Quality of life of children with cystic fibrosis.
To review health-related quality of life (QOL) and associated issues and to describe a study investigating "Child Health Questionnaire" (CHQ) scores in relationship to newborn screening (NBS) for cystic fibrosis (CF) and markers of disease severity. A total of 36 patients from 10-15.5 years old who were enrolled in the screened or control group of the Wisconsin CF Neonatal Screening Project completed the CHQ. Scale scores comprised the dependent variables. Independent variables included study group and measures of disease severity. Analyses included Fisher's exact, 2-sample Wilcoxon, and t tests. QOL did not differ significantly between the screened and control groups for any of the scales. None of the comparisons of CHQ scale scores across measures of disease severity were significant in this small sample, but the CHQ and power were limiting. Our results did not demonstrate a benefit of CF NBS on QOL; however, the CHQ may not be adequately sensitive to QOL in children with CF with disease severity comparable to our sample. The Cystic Fibrosis Questionnaire, a recently validated CF-specific QOL measure for pediatric samples, is likely to provide a more informative evaluation of the effects of CF NBS on patients' QOL.


Photosynthetic H2 metabolism in Chlamydomonas reinhardtii (unicellular green algae).
Unicellular green algae have the ability to operate in two distinctly different environments (aerobic and anaerobic), and to photosynthetically generate molecular hydrogen (H2). A recently developed metabolic protocol in the green alga Chlamydomonas reinhardtii permitted separation of photosynthetic O2-evolution and carbon accumulation from anaerobic consumption of cellular metabolites and concomitant photosynthetic H2-evolution. The H2 evolution process was induced upon sulfate nutrient deprivation of the cells, which reversibly inhibits photosystem-II and O2-evolution in their chloroplast. In the absence of O2, and in order to generate ATP, green algae resorted to anaerobic photosynthetic metabolism, evolved H2 in the light and consumed endogenous substrate. This study summarizes recent advances on green algal hydrogen metabolism and discusses avenues of research for the further development of this method. Included is the mechanism of a substantial tenfold starch accumulation in the cells, observed promptly upon S-deprivation, and the regulated starch and protein catabolism during the subsequent H2-evolution. Also discussed is the function of a chloroplast envelope-localized sulfate permease, and the photosynthesis-respiration relationship in green algae as potential tools by which to stabilize and enhance H2 metabolism. In addition to potential practical applications of H2, approaches discussed in this work are beginning to address the biochemistry of anaerobic H2 photoproduction, its genes, proteins, regulation, and communication with other metabolic pathways in microalgae. Photosynthetic H2 production by green algae may hold the promise of generating a renewable fuel from nature's most plentiful resources, sunlight and water. The process potentially concerns global warming and the question of energy supply and demand.


Radiological criteria for atypical features of femur fractures: what we can learn when applied in a clinical study setting.
The paper focuses on the identification of atypical fractures (AFFs). This paper examines the concordance between objective classification and expert subjective review. We believe the paper adds critical information about how to apply the American Society of Bone and Mineral Research (ASBMR) criteria to diagnose AFFs and is of high interest to the field. Assess American Society of Bone and Mineral Research (ASBMR) criteria for identifying atypical femoral fractures (AFFs). Two orthopedic surgeons independently evaluated radiographs of 372 fractures, applying ASBMR criteria. We assessed ease of applying ASBMR criteria and whether criteria-based assessment matched qualitative expert assessment. There was up to 27% uncertainty about how to classify specific features. 84% of films were classified similarly for the presence of AFF according to ASBMR criteria; agreement increased to 94% after consensus meeting. Of 37 fractures categorized as AFFs based on ASBMR criteria, 23 (62.2%) were considered AFFs according to expert assessment (not relying on criteria). Only one (0.5%) femoral shaft fracture that did not meet ASBMR criteria was considered an AFF per expert assessment. The number of major ASBMR features present (four vs five) and whether there was periosteal or endosteal thickening ("beaking" or "flaring") played major roles in the discrepancies between ASBMR criteria-based and expert-based determinations. ASBMR AFF criteria were useful for reviewers but several features were difficult to interpret. Expert assessments did not agree with the ASBMR classification in almost one-third of cases, but rarely identified an AFF when a femoral shaft fracture did not meet ASBMR AFF criteria. Experts identified lateral cortical transverse fracture line and associated new-bone formation along with no or minimal comminution as crucial features necessary for the definition of atypical femoral fractures.


Molecular cloning and characterization of acid phosphatase in venom of the endoparasitoid wasp Pteromalus puparum (Hymenoptera: Pteromalidae).
The present study describes cDNA cloning, sequencing, enzyme activity determination and localization, and mRNA expression of acid phosphatase in the venom apparatus of an endoparasitoid, Pteromalus puparum. This is the first report of cloning a venom acid phosphatase gene which has been described in parasitoid wasps. The cDNA consisted of 1378bp with 1215bp open reading frame and encoded a sequence of 405 amino acids. A 23 residues N-terminal signal peptide was followed by a short 15 residues (25-39) histidine acid phosphatases phosphohistidine signature and a long 302 residues (24-325) acid phosphatase family domain. The deduced amino acid sequence shared 32-88% identity to its counterparts from other insects. Enzyme activity was measured by using p-nitrophenyl phosphate (p-NPP) as substrate, and a high level of acid phosphatase activity in venom was detected. Optimal pH and temperature for this enzyme activity was 4.8 and 45 degrees C, respectively. Ultracytochemical analyses further revealed that strong enzyme activity was located in the nuclei and secretory vesicles of the venom gland secretory cells. Expression of the acid phosphatase gene was observed to be regulated at different developmental stages by RT-PCR analysis as it expressed immediately with low abundance after adult emergence, then increased to the high level at 2-4 days, followed by a drop to the low abundance after 4 days. Compared to the mRNA expression, a time-course-related enzyme activity in an individual venom apparatus was also found.


Early outcomes in human lung transplantation with Thymoglobulin or Campath-1H for recipient pretreatment followed by posttransplant tacrolimus near-monotherapy.
Acute and chronic rejection remain unresolved problems after lung transplantation, despite heavy multidrug immunosuppression. In turn, the strong immunosuppression has been responsible for mortality and pervasive morbidity. It also has been postulated to interdict potential mechanisms of alloengraftment. In 48 lung recipients we applied 2 therapeutic principles: (1) recipient pretreatment with antilymphoid antibody preparations (Thymoglobulin [SangStat, Fremont, Calif] or Campath [alemtuzumab; manufactured by ILEX Pharmaceuticals, LP, San Antonio, Tex; distributed by Berlex Laboratories, Richmond, Calif]) and (2) minimal posttransplant immunosuppression with tacrolimus monotherapy or near-monotherapy. Our principal analysis was of the events during the critical first 6 posttransplant months of highest immunologic and infectious disease risk. Results were compared with those of 28 historical lung recipients treated with daclizumab induction and triple immunosuppression (tacrolimus-prednisone-azathioprine). Recipient pretreatment with both antilymphoid preparations allowed the use of postoperative tacrolimus monotherapy with prevention or control of acute rejection. Freedom from rejection was significantly greater with Campath than with Thymoglobulin (P = .03) or daclizumab (P = .05). After lymphoid depletion with Thymoglobulin or Campath, patient and graft survival at 6 months was 90% or greater. Patient and graft survival after 9 to 24 months is 84.2% in the Thymoglobulin cohort, and after 10 to 12 months, it is 90% in the Campath cohort. There has been a subjective improvement in quality of life relative to our historical experience. Our results suggest that improvements in lung transplantation can be accomplished by altering the timing, dosage, and approach to immunosuppression in ways that might allow natural mechanisms of alloengraftment and diminish the magnitude of required maintenance immunosuppression.


Is there a minimum intensity threshold for resistance training-induced hypertrophic adaptations?
In humans, regimented resistance training has been shown to promote substantial increases in skeletal muscle mass. With respect to traditional resistance training methods, the prevailing opinion is that an intensity of greater than ~60 % of 1 repetition maximum (RM) is necessary to elicit significant increases in muscular size. It has been surmised that this is the minimum threshold required to activate the complete spectrum of fiber types, particularly those associated with the largest motor units. There is emerging evidence, however, that low-intensity resistance training performed with blood flow restriction (BFR) can promote marked increases in muscle hypertrophy, in many cases equal to that of traditional high-intensity exercise. The anabolic effects of such occlusion-based training have been attributed to increased levels of metabolic stress that mediate hypertrophy at least in part by enhancing recruitment of high-threshold motor units. Recently, several researchers have put forth the theory that low-intensity exercise (≤50 % 1RM) performed without BFR can promote increases in muscle size equal, or perhaps even superior, to that at higher intensities, provided training is carried out to volitional muscular failure. Proponents of the theory postulate that fatiguing contractions at light loads is simply a milder form of BFR and thus ultimately results in maximal muscle fiber recruitment. Current research indicates that low-load exercise can indeed promote increases in muscle growth in untrained subjects, and that these gains may be functionally, metabolically, and/or aesthetically meaningful. However, whether hypertrophic adaptations can equal that achieved with higher intensity resistance exercise (≤60 % 1RM) remains to be determined. Furthermore, it is not clear as to what, if any, hypertrophic effects are seen with low-intensity exercise in well-trained subjects as experimental studies on the topic in this population are lacking. Practical implications of these findings are discussed.


Differential expression of microRNAs in the human fetal left and right cerebral cortex.
Human brain is anatomically and functionally asymmetric. How brain asymmetry is initiated and established during fetal development is poorly understood. Accumulating evidence has shown that microRNAs (miRNAs) play crucial roles in brain development and function. In this study, we investigate miRNA expression profiles in left and right hemispheres of human fetal brains at 12 weeks post conception (PC), and identify 42 miRNAs showing differential expression between two hemispheres using Affymetrix microarray analyses. Target genes for left- and right-biased miRNAs are largely involved in developmental and functional regulations in the cortex such as axon guidance, GABAergic synapse and dopaminergic synapse pathways. Moreover, we find that predicted targets associated with canonical and non-canonical WNT signaling pathway show variations and differential expression between two hemispheres in response to left- and right-biased miRNAs. Our results highlight a potential role of miRNAs in regulating asymmetric development of human fetal brains.


Heart Rate Response Predicts 6-Minutes Walking Distance in Pulmonary Arterial Hypertension.
Because the 6-minute walking test (6MWT) is a self-paced submaximal test, the 6-minute walking distance (6MWD) is substantially influenced by individual effort level and physical condition, which is difficult to quantify. We aimed to explore the optimal indicator reflecting the perceived effort level during 6MWT. We prospectively enrolled 76 patients with pulmonary arterial hypertension and 152 healthy participants; they performed 2 6MWTs at 2 different speeds: (1) at leisurely speed, as performed in daily life without extra effort (leisure 6MWT) and (2) an increased walking speed, walking as the guideline indicated (standard 6MWT). The factors associated with 6MWD during standard 6MWT were investigated using a multiple linear regression analysis. The heart rate (HR) and Borg score increased and oxygen saturation (SpO2) decreased after walking in 2 6MWTs in both groups (all p <0.001). The ratio of difference in HR before and after each test (ΔHR) to HR before walking (HRat rest) and the difference in SpO2 (ΔSpO2) and Borg (ΔBorg) before and after each test were all significantly higher in both groups after standard 6MWT than after leisure 6MWT (all p <0.001). Multiple linear regression analysis revealed that ΔHR/HRat rest was an independent predictor of 6MWD during standard 6MWT in both groups (both p <0.001, adjusted R2 = 0.737 and 0.49, respectively). 6MWD and ΔHR/HRat rest were significantly lower in patients than in healthy participants (both p <0.001) and in patients with cardiac functional class III than in patients with class I/II (both p <0.001). In conclusion, ΔHR/HRat rest is a good reflector of combined physical and effort factors. HR response should be incorporated into 6MWD to better assess a participant's exercise capacity.


Achieving Sustainable Development Goal for Clean Water in India: Influence of Natural and Anthropogenic Factors on Groundwater Microbial Pollution.
Worldwide, >2 billion people (~1/3 world population), mostly living in economically stressed areas of Africa and South Asia, still do not have access to basic sanitation, and ~1 billion still practice open defecation. Water pollution due to open defecation may primarily be linked to economy, and other factors such as social and hygiene practices, land use and hydrogeological parameters could also have sufficient influence. The present study describes the effect of human development index (HDI, 2001-2015) and economic development (NL, 1992-2013) on groundwater microbial pollution (FC, 2002-2017) across India. Economic development pattern suggested discernable inverse relationship with FC in most areas, although areas with inferior water quality, improper human practices were found to outweigh economic development. Vulnerability modelling, using these data, along with measured FC in groundwater-sourced drinking water locations (n = 235) demonstrated the heterogeneity of FC distribution potential in areas of homogenous economy, social practices, and land use. High-resolution numerical modelling of the advective transport of the hypothetical FC particles in the aquifers, suggest up to ~24 times faster movement of pollutants under irrigation-induced pumping regimes. Hence, the results of our study highlight and quantify the potential pitfalls that are possible hindrance for achieving the United Nations sustainable development goal, despite social and economic development, across the spatial scales.


[Long-term results of the use of osteoplastic thoracoplasty in the treatment of destructive tuberculosis of the lungs in patients with antisocial behavior].
The results of osteoplastic thoracoplasty in 44 patients with antisocial behaviour and contraindications to lung resection because of the specific process marked activity are presented. Osteoplastic thoracoplasty is advantageous over the other collapse surgery procedures as there is no need of using therapeutic compressing bandages which makes it possible to discharge a patient from a hospital in case of infringing the hospital regimen. The use of osteoplastic thoracoplasty provided the clinical effect in 29.5 per cent of the patients. In 52.3 per cent of the patients it had a stabilizing effect before lung resection. On the whole, clinical rehabilitation at remote periods was stated in 81.8 per cent of the persons with antisocial behaviour.


Evaluating national guidelines for the prophylactic treatment of respiratory syncytial virus in children with congenital heart disease.
This is the first study to evaluate compliance with the 2003 Swedish national guidelines for prophylactic treatment of respiratory syncytial virus (RSV) in children with congenital heart disease (CHD). We estimated the relative risk (RR) of children with CHD being hospitalised with a RSV infection, studied the extent to which RSV prophylactic treatment with palivizumab corresponded to the guidelines and determined the morbidity of children with CHD who developed RSV infection despite prophylaxis. This national observational study comprised prospectively registered data on 219 children with CHD treated with palivizumab, medical records on RSV cases and information on hospitalisation rates of children with CHD and RSV infection. The calculated RR of children with CHD being hospitalised with RSV infection was 2.06 (95% CI 1.6-2.6; p < 0.0001) compared with children without CHD. Approximately half of the patients (49%) born before the RSV season and 25% born during the RSV season did not start treatment as recommended by the guidelines. Having CHD increased the rate and estimated RR of children being hospitalised with RSV infection. The guidelines were not followed for about half of the children born before a RSV season and a quarter of the children born during a RSV season and need updating.


Thinking about attention: Successive approximations to a productive taxonomy.
Attention, the recruitment of processing resources, is viewed as pivotal for understanding normal behaviour and thought as well as the disorganizations associated with brain damage and disease. A brief history foreshadows aspects of a proposed taxonomy of attention that builds upon Posner's tripartite taxonomy. Posner's influential taxonomy views attention as a set of isolable neural systems (alerting, orienting and executive control), often working together to organize behaviour. For measuring the efficacy of these three networks, Posner and colleagues created the Attention Network Test (ANT). The impact of the taxonomy and this model task for exploring it is illustrated by the facts that they have spawned numerous variants designed for different purposes and that one or another variant has been used in almost a thousand publications. We have previously built upon this conceptual framework by considering: two modes of control over resource allocation which we labelled exogenous and endogenous and three domains over which these modes of control are presumed to operate (space, time and task or activity). The Combined Attention Systems Test (or CAST) was developed to measure the efficacy of the six kinds of attention implied by revised taxonomy. Lastly, this taxonomic effort is further developed by incorporating the distinction between overt, observable behaviour in the "real" world and covert "behaviour" in the realm of thought and imagination.


SIDRE: Symptomatic Improvement of Dry Eye Study.
The aim of this study was to evaluate the effectiveness of lifitegrast 5% ophthalmic solution in reducing the symptoms of eye dryness using Ocular Surface Disease Index (OSDI) questionnaire. A single-center study was undertaken to evaluate the clinical outcomes. Fourteen subjects (12 female and 2 male) with symptoms of dry eye and a positive history of recent use of artificial tears were included in the study. OSDI questionnaire scores on the severity of symptoms, visual functionality, and quality of life related to the condition were recorded pre- and post-therapy. Subsequently, score data were analyzed for statistical significance. The mean age of the 14 subjects was 44.86 (standard deviation [SD] ±3.08) years, with a range of 23-62 years. Mean duration of the evaluation was 28.79 days with a range of 25-34 days. Baseline OSDI mean score was 49.40 (SD ±1.28), and post-therapy mean score was 42.26 (SD ±0.99). Data analysis revealed that the scores were statistically significantly improved post-lifitegrast therapy in comparison to baseline (p=0.00041). Lifitegrast 5% ophthalmic solution may be a beneficial therapeutic option in the management of symptoms associated with dry eye disease.


Effects of aging on protein expression in mice brain microvessels: ROS scavengers, mRNA/protein stability, glycolytic enzymes, mitochondrial complexes, and basement membrane components.
Differentially expressed (DE) proteins in the cortical microvessels (MVs) of young, middle-aged, and old male and female mice were evaluated using discovery-based proteomics analysis (> 4,200 quantified proteins/group). Most DE proteins (> 90%) showed no significant differences between the sexes; however, some significant DE proteins showing sexual differences in MVs decreased from young (8.3%), to middle-aged (3.7%), to old (0.5%) mice. Therefore, we combined male and female data for age-dependent comparisons but noted sex differences for examination. Key proteins involved in the oxidative stress response, mRNA or protein stability, basement membrane (BM) composition, aerobic glycolysis, and mitochondrial function were significantly altered with aging. Relative abundance of superoxide dismutase-1/-2, catalase and thioredoxin were reduced with aging. Proteins participating in either mRNA degradation or pre-mRNA splicing were significantly increased in old mice MVs, whereas protein stabilizing proteins decreased. Glycolytic proteins were not affected in middle age, but the relative abundance of these proteins decreased in MVs of old mice. Although most of the 41 examined proteins composing mitochondrial complexes I-V were reduced in old mice, six of these proteins showed a significant reduction in middle-aged mice, but the relative abundance increased in fourteen proteins. Nidogen, collagen, and laminin family members as well as perlecan showed differing patterns during aging, indicating BM reorganization starting in middle age. We suggest that increased oxidative stress during aging leads to adverse protein profile changes of brain cortical MVs that affect mRNA/protein stability, BM integrity, and ATP synthesis capacity.


Risk of cardiovascular disease in patients with HIV infection undergoing antiretroviral therapy.
The increased survival of patients with HIV infection thanks to antiretroviral therapy (ART) is accompanied by a higher rate of cardiovascular disease (CVD). We analysed the prevalence of the cardiovascular risk factors (CRFs) and estimated the risk of CVD in a cohort of patients with HIV in Spain. We conducted a cross-sectional, observational study of CRFs in the Spanish VACH cohort of patients with HIV who undergo ART. The study assessed 15,559 patients with HIV (76% men; mean age, 46 years). Some 3.7% had experienced at least 1 CVD event. The prevalence of CRFs was high (hyperlipidaemia, 64%; tobacco use, 47%; arterial hypertension, 22%; and diabetes, 16%). According to the Framingham scale, 10.9% of the patients presented a high CVD risk, and 28.8% presented a moderate risk. Of the patients with a high CVD risk, 49% took protease inhibitors and 43% took abacavir. Fifty-three percent of the patients diagnosed with arterial hypertension took antihypertensive drugs, and 2.6% of the patients with diabetes took antidiabetic agents. Classical CRFs are common in patients with HIV undergoing ART in Spain, and a large proportion of them have a moderate-high risk of CVD. Therefore, controlling the modifiable CRFs in patients with HIV should be improved, and the use of drugs with a better cardiovascular risk profile should be assessed.


Based on Histogram Analysis: ADCaqp Derived from Ultra-high b-Value DWI could be a Non-invasive Specific Biomarker for Rectal Cancer Prognosis.
Aquaporins (AQP) are not only water channel protein, but also potential prognostic indicator and therapeutic target for rectal cancer. Some previous studies have demonstrated the AQP expression could be estimated by ADCaqp value derived from ultra-high b-value diffusion-weighted imaging (DWI). We aim to determine whether ADCaqp could be a new and specific biomarker for indicating the AQP expression and prognostic factors of rectal cancer. 76 untreated patients with rectal cancer confirmed by colonoscopy biopsy were enrolled. ADCaqp value was generated from ultra-high b-value DWI with five b-values (1700-3500 s/mm2). AQP (AQP1, 3 and 5)staining intensity was estimated by both of software (QuPath) and manual manner. The relationships between histogram features of ADCaqp and AQP staining intensity were analyzed. The correlations between histogram features of ADCaqp and differentiation degrees (good, moderate, poor), T stage (T1-2 vs T3-4), and lymph node status (N+ vs N-) were also evaluated respectively. The mean, 75th percentile and 97.5th percentile of ADCaqp were correlated with AQP1 staining intensity (r = 0.237, 0.323 and 0.362, respectively, all P < 0.05) . No correlation was found between the histogram features of ADCaqp and AQP3 or AQP5 staining intensity. The mean, 50th percentile, 75th percentile and 97.5th percentile of ADCaqp value exhibited significant differences between differentiation status (all P < 0.05). Histogram features of ADCaqp value showed no significant differences in two subgroups of T stage and lymph node status (all P > 0.05). Histogram analysis showed that the ADCaqp value derived from ultra-high b-value DWI of rectal cancer could reflect AQP1's expression and rectal cancer's malignancy degree. ADCaqp might be a new imaging biomarker for evaluating rectal cancer.


Preparation and preclinical characterization of 111In-DTPA-Anti-MUC1 as a radioimmunoconjugate for diagnosis of breast cancer by single-photon emission computed tomography.
Targeting MUC1 antigens which are overexpressed in 80% of breast cancers can be widely used in the field of radioimmunoscintigraphy (RIS) of breast cancer. The aim of this study was to develop a new diagnostic labeled compound for breast cancer RIS. In this study, an efficient indirect labeling method of PR81 with Indium-111 was developed and preliminary preclinical qualifications were reported. 111In-DTPA-PR81 was prepared and its radiochemical purity and stabilities in human serum and in phosphate-buffered saline (PBS) buffer were surveyed. Furthermore, cellular studies including complex reactivity, binding specificity, cell toxicity, etc., were examined. Finally, biodistribution and scintigraphy of the complex were studied in normal and tumoral animals. Statistical analyses were performed using SPSS 10.0. 111In-DTPA-PR81 was prepared with a radiochemical purity of >99% at optimized conditions. Stability studies showed the radiochemical purity of >90% in PBS buffer after 96 h, while the stability in human serum showed decrement to 81% after 96 h. Reactivity of the complex with MUC1 was significantly (P < 0.005) higher than bovine serum albumin (BSA) (about 7-8 times), even though BSA concentration was about twice the MUC1. The binding specificity of the complex to the MUC1 antigen was confirmed by means of immunoreactivity assay. Cell toxicity examination showed no significant lethal effect of the radiolabeled compound on the cells. Biodistribution studies of the complex in normal rats were consistent with the biodistribution of antibodies and high accumulation was observed in the tissues expressing MUC1 antigen. The results of 111In-DTPA-PR81 scintigraphy in tumoral female BALB/c mice at 24 and 48 h after injection showed an increasement of the accumulation in the tumor site. 111In-DTPA-PR81 can be considered as a potential agent for imaging of the MUC1 +breast tumors.


Future of preventing and managing common chronic inflammatory diseases.
Chronic inflammation has emerged as a key factor that contributes to some common chronic diseases and reduces lifespan. Studies have identified multiple types of chronic inflammation ranging from autoimmune disease, which attacks specific tissues, to autoinflammatory diseases, which cause low-grade systemic inflammation and contribute to several common chronic diseases. This article highlights new perspectives on the role of chronic inflammation in cardiovascular disease (CVD). Such information is being leveraged to develop new treatment strategies for CVD and may inform how periodontal disease influences CVD.


Measuring tooth size discrepancies using Bolton analysis: a comparative cross-sectional study among major ethnicity in Malaysia.
The Bolton analysis is one of the commonly used tooth size analysis or diagnostic tools in deriving a treatment plan for orthodontic patients. Many studies have indicated and concluded that normal measurements for one group should not be considered normal for other ethnic groups. The aims and objectives of this study were to investigate the applicability of Bolton's ratios in the orthodontic population of Malaysian main ethnics, Malay, Chinese, and Indians. Comparisons were made in terms of size and distribution of tooth size discrepancy in the Malaysian orthodontic population and the findings were converted in terms of millimeters. Hundred fifty pre-orthodontic study casts comprised of 52 Malay, 54 Chinese, and 44 Indian patients were selected. Digital calipers (Fowler Pro-Max) linked to Hamilton Tooth Arch Software were used to measure the tooth width and ratios. Statistical analysis was carried out to test for gender differences (independent t-test), to identify the effects of malocclusion and ethnic groups (Two-way ANOVA), and to compare the means of the current study with Bolton's standards (one sample t-test). This study showed that there was no significant difference between the genders of the sample of each ethnicity. There was no correlation found between ethnic groups and malocclusion classes. There was a significant difference when comparing Bolton values with the Malay sample for both ratios. It was found that more Malay subjects presented with maxillary excess contrary to Chinese and Indians who presented more maxillary deficiency for the anterior and overall ratio. There was a significant difference found between the TSD of the three major ethnicities in Malaysia. The Bolton standards can be applied to Malaysian Chinese and Indians but not to Malays orthodontic populations for both anterior and overall ratios. Subsequently, a specific standard should be used for the Malays orthodontic population. It was found that more Malay subjects presented with maxillary excess contrary to Chinese and Indians who presented more maxillary deficiency for the anterior and overall ratio.


Respiratory depression in the intoxicated trauma patient: are opioids to blame?
Providing effective pain management to acutely intoxicated trauma patients represents a challenge of balancing appropriate pain management with the risk of potential respiratory depression from opioid administration. The objective of this study was to quantify the incidence of respiratory depression in trauma patients acutely intoxicated with ethanol who received opioids as compared with those who did not and identify potential risk factors for respiratory depression in this population. Retrospective medical record review was conducted for subjects identified via the trauma registry who were admitted as a trauma activation and had a detectable serum ethanol level upon admission. Risk factors and characteristics compared included demographics, Injury Severity Score, Glasgow Coma Score, serum ethanol level upon arrival, urine drug screen results, incidence of respiratory depression, and opioid and other sedative medication use. A total of 233 patients were included (78.5% male). Patients who received opioids were more likely to have a higher Injury Severity Score and initial pain score on admission as compared with those who did not receive opioids. Blood ethanol content was higher in patients who did not receive opioids (0.205 vs 0.237 mg/dL, P = .015). Patients who did not receive opioids were more likely to be intubated within 4 hours of admission (1.7% vs 12.1%, P = .02). Opioid administration was not associated with increased risk of respiratory depression (19.7% vs 22.4%, P = .606). Increased cumulative fentanyl dose was associated with increased risk of respiratory depression. Increased cumulative fentanyl dose, but not opioid administration alone, was found to be a risk factor for respiratory depression.


Hypertension-related stroke prevention in the elderly.
Hypertension is a major risk factor for cardiovascular events, including ischemic stroke and hemorrhagic stroke. Reduction of blood pressure by lifestyle measures and antihypertensive drug therapy reduces stroke in elderly men and women. The use of diuretics, beta blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers causes a similar reduction in reducing coronary events and stroke for a given reduction in blood pressure. The American College of Cardiology Foundation/American Heart Association 2011 expert consensus document on hypertension in the elderly recommended that the blood pressure should be reduced to less than 140/90 mm Hg in adults younger than 80 years at high risk for cardiovascular events. On the basis of data from the Hypertension in the Very Elderly trial, these guidelines recommended that the systolic blood pressure should be reduced to 140 to 145 mm Hg if tolerated in adults aged 80 years and older. The 2013 European Society of Hypertension guidelines recommended that reducing blood pressure to less than 130/80 mm Hg in adults at high risk for cardiovascular events was unsupported by prospective trial data. The systolic blood pressure should be reduced to less than 140 mm Hg in these adults and to between 140 to 150 mm Hg in adults aged 80 years and older.


Taiwanese Dermatological Association consensus for the management of atopic dermatitis: A 2020 update.
Atopic dermatitis (AD) is a chronic inflammatory disease commonly seen in children and increasingly recognized in adults. With recent advances in the therapeutic development for AD, the Taiwanese Dermatological Association (TDA) established a committee to update the consensus for AD management in Taiwan. This report describes the 2020 updated consensus for the management of AD. A panel of 11 core members was convened to review and discuss aspects of AD management and draft recommendation during the first two meetings. The 2015 TDA consensus and the 2017 European guideline, along with recent peer-reviewed articles, serve as the foundation for the update. In the third meeting, AD expert dermatologists selected on a national scale were invited to vote on the final statements. A total of 27 dermatologists attended the final meeting. The consensus was achieved when ratings of 7-9 (out of a total score of 9) accounted for ≥ 75% of the total votes. Consensus was achieved on the therapeutic options for AD by lines of treatment. A treatment algorithm was presented to illustrate the place of each modality in terms of basic care, acute disease control, and maintenance therapy. Special considerations for the pediatric population, as well as for women during pregnancy and lactation, are discussed. Topical corticosteroids with long-term emollient-based therapies remain the cornerstone of AD treatment. Systemic treatments are indicated when topical therapies and phototherapy fail to control the disease. The recent approval of dupilumab and emerging targeted therapies are expected to bring significant clinical benefit for patients whose disease is inadequately managed by existing options.


Comparison between a serum creatinine-and a cystatin C-based glomerular filtration rate equation in patients receiving amphotericin B.
Serum cystatin C (Cys C) has a number of advantages over serum creatinine in the evaluation of kidney function. Apart from Cys C level itself, several formulas have also been introduced in different clinical settings for the estimation of glomerular filtration rate (GFR) based upon serum Cys C level. The aim of the present study was to compare a serum Cys C-based equation with Cockcroft-Gault serum creatinine-based formula, both used in the calculation of GFR, in patients receiving amphotericin B. Fifty four adult patients with no history of acute or chronic kidney injury having been planned to receive conventional amphotericin B for an anticipated duration of at least 1 week for any indication were recruited. At three time points during amphotericin B treatment, including days 0, 7, and 14, serum cystatin C as well as creatinine levels were measured. GFR at the above time points was estimated by both creatinine (Cockcroft-Gault) and serum Cys C based equations. There was significant correlation between creatinine-based and Cys C-based GFR values at days 0 (R = 0.606, P = 0.001) and 7 (R = 0.714, P < 0.001). In contrast to GFR estimated by the Cockcroft-Gault equation, the mean (95 % confidence interval) Cys C-based GFR values at different studied time points were comparable within as well as between patients with and without amphotericin B nephrotoxicity. Our results suggested that the Gentian Cys C-based GFR equation correlated significantly with the Cockcroft-Gault formula at least at the early time period of treatment with amphotericin B. Graphical abstract Comparison between a serum creatinine-and a cystatin C-based glomerular filtration rate equation in patients receiving amphotericin B.


Indomethacin alters the effects of substance-P and VIP on isolated airway smooth muscle.
Both substance-P and vasoactive intestinal peptide (VIP) have previously been demonstrated to contract and relax, respectively, the isolated guinea pig trachea. In addition, substance-P and VIP have been localized within the pulmonary innervation of various species. In the present studies, substance-P was found to cause a concentration-related contraction of isolated lung parenchymal strips of the guinea pig, as well as isolated tracheal strips. VIP caused a significant concentration-related relaxation of the isolated tracheal strip, but not the lung parenchymal strip. Indomethacin, a prostaglandin synthetase inhibitor, potentiated the contractile response of the trachea to substance-P and inhibited the VIP- and isoproterenol-induced relaxation. These studies are potentially important in understanding the pathogenesis of bronchospastic disorders, since alterations in prostaglandin biosynthesis may result in hyperreactivity of airways to contractile agonists such as neurotransmitters, as well as an inhibition of relaxation induced by endogenous substances such as VIP or beta agonists.


Intensification of dilute acid hydrolysis of spent tea powder using ultrasound for enhanced production of reducing sugars.
Spent tea (ST) powder is one of the potential sustainable sources available abundantly and can be utilized to produce reducing sugars required for production of platform chemicals. The current study aims at intensifying the reducing sugars production based on ultrasound assisted dilute acid hydrolysis (UADAH). The effects of reaction time, solid liquid ratio, acid concentration and temperature on the yield of reducing sugars were investigated initially for UADAH process based on ultrasonic (US) horn. The highest yield of 24.75 g/L for the reducing sugars was obtained at solid liquid ratio of 1:8, acid concentration of 1% w/v and temperature of 60 °C within 120 min. Use of oxidants like hydrogen peroxide (H2O2) and Fenton's reagent to further intensify the production has also been studied. Use of H2O2 at optimum loading of 0.75 g/L resulted in reducing sugars yield of 26.2 g/L within 75 min while using same H2O2 loading with FeSO4 at loading of 0.75 g/L along with UADAH reduced the reaction time to 60 min for almost similar yield. Large scale studies performed using US flow cell revealed that yield of reducing sugars as 22.4 g/L is obtained in 120 min in the case of only UADAH, while in the case of UADAH along with H2O2 and Fenton's reagent, similar yield of reducing sugars was obtained in only 90 and 60 min respectively. UADAH in combination with oxidants has been demonstrated as an effective and intensified approach to produce reducing sugars from spent tea powder available as sustainable source.


Malignant large cell lymphoma of B-cell type with multilobated nuclei. Report of a case and review of the literature.
Malignant lymphomas with multilobated nuclei are rare, recently recognized neoplasms of the immune system initially thought to be of T-cell type. Reported is a case of large cell lymphoma with multilobated nuclei in which immunologic marker studies demonstrated that the neoplastic cells had characteristics of B-lymphocytes. The neoplastic cells possessed surface and cytoplasmic immunoglobulin of the IgG, lambda type, and stained diffusely with monoclonal antibodies to B1, Leu-10 and OKIaI antigens and focally with anti-B2. The lymphoma cells did not react with monoclonal antibodies directed against T-cells and monocytes/granulocytes. As documented here with multiple monoclonal antibody lymphocyte markers, the multilobated lymphoma can have a B-cell phenotype as well as the cell phenotype described previously. Thus, even the unique finding of multilobated nuclear morphologic features is unreliable in predicting the lymphocyte lineage.


Induction of human neutrophils chemotaxis by staphylococcal lipase.
Influence of highly purified staphylococcal lipase on chemotactic activity of human polymorphonuclear leukocytes (PMN), has been studied. Staphylococcal lipase exhibited both chemotactic and chemokinetic properties. Chemotactic response was stimulated at concentration as low as 10(-9) M and was dose-dependent. Pretreatment of PMN with lipase, strongly enhanced chemotactic response toward casein. At the same time, spontaneous migration of these PMN was inhibited. It has been demonstrated that staphylococcal lipase binds to the leukocyte surface. Several possible mechanisms of lipase-induced chemotactic response of human PMN are discussed.


Empowering caregivers in the radiotherapy process: the results of a randomized controlled trial.
The present study aims to evaluate the effectiveness of a mobile-assisted empowerment program developed specifically for caregivers of cancer patients undergoing radiotherapy. In this study, seventy-four individuals who gave care for cancer patients that received radiotherapy between September 2019 and May 2020 were randomized to receive a mobile-assisted empowerment program or standard care. The mobile-assisted empowerment program comprised of education and information related to the radiotherapy process, videos, activities, and question-and-answer modules to support caregivers during the radiotherapy process. Outcome measures were collected at baseline (day 1 of radiotherapy) and on day 21 and included caregiver demographics, distress, quality of life, and coping style using validated questionnaires. Compared with baseline, individuals' mean scores of distress were lower in the empowerment group than the control group (p < 0.001). General quality of life and sub-dimension mean scores were higher in the empowerment group than the control group (p ≤ 0.05). There was no difference in the coping style average scores (p ≥ 0.05) between the two groups. This study supports the findings that a mobile-supported empowerment program reduced the level of caregiver distress and increased quality of life during their loved one's treatment with radiotherapy.


[Contribution of endoscopic ultrasonography to the diagnosis of neuroendocrine pancreatic tumors].
Neuroendocrine pancreatic tumors (NEPT) are relatively infrequent tumors, with an incidence of approximately 1 case per 100.000 inhabitants, representing only 1-2% of pancreatic neoplasms. Localization and staging of NEPT prior to surgery is essential to allow treatment optimization. However, localizing these tumors is often difficult, mainly because of their small size. On ultrasound, NEPT usually appear as rounded, hypoechoic and homogeneous lesions, with precise limits and peripheral enhancement due to their significant vascularization. The most precise technique for the diagnosis and localization of NEPT is endoscopic ultrasound (EUS), with a sensitivity and specificity as high as 95%, clearly superior to those of other imaging procedures. Overall diagnostic accuracy may even be increased by associating EUS-guided fine-needle aspiration.


Variable numbers of calreticulin genes in Trypanosoma cruzi correlate with atypical morphology and protein expression.
Trypanosoma cruzi calreticulin (TcCalr, formerly known as TcCRT), upon binding to Complement (C) C1 and ficolins, inhibits the classical and lectin pathways and promotes infectivity. This virulence correlates with the expression of TcCalr. The TcCalr C inhibitory capacity was shown in a previous work using a clonal epimastigote cell line from the TCC T. cruzi strain, lacking one TcCalr allele (TcCalr+/-) or over expressing it (TcCalr+). In this work, we detected atypical morphology in TcCalr+/- and in TcCalr+ parasites, as compared to the wild-type (WT) strain. Polyclonal anti-TcCalr antibodies detected TcCalr presence mainly in the parasite nucleus. The number of TcCalr indicator gold particles, detected in electron microscopy and quantified in silico, correlated with the number of TcCalr coding genes. Both TcCalr+ and TcCalr +/- epimastigotes presented morphological alterations.


Simultaneous removal of antibiotics and nitrogen by microbial fuel cell-constructed wetlands: Microbial response and carbon-nitrogen metabolism pathways.
Microbial fuel cell-constructed wetlands (MFC-CWs) are attracted extensive attention due to their simultaneous removal performance during the co-occurrence of various pollutants in wastewater. This study explored the performance and mechanisms on the simultaneous removal of antibiotics and nitrogen from MFC-CWs which packed with coke (MFC-CW (C)) and quartz sand (MFC-CW (Q)) substrate. Results showed that removal of sulfamethoxazole (93.60 %), COD (77.94 %), NH4+-N (79.89 %), NO3-- N (82.67 %), and TN (70.29 %) significantly enhanced by MFC-CW (C) due to the enhancement of relative abundance of membrane transport, amino acid metabolism and carbohydrate metabolism pathways. The results indicated that coke substrate can generate more electric energy in MFC-CW. Firmicutes (18.56-30.82 %), Proteobacteria (23.33-45.76 %), and Bacteroidetes (17.1-27.85 %) were dominant phyla in the MFC-CWs. MFC-CW (C) posed significant effects on the microbial diversity and structure, which motivated the functional microbes involved in the transformation of antibiotics and nitrogen and bioelectricity generation. Given the overall performance of MFC-CW, packing with cost-effective substrate to electrode region of MFC-CWs was found to be an effective strategy for simultaneously removing antibiotics and nitrogen in the wastewater treatment.


Ischial hypoplasia, tibial hypoplasia and facial abnormalities: a new syndrome?
A child with facial abnormalities, short stature and a variety of skeletal alterations is reported. The facial abnormalities comprised low-set ears, short nose with a long philtrum, micrognathia and cleft palate. The skeletal alterations included ischial hypoplasia, malformations of the cervical spine, hypoplasia of the lesser trochanters, tibial hypoplasia with bowing of the lower legs, tibio-fibular diastasis with malformed distal tibial epiphyses, clubfeet and brachymesophalangy. The constellation of clinical and radiological findings in the present patient do not fit any known malformation syndrome.


Tetrachloroethene respiration in Sulfurospirillum species is regulated by a two-component system as unraveled by comparative genomics, transcriptomics, and regulator binding studies.
Energy conservation via organohalide respiration (OHR) in dehalogenating Sulfurospirillum species is an inducible process. However, the gene products involved in tetrachloroethene (PCE) sensing and signal transduction have not been unambiguously identified. Here, genome sequencing of Sulfurospirillum strains defective in PCE respiration and comparative genomics, which included the PCE-respiring representatives of the genus, uncovered the genetic inactivation of a two-component system (TCS) in the OHR gene region of the natural mutants. The assumption that the TCS gene products serve as a PCE sensor that initiates gene transcription was supported by the constitutive low-level expression of the TCS operon in fumarate-adapted cells of Sulfurospirillum multivorans. Via RNA sequencing, eight transcriptional units were identified in the OHR gene region, which includes the TCS operon, the PCE reductive dehalogenase operon, the gene cluster for norcobamide biosynthesis, and putative accessory genes with unknown functions. The OmpR-family response regulator (RR) encoded in the TCS operon was functionally characterized by promoter-binding assays. The RR bound a cis-regulatory element that contained a consensus sequence of a direct repeat (CTATW) separated by 17 bp. Its location either overlapping the -35 box or 50 bp further upstream indicated different regulatory mechanisms. Sequence variations in the regulator binding sites identified in the OHR gene region were in accordance with differences in the transcript levels of the respective gene clusters forming the PCE regulon. The results indicate the presence of a fine-tuned regulatory network controlling PCE metabolism in dehalogenating Sulfurospirillum species, a group of metabolically versatile organohalide-respiring bacteria.


Are the C-reactive protein/albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (NLR) novel inflammatory biomarkers in the early diagnosis of postoperative complications after laparoscopic sleeve gastrectomy?
C-reactive protein/albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are new generation inflammatory markers that have been investigated for use in determining disease prognosis or postoperative morbidity and mortality after many open surgeries. The aim of this study is to investigate the efficacy of CAR, NLR, and PLR on the early detection of postoperative complications (POC) after laparoscopic sleeve gastrectomy (LSG). The study included 448 patients, 16-65 years of age, who underwent LSG between 2015 and 2019. C-reactive protein (CRP) and albumin levels were measured on postoperative day 1 and 3 and CAR values were obtained. NLR and PLR values were evaluated preoperatively and on postoperative day 1 and 3. Statistical analyses were performed using the SPSS version 21.0 and MedCalc. A total of 326 patients with a mean age of 37 ± 11 years were analyzed. Both CAR1 and CAR3 values were correlated with the development of complications (r = 0.3, r = 0.3, respectively p < 0.001). Pre-op NLR value was found to be a significant risk factor on complication development (OR = 1.943, p = 0.043). The cut-off value for CAR1 and CAR3 were found as 0.78 and 1.25 mg/dL in ROC analysis (AUC = 0.808, AUC = 0.832, respectively). PLR3 value was diagnostic among other PLR values in the determination of POC (AUC = 0.703 Youden index = 0.36 p = 0.014). The most significant diagnostic value for the determination of POC was CAR3. It was followed by CAR1, CRP3, CRP1, and PLR3 values. Only preoperative NLR was found as a risk factor for the development of POC.


Three-dimensional in vivo motion analysis of normal knees employing transepicondylar axis as an evaluation parameter.
The transepicondylar axis (TEA) has been used as a flexion axis of the knee and a reference of the rotational alignment of the femoral component. However, no study has showed dynamic normal knee kinematics employing TEA as the evaluation parameter throughout the full range of motion in vivo. The purpose of this study was to analyze dynamic kinematics of the normal knee through the full range of motion via the 3-dimensional to 2-dimensional registration technique employing TEA as the evaluation parameter. Dynamic motion of the right knee was analyzed in 20 healthy volunteers (10 female, 10 male; mean age 37.2 years). Knee motion was observed as subjects squatted from standing with knee fully extended to maximum flexion. The following parameters were determined: (1) Anteroposterior translations of the medial and lateral ends of the TEA; and (2) changes in the angle of the TEA on the tibial axial plane (rotation angle). The medial end of the TEA demonstrated anterior translation (3.6 ± 3.0 mm) from full extension to 30° flexion and demonstrated posterior translation (18.1 ± 3.7 mm) after 30°, while the lateral end of the TEA demonstrated consistent posterior translation (31.1 ± 7.3 mm) throughout knee flexion. All subjects exhibited femoral external rotation (16.9 ± 6.2°) relative to the tibia throughout knee flexion. Compared to previously used parameters, the TEA showed bicondylar posterior translation from early flexion phase. These results provide control data for dynamic kinematic analyses of pathologic knees in the future and will be useful in the design of total knee prostheses.


Knowledge and attitudes towards ambulatory treatment of tuberculоsis in Kazakhstan.
Ambulatory based treatment of tuberculosis has been recently introduced in Kazakhstan. We sought to assess the attitudes of the general population, TB patients and their household members towards ambulatory TB treatment and identify how knowledge of TB is associated with these attitudes. New pulmonary TB cases and their household and community controls were recruited from three regions of Kazakhstan in 2012-2014. 1083 participants completed audio computer-assisted self interviews to assess their knowledge of TB and attitudes towards ambulatory care. Mixed effects logistic regression models were used to identify factors associated with attitudes toward ambulatory TB treatment. The proportion of people who considered ambulatory TB treatment as appropriate was very low (24.9%). Positive attitudes towards ambulatory TB treatment were significantly associated with region of residence, higher level of education, family support and experience with TB. The association between sufficient tuberculosis knowledge and favorable attitude toward ambulatory treatment was stronger among community controls compared to TB patients and their family members. This study provides insight into attitudes toward ambulatory TB treatment among different groups and the specific influence of TB knowledge on these attitudes. Our findings can inform the process of integration of new TB treatment strategies and the development of appropriate education and advocacy programs in the general population.


Transfection of tyrosine kinase deleted FGF receptor-1 into rat brain substantia nigra reduces the number of tyrosine hydroxylase expressing neurons and decreases concentration levels of striatal dopamine.
The effects of HSV-1 amplicon and polyethyleneimine (PEI)-mediated transfection of dominant negative FGF receptor-1 mutant FGFR1(TK-) into the rat brain substantia nigra (SN) were examined in vivo to model the reduced FGF signaling documented to occur in Parkinson's disease. The number of SN neurons that expressed tyrosine hydroxylase (TH) was significantly reduced following HSV-1 FGFR1(TK-) intranigral delivery and similar changes were observed after PEI-mediated FGFR1(TK-) transfections. Further, we also observed a significantly lower striatal dopamine content following the PEI transfection of FGFR1(TK-). Thus, we conclude that reduced FGF signaling in the SN of Parkinsonian patients could play a role in the impaired dopaminergic transmission associated with the degenerative disease.


Voltage and time dependence of the conductance of planar lipid bilayers doped with colicin A.
Voltage jump studies of planar bilayers doped with colicin A revealed two classes of time and voltage dependent conductance induced by colicin A. The first type of conductance, asymmetrically voltage dependent, measured as a time dependent process, was in agreement with previously described conductances of bilayers doped with colicin A or colicin E1. The second class of conductance appeared as a voltage dependent instantaneous conductance. The significance of this new type of conductance is discussed.


M2 Macrophage-Derived Exosomes Promote Angiogenesis and Growth of Pancreatic Ductal Adenocarcinoma by Targeting E2F2.
Pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive tumors all over the world, has a generally poor prognosis, and its progression is positively correlated with the density of blood vessels. Recently, tumor-associated macrophages (TAMs) were proven to be beneficial for angiogenesis, but their mechanism of action remains unclear. Our study indicated that M2 macrophages were positively correlated with the microvessel density (MVD) of PDAC tissues, and M2 macrophage-derived exosomes (MDEs) could promote the angiogenesis of mouse aortic endothelial cells (MAECs) in vitro. At the same time, the M2 MDEs could also promote the growth of subcutaneous tumors and increase the vascular density of mice. Moreover, we also found that miR-155-5p and miR-221-5p levels in the M2 MDEs were higher than those in M0 MDEs, and they could be transferred into MAECs, as demonstrated by RNA sequencing (RNA-seq) and qPCR analysis. Our data confirmed the interaction between TAMs and the angiogenesis of PDAC by exosomes. Additionally, targeting the exosomal miRNAs derived from TAMs might provide diagnostic and therapeutic strategies for PDAC.


Bulinus senegalensis (Mollusca: Planorbidae) in northern Nigeria.
Surveys in the South Chad Irrigation Project Area have revealed the presence of substantial populations of the important potential snail host for Schistosoma haematobium, Bulinus senegalensis. This is the first confirmed record of this species outside the Senegambian region and the habitats in which it occurs differ from those previously reported. The implications of this finding for the epidemiology of S. haematobium in the Sahel region are discussed.


Frozen section examination of the margins for resection of squamous cell carcinoma of the lower lip.
Our goal was to evaluate the role of frozen section margin examination in the surgical management of squamous cell carcinoma of the lower lip. We reviewed frozen section examination of the resection surfaces of 131 consecutive patients surgically treated for squamous cell carcinoma of the lower lip during the period January 1980 to January 1999. When invasive carcinoma or carcinoma in situ was present at the resection surface, the margin was defined as positive and re-resection was performed. A peroperative positive margin was seen in 18 of 131 (14%). In 8 patients (6%), a local recurrence developed. Frozen section examination for margin assessment in the surgical treatment of lip cancer is a reliable technique to control the radicality of the procedure; a secondary surgical procedure or postoperative radiotherapy can be reduced. However, a tumor-free resection surface does not guarantee that local recurrence will not occur.


Genomic insight into transmission mechanisms of carbapenem-producing Citrobacter spp. isolates between the WWTP and connecting rivers.
Carbapenem-resistant Enterobacteriaceae (CRE) poses major health risks worldwide. Most studies have focused on carbapenem resistance in Klebsiella pneumoniae and Escherichia coli; however, the occurrence and transmission of carbapenem-resistant Citrobacter spp. (CRCS) are poorly understood. In this study, we investigated the occurrence and potential transmission patterns of CRCS in different functional areas of an urban wastewater treatment plant (WWTP) and connecting rivers during one-year monitoring in Shandong Province, China. In total, 14 CRCS were detected in 376 environmental samples, including those from the WWTP inlet (n = 7), WWTP anaerobic tank (n = 2), and rivers (n = 5). Citrobacter braakii (n = 6) was the dominant subtype among 14 CRCS isolates, followed by Citrobacter freundii (n = 5), Citrobacter sedlakii (n = 2), and Citrobacter werkmanii (n = 1). All CRCS were resistant to imipenem, meropenem, ampicillin, amoxicillin/clavulanic acid, cefotaxime, ceftazidime, trimethoprim/sulfamethoxazole, and ciprofloxacin. Plasmid analysis showed that the blaKPC-2 gene was located on IncN and IncFII (Yp) plasmids, whereas the blaNDM gene was located on IncX3 and IncN2 plasmids. Clonal transmission of CRCS harboring carbapenem genes occurred between the WWTP and connecting rivers on a temporal or spatial scale. High genomic relatedness of NDM-5-producing C. sedlakii was identified between river water and WWTP aerosol, suggesting a potential exposure risk of CRCS for workers and surrounding residents near the WWTP. Furthermore, NDM-5-producing C. sedlakii isolated from rivers was related to C. sedlakii isolated from soil and well water in different regions of China, indicating that NDM-5-producing C. sedlakii may be widespread in China. These findings indicate that rare healthcare-associated pathogens such as CRCS can contribute to widespread carbapenem production in the environment; thus, CRCS should be continuously monitored.


Co2P@NiCo2O4 bi-functional electrocatalyst with low overpotential for water splitting in wide range pH electrolytes.
The Co2P@NiCo2O4 bi-functional electrocatalyst was fabricated for hydrogen evolution reaction and oxygen evolution reaction in acidic, neutral and alkaline media. The Co2P@NiCo2O4 in alkaline media exhibites an extremely low overpotential of 170 mV in oxygen evolution to achieve a current density of 10 mA cm-2 and produces stable water splitting nearly 30 h. The anchored-Co2P can enhance the electrochemical performance of pristine NiCo2O4 as well as increase the tolerance in acidic media of NiCo2O4. Additional, the Co2P is oxidized to oxides/hydroxides species during the electrocatalytic reaction, which acts as the active centers of the electrocatalysis. The Co2P@NiCo2O4 catalyst can be used as an effective bifunctional synergistic center in a wide range of pH values (from 0 to 14).


THE MANAGEMENT OF REPETITIVE SUBACUTE THYROIDITIS IN A MALE PATIENT HAVING HLA-B35:01 AND B41:02 ALLELES.
Subacute thyroiditis (SAT) is an inflammatory disease of the thyroid gland and commonly affects females. Despite adequate treatment, the recurrence of SAT can be seen in some patients. Although there is insufficient data about the reasons for recurrences, HLA predisposition is one of the reasons thought to be responsible and is a current issue for clinicians. This case report presented the management of 7 SAT attacks of a patient who had HLA-B35:01 and B41:02 alleles in the genotype analysis. A 37-year-old male patient who had consecutive 7 SAT attacks was presented in this report. Corticosteroid or non-steroidal anti-inflammatory drugs were initiated at each recurrence depending on the severity of clinical symptoms and laboratory findings. The genotype analysis showed the positivity for HLA-B35:01 and B41:02 alleles. The anti-thyroglobulin antibody was detected positive after the last attack. The patient was followed up as asymptomatic and euthyroid in the third month after the last attack. The management of some SAT cases may be challenging for clinicians. Although recurrence can be seen despite adequate treatment, repetitive seven attacks are extraordinary in SAT. HLA genotyping showed co-occurrence of HLA-B35:01 and B41:02 alleles in our patient. The co-occurrence of these alleles has been described firstly in this case. Explaining high recurrence rates of SAT with these HLA alleles is difficult, though the present case may shed light on further studies.


Integrating Neuropsychology Services in a Multidisciplinary Concussion Clinic.
To describe the integration of neuropsychology services in a multidisciplinary concussion clinic and provide descriptive information on patients, services, and initial health status. A university-based outpatient sports medicine concussion clinic. A consecutive sample of 338 patients ages 8 to 84 years (median 23.5 years, 35% 13-18 years), 49.1% male, seen between 2014 and 2018. Patients' injuries included sports 42%, work 28.4%, and vehicular 12.1% and 48.5% were students. Descriptive statistics with group comparisons. 12-Item Short Form Health Survey (SF-12) T scores (mean = 50, SD = 10) referenced to US population. Half of the patients were seen within 24 days of their injury and showed reduced physical functioning (40.2) and average mental (emotional) functioning (48.8). Patients seen after 24 days showed even more reduced physical functioning (33.9) and reduced mental functioning (41.0), both P < .0001. Average treatment time was also longer, 88.1 (173.9) versus 186.8 (211.1) days, P < .0001. Two-thirds of patients were referred for cervical or vestibular physical therapy at their initial visit. Early referral for specialized care, including neuropsychology services, may be beneficial.


Application of distal metaphyseal osteotomy for treatment of high intermetatarsal angle bunion deformities.
This is a retrospective study of 10 patients (13 feet) with moderate to severe hallux valgus who underwent a chevron or modified chevron osteotomy with multiple adjunctive soft-tissue releases for surgical treatment. Radiographic and subjective results were evaluated with an average follow-up of 24 months (range, 10-41). Preoperative criteria included an intermetatarsal (IM) angle of greater than 16 degrees (average of 18.4 degrees) and painful hallux valgus deformity. Average preop hallux abductus was 35.4 degrees (range, 25 degrees-48 degrees). The average reduction in the actual IM angle was (-) 5.2 degrees with a relative IM correction of (-) 11.6 degrees. Average postoperative hallux abductus angle was 7.0 degrees (range, 0 degree-22 degrees). Subjectively, all patients were satisfied with their results and stated they would have the procedure again. No complications were noted in this patient population, including, infection, avascular necrosis, hallux varus, and recurrence of deformity. The chevron osteotomy was found to be successful in this population with high intermetatarsal angles when appropriate consideration was given to correction of soft-tissue-deforming forces and contractures.


Choosing between good and better: optimal oviposition drives host plant selection when parents and offspring agree on best resources.
Insect preferences for particular plant species might be subjected to trade-offs among several selective forces. Here, we evaluated, through laboratory and field experiments, the feeding and ovipositing preferences of the polyphagous leafminer Liriomyza huidobrensis (Diptera: Agromyzidae) in relation to adult and offspring performance and enemy-free space. Female leafminers preferred laying their eggs on Vicia faba (Fabaceae) over Beta vulgaris var. cicla (Chenopodiaceae), in both laboratory and field choice experiments, although no oviposition preference was observed in no-choice tests. Females fed more often on B. v. var. cicla (no-choice test) or showed no feeding preference (choice test), even when their realized fecundity was remarkably higher on V. faba. Offspring developed faster, tended to survive better, and attained bigger adult size on the preferred host plant. Also, a field experiment showed higher overall parasitism rates for leafminers developing on B. v. var. cicla, with a nonsignificant similar tendency in field surveys. According to these results, host plant selection by L. huidobrensis appears to be driven mainly by variation in host quality. Moreover, the consistent oviposition choices for the best host and the labile feeding preferences observed here, suggest that host plant selection might be driven by maximization of offspring fitness even without a conflict of interest between parents and offspring. Overall, these results highlight the complexity of decisions performed by phytophagous insects regarding their host plants, and the importance of simultaneous evaluation of the various driving forces involved, in order to unravel the adaptive significance of female choices.


Salusins: newly identified bioactive peptides with hemodynamic and mitogenic activities.
The discovery of endogenous bioactive peptides has typically required a lengthy identification process. Computer-assisted analysis of cDNA and genomic DNA sequence information can markedly shorten the process. A bioinformatic analysis of full-length, enriched human cDNA libraries searching for previously unidentified bioactive peptides resulted in the identification and characterization of two related peptides of 28 and 20 amino acids, which we designated salusin-alpha and salusin-beta. Salusins are translated from an alternatively spliced mRNA of TOR2A, a gene encoding a protein of the torsion dystonia family. Intravenous administration of salusin-alpha or salusin-beta to rats causes rapid, profound hypotension and bradycardia. Salusins increase intracellular Ca2+, upregulate a variety of genes and induce cell mitogenesis. Salusin-beta stimulates the release of arginine-vasopressin from rat pituitary. Expression of TOR2A mRNA and its splicing into preprosalusin are ubiquitous, and immunoreactive salusin-alpha and salusin-beta are detected in many human tissues, plasma and urine, suggesting that salusins are endocrine and/or paracrine factors.


Preferred skin tones on mobile displays under illuminants having different correlated colour temperatures.
A psychophysical experiment was conducted to investigate preferred skin tones of 4 skin types under 5 illuminants varying in correlated colour temperatures. The experiments were performed on calibrated mobile display devices. Four facial skin tone images representing each skin type were captured and were rendered to 25 skin tone images to cover a large colour region. The facial skin tone images were assessed by a panel of 28 Chinese observers using an alternative forced choice psychophysical method. The ellipses based on observer preference rate were derived, and the preferred skin tone centres and 50% tolerance ellipse of different skin types under each test illuminants were obtained. According to the colour appearance shift of preferred skin tones under illuminants with varying CCTs, all data were transformed and compared in the a*b* plane under D65 and CIE 1931 Standard Colorimetric Observer condition. The results on the impact of illuminants on preferred skin tones were reported here. All types of skin tones had a good agreement under different illuminants.


CaMKII inhibition in human primary and pluripotent stem cell-derived chondrocytes modulates effects of TGFβ and BMP through SMAD signaling.
Upregulation of calcium/calmodulin-dependent kinase II (CaMKII) is implicated in the pathogenesis of osteoarthritis (OA) and reactivation of articular cartilage hypertrophy. However, direct inhibition of CaMKII unexpectedly augmented symptoms of OA in animal models. The role of CaMKII in OA remains unclear and requires further investigation. Analysis of CaMKII expression was performed in normal human and OA articular chondrocytes, and signaling mechanisms were assessed in articular, fetal and Pluripotent Stem Cell (PSC)-derived human chondrocytes using pharmacological (KN93), peptide (AC3-I) and small interfering RNA (siRNA) inhibitors of CaMKII. Expression levels of phospho-CaMKII (pCaMKII) were significantly and consistently increased in human OA specimens. BMP2/4 activated expression of pCaMKII as well as COLII and COLX in human adult articular chondrocytes, and also increased the levels and nuclear localization of SMADs1/5/8, while TGFβ1 showed minimal or no activation of the chondrogenic program in adult chondrocytes. Targeted blockade of CaMKII with specific siRNAs decreased levels of pSMADs, COLII, COLX and proteoglycans in normal and OA adult articular chondrocytes in the presence of both BMP4 and TGFβ1. Both human fetal and PSC-derived chondrocytes also demonstrated a decrease of chondrogenic differentiation in the presence of small molecule and peptide inhibitors of CaMKII. Furthermore, immunoprecipitation for SMADs1/5/8 or 2/3 followed by western blotting for pCaMKII showed direct interaction between SMADs and pCaMKII in primary chondrocytes. Current study demonstrates a direct role for CaMKII in TGF-β and BMP-mediated responses in primary and PSC-derived chondrocytes. These findings have direct implications for tissue engineering of cartilage tissue from stem cells and therapeutic management of OA.


Diffusion Restriction in Bilateral Thalami: Beyond Artery of Percheron Infarct.
Bilateral thalamic infarction, especially the medial thalamus, has been characteristically described in the artery of Percheron (AOP) affection. However, bilateral thalamic restriction has been described in many entities beyond the AOP infarction. Here we describe a case series (three cases) with infection as an etiology for bilateral thalamic lesions in the topographic distribution of the AOP from a tertiary care center in tropical India. : Case series during a 1-year period collecting cases with bilateral thalamic diffusion restriction on MRI who did not have thalamic infarcts and their outcomes. : Bilateral thalamic lesion can occur in both bacterial and viral infections such as tuberculosis, dengue, and SARS-COV-2. Thus, we intend to add infections as one of the etiologies in the ever-expanding list of conditions that produce bilateral thalamic restriction. All the acute symmetric thalamic lesions are not always secondary to vascular insult. Accurate assessment and prompt diagnosis can prevent unnecessary delays in treatment. To our knowledge, this is the first case series in the literature that throws light on the bilateral thalamic lesions in the topographic distribution of the AOP secondary to infections in a tropical country like India.


Let-7d inhibits intratumoral macrophage M2 polarization and subsequent tumor angiogenesis by targeting IL-13 and IL-10.
The microRNA let-7d has been reported to be a tumor suppressor in renal cell carcinoma (RCC). Tumor-associated macrophages (TAM) are M2-polarized macrophages that can enhance tumor growth and angiogenesis in many human cancers. However, the role of let-7d in TAM-associated RCC progression remains elusive. First, we observed a strongly inverse correlation between let-7d expression and microvessel density in RCC tissues. Furthermore, the proliferation, migration, and tube formation of HUVECs were significantly inhibited by conditioned medium from a coculture system of the phorbol myristate acetate pretreated human THP-1 macrophages and let-7d-overexpressing RCC cells. Moreover, the proportion of M2 macrophages was significantly lower in the group that was cocultured with let-7d-overexpressing RCC cells. Subcutaneous xenografts formed by the injection of let-7d-overexpressing RCC cells together with THP-1 cells resulted in a significant decrease in the M2 macrophage ratio and microvessel density compared with those formed by the injection of control RCC cells with THP-1 cells. In silico and experimental analysis revealed interleukin-10 (IL-10) and IL-13 as let-7d target genes. Importantly, the addition of IL-10 and IL-13 counteracted the inhibitory effects of the conditioned medium from the coculture system with let-7d-overexpressing RCC cells in vitro. Additionally, overexpression of IL-10 and IL-13 reversed the effects of let-7d on macrophage M2 polarization and tumor angiogenesis in vivo. Finally, the expression of IL-10 and IL-13 were inversely correlated with the expression of let-7d in RCC clinical specimens. These results suggest that let-7d may inhibit intratumoral macrophage M2 polarization and subsequent tumor angiogenesis by targeting IL-10 and IL-13.


Parental Perspectives: How Sensory Sensitivities Impact the Transition to Adulthood in Adolescents and Young Adults with Autism Spectrum Disorder.
Sensory sensitivities are common in autism spectrum disorder (ASD) and impact daily life, but research has largely focused on children, neglecting older individuals. Likewise, while there is research regarding parental concerns for their autistic children's transition to adulthood, little is known about the role of sensory sensitivities. To address this gap, 66 parents of autistic adolescents and young adults were interviewed and their responses were qualitatively analyzed. All parents believed their children's sensory sensitivities impacted their transition to adulthood, primary developmentally/psychologically, interpersonally/socially, and managerially. These beliefs did not significantly differ by child characteristics, such as age and ASD severity. Parent perceptions were modality and context specific. Given these findings, transition planning should consider individual's specific sensory sensitivities to optimize independence.


The Patient Protection and Affordable Care Act: what every provider of gynecologic oncology care should know.
The Patient Protection and Affordable Care Act (ACA) was signed into law by President Barack Obama in 2010. While initial implementation of the law began shortly thereafter, the full implementation will take place over the next few years. With respect to cancer care, the act was intended to make care more accessible, affordable, and comprehensive across different parts of the country. For our cancer patients and our practices, the ACA has implications that are both positive and negative. The Medicaid expansion and access to insurance exchanges are intended to increase the number of insured patients and thus improve access to care, but many states have decided to opt out of the Medicaid program and in these states access problems will persist. Screening programs will be put in place for insured patients but may supplant federally funded programs that are currently in place for uninsured patients and may not follow current screening guidelines. Both hospice and home health providers will be asked to provide more services with less funding, and quality measures, including readmission rates, will factor into reimbursement. Insured patients will have access to all phases of clinical trial research. There is a need for us as providers of Gynecologic Oncology care to be active in the implementation of the ACA in order to ensure that our patients and our practices can survive and benefit from the changes in health care reimbursement, with the ultimate goals of improving access to care and quality while reducing unsustainable costs.


Increased atmospheric deposition of mercury in reference lakes near major urban areas.
Atmospheric deposition of Hg is the predominant pathway for Hg to reach sensitive ecosystems, but the importance of emissions on near-field deposition remains unclear. To better understand spatial variability in Hg deposition, mercury concentrations were analyzed in sediment cores from 12 lakes with undeveloped watersheds near to (<50 km) and remote from (>150 km) several major urban areas in the United States. Background and focusing corrected Hg fluxes and flux ratios (modern to background) in the near-urban lakes (68 ± 6.9 μg m(-2) yr(-1) and 9.8 ± 4.8, respectively) greatly exceed those in the remote lakes (14 ± 9.3 μg m(-2) yr(-1) and 3.5 ± 1.0) and the fluxes are strongly related to distance from the nearest major urban area (r(2) = 0.87) and to population and Hg emissions within 50-100 km of the lakes. Comparison to monitored wet deposition suggests that dry deposition is a major contributor of Hg to lakes near major urban areas.


Complex etiology and pathology of mycotoxic nephropathy in South African pigs.
Spontaneous nephropathy in pigs seen in South Africa was found to have multi-mycotoxic etiology involving several mycotoxins such as ochratoxin A (OTA), penicillic acid (PA) and fumonisin B1 (FB1) in addition to a not yet identified mycotoxin. Contamination levels of OTA were comparatively low (67-75 μg/kg) in contrast to high contamination levels of FB1 (5,289-5,021 μg/kg) and PA (149-251 μg/kg). A heavy contamination with Gibberella fujikuroi var. moniliformis and Penicillium aurantiogriseum complex (mainly P. polonicum) was observed in the fed forages in contrast to the light contamination with Aspergillus ochraceus, P. verrucosum and P. citrinum. The pathomorphological picture of this nephropathy was found to differ from the classical description of mycotoxic porcine nephropathy as originally made in Scandinavia by the extensive vascular changes.


The single-cell transcriptional landscape of innate and adaptive lymphocytes in pediatric-onset colitis.
Innate lymphoid cells (ILCs) are considered innate counterparts of adaptive T cells; however, their common and unique transcriptional signatures in pediatric inflammatory bowel disease (pIBD) are largely unknown. Here, we report a dysregulated colonic ILC composition in pIBD colitis that correlates with inflammatory activity, including accumulation of naive-like CD45RA+CD62L- ILCs. Weighted gene co-expression network analysis (WGCNA) reveals modules of genes that are shared or unique across innate and adaptive lymphocytes. Shared modules include genes associated with activation/tissue residency, naivety/quiescence, and antigen presentation. Lastly, nearest-neighbor-based analysis facilitates the identification of "most inflamed" and "least inflamed" lymphocytes in pIBD colon with unique transcriptional signatures. Our study reveals shared and unique transcriptional signatures of colonic ILCs and T cells in pIBD. We also provide insight into the transcriptional regulation of colonic inflammation, deepening our understanding of the potential mechanisms involved in pIBD.


Luminal and basolateral polyamine uptake by rat small intestine stimulated to grow by Phaseolus vulgaris lectin phytohaemagglutinin in vivo.
Luminal and basolateral uptake of polyamines by the rat small intestine was studied in vivo. In the concentration range studied (0.1-5 mg per rat) 23-47% of the individual polyamines given intragastrically were found in the body after 1 h, with the small intestine retaining 4-12% of the dose. With spermidine or spermine, labelled polyamines accounted for 85-96% of the counts in the small intestine and between 72-82% were in the form given. However, with putrescine only 29-39% of the label found in the tissue remained in polyamine form and even less, 11-15%, as putrescine. Luminal uptake of polyamines was linear, non-saturable and was not stimulated when small intestinal growth was stimulated by phytohaemagglutinin (PHA). On the basolateral side of the gut, polyamine uptake was stimulated by PHA in a time-dependent way in advance of detectable growth. Overall polyamine recoveries were high (89-99%) with intraperitoneally administered spermidine and spermine. Moreover, a large proportion of the counts in the tissue (63-89%) were still in the original form. Even with putrescine, total recoveries of polyamines (72-88%) and putrescine (24-33%) were elevated in comparison with those from the lumen. Treatment of rats with alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, reduced tissue polyamine content, although it had slight effects only on basolateral polyamine transport. The PHA-stimulated increase of polyamine uptake was not abolished in the presence of DFMO.


Biliary tract disease. Is there a difference in men?
A retrospective chart review of 507 patients who underwent cholecystectomies over an 18 month period was performed. There were 345 female patients and 162 male patients. Of the female patients, 90 (26 percent) presented with complicated disease, which was severe in 38 (11 percent). The mortality rate was 0.87 percent in the total group of female patients (3 deaths), or 7.9 percent in the 38 patients with severe disease. In the male patients, on the other hand, 96 (59 percent) presented with complicated disease, which was severe in 57 (35 percent). There were 6 deaths, for a mortality rate of 3.7 percent in the total group of male patients, or 10.5 percent in the 57 patients with severe disease. This study supports our observation that biliary tract disease is more life-threatening in men. It appears that elective cholecystectomy should be considered in the male patient who presents with asymptomatic cholelithiasis.


Role in decision making among congestive heart failure patients and its association with patient outcomes: a baseline analysis of the SCOPAH study.
We investigated the predictors of patient-experienced and preferred roles for decision making, and the association between patient-experienced role in decision making and patient outcomes among congestive heart failure (HF) patients in a multi-ethnic Asian population. We surveyed 246 HF patients classified as New York Heart Association class 3/4. Multivariable regressions were used to analyse the associations between patient-experienced roles and patient outcomes. Patients who were male, attained higher education, and had a higher cognitive score were more likely to experience and prefer active roles in decision making. Younger patients and patients with lower symptom burden were more likely, while married patients were less likely to prefer leading decision making. Patients with collaborative (family and/or physician) decision making reported higher emotional well-being and sense of meaning/peace. Collaborative and patient-led decision making were associated with higher perceived control over illness. Those who were led by others or made decisions alone reported lower quality of physician communication. Collaborative decision making was associated with higher emotional well-being, sense of meaning/peace, and higher perceived control over illness among HF patients. Physicians should explain the benefits of shared decision making and encourage patients to participate in treatment decisions.


A three-stage culture process for improved exopolysaccharide production by Tremella fuciformis.
Tremella fuciformis produces several bioactive secondary metabolites including exopolysaccharides. Cultivation of the fungus was carried out in a three-stage process consisting of a 1.5-day cultivation with orbital shaking at 200 rpm, a 1.5-day cultivation with reciprocal shaking at 200 strokes, and a 1.5-day cultivation with orbital shaking at 200 rpm. Exopolysaccharide production and specific production rate reached 5.80 g L(-1) and 0.15 d(-1), respectively, which is an increase of 260% and 200% compared with the corresponding values for fermentations with orbital shaking only, and of 243% and 150% compared with the corresponding values for fermentations with reciprocal shaking only. The three-stage culture method is time-saving and easy to operate.


Changes in tumor cell response due to prolonged dose delivery times in fractionated radiation therapy.
Dynamic radiation therapy, such as intensity-modulated radiation therapy, delivers more complex treatment fields than conventional techniques. The increased complexity causes longer dose delivery times for each fraction. The cellular damage after a full treatment may depend on the dose rate, because sublethal radiation damage can be repaired more efficiently during prolonged dose delivery. The goal of this study was to investigate the significance of this effect in fractionated radiation therapy. The lethal/potentially lethal model was used to calculate lesion induction rates for repairable and nonrepairable lesions. Dose rate effects were analyzed for 9 different cell lines (8 human tumor xenografts and a C3H10T1/2 cell line). The effects of single-fraction as well as fractionated irradiation for different dose rates were studied. Significant differences can be seen for dose rates lower than about 0.1 Gy/min for all cell lines considered. For 60 Gy delivered in 30 fractions, the equivalent dose is reduced by between 1.3% and 12% comparing 2 Gy delivery over 30 min per fraction with 2 Gy delivery over 1 min per fraction. The effect is higher for higher doses per fraction. Furthermore, the results show that dose rate effects do not show a simple correlation with the alpha/beta ratio for ratios between 3 Gy and 31 Gy. If the total dose delivery time for a treatment fraction in radiation therapy increases to about 20 min, a correction for dose rate effects may have to be considered in treatment planning. Adjustments in effective dose may be necessary when comparing intensity-modulated radiation therapy with conventional treatment plans.


An evaluation of an advanced practice role in palliative radiation therapy.
The purpose of the study was to evaluate the palliative advanced practice radiation therapy (APRT) role with respect to the impact on waiting times for patients from referral to radiation treatment delivery, the ability of the APRT to define palliative radiation therapy fields and patient satisfaction. The evaluation of the impact of the APRT role and referral pathway on patient waiting times has been previously published. Patients were allocated to two different pathways; APRT and standard. Patients in the APRT pathway had their radiotherapy treatment managed by the APRT including defining their palliative fields blinded to the radiation oncologist (RO). Of the 150 palliative patients, 94 had their radiation therapy managed by the APRT and 56 were managed through the standard pathway. 82/92 APRT defined fields were accepted by the RO. Inter-observer variability between the APRT and the RO in defining palliative radiation therapy fields is similar to that reported in the literature between clinicians. With previously published reduced wait times from referral to treatment for palliative patients, the establishment of the APRT role is justified.


Implementing enhanced recovery after surgery programmes in a healthcare facility: issues and economic impacts.
For many specialties and operating techniques, enhanced recovery after surgery provides greater economic benefit if it is deployed across a whole healthcare institution rather than in just one or two departments. As with all innovations in the world of hospital care, the adoption of new procedures is a slow process because it is based on a consensual approach. To promote the dissemination and uptake of new practices at the local, national or institutional level, incentives must be developed and examples must be given. Successful deployment within a healthcare institution requires strategic adaptations in three areas: (i) the management of human resources dedicated to the patient pathway, (ii) a care unit architecture that facilitates working practices and patient management, and (iii) the use of digital tools and smart objects. Hospital decision-makers need to have a clear understanding of what is at stake, so that they can implement coordinated actions and encourage adoption. The investment required is hard to define because it results from a combination of skills and knowledge. At the institutional level, the return on investment is greater when the strategy is applied to all surgical specialties at once, since the structure can provide more care with fewer beds and fewer care units while maintaining the quality of patient management.


Modulation of the secondary Bjerknes force in multi-bubble systems.
The behaviours of insonated bubble clusters are regulated by the secondary Bjerknes force between bubble pairs. While the force has been investigated extensively for two-bubble systems, the modulation of the force by nearby bubbles remains unclear. This problem is investigated in this paper by theoretical analyses and numerical simulations of a three bubble system. For weak oscillations, the third bubble is found to have strong effects when its radius is close to the resonant radius. The equilibrium distance between the bubble pair is reduced when the radius of the third bubble is smaller than the resonant threshold, and increased when it is larger. For strong oscillations of bubbles with radii of a few microns, the third bubble reduces the magnitude of the force, hence increasing the equilibrium distance. The modulation effects depend strongly on the relative sizes of the bubbles. Stronger effects can be produced when the third bubble is placed closer to the smaller bubble in the bubble pair. The findings highlight the need for a more accurate parametrization of the secondary Bjerknes force in the simulation and manipulation of bubble clusters.


Eculizumab therapy for atypical haemolytic uraemic syndrome due to a gain-of-function mutation of complement factor B.
Atypical haemolytic uraemic syndrome (aHUS) is caused by dysregulated complement activation. A humanised anti-C5 monoclonal antibody has recently become available for treatment of this condition We present the first description of an infant with an activating mutation of complement factor B successfully treated with eculizumab. On standard doses she had evidence of ongoing C5 cleavage despite a good clinical response. Eculizumab is effective therapy for aHUS associated with factor B mutations, but recommended doses may not be adequate for all patients.


Diagnosis of SARS-CoV-2 infection from breath - a proof-of-concept study.
Bioaerosol capture and analysis is emerging as a non-invasive diagnostic method for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this proof-of-concept study conducted in Lesotho, we evaluated the novel and simple AL2 bioaerosol detection device in comparison to conventional nasopharyngeal sampling methods. We demonstrated for the first time that SARS-CoV-2 can be detected using the AL2 bioaerosol capture device. However, studies with a larger sample size are needed to further evaluate this bioaerosol capture device for the detection of SARS-CoV-2.


People with autism perceive drastic illusory changes for repeated verbal stimuli.
A core symptom of autism spectrum disorder (ASD) is restricted and repetitive behavior, characterized partly by insistence on sameness and excessively focused interest. This behavior has often been interpreted as a manifestation of anxiety and fear triggered by resistance to change. The implicit assumption underlying this interpretation is that perception per se (such as the judgment of sameness and changes in sensory stimuli) is not different between ASD and typically developed (TD) individuals, but that only the emotional response to the same amount of perceived change is. However, few studies have examined how individuals with ASD actually perceive a repeated presentation of the same sensory stimulus. To explore this issue, we conducted a listening test to compare perception of a repeated sound pattern, namely a spoken word, between ASD and TD groups. Prolonged listening to a repeated word without a pause may induce perceptual changes, which is known as the verbal transformation effect. We discovered that individuals with ASD tend to perceive more drastic changes or differences for the same repeated auditory pattern. This suggests that such variable perception incites individuals with ASD to persist for sameness.


Direct conversion of CO2 to a jet fuel over CoFe alloy catalysts.
The direct conversion of carbon dioxide (CO2) using green hydrogen is a sustainable approach to jet fuel production. However, achieving a high level of performance remains a formidable challenge due to the inertness of CO2 and its low activity for subsequent C-C bond formation. In this study, we prepared a Na-modified CoFe alloy catalyst using layered double-hydroxide precursors that directly transforms CO2 to a jet fuel composed of C8-C16 jet-fuel-range hydrocarbons with very high selectivity. At a temperature of 240°C and pressure of 3 MPa, the catalyst achieves an unprecedentedly high C8-C16 selectivity of 63.5% with 10.2% CO2 conversion and a low combined selectivity of less than 22% toward undesired CO and CH4. Spectroscopic and computational studies show that the promotion of the coupling reaction between the carbon species and inhibition of the undesired CO2 methanation occur mainly due to the utilization of the CoFe alloy structure and addition of the Na promoter. This study provides a viable technique for the highly selective synthesis of eco-friendly and carbon-neutral jet fuel from CO2.


Sex steroid profiles and pair-maintenance behavior of captive wild-caught zebra finches (Taeniopygia guttata).
Here, we studied the life-long monogamous zebra finch, to examine the relationship between circulating sex steroid profiles and pair-maintenance behavior in pairs of wild-caught zebra finches (paired in the laboratory for >1 month). We used liquid chromatography-tandem mass spectrometry to examine a total of eight androgens and progestins [pregnenolone, progesterone, dehydroepiandrosterone (DHEA), androstenediol, pregnan-3,17-diol-20-one, androsterone, androstanediol, and testosterone]. In the plasma, only pregnenolone, progesterone, DHEA, and testosterone were above the limit of quantification. Sex steroid profiles were similar between males and females, with only circulating progesterone levels significantly different between the sexes (female > male). Circulating pregnenolone levels were high in both sexes, suggesting that pregnenolone might serve as a circulating prohormone for local steroid synthesis in zebra finches. Furthermore, circulating testosterone levels were extremely low in both sexes. Additionally, we found no correlations between circulating steroid levels and pair-maintenance behavior. Taken together, our data raise several interesting questions about the neuroendocrinology of zebra finches.


Effect and fate of intravenously administered porphobilin in rats.
In rats after i.v. porphobilin, blood pressure and pulse rate remained stable, the animals were calm and moved freely with no symptoms or signs of nervous effect. Porphobilin was rapidly excreted in the urine.