutrition Examination Survey 1999-2004 and used childhood-to-adult longitudinal correlation analyses to simulate the tracking of BP. We then used the coronary heart disease policy model to estimate lifetime coronary heart disease events, costs, and quality-adjusted life years (QALY). Among screen-and-treat strategies, finding and treating the adolescents at highest risk (eg, left ventricular hypertrophy) was most cost-effective ($18000/QALY [boys] and $47000/QALY [girls]). However, all screen-and-treat strategies were dominated by population-wide strategies such as salt reduction (cost-saving [boys] and $650/QALY [girls]) and increasing physical education ($11000/QALY [boys] and $35000/QALY [girls]). Routine adolescents BP screening is moderately effective, but population-based BP interventions with broader reach could potentially be less costly and more effective for early cardiovascular disease prevention and should be implemented in parallel.


Lymphocyte subsets in human thymoma studied with monoclonal antibodies.
Lymphocyte subsets were investigated using OKT series monoclonal antibodies and flowcytometry in 16 cases of thymoma. From the viewpoint of lymphocyte subsets, thymoma could be divided into three types: thymus lymphocyte type, peripheral lymphocyte type, and intermediate type. In thymus lymphocyte type, the number of OKT-6+ cells exceed that of OKT-3+ cells, and are more than 50%. In peripheral lymphocyte type, the number of OKT-6+ cells are less than that of OKT-3+ cells and less than 10%. In intermediate type, OKT-6+ cells are between 10% and 30%. These three types correlate well with the histologic features with respect to the number and distribution of lymphocytes in thymoma tissue. Lymphocytes were infiltrating abundantly and intermingled in the tumor cell nests in thymus lymphocyte type, and were infiltrating rather scantly and outside the nests in peripheral lymphocyte type.


Effect of 4-aminopyridine in acute spinal cord injury.
The demyelination process has been proven to be an important factor contributing to long-term sensory and motor impairments after spinal cord injury (SCI). The loss of myelin promotes exposure of K+ channels in internodal region of the damaged myelinated axons leading to K+ efflux into the neurons with subsequent blockage of action potentials. The potassium channel blocker 4-aminopyridine (4-AP) has been effective in restoring some sensory and motor impairment in incomplete SCI patients. The effect of this compound given immediately after an acute injury is not known. The objective of this study was to determine if blockage of K+ ions efflux immediately after an acute SCI would improve neuronal conduction in this model of injury. Cortical somatosensory evoked potentials (SSEPs) were recorded before and after a weight-induced compression injury of 120 grams, and were monitored up to 5 hours postinjury. A randomized treatment was initiated with administration of either vehicle or 4-AP. All 4-AP treatments were given as intravenous bolus injections of 1.0, 0.5, and 0.3 mg/kg at 1, 2, and 3 hours after the trauma. The SSEPs were abolished immediately after the injury in all control and treated animals. Both groups showed spontaneous recovery of the SSEPs at the rate of 44.5% for the 4-AP treated and nontreated groups at the second hour postinjury. This recovery rate remained the same for both groups at the end of the experiments. Based on the recovery of the SSEPs, our data indicate that early administration of 4-AP lacks any beneficial effect on axonal function during acute stage of spinal cord injury.


A restrictor complex of ZC3H4, WDR82, and ARS2 integrates with PNUTS to control unproductive transcription.
The transcriptional termination of unstable non-coding RNAs (ncRNAs) is poorly understood compared to coding transcripts. We recently identified ZC3H4-WDR82 ("restrictor") as restricting human ncRNA transcription, but how it does this is unknown. Here, we show that ZC3H4 additionally associates with ARS2 and the nuclear exosome targeting complex. The domains of ZC3H4 that contact ARS2 and WDR82 are required for ncRNA restriction, suggesting their presence in a functional complex. Consistently, ZC3H4, WDR82, and ARS2 co-transcriptionally control an overlapping population of ncRNAs. ZC3H4 is proximal to the negative elongation factor, PNUTS, which we show enables restrictor function and is required to terminate the transcription of all major RNA polymerase II transcript classes. In contrast to short ncRNAs, longer protein-coding transcription is supported by U1 snRNA, which shields transcripts from restrictor and PNUTS at hundreds of genes. These data provide important insights into the mechanism and control of transcription by restrictor and PNUTS.


Adenomatoid odontogenic tumour. A survey of 21 cases from Sri Lanka.
A series of 21 cases of adenomatoid odontogenic tumour is reported from Sri Lanka. They formed 8.6% of odontogenic tumours, excluding odontomes, in the 10-year period reviewed. 85% of cases occurred in the anterior maxilla. Most cases were diagnosed clinically as dentigerous cysts. There were no recurrences following conservative surgery in follow-up periods ranging from 2 to 11 years.


Accuracy of referrals from an orthoptic vision screening program for 3- to 4-year-old preschool children.
To determine the accuracy of orthoptist referrals from a preschool-based vision screening program for children 3-4 years of age and to report the outcomes of referred children. This was a retrospective review of records of participants in the preschool vision screening program in the Walsall, United Kingdom, area for the 2006-2007 school year. Screening examinations were performed by orthoptists and included assessment of visual acuity, ocular alignment, ocular motility, and stereoacuity. For the 2006-2007 school year, 2,830 of 3,623 children (78%) were screened, Of these, 413 were referred to the Hospital Eye Service. Comparison of the screening results and the Hospital Eye Service examination revealed that recorded visual acuities were similar in 81% of subjects and ocular alignment in 94%. Visual acuity was 6/9 or better at the hospital examination in 87% of referred children, with 46% requiring spectacle use only; 17% of referrals were diagnosed with amblyopia. Although the Walsall vision screening program diverged from UK national guidelines by testing at an earlier age, there was no evidence that earlier screening led to a large number of incorrect referrals, and early screening may allow for better outcomes. Sensitivity of screening was not tested, and orthoptist screening in the United Kingdom is likely to be more accurate in this age group than nonspecialist or lay screening that is performed in many other areas.


Cryoglobulinemia in primary Sjögren's syndrome: prevalence and clinical characteristics in a series of 115 patients.
To determine the prevalence and nature of cryoglobulins in a large series of patients with primary Sjögren's syndrome (SS) and identify the clinical and immunologic features related to their presence. In a cross-sectional study, we investigated 115 consecutive patients (107 women and eight men) with primary SS. All patients fulfilled four or more of the preliminary diagnostic criteria for SS proposed by the European Community Study Group in 1993. Serum cryoglobulinemia was measured in all patients. Serum samples were obtained at 37 degrees C, and cryoglobulinemia was estimated by centrifugation after incubation at 4 degrees C for 7 days. The type of cryoglobulinemia was identified by agarose gel electrophoresis and immunofixation. Cryoglobulins were detected in the sera of 18 (16%) of our patients with primary SS; most were IgMkappa monoclonal/IgG polyclonal. When compared with patients without cryoglobulins, those with cryoglobulins presented a higher prevalence of leukocytoclastic cutaneous vasculitis (56% v8%, P < .001), hypocomplementemia (75% v 2%; P < 0.001) and antibodies to hepatitis C virus (HCV) (47% v8%, P < .001). Liver involvement (clinical signs, biochemical features, or ultrasound/histological data of liver disease) was present in all patients (100%) with cryoglobulins and HCV infection but in only 11% of patients with cryoglobulins without HCV infection (P < .001). Leukocytoclastic cutaneous vasculitis, hypocomplementemia, and HCV infection are associated with the presence of cryoglobulins in the sera of patients with primary SS. Testing for HCV infection is recommended for patients with SS and cryoglobulinemia because of its high prevalence and its strong association with liver disease.


Antibiotic consumption by Access, Watch and Reserve index in public sector of Limpopo province, South Africa: 2014-2018.
The World Health Organization (WHO) classified antibiotics into three categories in 2017 - Access, Watch and Reserve (AWaRe) - intending to reduce the consumption of Watch and Reserve antibiotics while increasing the use of Access antibiotics. Antibiotic consumption by AWaRe in South Africa is undetermined because of data and research scarcity. The aim of this study was to quantify, describe and track antibiotic consumption between 2014 and 2018 in the public sector of the Limpopo province, South Africa, using the WHO's AWaRe classification for 2021. Antibiotic consumption was quantified from pharmaceutical sales data for 2014-2018 by defined daily dose (DDD) per 1000 inhabitants per day (DID) and described according to the AWaRe classification. The change in antibiotic consumption was measured by compound annual growth rate (CAGR), Access-to-Watch index (AW-I), 75% drug utilisation index (DU75%) and amoxicillin index (AI). The absolute consumption of Access antibiotics decreased by a 4.0% CAGR from 3.7 DID in 2014 to 3.0 DID in 2018, with relative consumption remaining above 80.0%. Relative consumption of Watch antibiotics increased by 15.8% CAGR from 7.8% in 2014 to 19.7% by 2018. The AW-I decreased from 10.4 in 2015 to 4.1 in 2018. The AI increased from 17.8% in 2015 to 42.0% in 2018. Parenteral formulations' DU75% comprised one Watch (ceftriaxone) and two Access (metronidazole and benzylpenicillin) antibiotics. In Limpopo province's public sector, the consumption of Watch antibiotics increased, while Access antibiotics consumption decreased, as reflected by both relative consumption and the decrease in the AW-I. The determinants of the Watch antibiotics increase require research attention. Our study addressed the paucity of surveillance and research data on antibiotic consumption in the Limpopo province, South Africa, according to the WHO AWaRe classification.


Phase I/II trial of intraperitoneal 5-Fluorouracil with and without intravenous vasopressin in non-resectable pancreas cancer.
Systemic palliative treatment with chemotherapy against advanced pancreas cancer has low effectiveness despite considerable toxicity. To investigate the safety, toxicity and tumour response of intraperitoneal 5-Fluorouracil (5-FU) with intravenous Leucovorin and to monitor 5-FU pharmacokinetics in plasma during intraperitoneal instillation with and without vasopressin in patients with non-resectable pancreas cancer. Between 1994 and 2003, 68 patients with non-resectable pancreas cancer TNM stage III and IV, were enrolled to receive intraperitoneal5-FU instillation 750-1500 mg/m2 and intravenous Leucovorin 100 mg/m2 for two days every third week. Tumour response, performance status and toxicity were recorded. Seventeen patients were also treated with intravenous vasopressin 0.1 IU/minute for 180 minutes, during intraperitoneal 5-FU instillation. Area under the curve (AUC) and peak concentration (Cmax) of 5-FU in plasma were analysed. The treatment was well tolerated with minor toxicity. One complete response (54.1+ months) and 2 partial responses were observed. Time to progression was 4.4 months (0.8-54.1+), and median survival was 8.0 months (0.8-54.1+). There was a significant reduction of 5-FU Cmax in plasma the second day of treatment if vasopressin was used (3.4+/-2.5 and 6.1+/-5.4 mumol/l, respectively, p<0.05). 5-FU AUC in plasma was not significantly affected by vasopressin either day of treatment. Intraperitoneal 5-FU is a safe treatment with low toxicity to patients with non-resectable pancreas cancer. Tumour response was 4.4% and median survival time 8.0 months. Addition of vasopressin did not significantly decrease plasma 5-FU AUC but reduced Cmax on day 2 of treatment.


Protective effect of Jasonia montana against ethinylestradiol-induced cholestasis in rats.
Estrogens, and particularly glucuronides such as ethinylestradiol (EE), have been shown to cause cholestasis in animal studies, by reducing bile acid uptake by hepatocytes. The aim of the present article is to investigate anticholestatic activity of the ethanolic extract of the aerial parts of Jasonia montana against liver cholestasis induced by EE in adult female rats in an attempt to understand its mechanism of action, which may pave the way for possible therapeutic applications. Subcutaneous administration of 100 μg/kg b.w. ethinylestradiol to rats induced hepatocellular cholestasis with a significant decrease in serum cholesterol, bile acids and bilirubin levels as well as in hepatic superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) activities and hepatic total, protein-bound and non-protein sulfhydryl groups. Also, treatment with EE produced significant increase in serum Pi-glutathione-s-transferase (Pi-GST), gamma glutamyl transpeptidase (γ-GT) and alpha-glutathione-s-transferase (α-GST) activities as well as serum nitric oxide (NO) and tumor necrosis factor alpha (TNF-α) level and hepatic malondialdehyde (MDA) level as compare to control group. Oral administration of the aerial parts of ethanolic extract at a concentration of 150 mg/kg b.w. daily to rats treated with EE for 15 days showed a significant protection against-induced decrease in serum cholesterol, bile acids and bilirubin levels. The treatment also resulted in a significant increase in hepatic SOD, GPx and GR activities as well as hepatic total, protein-bound and non-protein sulfhydryl groups. In addition, the extract could inhibit serum Pi-GST, γ-GT and α-GST activities as well as reduce serum TNF-α, NO and hepatic MDA as compare to ethinylestradiol treated rats. High content of flavonoids and phenolic compounds was found in ethanolic extract, which may be responsible for free radical activity. The results clearly suggest that the aerial parts of J. montana extract may effectively normalize the impaired antioxidant status in ethinylestradiol (EE)-cholestatic model. Thus the extract may have a therapeutic value in drug-induced biliary cholestasis as well as in hormonal therapy.


[Carcinoid tumors of the lung and asbestos. Clinical aspects for insurance medicine].
Lung dust analyses were performed on tumor-free lung tissue from surgical samples of 28 carcinoid tumors. The measured levels in one surgical sample may easily be correlated with the increased asbestos load of the lung due to the patients' occupation as stone mason. No evidence supporting the correlation of increased chronic asbestos load of the lungs and the development of typical carcinoid tumors of the lung was found.


Effects of Nanotexture on Electrical Profiling of Single Tumor Cell and Detection of Cancer from Blood in Microfluidic Channels.
Microfluidic channels have been implemented to detect cancer cells from blood using electrical measurement of each single cell from the sample. Every cell provided characteristic current profile based on its mechano-physical properties. Cancer cells not only showed higher translocation time and peak amplitude compared to blood cells, their pulse shape was also distinctively different. Prevalent microfluidic channels are plain but we created nanotexture on the channel walls using micro reactive ion etching (micro-RIE). The translocation behaviors of the metastatic renal cancer cells through plain and nanotextured PDMS microchannels showed clear differences. Nanotexture enhanced the cell-surface interactions and more than 50% tumor cells exhibited slower translocation through nanotextured channels compared to plain devices. On the other hand, most of the blood cells had very similar characteristics in both channels. Only 7.63% blood cells had slower translocation in nanotextured microchannels. The tumor cell detection efficiency from whole blood increased by 14% in nanotextured microchannels compared to plain channels. This interesting effect of nanotexture on translocation behavior of tumor cells is important for the early detection of cancer.


MicroRNA-143 targets MACC1 to inhibit cell invasion and migration in colorectal cancer.
MicroRNAs (miRNAs) have been suggested to play a vital role in tumor initiation and progression by negatively regulating oncogenes and tumor suppressors. Quite recently, studies have identified some miRNAs operating to promote or suppress tumor invasion or metastasis via regulating metastasis-related genes, providing potential therapeutic targets on anti-metastasis strategy. Metastasis-associated in colon cancer-1 (MACC1) has been newly identified to express highly in colorectal cancer (CRC) and promote tumor metastasis through transactivating metastasis-inducing HGF/MET signaling pathway. In this study, we investigated whether miRNA 143 is involved in the regulation of MACC1 and thus plays a functional role in CRC. Using both in silico prediction and western blot assay, we found the previously reported tumor suppressive miR-143 targeted MACC1 in CRC. The direct interaction between them was confirmed by 3' UTR luciferase reporter gene. In concordance with the inhibitory effects induced by siRNA mediated knockdown of MACC1, restoration of miR-143 by mimics in SW620 cells significantly attenuated cell growth, migration and invasion. It is notable that combined treatment of miR-143 mimics and MACC1 siRNA induced synergistic inhibitory effects compared to either miR-143 mimics or MACC1 siRNA treatment alone. Conversely, reduction of miR-143 by inhibitors in SW480 cells apparently stimulated these phenotypes. Furthermore, we observed that miR-143 level was inversely correlated with MACC1 mRNA expression in CRC tissues. Our findings newly described miR-143/MACC1 link and provided a potential mechanism for MACC1 dysregulation and contribution to CRC cell invasion. It may help to estimate the therapeutic utility of miR-143 in CRC.


Prevalence of Severe and Profound Sensorineural Hearing Loss in School Children in West Bengal, India.
There is pressing need for reliable information about prevalence of sensorineural hearing loss in children in India. Without this basic information it is difficult to plan services on a rational basis. In this stratified cross sectional study, we aimed to determine the prevalence of severe and profound sensorineural hearing loss in school children in West Bengal, India. We hypothesized that all children with severe or profound hearing loss in elementary schools (age 6-14 years) would be among those identified as 'children with special need' because of their marked problems with hearing, speech or communication. First stratum of our study included all 6-14 years old mainstream elementary school 'children with special need', with known or suspected hearing problem. Second stratum covered all 6-14 years old hearing impaired children attending special schools. Comprehensive audiological assessment of 10,763 'children with special need' in mainstream elementary schools identified 3984 children showing severe or profound SNHL (≥71 dB). A further 1022 children were identified with similar loss in special schools, giving a total of 5006 children with severe or profound sensorineural loss among a school population of 8,654,057, with estimated prevalence of 0.58 (CI 0.57-0.59) per 1000 children. This is the first large scale study of the epidemiology of severe and profound sensorineural hearing loss in school children in India. Although further studies are needed from other parts of India, in the interim, findings of this study can form the basis for planning resource allocation, service provision, investigation into etiology and prevention of sensorineural deafness in children in India.


Modulation of Ca2+ exchange with the Ca(2+)-specific regulatory sites of troponin C.
Calcium (Ca2+) binding to the N-terminal Ca(2+)-specific sites on troponin C (TnC) regulate the contraction-relaxation cycle of skeletal muscle. A mutant TnC (F29W) and dansylaziridine-labeled TnC undergo large fluorescence increases when Ca2+ binds to their Ca(2+)-specific sites (half-maximal at pCa 5.8). Calmidazolium and the additional mutation of Met-82 to Gln (F29W,M82Q) increased Ca2+ affinity at these Ca2+ sites by approximately 4-fold (half-maximal at pCa approximately 6.4). Calmidazolium and the M82Q mutation decreased the rate of Ca2+ dissociation from the Ca(2+)-specific sites approximately 3.4-fold (from approximately 462 +/- 84/s to approximately 138 +/- 30/s) at 22 degrees C. Ca2+ associated with the Ca(2+)-specific sites of these proteins at 1-2 x 10(8) M-1 s-1 at 4 degrees C. These drug- and mutation-induced increases in Ca2+ affinity occur solely from large decreases in the Ca2+ off-rate without an effect on the Ca2+ on-rate. Thus, Ca2+ can bind to the Ca(2+)-specific sites of TnC as rapidly as it can diffuse to the protein, consistent with the extreme speed of skeletal muscle contraction. Drugs and/or site-directed mutagenesis can modify the Ca2+ sensitivity and the rate of Ca2+ exchange with TnC's Ca(2+)-specific sites to perhaps alter the rate of relaxation and/or the rate of rise of tension.


Excitatory binocular interactions in two cases of alternating strabismus.
Individuals with alternating fixation due to strabismus have often been considered prime examples of monocular visual function. A growing body of evidence suggests, however, that, at least in the case of a fixed-angle strabismus, excitatory binocular function is possible in the strabismic visual cortex if interocular suppression is taken into account. We investigated whether excitatory binocular function might also be possible for patients with alternating strabismus. Suprathreshold binocular interaction was tested in two individuals with alternating fixation and no amblyopia using a dichoptic motion coherence paradigm that can measure and account for interocular suppression. Both participants exhibited strong interocular suppression when stimuli of the same contrast were presented to each eye, whereas no such suppressive interactions were present for controls; however, in significantly reducing the contrast of the stimuli presented to the fixing eye, excitatory binocular interactions were demonstrated in both participants similar to those measured in controls without the contrast imbalance. The cortical mechanisms necessary for combining information from the two eyes seem to have been present but suppressed in our 2 participants with alternating fixation, just as they have been shown to be present in patients with fixed-angle strabismus.


Serum biomarkers for monitoring response to tuberculosis treatment: an assessment of the effect of different covariates among slow and fast treatment responders.
The long duration of tuberculosis treatment, as well as the 2-year post-treatment follow-up period often required for predicting relapse, present a hindrance to drug development and treatment monitoring efforts. Therefore, there is need for treatment response biomarkers to inform treatment time shortening, clinical decision-making, and inform clinical trials. To assess the abilities of serum host biomarkers to predict treatment response among active PTB patients. Active pulmonary TB patients (n = 53) as confirmed by sputum MGIT culture were enrolled at a TB treatment centre in Kampala, Uganda. We evaluated concentrations of 27 serum host biomarkers at baseline, month 2, and month 6 following the initiation of anti-tuberculosis treatment using the luminex platform for their ability to predict sputum culture status at month-2 post treatment initiation. There were significant differences in concentrations of IL1ra, IL1β, IL6, IP10, MCP-1, and IFNγ during treatment. A bio-signature comprising TTP, TNFα, PDGF-BB, IL9, and GCSF best predicted month 2 culture conversion with sensitivity and specificity of 82% (95% CI; 66 -92% and 57 -96% respectively). Slow anti-TB treatment responders had higher pro-inflammatory marker levels during treatment. The strongest correlation was observed between VEGF and IL12p70 (0.94), IL17A and basic FGF (0.92), basic FGF, and IL2 (0.88), and IL10 with IL17A (0.87). We identified host biomarkers that predicted early response to PTB treatment, which may be valuable in future clinical trials and treatment monitoring. Similarly, strong correlations between biomarkers provide options for biomarkers substitutions during the development of treatment response monitoring tools or point of care tests.


Randomized study of natural orifice transluminal endoscopic surgery and endoscopy shows similar hemodynamic impact in a porcine model.
A previous porcine study showed a significant difference in heart rate and diastolic blood pressure (DBP) between natural orifice transluminal endoscopic surgery (NOTES) and laparoscopy. This study evaluated the hemodynamics during endoscopy, laparoscopy, and transluminal access. For this study, 37 female swine were randomized and invasively monitored in terms of blood and abdominal pressure, heart rate, and arterial blood gas (ABG) during 90-min procedures. Group 1 (n = 11) underwent NOTES peritoneoscopy; group 2 (n = 14) underwent 45-min diagnostic endoscopy, a 10-min washout period, and 35-min laparoscopy with mesh placement; and group 3 (n = 12) NOTES had transgastric mesh placement. The groups were compared using a mixed model and a Spearman trend test. This study was approved by Institutional Animal Care and Use Committee (IACUC). No difference in the systolic blood pressure (SBP) was noted. During the initial 30 min, DBP increased significantly from baseline in groups 1 (p < 0.001) and 2 (p = 0.01), but not in group 3 (p = 0.08). The mean DBP did not differ between the groups. During laparoscopy, the average end-tidal carbon dioxide (CO(2)) level was 6.6 mmHg higher in group 2 than in group 1 (p = 0.01). The heart rate and ABG values did not differ between the groups (p ≥ 0.10). Heart rate and DBP were similar for NOTES and endoscopy. The differences seen in a previous trial comparing NOTES and laparoscopy were not duplicated. The initial DBP increased for the endoscopy and diagnostic NOTES animals. Differences in end-tidal CO(2) were encountered again during the shortened laparoscopy segment.


Effect of a Rational Drug Use Policy on the prescribing safety in outpatient settings in Thailand.
In Thailand, the 'Rational Drug Use (RDU) policy' has been implemented in the Ministry of Public Health (MOPH) hospitals since October 2016. This study aimed to explore the effects of the RDU policy on prescribing safety indicators for elderly patients and those with common chronic diseases. Electronic outpatient databases were obtained from 15 MOPH hospitals. The selected indicators were the (1) glibenclamide prescribing in patients with diabetes mellitus who were elderly or had renal impairment; (2) duplicate prescribing of renin angiotensin system (RAS) blockers in patients with hypertension; (3) non-steroidal anti-inflammatory drugs (NSAIDs) prescribing in patients with chronic kidney disease stages 3-5; and (4) long-acting benzodiazepines prescribing in patients ≥65 years. The policy effects in terms of changes in prescribing trends were estimated using interrupted time-series analysis based on quarterly (Q) data. The postpolicy trends (2016, Q4-2017, Q4) were compared with the prepolicy trend (2014, Q1-2016, Q3). The unsafe prescribing of glibenclamide in patients with diabetes mellitus was 19.2% in Q1, 2014 and decreased significantly due to the RDU policy to 11.0% in Q4, 2017 (-4.23 percentage points quarterly, P < 0.001). The unsafe prescribing of RAS blockers and long-acting benzodiazepines was relatively low in Q1, 2014 (1.0% and 1.1%, respectively) and did not decrease further after the RDU policy. The unsafe prescribing of NSAIDs was 4.2% in Q1, 2014, increased abruptly one quarter after the policy and decreased afterwards. The RDU policy seemed to be a contributing factor that decreased the unsafe prescribing of glibenclamide, while the policy effect was minimal for the other indicators.


Efficacy and safety of total parathyroidectomy with autotransplantation vs. subtotal parathyroidectomy for secondary hyperparathyroidism: A retrospective study.
No consensus has been reached on the best surgical approach for secondary hyperparathyroidism (SHPT). We evaluated the short-term and long-term efficacy and safety of total parathyroidectomy with autotransplantation (TPTX + AT) and subtotal parathyroidectomy (SPTX). We retrospectively analyzed the data of 140 patients undergoing TPTX + AT and 64 undergoing SPTX between 2010 and 2021 in Second Affiliated Hospital of Soochow University, and carried out follow-up. We compared the differences in symptoms, serological examinations, complications and mortality between the two methods, and explored the independent risk factors of secondary hyperparathyroidism recurrence. In short time after surgery, serum intact parathyroid hormone and calcium level was lower in TPTX + AT group than that in SPTX group (both P < 0.05). Severe hypocalcemia was more common in TPTX group (P = 0.003). The recurrent rate was 17.1% for TPTX + AT and 34.4% for SPTX (P = 0.006). There was no statistical difference in all-cause mortality, cardiovascular events, cardiovascular mortality between the two methods. Higher preoperative serum phosphorus level (HR: 1.929 95% CI 1.045-3.563, P = 0.011) and the SPTX surgical method (HR: 2.309, 95% CI 1.276-4.176, P = 0.006) were found to be independent risk factors for SHPT recurrence. Compared with SPTX, TPTX + AT is more effective in reducing the recurrent risk of SHPT without increasing the risk of all-cause mortality and cardiovascular events.


Adsorptive voltammetric investigation of the interaction of cisplatin with cystine and human serum albumin.
The interaction of the anti-cancer drug cisplatin with human serum albumin and cystine has been investigated using differential pulse adsorptive voltammetry. Based on an understanding of the voltammetric behaviour of these biological molecules, which rely on the presence of the disulphide groups within their molecular structure for their electroactivity, it has been postulated that binding of cisplatin to these molecules occurs at the disulphide bond. A fractional coefficient for the binding of cisplatin to human serum albumin at pH 7.4 was calculated to be 0.32. The reactivity of hydrolysis products of cisplatin was shown to be greater than that of the parent drug.


Survival analysis of surgically evacuated supratentorial spontaneous intracerebral hemorrhage with intraventricular extension.
To conduct a survival study and evaluation of surgical treatment in a cohort of patients with diagnosis of supratentorial spontaneous intracerebral hemorrhage (ICH). The study included all consecutive patients with supratentorial ICH admitted to the Intensive Care Units of three Spanish hospitals with Neurosurgery Department between 2009 and 2012. age, APACHE-II, Glasgow Coma Score (GCS), and pupillary anomalies on admission, intracerebral hemorrhage (ICH) score, location/volume of hematoma, intraventricular hemorrhage (IVH), surgical evacuation alone or with additional external ventricular drain, and 30-days survival and at hospital discharge A total of 263 patients were included. Mean age: 59.74±14.14 years. GCS: 8±4 points, APACHE II: 20.7±7.68 points. ICH Score: 2.32+1.04 points. Pupillary anomalies were observed in 30%. The 30-day mortality: 51.3% (45.3% predicted by ICH-score), and 53.2% at hospital discharge. A significant difference (p=0.004) was observed in hospital mortality rates between surgically treated patients (39.7%, n=78) versus those conservatively managed (58.9%, n=185); specifically in those with IVH surgically treated (34.2%, n=38) versus non-operated IVH (67.2%, n=125), p<0.001. No significant difference was found between mortality rates in patients without IVH. Multiple logistic regression analysis showed an OR for surgery of 1.04 (95% CI; 0.33-3.22) in patients without IVH versus 0.19 (95% CI; 0.07-0.53) in patients with IVH (decreased mortality with surgical treatment). The propensity score analysis for IVH patients showed improved survival of operated group (OR 0.23, 95% CI; 0.07-0.75), p=0.01. Hospital mortality was lower in patients who underwent surgery compared to patients conservatively managed, specifically for the subgroup of patients with intraventricular hemorrhage.


Using molecular beacons to study dispersal of mRNPs from the gene locus.
Before leaving the site of transcription, newborn messenger RNAs (mRNAs) become associated with a number of different proteins. How these large messenger ribonucleoprotein (mRNP) complexes then move through the dense nucleoplasm to reach the nuclear periphery has been a fascinating question for the last few years. We have studied the mechanism of this process by tracking individual mRNPs in real time. We were able to track mRNPs at single-molecule resolution because we utilized mRNAs that were engineered to have a sequence motif repeated 96 times in their untranslated region. These mRNAs were visualized with the help of molecular beacons that were specific for the repeated sequence; the binding of 96 molecular beacons to each mRNA molecule rendered them so intensely fluorescent that they were visible as fine fluorescent spots that could be tracked by high-speed video microscopy. In this chapter, we describe the details of the construction of genes containing the tandem repeats, the integration of such genes into the genome of a cell line, the design and testing of molecular beacons, time-lapse imaging of mRNPs, and computer-aided generation and analysis of the tracks of the individual mRNPs. These methods will be useful for studies of other dynamic processes such as mRNA export, splicing, and decay.


Hyponatremia associated with levamisole-adulterated cocaine use in emergency department patients.
An increasing percentage of US cocaine has been adulterated with levamisole, an immunomodulator associated with agranulocytosis. We describe 3 emergency department patients with hyponatremia and cocaine use. Despite extensive evaluation, the cause of the hyponatremia was not elucidated but resolved during hospitalization. Because hyponatremia has not previously been associated with cocaine, we sought to uncover a plausible explanation that might be contributing to this new finding. Levamisole was detected in all 3 patients. Although we are unable to confirm causality, we propose that levamisole-adulterated cocaine may have contributed to the hyponatremia described in these patients.


African Swine Fever: Epidemiology, the Design of New Diagnostic Methods, and Vaccine Development.
African swine fever (ASF) is a pandemic viral disease that poses a major threat to the health of wild and domestic pigs, national economies, and subsistence livelihoods around the world [...].


Evolution of non-dissolved particulate organic matter during composting of sludge with straw.
Long term composting induces loss of C and organic matter stabilisation. These two processes may have opposite effects on long term carbon storage in soils. To check whether raw materials should be composted or not before being spread on the soil, changes in particle size fractions were quantified during composting of 9 tons of sewage sludge and straw. Both the mass of the fine fraction (<2 microm) and the amount of carbon contained in it increased after seven months, respectively, +37% and +43%. The fine fraction contributes to carbon sequestration. A literature review supported the assumption that composting should increase long term C storage. Nevertheless, soil texture or agricultural practices modify the behaviour of this fraction. Thus, the fractionation method used for soils is relevant to predict the effect of composting as a mitigation option in greenhouse gas reduction strategies, but is not sufficient in itself.


Association between itch and cancer in 16,925 patients with pruritus: Experience at a tertiary care center.
Pruritus has been associated with cancer. However, limited data are available on the types of underlying malignancies associated with pruritus. We sought to characterize the association between pruritus and different cancer types, as well as variations by racial group. Cross-sectional study of patients ≥18 years of age seen at the Johns Hopkins Health System during 2013-2017. Patients with pruritus were compared with patients without pruritus. Analyses were stratified by race. Patients with pruritus were more likely to have concomitant malignancy than those without pruritus (odds ratio 5.76, 95% confidence interval 5.53-6.00). Most strongly associated were cancers of the liver, gallbladder and biliary tract, hematopoietic system, and skin. Compared with white patients, black patients more frequently had soft tissue, dermatologic, and hematologic malignancies and less frequently had liver, respiratory, gastrointestinal, and gynecologic malignancies. The cross-sectional design precludes analysis of the temporal association between pruritus and malignancy. The study is limited to a single tertiary care center. Pruritus is most strongly associated with cancers of the liver, skin, and hematopoietic system. Black patients with pruritus have a higher likelihood of skin, soft tissue, and hematologic malignancies than white patients, while whites have higher likelihoods of liver, respiratory, gastrointestinal, and gynecologic malignancies.


Evaluation of Auditory Functions in Patients with Psoriasis.
Our study aims to evaluate the functions of the middle and inner ear and the efferent auditory system in psoriasis. Hearing thresholds, resonance frequency, otoacoustic emission amplitudes with and without contralateral acoustic stimulation, contralateral suppression levels were evaluated in 35 psoriasis patients and 40 controls. The air-conduction hearing thresholds of the patients were significantly higher than the controls at 125, 250, 500, 1000, 2000, 4000, and 12,000 Hz frequencies in the left ear, and 125, 250, 500, 1000, 2000, and 4000 Hz frequencies in the right ear, and the bone-conduction hearing thresholds of the patients were found to be significantly higher than the controls at all frequencies in the left ear, and 250, 500, 1000 and 2000 Hz in the right ear (p < 0.05). The resonance frequencies of patients were found to be significantly lower than the controls (p < 0.001). The emission amplitudes obtained with contralateral acoustic stimulation were significantly lower than without contralateral acoustic stimulation at 1 kHz frequency in both groups (p < 0.01). There was no significant difference in contralateral suppression levels of the two groups (p > 0.05). Our findings indicate that middle ear mechanics can be affected by psoriasis. There was no significant difference between psoriasis patients and healthy controls in terms of efferent auditory functions. There was a significant difference at limited frequency in hearing thresholds and emission amplitudes between the groups.


A fluorescent "2 in 1" proton sensor and polarity probe based on core substituted naphthalene diimide.
A new core-substituted naphthalene diimide (cNDI) compound that is sensitive to both H(+) and solvent polarity has been synthesised and characterised. Optical absorption and emission change upon protonation while emission quantum yield and decay kinetics of the unprotonated form vary significantly with solvent polarity due to delayed fluorescence.


Xin-Jia-Xiang-Ru-Yin alleviated H1N1-induced acute lung injury and inhibited the IFN-γ-related regulatory pathway in summer flu.
Seasonal influenza is an acute viral infection caused by influenza virus, which is often prevalent in summer and winter. In contrast to the prevalent focus on winter flu, summer flu is often ignored by epidemiological researchers. However, summer flu should be studied because of the special immune status and the influenza spread mechanism in the hot and humid environment. Moreover, people are more likely to catch a summertime cold upon suddenly entering relatively cool air conditioning from the hot and humid environment. To simulate summer flu, we established a flu animal model under a high temperature and humidity environment during the day with a relatively low temperature at night to investigate the anti-influenza virus effect and mechanism of Xin-Jia-Xiang-Ru-Yin. The results of RT-qPCR verified virus replication, while pathological sections showed inflammation. The expression of the IFN-γ-related regulatory pathway was measured by PCR and immunohistochemistry. We concluded that Xin-Jia-Xiang-Ru-Yin, which combined antiviral therapy and immune modulation effects, might have important therapeutic benefits against summer flu.


Individuals With Traumatic Brain Injury and Their Significant Others' Perceptions of Information Given About the Nature and Possible Consequences of Brain Injury: Analysis of a National Survey.
An online survey was developed to assess how well individuals with brain injuries and family/friends of those with traumatic brain injury (TBI) (significant others) felt they were informed about the nature and consequences of brain injury. A total of 117 significant others completed the survey. They were primarily female (84.6%), white (94.9%), and well educated (81.2%). A total of 149 individuals with brain injuries completed the survey and again were primarily female (63.8%), white (88.2%), and well educated (82.9%). More than half of the significant other respondents indicated that they were not provided enough information about TBI (53.5%). Up to 53.8% of the respondents with TBI felt that they were not provided enough information, with 43% reporting dissatisfaction with services. Female survivors and those with mild brain injuries were significantly more likely to feel that they were not provided sufficient rehabilitation or information. Increased satisfaction with services was correlated with decreased time since injury (r = -0.165, p = .049). Qualitative analysis revealed key themes about prognostic information and the adequacy of discharge planning and resources. Given that more than half of all surveyed indicated that they were not well-informed about brain injury and its possible effects, it is evident that case managers and their teams need to be aware of and invested in their efforts to educate both individuals with brain injuries and their significant others (family and friends) about both the nature and consequences of brain injury. Specific recommendations for practice are included.


Epidemiology of needlestick and sharps injuries among nurses in a Japanese teaching hospital.
The epidemiology of needlestick and sharps injuries (NSIs) was investigated among a complete cross-section of 1,162 nurses from a large hospital in southern Japan (response rate 74.0%). Forty-six percent had experienced an NSI in the previous year. Most were caused by ampoules or vials, which injured 32.3% of all nurses and accounted for 42.9% of all NSI events. Twenty-two percent of all NSIs involved a device that had been used on a patient prior to the NSI (contaminated device), while the usage status of a further 2.8% of devices was unknown. Logistic regression indicated that nurses younger than 25 years of age were 2.18 times more likely to have sustained a single NSI in the past 12 months [odds ratio (OR) 2.18, 95% confidence intervals (CI) 1.15-4.17] and 2.39 times more likely to have sustained multiple NSIs (OR 2.39, 95% CI 1.08-5.34). Working mixed shifts (rotating day and night, as opposed to day shifts alone) was associated with a 1.67-fold increased risk of sustaining any NSI (OR 1.67, 95% CI 1.01-2.85) and a 2.72 times greater risk of sustaining an NSI from a contaminated device (OR 2.72, 95% CI 1.71-4.44). Nurses who reported significant fatigue after work were 1.87 times more likely to sustain multiple NSIs (OR 1.87, 95% CI 1.13-3.13) and 1.94 times more likely not to report their NSIs (OR 1.94, 95% CI 1.03-3.71). Perceived high mental pressure was associated with a 1.75-fold increased risk of sustaining an NSI from a contaminated device (OR 1.75, 95% CI 1.07-2.88). Nurses who reported suboptimal staffing levels in their wards were 2.21 times more likely not to report any NSIs they sustained in the previous year (OR 2.21, 95% CI 1.06-4.89). Overall, this study suggests that NSIs represent a complex and multi-faceted problem for Japanese nurses. Intervention strategies should consider the emerging complicity of psychosocial factors on NSI among hospital staff in Japan, as elsewhere.


Synaptic organization of cholinergic amacrine cells in the rhesus monkey retina.
In the rhesus monkey retina, choline acetyltransferase (ChAT) immunoreactivity has been used to study the localization and synaptic organization of cholinergic neurons by both light and electron microscopy with peroxidase-antiperoxidase immunohistochemistry. ChAT-containing neurons are a type of amacrine cell with 97.5% of their cell bodies localized to the ganglion cell layer and the remainder in the inner nuclear layer. Their processes arborize in a single narrow band in the inner plexiform layer in a plane dividing the outer two-thirds from the inner one-third of this synaptic region. With electron microscopy, ChAT-immunoreactive amacrine cell processes were observed to be primarily postsynaptic to the diffuse invaginating cone bipolar cells and presynaptic to ganglion cells, although they are both post- and presynaptic to immunohistochemically unlabeled amacrine cell profiles and to ChAT-containing amacrine cell processes as well.


Effectiveness and safety of atosiban versus conventional treatment in the management of preterm labor.
To compare the efficacy of atosiban with conventional treatment of the threatened preterm labor. All the data of pregnant women with threatened preterm labor from January 1 to December 31, 2017, who received atosiban were collected. Pregnant women with conventional treatment (including β-agonists, indomethacin, magnesium sulphate and calcium channel blockers, alone or in combination) were used as control. The proportion of women not requiring an alternative tocolytic treatment within 48 h and remaining undelivered was significantly higher in atosiban treatment group (89.3%; n = 25/28) compared with conventional treatment (24.2%; n = 8/33) (P < 0.0001). For therapy efficacy, there was also no significant difference between atosiban groups and conventional treatment groups in the low gestational ages. However, for the high gestational ages, atosiban treatment group showed higher efficacy (84%; n = 21/25 vs. 37.5%; n = 3/8) (P < 0.05). Moreover, a significantly higher proportion of women in the atosiban treated group (89.3%; n = 25/28) was observed compared with the conventional treatment groups (51.5%; n = 17/33) who did not receive an alternative tocolytic within 48 h (P < 0.01). Maternal and fetal safety was significantly superior with atosiban treatment. Our results support that atosiban would represent an advance over current tocolytic therapy especially for the high gestational ages.


Mothers' perceptions of the behavior and problem-solving skills of their developmentally delayed sons.
Mothers of 17 developmentally delayed preschool boys and 17 age-matched control boys were asked to predict how well their sons would score on the Preschool Embedded Figures Test, to estimate "the average child's" score on the test, and to evaluate their son's attentiveness and cooperation during testing. Mothers of delayed boys were found to hold an idealized view of "the average child's" problem-solving skills, were significantly less accurate than were mothers of control boys in predicting their sons' level of performance, and tended to rate their sons as less cooperative and attentive than the boys were rated by an independent observer. The impact of such distortions in maternal perceptions and expectations were discussed.


Ursodeoxycholic Acid Suppresses Lipogenesis in Mouse Liver: Possible Role of the Decrease in β-Muricholic Acid, a Farnesoid X Receptor Antagonist.
The farnesoid X receptor (FXR) is a major nuclear receptor of bile acids; its activation suppresses sterol regulatory element-binding protein 1c (SREBP1c)-mediated lipogenesis and decreases the lipid contents in the liver. There are many reports showing that the administration of ursodeoxycholic acid (UDCA) suppresses lipogenesis and reduces the lipid contents in the liver of experimental animals. Since UDCA is not recognized as an FXR agonist, these effects of UDCA cannot be readily explained by its direct activation of FXR. We observed that the dietary administration of UDCA in mice decreased the expression levels of SREBP1c and its target lipogenic genes. Alpha- and β-muricholic acids (MCA) and cholic acid (CA) were the major bile acids in the mouse liver but their contents decreased upon UDCA administration. The hepatic contents of chenodeoxycholic acid and deoxycholic acid (DCA) were relatively low but were not changed by UDCA. UDCA did not show FXR agonistic or antagonistic potency in in vitro FXR transactivation assay. Taking these together, we deduced that the above-mentioned change in hepatic bile acid composition induced upon UDCA administration might cause the relative increase in the FXR activity in the liver, mainly by the reduction in the content of β-MCA, a farnesoid X receptor antagonist, which suggests a mechanism by which UDCA suppresses lipogenesis and decreases the lipid contents in the mouse liver.