Prevention and control of anemia: Thailand experiences.
Thailand has addressed nutrition in national development policy since the mid-1970s, including efforts to reduce iron deficiency anemia. Nutritional improvement has been implemented as an integral part of primary health care and community development extending beyond government services to include community participation. Utilization of village health volunteers has been a crucial feature of the program. Available data indicate that anemia rates have declined among pregnant women and preschool children, although there has been no formal evaluation of the program effect. Universal iron supplementation has been the major strategy for pregnant women, using village health volunteers to encourage continuation of the antenatal care schedule and encouraging a preventive approach by health service providers. Program obstacles have included lack of access to iron tablets by some populations and lack of understanding of the importance of anemia. Women's compliance was complicated by fear of having a large fetus, forgetfulness and side effects. Weekly iron supplementation of school children was piloted in 2000, and is now being extended. Other strategies utilized to address iron deficiency include food fortification, dietary improvement and complementary public health measures. Program monitoring and evaluation require strengthening to assess the effectiveness of intervention strategies and provide proper data for decision-making.


Treatment of vancomycin-resistant Enterococcus faecium infections.
To define the clinical characteristics of patients infected with vancomycin-resistant enterococci (VRE) and the outcome of the infections without the availability of effective antimicrobial therapy. Charts of 28 patients with VRE infections were reviewed for demographics, clinical findings at the time of isolation of VRE, underlying medical problems, surgical procedures, invasive devices, treatment with antimicrobial agents, microbiological data, and patients' responses and outcomes. The infections included 6 cases of bacteremia, 9 surgical site infections (SSIs), 4 cases of peritonitis, 2 pelvic abscesses, 7 urinary tract infections (UTIs), and 2 soft tissue infections (STIs). Four of the 6 bacteremia cases were central-line related and resolved with line removal alone; 1 was treated with a combination product of quinupristin and dalfopristin (Synercid) and 1 had persistent bacteremia in the presence of a ventriculoperitoneal shunt. Seven of 9 SSIs resolved with surgical debridement and 2 of the 9 patients received antibiotics for organisms other than VRE. Similarly, 2 patients with STIs were treated with local debridement and antibiotics directed at organisms other than VRE and 2 patients with pelvic abscesses were treated with drainage and surgical debridement with antibiotics directed at other organisms; the infections resolved completely. Patients with peritonitis were treated with removal of their Tenckhoff catheters, drainage, and irrigation and 1 patient was treated with quinupristin-dalfopristin; 3 of 4 patients were cured. Two of 7 patients with UTIs were treated with nitrofurantoin and their urine cultures showed no growth after treatment; however, most patients with UTIs experienced resolution despite a lack of specific antimicrobial therapy. Although no antimicrobial agents are currently available for VRE infections, VRE line-related bacteremias could be treated by line removal alone. Surgical site infections, STIs, and abscesses could be managed by surgical debridement and drainage without specific antimicrobial agents against VRE and UTIs could be resolved with nitrofurantoin or removal of Foley catheters. Removal of foreign devices, debridement, and surgical drainage seemed to be important in the resolution of VRE infections.


A Mobile Phone Text Messaging Intervention to Manage Fatigue for People With Multiple Sclerosis, Spinal Cord Injury, and Stroke: Development and Usability Testing.
Fatigue significantly affects daily functioning in persons with disabilities. Fatigue management can be challenging, and the information provided during routine physician visits to manage fatigue can be overwhelming. One way to address fatigue is to increase knowledge, skills, and confidence for self-management (ie, patient activation). Self-management programs have shown promising effects in targeting fatigue in persons with disabilities. However, satisfaction with self-management programs is low for persons with disabilities, and tailoring interventions to personalized needs has been recommended. SMS text messaging is increasingly being used to implement health behavior change interventions in a person's natural environment. Little has been done to link mobile health approaches with patient activation and self-management to address fatigue in persons with disabilities. This study aimed to develop and test a mobile phone-based fatigue self-management SMS text messaging intervention targeting patient activation in 3 groups of persons with disabilities: persons with multiple sclerosis, persons who had a stroke, and persons with a spinal cord injury. We used evidence-based resources and input from a consumer advisory board (CAB; composed of 2 participants from each of the 3 disability groups) and a neurologist to develop the intervention. The study was conducted using a 4-step process: development of the initial SMS text messaging library and categorization of the content into 9 content areas, review and modification of the SMS text messages by the neurologist and CAB, integration of the content library into a digital platform, and utility testing by CAB members. A total of 6 CAB participants rated SMS text messages covering 9 domain areas of fatigue self-management with good clarity (mean ratings=3.5-5.0 out of 5) and relevance (mean ratings=3.2-5.0 out of 5). Overall, SMS text messaging content was reported by CAB participants as helpful, clear, and well suited for a mobile health intervention. The CAB reached consensus on the time of day that SMS text messages should be sent (morning) and their frequency (once per day). This feedback led the research team to narrow down the program to deliver 48 SMS text messages, 1 per day, Monday through Thursday only, a total of 4 SMS text messages per week, over a 12-week period. The final set of SMS text messages was programmed into a digital platform with a predefined delivery schedule. The usability of the intervention was high, with 55 (83%) out of 66 responses endorsing the highest rating. This study demonstrates a step-by-step process for developing a fatigue self-management SMS text messaging intervention for persons with disabilities. For this population, whose access to health services is often limited, this intervention provides an alternative delivery model to increase access to fatigue information and deliver content that aligns with the person's needs.


Isolated non-hemorrhagic cecal varices.
Ectopic varices (those outside of the gastro-esophageal region) are occasionally found on endoscopy in patients with portal hypertension; however they account for a small minority of all variceal bleeds. Cases of isolated cecal varices are quite rare and, when described, often present with acute hemorrhage or evidence of occult bleeding. We present the case of a 29-year-old male with a history of idiopathic portal vein thrombosis and known esophageal varices, who presented for evaluation of abdominal pain. Cecal varices were found on endoscopy, without evidence of bleeding and without varices in the remainder of the colon or rectum. Endoscopic ultrasound and computed tomography were useful in confirming the diagnosis and natural history of these unusual varices.


Use of internal splinting to realign a noncompliant sternum in a cat with pectus excavatum.
A 5.5-month-old female domestic longhair cat was examined because of dorsal deviation of the caudal aspect of the sternum and progressively worsening dyspnea during play activities. A diagnosis of pectus excavatum was made clinically and confirmed radiographically. The cardiac silhouette was shifted into the right hemithorax. The vertebral index (VI) and frontosagittal index (FSI), which are radiographic indices used to grade the extent of the deformity, were 5.2 and 3.0, respectively. Minimum thoracic height was 13 mm at this time. The sternal malposition was corrected during surgery; for stabilization, an internal splint was provided by use of a plate that was applied to the ventral side of the sternum. Radiographic indices improved until day 85; at that time, an increase in the distance between plate and sternum was detected, and plate removal was advised. The radiographic indices improved again after plate removal. At 310 days after surgery, VI was 9.6, FSI was 1.6, and minimum thoracic height was 34 mm. No dyspnea was evident during physical examination. Results of treatment suggest that this technique may be useful as an alternative surgical option for cats with pectus excavatum that have a noncompliant sternum.


Systemic barriers to reporting work injuries and illnesses in contexts of language barriers.
Workers who experience language barriers are at increased risk of work-related injuries and illnesses and face difficulties reporting these health problems to their employer and workers' compensation. In the existing occupational health and safety literature, however, such challenges are often framed in individual-level terms. We identify systemic barriers to reporting among injured workers who experience language barriers within the varying contexts of Ontario and Quebec, Canada. This study merges data from two qualitative studies that investigated experiences with workers' compensation and return-to-work, respectively, for injured workers who experience language barriers. We conducted semi-structured interviews with 39 workers and 70 stakeholders in Ontario and Quebec. Audio recordings were transcribed and coded using NVivo software. The data was analysed thematically and iteratively. Almost all workers (34/39) had filed a claim, though most had initially delayed reporting their injuries or illnesses to their employer or to workers' compensation. Workers faced several obstacles to reporting, including confusion surrounding the cause and severity of injuries and illnesses; lack of information, misinformation, and disinformation about workers' compensation; difficulties accessing and interacting with care providers; fear and insecurity linked to precarity; claim suppression by employers; negative perceptions of, and experiences with, workers' compensation; and lack of supports. Language barriers amplified each of these difficulties, resulting in significant negative impacts in economic, health, and claim areas. Improving the linguistic and cultural competence of organizations and their representatives is insufficient to address under-reporting among workers who experience language barriers. Efforts to improve timely reporting must tackle the policies and practices that motivate and enable under-reporting for workers, physicians, and employers.


Patterns of selective constraints in noncoding DNA of rice.
Several studies have investigated the relationships between selective constraints in introns and their length, GC content and location within genes. To date, however, no such investigation has been done in plants. Studies of selective constraints in noncoding DNA have generally involved interspecific comparisons, under the assumption of the same selective pressures acting in each lineage. Such comparisons are limited to cases in which the noncoding sequences are not too strongly diverged so that reliable sequence alignments can be obtained. Here, we investigate selective constraints in a recent segmental duplication that includes 605 paralogous intron pairs that occurred about 7 million years ago in rice (O. sativa). Our principal findings are: (1) intronic divergence is negatively correlated with intron length, a pattern that has previously been described in Drosophila and mammals; (2) there is a signature of strong purifying selection at splice control sites; (3) first introns are significantly longer and have a higher GC content than other introns; (4) the divergences of first and non-first introns are not significantly different from one another, a pattern that differs from Drosophila and mammals; and (5) short introns are more diverged than four-fold degenerate sites suggesting that selection reduces divergence at four-fold sites. Our observation of stronger selective constraints in long introns suggests that functional elements subject to purifying selection may be concentrated within long introns. Our results are consistent with the presence of strong purifying selection at splicing control sites. Selective constraints are not significantly stronger in first introns of rice, as they are in other species.


The static magnetic field effects on ouabain H3 binding by cancer tissue.
Radioactive labeled ouabain was used for estimating the static magnetic field (SMF) induced cell volume changes. Ouabain is a specific inhibitor of Na+/K+ ATPase, and can be used for estimating its quantity--thus giving information about the cell volume changes. Ouabain binding by cancer and normal glandular tissues of breast cancer patients and normal glandular tissues of healthy women was measured after exposure of tissues to SMF 0.2T. SMF exposure led to a decrease of ouabain binding in both normal and cancer tissues when ouabain concentration in the external medium was 10(-9) M, while in the case of higher concentrations of ouabain (10(-7) M, 10(-6) M) an increase of ouabain binding was seen. The normal glandular tissues of healthy women were sensitive to SMF only at the highest concentrations of ouabain used in our experiments. The SMF-induced decrease of binding at low ouabain concentrations was considered as an evidence for the dehydration effect of SMF. It is suggested that the SMF could influence the cancer cell metabolism through cell hydration changes.


Acetylation of prostaglandin H2 synthases by aspirin is inhibited by redox cycling of the peroxidase.
Aspirin exerts its unique pharmacological effects by irreversibly acetylating a serine residue in the cyclooxygenase site of prostaglandin-H2-synthases (PGHSs). Despite the irreversibility of the inhibition, the potency of aspirin varies remarkably between cell types, suggesting that molecular determinants could contribute to cellular selectivity. Using purified enzymes, we found no evidence that aspirin is selective for either of the two PGHS isoforms, and we showed that hydroperoxide substrates of the PGHS peroxidase inhibited the rate of acetylation of PGHS-1 by 68%. Using PGHS-1 reconstituted with cobalt protoporphyrin, a heme devoid of peroxidase activity, we demonstrated that reversal by hydroperoxides of the aspirin-mediated acetylation depends upon the catalytic activity of the PGHS peroxidase. We demonstrated that inhibition of PGHS-2 by aspirin in cells in culture is reversed by 12-hydroperoxyeicosatetraenoic acid dose-dependently (ED50=0.58+/-0.15 microM) and that in cells with high levels of hydroperoxy-fatty acids (RAW264.7) the efficacy of aspirin is markedly decreased as compared to cells with low levels of hydroperoxides (A549; IC50s=256+/-22 microM and 11.0+/-0.9 microM, respectively). Together, these findings indicate that acetylation of the PGHSs by aspirin is regulated by the catalytic activity of the peroxidase, which yields a higher oxidative state of the enzyme.


Removal Efficacy of Opportunistic Pathogens and Bacterial Community Dynamics in Two Drinking Water Treatment Trains.
Drinking water treatment processes (DWTPs) impact pathogen colonization and microbial communities in finished water; however, their efficacies against opportunistic pathogens are not fully understood. In this study, the effects of treatment steps on the removal of Legionella spp., Legionella pneumophila, nontuberculous mycobacteria, Mycobacterium avium, and two amoeba hosts (Vermamoeba vermiformis, Acanthamoeba) are evaluated in two parallel trains of DWTPs equipped with different pretreatment units. Quantitative polymerase chain reaction analysis demonstrates significantly reduced numbers of total bacteria, Legionella, and mycobacteria during ozonation, followed by a rebound in granular activated carbon (GAC) filtration, whereas sand filtration exerts an overarching effect in removing microorganisms in both treatment trains. V. vermiformis is more prevalent in biofilm (34%) than water samples (7.7%), while Acanthamoeba is not found in the two trains of DWTPs. Illumina sequencing of bacterial 16S rRNA genes reveals significant community shifts at different treatment steps, as well as distinct bacterial community structures in water and biofilm samples in parallel units (e.g., ozonation, GAC, sand filtration) between the two trains (analysis of similarities (ANOSIM), p < 0.05), implying the potential influence of different pretreatment steps in shaping the downstream microbiome. Overall, the results provide insights to mitigation of opportunistic pathogens and engineer approaches for managing bacterial communities in DWTPs.


Network graph analysis of gene-gene interactions in genome-wide association study data.
Most common complex traits, such as obesity, hypertension, diabetes, and cancers, are known to be associated with multiple genes, environmental factors, and their epistasis. Recently, the development of advanced genotyping technologies has allowed us to perform genome-wide association studies (GWASs). For detecting the effects of multiple genes on complex traits, many approaches have been proposed for GWASs. Multifactor dimensionality reduction (MDR) is one of the powerful and efficient methods for detecting high-order gene-gene (GxG) interactions. However, the biological interpretation of GxG interactions identified by MDR analysis is not easy. In order to aid the interpretation of MDR results, we propose a network graph analysis to elucidate the meaning of identified GxG interactions. The proposed network graph analysis consists of three steps. The first step is for performing GxG interaction analysis using MDR analysis. The second step is to draw the network graph using the MDR result. The third step is to provide biological evidence of the identified GxG interaction using external biological databases. The proposed method was applied to Korean Association Resource (KARE) data, containing 8838 individuals with 327,632 single-nucleotide polymorphisms, in order to perform GxG interaction analysis of body mass index (BMI). Our network graph analysis successfully showed that many identified GxG interactions have known biological evidence related to BMI. We expect that our network graph analysis will be helpful to interpret the biological meaning of GxG interactions.


A novel all-trans retinoid acid derivative N-(3-trifluoromethyl- phenyl)- retinamide inhibits lung adenocarcinoma A549 cell migration through down-regulating expression of myosin light chain kinase.
To observe the effects of a novel all-trans retinoid acid (ATRA) derivative, N-(3-trifluoromethyl-phenyl)- retinamide (ATPR), on lung adenocarcinoma A549 cells and to explore the potential mechanism of ATPR inhibiting of A549 cell migration. The cytotoxicity of ATRA and ATPR on A549 cells was assessed using MTT assay. Wound healing assays were used to analyze the influences of ATRA, ATPR, ML-7 (a highly selective inhibitor of myosin light chain kinase (MLCK)), PMA (an activator of MAPKs) and PD98059 (a selective inhibitor of ERK1/2) on the migration of A549 cells. Expression of MLCK and phosphorylation of myosin light chain (MLC) were assessed by Western blotting. ATRA and ATPR inhibited the proliferation of A549 cells in a dose- and time-dependent manner, and the effect of ATPR was much more remarkable compared with ATRA. Relative migration rate and migration distance of A549 cells both decreased significantly after treatment with ATPR or ML-7. The effect on cell migration of PD98059 combining ATPR treatment was more notable than that of ATPR alone. Moreover, compared with control groups, the expression levels of MLCK and phosphorylated MLC in A549 cells were both clearly reduced in ATRA and ATPR groups. ATPR could suppress the migration and invasion of A549 cells, and the mechanism might be concerned with down- regulating the expression of MLCK in the ERK-MAPK signaling pathway, pointing to therapeutic prospects in lung cancer.


The relationship between cigarette use, nicotine dependence, and craving in laboratory volunteers.
Data from epidemiological studies suggest that individual differences in cigarettes per day (CPD) and duration of smoking account for only a small portion of the variance in Diagnostic and Statistical Manual of Mental Disorders (4th ed.) (DSM-IV) nicotine dependence. However, DSM-IV may be an insensitive measure of nicotine dependence; other measures might better reflect the true nature of the relationship between use and dependence. This paper describes the relationship between cigarettes per day (CPD) and years smoking and the severity of nicotine dependence as measured by the Nicotine Dependence Syndrome Scale (NDSS). Furthermore, we assessed the validity of individual differences in nicotine dependence by determining whether they related to cue-evoked craving during abstinence. Data were pooled from five laboratory studies of 489 regular (i.e., 15+ CPD) smokers. In contrast to previously reported data demonstrating a relatively strong relationship between CPD and dependence in chippers (Shiffman & Sayette, 2005), CPD and years smoking accounted for a statistically significant, but small (<6%), portion of the variance in nicotine dependence in daily smokers. Individual differences in both CPD and years smoking had little or no relationship with craving. However, the magnitude of craving was significantly related to the degree of nicotine dependence even after controlling for use variables and excluding craving-related items on the NDSS. These data suggest that among moderate to heavy daily smokers, meaningful individual differences in nicotine dependence are observed independent of differences in current daily cigarette consumption and duration of smoking. Further research into the sources of this variance is critical to understanding the process of and risk for nicotine dependence.


Controlled release, chitosan-tethered luteolin phytocubosomes; Formulation optimization to in-vivo antiglaucoma and anti-inflammatory ocular evaluation.
A chitosan-coated luteolin-loaded phytocubosomal system was prepared to improve the pharmacodynamic performance of luteolin in the treatment of glaucoma and ocular inflammation after topical ocular administration. Luteolin, a potent anti-oxidant herbal drug with poor aqueous solubility, was complexed with phospholipid. The prepared phytocubosomes were coated with chitosan, producing homogenously distributed nanosized particles (258 ± 9.05 nm) with a positive charge (+49 ± 6.09 mV), improved EE% (96 %), and increased concentration of encapsulated drug to 288 μg/ml. Polarized light microscopy revealed a cubic phase. Chitosan-coated phytocubosomes showed a sustained drug release profile (38 % over 24 h) and improved anti-oxidant activity (IC50 of 32 μg/ml). Ex vivo transcorneal permeation was higher by 3.60 folds compared to luteolin suspension. Irritancy tests confirmed their safety in ocular tissues after single and multiple administrations. The pharmacodynamic studies on glaucomatous rabbit eyes demonstrated 6.46-, 3.88-, and 1.89-fold reductions in IOP of chitosan-coated phytocubosomes compared to luteolin suspension, cubosomes, and phytocubosomes, respectively. Pharmacodynamic anti-inflammatory studies revealed faster recovery capabilities of chitosan-coated phytocubosomes over other formulations. Thus, chitosan-coated phytocubosomes could be a promising ocular hybrid system for delivering herbal lipophilic drugs such as luteolin.


Analysis of dysgenesis-induced lethal mutations on the X chromosome of a Q strain of Drosophila melanogaster.
The Q strain known as v6 was tested for its ability to induce X-linked lethal mutations in male and female hybrids from crosses with M strains in the P-M system of hybrid dysgenesis. All measurements of the mutation rate were made on the X chromosome derived from the v6 strain. The lethal rate for young hybrid males from the cross M female X v6 male was 1.11% per chromosome. For older males, it was only 0.44%, suggesting that there is less mutational or more repair activity in the germ cells of the older males or that mutant cells are selectively eliminated as the hybrid males age. The lethal rate for hybrid females from comparable crosses was approximately the same for both ages that were tested. However, it was substantially less than the rate for the hybrid males--only 0.26% per chromosome. Genetically identical hybrid females from reciprocal crosses also showed a low mutation rate, 0.13% per chromosome. Again, there was no difference between young and old flies. Mapping experiments established that most of the lethal mutations that were recovered from the male and female hybrids were located in two regions on the X chromosome, one between bands 14B13 and 15A9 , the other between bands 19A1 and 20A , which encompasses the maroonlike locus. More refined mapping of the lethals in the maroonlike region demonstrated that the vast majority of these affected a single gene located in band 19C4 . Cytological analysis of the lethal chromosomes revealed that several carried rearrangements, including inversions, duplications and deficiencies. Chromosome breakage occurred primarily in bands 14D1 -3 and 18F- 20A , and most of the breaks in the latter segment were located in 19C . However, rearrangements involving 19C and mutations of the gene in 19C4 were mutually exclusive events. In situ hybridization of a P element probe to the chromosomes of v6 demonstrated that P elements reside at a minimum of five sites on the X chromosome. These P element sites correspond to the mutational and breakage hot spots on that chromosome. The combined genetic and cytological data imply that most of the X-linked lethal mutations that occur in M X v6 hybrids are due to local P element action. Consideration of these and other data suggest that v6 is a weak P strain in the P-M system of hybrid dysgenesis and that other Q strains might also be regarded in this way.


Protective role of hesperetin in sorafenib-induced hepato- and neurotoxicity in mice via modulating apoptotic pathways and mitochondrial reprogramming.
Sorafenib, an FDA-approved standard chemotherapy for advanced hepatocellular carcinoma, is associated with numerous adverse effects that significantly impact patients' physiological well-being. Consequently, identifying agents that mitigate these side effects while enhancing efficacy is crucial. Hesperetin, a flavone present in fruits and vegetables, possesses antioxidant, anti-inflammatory, and anti-cancer properties. This study aimed to investigate the hepatotoxic and neurotoxic effects of sorafenib and the potential protective role of hesperetin. Swiss albino mice were orally administered sorafenib (100 mg/kg) alone or in combination with hesperetin (50 mg/kg) over 21 days. Behavioral assessments for anxiety and depressive-like behaviors were conducted. Additionally, evaluations encompassed apoptotic activity, mitochondrial integrity, liver enzyme levels, proliferation rates, and histopathological changes. Combining hesperetin with sorafenib showed improvements in behavioral alterations, liver damage, brain mitochondrial dysfunction, and liver apoptosis compared to the sorafenib-only group in mice. Hesperetin exhibits potential as an adjunct to sorafenib, mitigating its side effects by attenuating its toxicity, enhancing efficacy, and potentially reducing the occurrence of sorafenib-induced resistance through the downregulation of hepatocyte growth factor levels.


Column-based removal of high concentration microplastics in synthetic wastewater using granular activated carbon.
Microplastic (MP) is an emerging contaminant of concern due to its abundance in the environment. Wastewater treatment plant (WWTP) can be considered as one of the main sources of microplastics in freshwater due to its inefficiency in the complete removal of small MPs. In this study, a column-based MP removal which could serve as a tertiary treatment in WWTPs is evaluated using granular activated carbon (GAC) as adsorbent/filter media, eliminating clogging problems commonly caused by powder form activated carbon (PAC). The GAC is characterized via N2 adsorption-desorption isotherm, field emission scanning electron microscopy, and contact angle measurement to determine the influence of its properties on MP removal efficiency. MPs (40-48 μm) removal up to 95.5% was observed with 0.2 g/L MP, which is the lowest concentration tested in this work, but still higher than commonly used MP concentration in other studies. The performance is reduced with further increase in MP concentration (up to 1.0 g/L), but increasing the GAC bed length from 7.5 to 17.5 cm could lead to better removal efficiencies. MP particles are immobilized by the GAC predominantly by filtration process by being entangled with small GAC particles/chips or stuck between the GAC particles. MPs are insignificantly removed by adsorption process through entrapment in GAC porous structure or attachment onto the GAC surface.


[Surgical treatment of nodular endemic goiter].
The article analyzes results of the surgical treatment of 142 patients with nodular endemic goiters in Algeria. Intracapsular, extracapsular and combined methods were used. The selection of the method for different clinico-anatomical features of the goiter is grounded. The extracapsular method is thought to be the method of choice in diffuse-nodular and nodular goiters of a huge size.


What is leadership?
The demand for more effective leadership is heard throughout the health professions. Modern concepts of leadership differ from the traditional definition of a charismatic individual leader. Historically, leadership has been vested in positions, while today leadership is seen as a role one moves continuously into and out of, depending on the circumstance. Leadership ideas have evolved so that newer characteristics of leaders include being a team builder; possessing creative and strategic thinking skills; demonstrating honesty and integrity; and having the ability to motivate others to action. This article discusses some of the history of leadership, current thoughts on attributes of effective leaders, and the differences and similarities between leaders and managers; identifies selected teachable leadership tools; and describes various styles and purposes of existing leadership programs.


HIV: challenging the health care delivery system.
HIV offers a lens through which the underlying problems of the US health care system can be examined. New treatments offer the potential of prolonged quality of life for people living with HIV if they have adequate access to health care. However, increasing numbers of new cases of HIV occur among individuals with poor access to health care. Restrictions on eligibility for Medicaid (and state-by-state variability) contribute to uneven access to the most important safety net source of HIV care financing, while relatively modest discretionary programs attempt to fill in the gap with an ever-increasing caseload. Many poor people with HIV are going without care, even though aggregate public spending on HIV-related care will total $7.7 billion in fiscal year 2000, an amount sufficient to cover the care costs of one half of those living with HIV. But inefficiencies and inequities in the system (both structural and geographic) require assessment of the steps that can be taken to create a more rational model of care financing for people living with HIV that could become a model for all chronic diseases.


Adherence to a Videogame-Based Physical Activity Program for Older Adults with Schizophrenia.
Adults with schizophrenia are a growing segment of the older adult population. Evidence suggests that they engage in limited physical activity. Interventions are needed that are tailored around their unique limitations. An active videogame-based physical activity program that can be offered at a treatment facility can overcome these barriers and increase motivation to engage in physical activity. The purpose of this report is to describe the adherence to a videogame-based physical activity program using the Kinect(®) for Xbox(®) 360 game system (Microsoft(®), Redmond, WA) in older adults with schizophrenia. This was a descriptive longitudinal study among 34 older adults with schizophrenia to establish the adherence to an active videogame-based physical activity program. In our ongoing program, once a week for 6 weeks, participants played an active videogame, using the Kinect for Xbox 360 game system, for 30 minutes. Adherence was measured with a count of sessions attended and with the total minutes attended out of the possible total minutes of attendance (180 minutes). Thirty-four adults with schizophrenia enrolled in the study. The mean number of groups attended was five out of six total (standard deviation=2), and the mean total minutes attended were 139 out of 180 possible (standard deviation=55). Fifty percent had perfect attendance. Older adults with schizophrenia need effective physical activity programs. Adherence to our program suggests that videogames that use the Kinect for Xbox 360 game system are an innovative way to make physical activity accessible to this population.


Cognitive domains that predict time to diagnosis in prodromal Huntington disease.
Prodromal Huntington's disease (prHD) is associated with a myriad of cognitive changes but the domains that best predict time to clinical diagnosis have not been studied. This is a notable gap because some domains may be more sensitive to cognitive decline, which would inform clinical trials. The present study sought to characterise cognitive domains underlying a large test battery and for the first time, evaluate their ability to predict time to diagnosis. Participants included gene negative and gene positive prHD participants who were enrolled in the PREDICT-HD study. The CAG-age product (CAP) score was the measure of an individual's genetic signature. A factor analysis of 18 tests was performed to identify sets of measures or latent factors that elucidated core constructs of tests. Factor scores were then fit to a survival model to evaluate their ability to predict time to diagnosis. Six factors were identified: (1) speed/inhibition, (2) verbal working memory, (3) motor planning/speed, (4) attention-information integration, (5) sensory-perceptual processing and (6) verbal learning/memory. Factor scores were sensitive to worsening of cognitive functioning in prHD, typically more so than performances on individual tests comprising the factors. Only the motor planning/speed and sensory-perceptual processing factors predicted time to diagnosis, after controlling for CAP scores and motor symptoms. Conclusions The results suggest that motor planning/speed and sensory-perceptual processing are important markers of disease prognosis. The findings also have implications for using composite indices of cognition in preventive Huntington's disease trials where they may be more sensitive than individual tests.


Patients' perception and actual practice of informed consent, privacy and confidentiality in general medical outpatient departments of two tertiary care hospitals of Lahore.
The principles of informed consent, confidentiality and privacy are often neglected during patient care in developing countries. We assessed the degree to which doctors in Lahore adhere to these principles during outpatient consultations. The study was conducted at medical out-patient departments (OPDs) of two tertiary care hospitals (one public and one private hospital) of Lahore, selected using multi-stage sampling. 93 patients were selected from each hospital. Doctors' adherence to the principles of informed consent, privacy and confidentiality was observed through client flow analysis performed by trained personnel. Overall patient perception was also assessed regarding these practices and was compared with the assessment made by our data collectors. Some degree of informed consent was obtained from only 9.7% patients in the public hospital and 47.8% in the private hospital. 81.4% of patients in the public hospital and 88.4% in the private hospital were accorded at least some degree of privacy. Complete informational confidentiality was maintained only in 10.8% and 35.5% of cases in public & private hospitals respectively. Informed consent and confidentiality were better practiced in the private compared to the public hospital (two-sample t-test > 2, p value < 0.05). There was marked disparity between the patients' perspective of these ethical practices and the assessment of our trained data collectors. Observance of medical ethics is inadequate in hospitals of Lahore. Doctors should be imparted formal training in medical ethics and national legislation on medical ethics is needed. Patients should be made aware of their rights to medical ethics.


Can muscle protein metabolism be specifically targeted by exercise training in COPD?
Patients with stable chronic obstructive pulmonary disease (COPD) frequently exhibit unintentional accentuated peripheral muscle loss and dysfunction. Skeletal muscle mass in these patients is a strong independent predictor of morbidity and mortality. Factors including protein anabolism/catabolism imbalance, hypoxia, physical inactivity, inflammation, and oxidative stress are involved in the initiation and progression of muscle wasting in these patients. Exercise training remains the most powerful intervention for reversing, in part, muscle wasting in COPD. Independently of the status of systemic or local muscle inflammation, rehabilitative exercise training induces up-regulation of key factors governing skeletal muscle hypertrophy and regeneration. However, COPD patients presenting similar degrees of lung dysfunction do not respond alike to a given rehabilitative exercise stimulus. In addition, a proportion of patients experience limited clinical outcomes, even when exercise training has been adequately performed. Consistently, several reports provide evidence that the muscles of COPD patients present training-induced myogenic activity limitation as exercise training induces a limited number of differentially expressed genes, which are mostly associated with protein degradation. This review summarises the nature of muscle adaptations induced by exercise training, promoted both by changes in the expression of contractile proteins and their function typically controlled by intracellular signalling and transcriptional responses. Rehabilitative exercise training in COPD patients stimulates skeletal muscle mechanosensitive signalling pathways for protein accretion and its regulation during muscle contraction. Exercise training also induces synthesis of myogenic proteins by which COPD skeletal muscle promotes hypertrophy leading to fusion of myogenic cells to the myofiber. Understanding of the biological mechanisms that regulate exercise training-induced muscle growth and regeneration is necessary for implementing therapeutic strategies specifically targeting myogenesis and hypertrophy in these patients.


A novel method of estimating effective dose from the point dose method: a case study--parathyroid CT scans.
The purpose of this study was to validate a novel approach of applying a partial volume correction factor (PVCF) using a limited number of MOSFET detectors in the effective dose (E) calculation. The results of the proposed PVCF method were compared to the results from both the point dose (PD) method and a commercial CT dose estimation software (CT-Expo). To measure organ doses, an adult female anthropomorphic phantom was loaded with 20 MOSFET detectors and was scanned using the non-contrast and 2 phase contrast-enhanced parathyroid imaging protocols on a 64-slice multi-detector computed tomography scanner. E was computed by three methods: the PD method, the PVCF method, and the CT-Expo method. The E (in mSv) for the PD method, the PVCF method, and CT-Expo method was 2.6 ± 0.2, 1.3 ± 0.1, and 1.1 for the non-contrast scan, 21.9 ± 0.4, 13.9 ± 0.2, and 14.6 for the 1st phase of the contrast-enhanced scan, and 15.5 ± 0.3, 9.8 ± 0.1, and 10.4 for the 2nd phase of the contrast-enhanced scan, respectively. The E with the PD method differed from the PVCF method by 66.7% for the non-contrast scan, by 44.9% and by 45.5% respectively for the 1st and 2nd phases of the contrast-enhanced scan. The E with PVCF was comparable to the results from the CT-Expo method with percent differences of 15.8%, 5.0%, and 6.3% for the non-contrast scan and the 1st and 2nd phases of the contrast-enhanced scan, respectively. To conclude, the PVCF method estimated E within 16% difference as compared to 50-70% in the PD method. In addition, the results demonstrate that E can be estimated accurately from a limited number of detectors.


Cooling of a Zero-Nuclear-Spin Molecular Ion to a Selected Rotational State.
We demonstrate rotational cooling of the silicon monoxide cation via optical pumping by a spectrally filtered broadband laser. Compared with diatomic hydrides, SiO^{+} is more challenging to cool because of its smaller rotational interval. However, the rotational level spacing and the large dipole moment of SiO^{+} allows for direct manipulation by microwaves, and the absence of hyperfine structure in its dominant isotopologue greatly reduces demands for pure quantum state preparation. These features make ^{28}Si^{16}O^{+} a good candidate for future applications such as quantum information processing. Cooling to the ground rotational state is achieved on a 100 ms timescale and attains a population of 94(3)%, with an equivalent temperature T=0.53(6) K. We also describe a novel spectral-filtering approach to cool into arbitrary rotational states and use it to demonstrate a narrow rotational population distribution (N±1) around a selected state.


[A new human hepatoma cell line: establishment and characterization].
We have grown a human hepatoma cell line, designated as HA22T/VGH, from a 52-yr-old male hepatoma patient since July 1, 1980. This cell line has been subcultured more than 100 passages. The chromosome analysis of HA22T/VGH indicated that the chromosome numbers varied from 70 to 146, with the mode of 73. Methylcellulose soft agar assay showed that approximately 40% of the HA22T/VGH cells formed colonies. The HA22T/VGH produced tumors in nude mice. Histopathological studies of the tumor revealed the arrangement of hepatoma. Detected by the complement fixation method HA22T/VGH cells secreted ceruloplasmin, Factor B, C3, C4, Gc-globulin and alpha 1-acid-glycoprotein. These cells contained the liver associated enzymes: alanine amino transferase, tyrosine amino transferase and gamma-glutamyl transferase. HBsAg and alpha-fetoprotein were not detectable in the HA22T/VGH culture media or cell lysates by the radioimmunoassay.


Lipopolysaccharide-activated microglia lower P-glycoprotein function in brain microvascular endothelial cells.
P-glycoprotein, an efflux transporter that is highly expressed at the blood-brain barrier (BBB), is involved in the traffic of several compounds across the BBB. BBB disruption under pathological conditions is observed in parallel with microglial activation. Previous studies of the interaction between rat brain endothelial cells (RBECs) and microglia have shown that lipopolysaccharide (LPS) activated microglia increase the permeability of RBECs through a mechanism involving NADPH oxidase. In this study, to investigate whether LPS-activated microglia are linked to P-gp dysfunction at the BBB, we examined the effect of LPS on P-gp function in a coculture system with RBECs and rat microglia. When LPS at a concentration showing no effect on the RBEC monolayer was added for 6h to the abluminal side of the RBEC monolayer and RBEC/microglia cocultures, cellular accumulation of the P-gp substrate rhodamine 123, in RBECs, was increased by LPS in the RBEC/microglia coculture. This increased accumulation of rhodamine 123 in RBECs was blocked by diphenyleneiodoniumchloride, an NADPH oxidase inhibitor. P-gp expression on RBECs was not influenced by treatment with LPS in either RBEC monolayers or RBEC/microglia cocultures. These findings suggest that activated microglia induce P-gp dysfunction at the BBB through an NADPH oxidase-dependent pathway.


Monoclonal antibody-based therapy as a new treatment strategy in multiple myeloma.
The introduction of autologous stem cell transplantation combined with the introduction of immunomodulatory drugs (IMiDs) and proteasome inhibitors has significantly improved survival of multiple myeloma patients. However, ultimately the majority of patients will develop refractory disease, indicating the need for new treatment modalities. In preclinical and clinical studies, promising results have been obtained with several monoclonal antibodies (mAbs) targeting the myeloma tumor cell or the bone marrow microenvironment. The mechanisms underlying the therapeutic efficacy of these mAbs include direct induction of tumor cell apoptosis via inhibition or activation of target molecules, complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC). The capability of IMiDs to enhance ADCC and the modulation of various important signaling cascades in myeloma cells by both bortezomib and IMiDs forms the rationale to combine these novel agents with mAbs as new treatment strategies for myeloma patients. In this review, we will give an overview of various mAbs directly targeting myeloma tumor cells or indirectly via effects on the bone marrow microenvironment. Special focus will be on the combination of these mAbs with IMiDs or bortezomib.


Modification of Chin Projection and Aesthetics With OnabotulinumtoxinA Injection.
Because of the soft-tissue envelope and the dimensional complexity of the muscular contraction of the mentalis muscle, the projection and shape of the chin is not determined by only the bony projection. In a subset of patients with a seemingly underprojected chin, a hyperactive, high-riding mentalis muscle contributes to a blunted chin contour. To evaluate the use of onabotulinumtoxinA (botulinum toxin A) for improving chin aesthetics in patients with an underprojected bony chin and a high-riding hyperactive mentalis muscle. This case series and photographic analysis included 11 patients presenting with an underprojected bony chin and a high-riding hyperactive mentalis muscle at a private facial plastic surgery practice from August 25, 2006, to November 10, 2012. Data were analyzed from November 13, 2012, to April 9, 2013. Injection with 12 to 15 U of onabotulinumtoxinA into the mentalis muscle. Photographic analysis of the vertical and horizontal positions of the pogonion relative to fixed facial points before and after injection. A patient satisfaction scale was also used to assess improvement in overall chin aesthetic. Eleven patients (3 men and 8 women; mean [SD] age, 46.3 [16.4] years) participated in the study, including 2 who had undergone prior chin implantation. The vertical position of the pogonion was more inferior after injection in 10 of 11 patients (mean [SD] vertical position, 1.36 [0.18] preinjection and 1.44 [0.18] postinjection; P = .005). Although the horizontal position of the pogonion changed in all patients, this change was not statistically significant (mean [SD] horizontal position, 0.11 [0.13] preinjection and 0.14 [0.13] postinjection; P = .32). All patients experienced improvement in their overall chin aesthetic and a subjective decrease in chin tension. Chin contour was improved, with soft-tissue volume overall displaced more inferiorly with a rounded rather than blunted appearance. No adverse effects were reported after injection. OnabotulinumtoxinA is effective at improving chin aesthetics by altering the position of the pogonion. In this first photographic analysis to date of the influence of onabotulinumtoxinA treatment, patients demonstrated a measurable change in the position of the pogonion, in addition to improvements to the chin contour on profile. This nonsurgical mentoplasty may be used as an independent procedure or as an adjunct to optimize traditional chin augmentation in carefully selected patients. 4.


Chinese herbal medicine for atopic eczema.
Traditional Chinese herbal mixtures have been used to treat atopic eczema for many years. Their efficacy has attracted public attention and recently some clinical trials have been undertaken. To assess the effects of Chinese herbal mixtures in the treatment of atopic eczema. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) ( January 2004), the Cochrane Skin Group Specialised Register (January 2004), MEDLINE (1966 to January 2004), EMBASE (1980 to January 2004), CINHL (1980 to January 2004) and a number of complementary medicine databases. In addition, the cited references of all trials identified and key review articles were searched. Pharmaceutical companies involved in oral traditional Chinese herbs and experts in the field were contacted. Randomised controlled trials of Chinese herbal mixtures used in the treatment of atopic eczema. Two reviewers independently applied eligibility criteria, assessed the quality of the trials and extracted data. Any discrepancies were discussed to achieve consensus. Four randomised controlled trials, with eight weeks for each phase, met the inclusion criteria. The trials randomised 159 participants aged from 1 to 60 years. The withdrawal rates ranged from 7.5% to 22.5% and no trial used intention to treat analysis. Three trials were randomised placebo controlled, two-phase cross-over designs assessing the same Chinese herbal mixture, Zemaphyte. In two of these three trials the reduction in erythema and surface damage was greater on Zemaphyte than on placebo, and participants slept better and expressed a preference for Zemaphyte. One trial also reported that participants itched less. The fourth trial was an open-label design comparing Zemaphyte in herbal form with Zemaphyte as a freeze dried preparation. There was a reduction in erythema and surface damage with both formulations, but no comparison between the two formulations was reported. Some adverse effects were reported in all four trials, but none were regarded as serious. Chinese herbal mixtures may be effective in the treatment of atopic eczema. However, only four small poorly reported RCTs of the same product, Zemaphyte, were found and the results were heterogeneous. Further well-designed, larger scale trials are required, but Zemaphyte is no longer being manufactured.


Supporting doctors' well-being and resilience during COVID-19: A framework for rapid and rigorous intervention development.
This paper aims to outline the development of a theoretically informed and evidence-based intervention strategy to underpin interventions to support the well-being of doctors during COVID-19 and beyond; delineate new ways of working were employed to ensure a rapid and rigorous process of intervention development and present the resulting novel framework for intervention development. The research comprised four workstreams: literature review (WS1), qualitative study (WS2), intervention development and implementation (WS3) and evaluation (WS4). Due to time constraints, we employed a parallel design for WS1-3 with the findings of WS1-2 informing WS3 on a continual basis. WS3 was underpinned by the Behaviour Change Wheel. We recruited expert panels to assist with intervention development. We reflected on decisions taken to facilitate the rapid yet rigorous process of intervention development. The empirical output was a theoretically informed and evidence-based intervention strategy to underpin interventions to support doctors' well-being during COVID-19 and beyond. The methodological output was a novel framework that facilitates rapid and rigorous development of interventions. The intervention strategy provides a foundation for development and evaluation of tailored interventions to support doctors' well-being. The novel framework provides guidance for the development of interventions where the situation demands a rapid yet rigorous development process.


The HPr proteins from the thermophile Bacillus stearothermophilus can form domain-swapped dimers.
The study of proteins from extremophilic organisms continues to generate interest in the field of protein folding because paradigms explaining the enhanced stability of these proteins still elude us and such studies have the potential to further our knowledge of the forces stabilizing proteins. We have undertaken such a study with our model protein HPr from a mesophile, Bacillus subtilis, and a thermophile, Bacillus stearothermophilus. We report here the high-resolution structures of the wild-type HPr protein from the thermophile and a variant, F29W. The variant proved to crystallize in two forms: a monomeric form with a structure very similar to the wild-type protein as well as a domain-swapped dimer. Interestingly, the structure of the domain-swapped dimer for HPr is very different from that observed for a homologous protein, Crh, from B.subtilis. The existence of a domain-swapped dimer has implications for amyloid formation and is consistent with recent results showing that the HPr proteins can form amyloid fibrils. We also characterized the conformational stability of the thermophilic HPr proteins using thermal and solvent denaturation methods and have used the high-resolution structures in an attempt to explain the differences in stability between the different HPr proteins. Finally, we present a detailed analysis of the solution properties of the HPr proteins using a variety of biochemical and biophysical methods.


Moving nonradiating kinks in nonlocal φ4 and φ4-φ6 models.
We explore the existence of moving nonradiating kinks in nonlocal generalizations of φ(4) and φ(4)-φ(6) models. These models are described by nonlocal nonlinear Klein-Gordon equation, u(tt)-Lu+F(u)=0, where L is a Fourier multiplier operator of a specific form and F(u) includes either just a cubic term (φ(4) case) or cubic and quintic (φ(4)-φ(6) case) terms. The general mechanism responsible for the discretization of kink velocities in the nonlocal model is discussed. We report numerical results obtained for these models. It is shown that, contrary to the traditional φ(4) model, the nonlocal φ(4) model does not admit moving nonradiating kinks but admits solitary waves that do not exist in the local model. At the same time the nonlocal φ(4)-φ(6) model describes moving nonradiating kinks. The set of velocities allowed for these kinks is discrete with the highest possible velocity c(1). This set of velocities is unambiguously determined by the parameters of the model. Numerical simulations show that a kink launched at the velocity c higher than c(1) starts to decelerate, and its velocity settles down to the highest value of the discrete spectrum c(1).


Using signage to promote stair use on a university campus in hidden and visible stairwells.
This study tested the effectiveness of a stair use promotion strategy in visible and hidden stairwells during intervention and post intervention follow up. A quasi-experimental study design was used with a 1 week baseline, a 3 week intervention, and post intervention at 2 and 4 weeks in 4 university buildings in San Antonio, Texas with stairwells varying in visibility. Participants were students, faculty, staff, and visitors to the 4 buildings. A total of 8431 observations were made. The intervention incorporated motivational signs with direction to nearby stairwells placed by elevators to promote stair use. Stair and elevator use was directly observed and recorded. Logistic regression analyses were used to test whether stair versus elevator use varied by intervention phase and stairwell visibility. Stair use increased significantly (12% units) during the intervention period and remained above baseline levels during post intervention follow-up. At baseline, visible stairs were 4 times more likely to be used than hidden stairs; however, the increase in stair use during intervention was similar in both types of stairwells. Motivational and directional signage can significantly increase stair use on a university campus. Furthermore, stairwell visibility is an important aspect of stair use promotion.


Comparison of the performance of aerosol sampling devices for measuring infectious SARS-CoV-2 aerosols.
To assess the risk of aerosol transmission of SARS-CoV-2, measurements of the airborne viral concentrations in proximity to infected individuals, the persistence of the virus in aerosols, and the dose of the virus needed to cause infection following inhalation are required. For studies aimed at quantifying these parameters, an aerosol sampling device needs to be employed. A number of recent studies have reported the detection of both genetic material and infectious SARS-CoV-2 virus in air samples collected in clinical settings. Previous studies have demonstrated that the efficiency of different samplers for collection and preservation of the infectivity of microorganisms can vary as a function of the specific microorganism. In the present study, the performance of eight common low-flow aerosol sampling devices were compared for their ability to collect and preserve the infectivity of airborne SARS-CoV-2 contained in small particle aerosols. The influence of sampling duration on recovery of infectious virus was also evaluated. Similar concentrations of infectious SARS-CoV-2 were measured in aerosols for the majority of the samplers tested, with the exception of the midget impingers, which measured significantly lower concentrations of SARS-CoV-2. Additionally, in three of the four impingers tested, additional clean airflow through the device following collection of infectious virus resulted in a decrease of the infectious concentration of virus over time, suggesting that virus was being inactivated and these devices may not be suitable for sampling for long durations. Further, RNA copies in the samples over time did not correspond with the losses of infectious SARS-CoV-2 observed in the impingers samples. These data can be utilized to inform interpretation of current studies on the SARS-CoV-2 viral loads in air samples, as well as inform sampling device selection in future studies.


Polymer films doped with fluorescent sensor for moisture and water droplet based on photo-induced electron transfer.
Anthracene-(aminomethyl)phenylboronic acid pinacol ester (AminoMePhenylBPin) OF-2 acts as a PET (photo-induced electron transfer)-type fluorescent sensor for determination of a trace amount of water: the addition of water to organic solvents containing OF-2 causes a drastic and linear enhancement of fluorescence emission as a function of water content, which is attributed to the suppression of PET. Indeed, detection limits (DLs) for OF-2 were as low as 0.01-0.008 wt% of water in solvents, that is, the PET method makes it possible to visualize, detect, and determine a trace amount of water. Thus, in this work, in order to develop fluorescent polymeric materials for visualization and detection of water, we have achieved the preparation of various types of polymer films (polystyrene (PS), poly(4-vinylphenol) (PVP), polyvinyl alcohol (PVA), and polyethylene glycol (PEG)) which were doped with OF-2, and investigated the optical sensing properties of the OF-2-doped polymer films for water. As-prepared OF-2-doped polymer films initially exhibited green excimer emission in the PET active state, but blue monomer emission in the PET inactive state upon exposure to moisture or by water droplet. Moreover, it was found that the OF-2-doped polymer films show the reversible fluorescence properties in the dry-wet process. Herein we propose that polymer films doped with PET-type fluorescent sensors for water based on a fluorescence enhancement (turn-on) system are one of the most promising and convenient functional materials for visualizing moisture and water droplets.


Efficacy and Safety of Pembrolizumab in Patients Enrolled in KEYNOTE-030 in the United States: An Expanded Access Program.
KEYNOTE-030 (ClinicalTrials.gov ID, NCT02083484) was a global expanded access program that allowed access to pembrolizumab, an antiprogrammed death 1 antibody, for patients with advanced melanoma before its regulatory approval. Patients with unresectable stage III/IV melanoma that progressed after standard-of-care therapy, including ipilimumab and, if BRAF mutant, a BRAF inhibitor, were eligible to receive pembrolizumab 2 mg/kg every 3 weeks. Response was assessed by immune-related response criteria by investigator review. Adverse events (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. In the United States, 979 patients enrolled between April and September 2014. Of the 947 evaluable patients, 621 (65.6%) remained on treatment and transitioned to receive commercial pembrolizumab following approval by the Food and Drug Administration, whereas 326 (34.4%) discontinued, most commonly for disease progression (39.6%) or death (26.4%). Objective response rate was 14.5% (95% confidence interval, 12.2%-16.8%) in the treated population (n=947) and 22.1% (95% confidence interval, 18.8%-25.5%) in patients who had ≥1 response assessment reported (n=619). Twelve patients achieved complete response. One hundred eighty-one (19.1%) patients experienced ≥1 treatment-related AE, most commonly general disorders (8.0%), skin/subcutaneous tissue disorders (7.3%), and gastrointestinal disorders (6.4%); 29 (3.1%) patients experienced ≥1 grade 3/4 treatment-related AE. Immune-mediated AEs were also reported. There were no treatment-related deaths. The safety and efficacy observed in this expanded access program were consistent with those previously reported for similar populations and support the use of pembrolizumab for patients with advanced melanoma.


TRUNCATULIX--a data warehouse for the legume community.
Databases for either sequence, annotation, or microarray experiments data are extremely beneficial to the research community, as they centrally gather information from experiments performed by different scientists. However, data from different sources develop their full capacities only when combined. The idea of a data warehouse directly adresses this problem and solves it by integrating all required data into one single database - hence there are already many data warehouses available to genetics. For the model legume Medicago truncatula, there is currently no such single data warehouse that integrates all freely available gene sequences, the corresponding gene expression data, and annotation information. Thus, we created the data warehouse TRUNCATULIX, an integrative database of Medicago truncatula sequence and expression data. The TRUNCATULIX data warehouse integrates five public databases for gene sequences, and gene annotations, as well as a database for microarray expression data covering raw data, normalized datasets, and complete expression profiling experiments. It can be accessed via an AJAX-based web interface using a standard web browser. For the first time, users can now quickly search for specific genes and gene expression data in a huge database based on high-quality annotations. The results can be exported as Excel, HTML, or as csv files for further usage. The integration of sequence, annotation, and gene expression data from several Medicago truncatula databases in TRUNCATULIX provides the legume community with access to data and data mining capability not previously available. TRUNCATULIX is freely available at http://www.cebitec.uni-bielefeld.de/truncatulix/.


Real-World Evaluation of an Automated Algorithm to Detect Patients With Potentially Undiagnosed Hypertension Among Patients With Routine Care in Hawai'i.
This real-world evaluation considers an algorithm designed to detect patients with potentially undiagnosed hypertension, receiving routine care, in a large health system in Hawai'i. It quantifies patients identified as potentially undiagnosed with hypertension; summarizes the individual, clinical, and health system factors associated with undiagnosed hypertension; and examines if the COVID-19 pandemic affected detection. We analyzed the electronic health records of patients treated across 6 clinics from 2018 to 2021. We calculated total patients with potentially undiagnosed hypertension and compared patients flagged for undiagnosed hypertension to those with diagnosed hypertension and to the full patient panel across individual characteristics, clinical and health system factors (eg, clinic of care), and timing. Modified Poisson regression was used to calculate crude and adjusted risk ratios. Among the eligible patients (N=13 364), 52.6% had been diagnosed with hypertension, 2.7% were flagged as potentially undiagnosed, and 44.6% had no evidence of hypertension. Factors associated with a higher risk of potentially undiagnosed hypertension included individual characteristics (ages 40-84 compared with 18-39 years), clinical (lack of diabetes diagnosis) and health system factors (clinic site and being a Medicaid versus a Medicare beneficiary), and timing (readings obtained after the COVID-19 Stay-At-Home Order in Hawai'i). This evaluation provided evidence that a clinical algorithm implemented within a large health system's electronic health records could detect patients in need of follow-up to determine hypertension status, and it identified key individual characteristics, clinical and health system factors, and timing considerations that may contribute to undiagnosed hypertension among patients receiving routine care.


Sugar-binding sites on the surface of the carbohydrate-binding module of CBH I from Trichoderma reesei.
Molecular dynamics simulations were carried out for a system consisting of the carbohydrate-binding module (CBM) of the cellulase CBH I from Trichoderma reesei (Hypocrea jecorina) in a concentrated solution of β-D-glucopyranose, to determine whether there is any tendency for the sugar molecules to bind to the CBM. In spite of the general tendency of glucose to behave as an osmolyte, a marked tendency for the sugar molecules to bind to the protein was observed. However, the glucose molecules tended to bind only to specific sites on the protein. As expected, the hydrophobic face of the sugar molecules, comprising the axial H1, H3, and H5 aliphatic protons, tended to adhere to the flat faces of the three tyrosine side chains on the planar binding surface of the CBM. However, a significant tendency to bind to a groove-like feature on the upper surface of the CBM was also observed. These results would not be inconsistent with a model of the mechanism for this globular domain in which the cellodextrin chain being removed from the surface of crystalline cellulose passes over the upper surface of the CBM, presumably then available for hydrolysis in the active site tunnel of this processive cellulase.


Self-aligned micropatterns of bifunctional polymer surfaces with independent chemical and topographical contrast.
Bifunctional surfaces are micropatterned using a self-aligned, dual-purpose lithographic mask and pairs of conformally deposited iCVD polymers. A first layer is deposited, then physically masked and etched in oxygen plasma. A second layer is deposited with the mask still in place. Lift-off reveals the micropatterned surface. The thicknesses of the two layers are independently controlled so that the resultant surface displays both chemical and topographical contrast. The patterning scheme is independent of the polymers used and order of deposition. We use this scheme to create surfaces that spatially confine microcondensation, as well as chemical functionality. We also demonstrate microwells whose depth can be altered in response to a water stimulus.


Targeted Sequencing of Pancreatic Adenocarcinomas from Patients with Metachronous Pulmonary Metastases.
Mutation spectra of 250 cancer driver, druggable, and actionable genes were analyzed in surgically resected pancreatic ductal adenocarcinoma (PDAC) patients who developed metachronous pulmonary metastases. Targeted sequencing was performed in DNA from blood and archival samples of 15 primary tumors and three paired metastases. Results were complemented with the determination of G12V mutation in KRAS by droplet digital PCR. The median number of protein-changing mutations was 52 per patient. KRAS and TP53 were significantly enriched in fractions of mutations in hotspots. Individual gene mutation frequencies or mutational loads accounting separately for drivers, druggable, or clinically actionable genes, did not significantly associate with patients' survival. LRP1B was markedly mutated in primaries of patients who generalized (71%) compared to those developing solitary pulmonary metastases (0%). FLG2 was mutated exclusively in primary tumors compared to paired metastases. In conclusion, signatures of prognostically differing subgroups of PDAC patients were generated for further utilization in precision medicine.


The protective role of TLR6 in a mouse model of asthma is mediated by IL-23 and IL-17A.
TLRs are a family of receptors that mediate immune system pathogen recognition. In the respiratory system, TLR activation has both beneficial and deleterious effects in asthma. For example, clinical data indicate that TLR6 activation exerts protective effects in asthma. Here, we explored the mechanism or mechanisms through which TLR6 mediates this effect using mouse models of Aspergillus fumigatus-induced and house dust mite antigen-induced (HDM antigen-induced) chronic asthma. Tlr6-/- mice with fungal- or HDM antigen-induced asthma exhibited substantially increased airway hyperresponsiveness, inflammation, and remodeling compared with WT asthmatic groups. Surprisingly, whole-lung levels of IL-23 and IL-17 were markedly lower in Tlr6-/- versus WT asthmatic mice. Tlr6-/- DCs generated less IL-23 upon activation with lipopolysaccharide, zymosan, or curdlan. Impaired IL-23 generation in Tlr6-/- mice also corresponded with lower levels of expression of the pathogen-recognition receptor dectin-1 and expansion of Th17 cells both in vivo and in vitro. Exogenous IL-23 treatment of asthmatic Tlr6-/- mice restored IL-17A production and substantially reduced airway hyperresponsiveness, inflammation, and lung fungal burden compared with that in untreated asthmatic Tlr6-/- mice. Together, our data demonstrate that TLR6 activation is critical for IL-23 production and Th17 responses, which both regulate the allergic inflammatory response in chronic fungal-induced asthma. Thus, therapeutics targeting TLR6 activity might prove efficacious in the treatment of clinical asthma.


Vitamin D and executive functioning: Are higher levels better?
Insufficiency of 25-hydroxyvitamin D has been associated with cognitive impairment, particularly worse executive functioning. However, it remains unclear whether supratherapeutic levels (≥100 nmol L(-1)) are associated with even better performance than sufficient levels (defined as ≥50 nmol L(-1) or even ≥75 nmol L(-1)). The current investigation sought to examine this question. Healthy adults (n = 142) were tested on four measures of executive functioning, including verbal fluency, digit span backward, CANTAB® Spatial Working Memory, and One Touch Stockings of Cambridge. A measure of attention (digit span forward) and memory (CANTAB® Verbal Recognition) were also assessed. Based on blood 25-hydroxyvitamin D [25(OH)D] levels, participants were divided into four groups: insufficient (<50 nmol L(-1)), low sufficient (50 to <75 nmol L(-1)), high sufficient (75 to <100 nmol L(-1)), and supratherapeutic (≥100 nmol L(-1)). Relationships between vitamin D status and cognition were assessed by analyses of covariance and hierarchical multiple regression, adjusted for age, education, sex, body mass index, mood, and physical activity level. Multivariate regression spline analyses were utilized to investigate nonlinearity. Performance on verbal fluency, but not other measures, differed by vitamin D status, analysis of covariance (ANCOVA), F(3, 127) = 2.70, p = .048; d = 0.50. Specifically, participants with supratherapeutic levels provided a greater number of words (M = 16.1, SE = 1.0) than those with insufficient (M = 12.0, SE = 1.0; p = .007, d = 0.78), low (M = 13.4, SE = 0.7; p = .026, d = 0.51), and high sufficient levels (M = 13.9, SE = 0.9; p = .080, d = 0.42). Similarly, vitamin D status was a significant independent predictor of verbal fluency (p = .025, d = 0.40). Spline analyses revealed that there is a positive, near-linear association between verbal fluency and 25(OH)D levels up to and exceeding 100 nmol L(-1). Supratherapeutic levels of vitamin D were associated with significantly better performance on verbal fluency. Importantly, commonly used cutoff levels and sufficiency categories have been based on bone health and optimal levels for cognition are unknown. These findings suggest that levels exceeding 100 nmol L(-1) may be optimal for at least some aspects of executive functioning.


Mechanistic and dynamic insights into ligand encapsulation by helical arylamide foldamers.
Molecular capsules have been extensively used in catalysis, drug delivery, molecular recognition and protection of ligands from degradation. Novel "apple peel" shaped helical arylamide capsules have been experimentally pursued due to their flexible nature and designability. They were found to encapsulate a variety of small molecules. The apple peel shape of the capsules led to a hypothesis that binding and release of ligands involve partial unfolding. However, the exact mechanism is unknown. Using molecular dynamics simulations with our new aryl-amide force field parameters, we identify two low energy barrier binding/release mechanisms, in which the capsule's helical structure is either minimally disturbed or restored quickly (within 100 ps). Furthermore, we determine the effects of ligand sizes, their chemical nature (hydrogen bonding capabilities), and solvents on binding modes and stabilities. Our findings not only support experimental observations but also provide underlying principles that allow for rational design of foldamer capsules.


Rapid changes in tissue mechanics regulate cell behaviour in the developing embryonic brain.
Tissue mechanics is important for development; however, the spatio-temporal dynamics of in vivo tissue stiffness is still poorly understood. We here developed tiv-AFM, combining time-lapse in vivo atomic force microscopy with upright fluorescence imaging of embryonic tissue, to show that during development local tissue stiffness changes significantly within tens of minutes. Within this time frame, a stiffness gradient arose in the developing Xenopus brain, and retinal ganglion cell axons turned to follow this gradient. Changes in local tissue stiffness were largely governed by cell proliferation, as perturbation of mitosis diminished both the stiffness gradient and the caudal turn of axons found in control brains. Hence, we identified a close relationship between the dynamics of tissue mechanics and developmental processes, underpinning the importance of time-resolved stiffness measurements.


[Chronic juvenile arthritis with serum antinuclear antibodies. Study of 136 cases].
The charts of 136 patients presenting with juvenile chronic arthritis and antinuclear antibodies were reviewed. Mean age at onset was 3.6 yrs and 120 patients were females. Twenty-one patients presented with the polyarticular type of the disease from onset. Among them, 3 had polyarthritis with presence of rheumatoid factors. During the first year of follow-up, 40% of the pauciarticular forms became polyarticular. They may be subdivided into extended pauciarticular (5 to 9 arthritis = 26% of cases) or polyarticular (greater than 9 arthritis = 15% of cases) forms. The ocular involvement, present in 50 patients, preceded the articular manifestations in 5 cases (for a maximum of 4 years) whereas it followed in 30 cases (maximum delay of 14 years). Inflammatory articular involvement is not always correlated with the risk of ocular involvement. Long-term articular prognosis is generally fair. Only 15 children present with clearcut functional handicaps, of whom 4 are requiring the help of a third person.


An improved impression technique for implants.
A modified impression technique is proposed to simplify chairside procedures for the IMZ implant system. This technique saves time and reduces the need for a comprehensive stock of system components. It further facilitates the fabrication of suprastructures on convergently or divergently placed implants.


Prevalence and risk factors for liver biochemical abnormalities in Canadian patients with systemic lupus erythematosus.
To determine the prevalence of abnormal liver enzymes in patients with systemic lupus erythematosus (SLE) and whether further investigations were done, and the differences in SLE-related and/or metabolic factors in patients with and without liver biochemical abnormalities. Patients from the University of Toronto Lupus Clinic who met at least 4 of the American College of Rheumatology classification criteria for SLE and had 1.5 times the upper limit for aspartate transaminase or alanine transaminase on 2 consecutive visits within a 2-year period were matched with controls for age, sex, and SLE duration. Demographic, clinical, and laboratory data were extracted at the time of the first appearance of liver enzyme abnormality for the cases and at the reference point for the controls. From the 1533 patients reviewed, 134 (8.7%) met the inclusion criteria. Thirty of these patients were evaluated by a hepatologist, 75 had imaging studies (41 were done specifically for liver investigation), and 13 had liver biopsies. Results based on these investigations showed 31 fatty livers, 35 cases of drug-induced hepatotoxicity, 10 autoimmune etiologies, and 3 cases of viral hepatitis. Compared to controls, cases were higher in body mass index, anti-dsDNA antibody, prevalence of hypertension, antiphospholipid syndrome, and use of immunosuppressive medication, especially azathioprine and methotrexate; they were lower in IgM. Metabolic abnormalities such as obesity and hypertension and hepatotoxic effects of medication used to treat SLE may contribute more than SLE-related factors to liver biochemical abnormalities in patients with SLE.


Disintegration of solid foods in human stomach.
Knowledge of the disintegration of solid foods in human stomach is essential to assess the bioavailability of nutrients in the gastrointestinal (GI) tract. A comprehensive review of food gastric digestion, focusing on disintegration of solid foods, is presented. Most of the research reviewed in this paper is contained in the medical, pharmaceutical, food, and nutritional literature. Stomach physiology is briefly introduced, including composition and rheological properties of gastric contents, stomach wall motility in fed/fasted states, and hydrodynamic and mechanical forces that act on the ingested food. In vivo and in vitro methods used for studying food and drug digestion in GI are summarized. Stomach emptying rate, which controls the rate of absorption of nutrients, is highly related to the disintegration of foods. This topic is highlighted with focus on the important mechanisms and the influence of chemical and physical properties of foods. Future research in this area is identified to increase our fundamental understanding of the food digestion process in the stomach as related to the food composition, material properties such as texture and microstructure, and chemical characteristics. This information is necessary to develop new guidelines for seeking innovative processing methods to manufacture foods specifically targeted for health.


Achromatic correction of diffractive dispersion in white light SLM imaging.
In contemporary optics, the spatial light modulator (SLM) is effectively used as a flexible optoelectronic device playing the key role in a number of experiments of science and technology. Its operation is optimal when using almost monochromatic light but an extremely strong diffractive dispersion occurs when white light is applied. In this paper, the design concepts are proposed resulting in optimization and implementation of a refractive corrector cooperating with the SLM. The corrector maintains the operation of the SLM unchanged for the central wavelength of light and ensures an achromatic dispersion compensation throughout the visible region in applications based on a lens-pattern formation. A significant improvement of the imaging performance of the achromatic SLM was proved by the computer simulation and measurement of the chromatic focal shift and the image contrast of the resolution target.


Comparative genomic analysis of the R2R3 MYB secondary cell wall regulators of Arabidopsis, poplar, rice, maize, and switchgrass.
R2R3 MYB proteins constitute one of the largest plant transcription factor clades and regulate diverse plant-specific processes. Several R2R3 MYB proteins act as regulators of secondary cell wall (SCW) biosynthesis in Arabidopsis thaliana (At), a dicotyledenous plant. Relatively few studies have examined SCW R2R3 MYB function in grasses, which may have diverged from dicots in terms of SCW regulatory mechanisms, as they have in cell wall composition and patterning. Understanding cell wall regulation is especially important for improving lignocellulosic bioenergy crops, such as switchgrass. Here, we describe the results of applying phylogenic, OrthoMCL, and sequence identity analyses to classify the R2R3 MYB family proteins from the annotated proteomes of Arabidposis, poplar, rice, maize and the initial genome (v0.0) and translated transcriptome of switchgrass (Panicum virgatum). We find that the R2R3 MYB proteins of the five species fall into 48 subgroups, including three dicot-specific, six grass-specific, and two panicoid grass-expanded subgroups. We observe four classes of phylogenetic relationships within the subgroups of known SCW-regulating MYB proteins between Arabidopsis and rice, ranging from likely one-to-one orthology (for AtMYB26, AtMYB103, AtMYB69) to no homologs identifiable (for AtMYB75). Microarray data for putative switchgrass SCW MYBs indicate that many maintain similar expression patterns with the Arabidopsis SCW regulators. However, some of the switchgrass-expanded candidate SCW MYBs exhibit differences in gene expression patterns among paralogs, consistent with subfunctionalization. Furthermore, some switchgrass representatives of grass-expanded clades have gene expression patterns consistent with regulating SCW development. Our analysis suggests that no single comparative genomics tool is able to provide a complete picture of the R2R3 MYB protein family without leaving ambiguities, and establishing likely false-negative and -positive relationships, but that used together a relatively clear view emerges. Generally, we find that most R2R3 MYBs that regulate SCW in Arabidopsis are likely conserved in the grasses. This comparative analysis of the R2R3 MYB family will facilitate transfer of understanding of regulatory mechanisms among species and enable control of SCW biosynthesis in switchgrass toward improving its biomass quality.


Structure-Based Drug Design Strategies and Challenges.
Over the past ten years, the number of three-dimensional protein structures identified by advanced science and technology increases, and the gene information becomes more available than ever before as well. The development of computing science becomes another driving force which makes it possible to use computational methods effectively in various phases of the drug design and research. Now Structure-Based Drug Design (SBDD) tools are widely used to help researchers to predict the position of small molecules within a three-dimensional representation of the protein structure and estimate the affinity of ligands to target protein with considerable accuracy and efficiency. They also accelerate discovery speed of potent drug and reduce the cost and times for drug research. Here we present an overview of SBDD used in drug discovery and highlight its recent successes and major challenges to current SBDD methodologies.


Unexplained fatigue syndromes in a multinational primary care sample: specificity of definition and prevalence and distinctiveness from depression and generalized anxiety.
The authors investigated whether narrow definitions of unexplained fatigue syndromes that require additional minor somatic symptoms are more strongly associated with psychiatric morbidity than wider ones. This was a secondary analysis of the World Health Organization Collaborative Project on Psychological Problems in General Health Care. A total of 5,438 primary care patients from 14 countries were assessed with the Composite International Diagnostic Interview. The prevalence of fatigue syndromes fell from 7.99 to 1.69 as somatic criteria were added. Patients with depression or anxiety were more likely to report unexplained fatigue, but this association was stronger for definitions of unexplained fatigue with more somatic criteria. Definitions of unexplained fatigue syndromes that require more somatic criteria selected more patients with psychiatric disorders in this culturally diverse sample. These findings might have implications for the revision of existing international diagnostic criteria for neurasthenia or chronic fatigue syndrome.


Telephone Encounters Predict Future High Financial Expenditures in Inflammatory Bowel Disease Patients: A 3-Year Prospective Observational Study.
Telephone activity is essential in management of complex chronic diseases including inflammatory bowel disease (IBD). Telephone encounters logged in the electronic medical record have recently been proposed as a surrogate marker of disease activity and impending health care utilization; however, the association between telephone calls and financial expenditures has not been evaluated. We performed a 3-year prospective observational study of telephone encounters logged at a tertiary referral IBD center. We analyzed patient demographics, disease characteristics, comorbidities, clinical activity, and health care financial charges by telephone encounter frequency. Eight hundred one patients met inclusion criteria (52.3% female; mean age, 44.1 y), accounted for 12,669 telephone encounters, and accrued $70,513,449 in charges over 3 years. High telephone encounter frequency was associated with female gender (P=0.003), anxiety/depression (P<0.001), and prior IBD surgery (P<0.001). High telephone encounter categories had significantly more hospitalizations (P<0.001), IBD surgery (P<0.001), worse quality of life (P<0.001), more corticosteroid (P<0.001), biological (P<0.001), and opiate prescriptions (P<0.001). High telephone encounter frequency patients amassed higher total available charges in each year (P<0.001) and over the 3 years (P<0.001). Telephone encounters in 2009 (P=0.02) and 2010 (P<0.001) were significantly associated with financial charges the following year after controlling for demographic, utilization, and medication covariates. Increased telephone encounters are associated with significantly higher health care utilization and financial expenditures. Increased call frequency is predictive of future health care spending. Telephone encounters are a useful tool to identify patients at risk of clinical deterioration and large financial expense.


Clinical comparison of sub-mm high-resolution non-contrast coronary CMR angiography against coronary CT angiography in patients with low-intermediate risk of coronary artery disease: a single center trial.
The widespread clinical application of coronary cardiovascular magnetic resonance (CMR) angiography (CMRA) for the assessment of coronary artery disease (CAD) remains limited due to low scan efficiency leading to prolonged and unpredictable acquisition times; low spatial-resolution; and residual respiratory motion artefacts resulting in limited image quality. To overcome these limitations, we have integrated highly undersampled acquisitions with image-based navigators and non-rigid motion correction to enable high resolution (sub-1 mm3) free-breathing, contrast-free 3D whole-heart coronary CMRA with 100% respiratory scan efficiency in a clinically feasible and predictable acquisition time. To evaluate the diagnostic performance of this coronary CMRA framework against coronary computed tomography angiography (CTA) in patients with suspected CAD. Consecutive patients (n = 50) with suspected CAD were examined on a 1.5T CMR scanner. We compared the diagnostic accuracy of coronary CMRA against coronary CTA for detecting a ≥ 50% reduction in luminal diameter. The 50 recruited patients (55 ± 9 years, 33 male) completed coronary CMRA in 10.7 ± 1.4 min. Twelve (24%) had significant CAD on coronary CTA. Coronary CMRA obtained diagnostic image quality in 95% of all, 97% of proximal, 97% of middle and 90% of distal coronary segments. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy were: per patient (100%, 74%, 55%, 100% and 80%), per vessel (81%, 88%, 46%, 97% and 88%) and per segment (76%, 95%, 44%, 99% and 94%) respectively. The high diagnostic image quality and diagnostic performance of coronary CMRA compared against coronary CTA demonstrates the potential of coronary CMRA as a robust and safe non-invasive alternative for excluding significant disease in patients at low-intermediate risk of CAD.


The incidence and predictors of job burnout in first-year internal medicine residents: a five-institution study.
Job burnout is prevalent among U.S. internal medicine (IM) residents and may lead to depression, suboptimal patient care, and medical errors. This study sought to identify factors predicting new burnout to better identify at-risk residents. The authors administered surveys to first-year IM residents at five institutions twice between June 2008 and June 2009, linking individual pre- and postresponses. Surveys measured job burnout, sleepiness, personality traits, and other characteristics. Burnout was defined using the most commonly identified definition and another stricter definition. Of 263 eligible residents, 185 (70%) completed both surveys. Among 114 residents who began free of burnout and completed both surveys, 86 (75%) developed burnout, with no differences across institutions. They were significantly more likely to report a disorganized personality style (9 versus 0; 11% versus 0%; P = .019) and less likely to report receiving regular performance feedback (34 versus 13; 63% versus 87%; P = .057). Using a stricter definition, 50% (78/156) of residents developed burnout. They were less likely to plan to pursue subspecialty training (49 versus 63; 78% versus 93%; P = .016) or have a calm personality style (59 versus 70; 77% versus 90%; P = .029). There were no significant associations between burnout incidence and duty hours, clinical rotation, demographics, social supports, loan debt, or psychiatric history. This study identified a high burnout incidence. The associations observed between burnout incidence and personality style, lack of feedback, and career choice uncertainty may inform interventions to prevent burnout and associated hazards.


Self-reported involvement in road traffic crashes in Kenya: A cross-sectional survey of a nationally representative sample.
Road traffic crashes (RTCs) are a global public health burden whose resulting morbidity and mortality disproportionately impact low- and middle-income countries with stressed health systems. There is a paucity of published studies that evaluate the sociodemographic distribution of RTCs using nationally representative samples from the African region. To examine population-wide associations between sociodemographic factors and involvement in RTCs in Kenya. Data were obtained from the 2014 Kenyan Demographic Health Survey, representing all 47 counties in Kenya, from May to October of 2014. We estimated the prevalence of RTCs and utilized logistic regression for bivariate and multivariable analyses to determine the sociodemographic factors associated with RTCs. Study variables included age, place of residence, household wealth index, educational attainment, and history of alcohol consumption. We computed odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). A higher prevalence was reported among men (8.76%) versus women (3.22%). The risk factors among men included being 20-34 years of age, living in a rural area (OR 1.38, 95% CI 1.09, 1.74), drinking alcohol (OR 1.33, 95% CI 1.11, 1.59), and having not higher than a primary (OR 1.90, 95% CI 1.19, 3.03) or secondary (OR 1.68, 95% CI 1.04, 2.71) education. The strongest risk factors for women included the being aged 45-49 (OR 2.30, 95% CI 1.44, 3.67) and 20-24 years (OR 1.81, 95% 1.17, 2.79) as well as being in the fourth wealth quintile (OR 1.83, 95% CI 1.15, 2.91). Men and the most economically productive age groups were more likely to report being involved in RTCs. Strategies to reduce the occurrences of RTCs should prioritize the most vulnerable sociodemographic groups.


[Plastic surgery in patients with facial palsy].
In short-term irreversible paralysis caused by facial nerve problems the aim is to re-innervate the paralysed facial musculature. Whenever a paralysis remains untreated for longer than 12-18 months successful re-innervation is unlikely. In longer-term paralysis the symmetry of the face at rest can be restored by a static procedure, a skin resection or a fascial suspension for example. Restoration of movement in the paralysed side of the face is possible by means of a dynamic procedure. For many years the temporal muscle and the masseter muscle have been used to improve the position of the mouth and closure of the eye. Spontaneous laughter can again be made possible by using a muscle from elsewhere in the body (e.g. the gracilis or possibly pectoralis minor) and attaching it to the nerve supply of the opposite side of the face.


Coupled atmospheric chemistry, radiation, and dynamics of an exoplanet generate self-sustained oscillations.
Nonlinearity in photochemical systems is known to allow self-sustained oscillations, but they have received little attention in studies of planetary atmospheres. Here, we present a unique, self-oscillatory solution for ozone chemistry of an exoplanet from a numerical simulation using a fully coupled, three-dimensional (3D) atmospheric chemistry-radiation-dynamics model. Forced with nonvarying stellar insolation and emission flux of nitric oxide (NO), atmospheric ozone abundance oscillates by a factor of thirty over a multidecadal timescale. As such self-oscillations can only occur with biological nitrogen fixation contributing to NO emission, we propose that they are a unique class of biosignature. The resulting temporal variability in the atmospheric spectrum is potentially observable. Our results underscore the importance of revisiting the spectra of exoplanets over multidecadal timescales to characterizing the atmospheric chemistry of exoplanets and searching for exoplanet biosignatures. There are also profound implications for comparative planetology and the evolution of the atmospheres of terrestrial planets in the solar system and beyond. Fully coupled, 3D atmospheric chemistry-radiation-dynamics models can reveal new phenomena that may not exist in one-dimensional models, and hence, they are powerful tools for future planetary atmospheric research.


Secondary Metabolites, Ferulic Acid and p-Hydroxybenzoic Acid Induced Toxic Effects on Photosynthetic Process in Rumex acetosa L.
The elimination of broadleaf weeds from agricultural fields has become an urgent task in plant and environment protection. Allelopathic control is considered a potential approach because of its exclusive and ecological safety measures. Plant secondary metabolites also called allelochemicals are released from plant leaves, roots, stem, bark, flowers and play significant roles in soil rhizosphere signaling, chemical ecology, and plant defense. The present study was carried out to evaluate the impact of two allelochemicals; ferulic acid (FA) and p-hydroxybenzoic acid (pHBA) on photosynthetic characteristics; Fv/Fm: efficiency of photosystem II photochemistry in the dark-adapted state; ΦPSII: photosynthetic quantum yield; NPQ, non-photochemical quenching; qP, photochemical quenching, and photon energy dissipation (1-qP)/NPQ in Rumex acetosa following 6 days exposure. R. acetosa seedlings were grown in perlite culture, irrigated with Hoagland solution and treated with allelopathic compounds FA and pHBA and were evaluated against the photosynthetic attributes. Both compounds behaved as potent inhibitors of photosynthetic traits such as Fv/Fm, ΦPSII, qP, and NPQ in R. acetosa. Photon energy dissipation (1-qP)/NPQ increased significantly from days 3 to 6. Higher dissipation of absorbed energy indicates the inactivation state of reaction centers and their inability to effectively use the absorbed energy in photosynthesis. These results indicated the potential allelopathic application of FA and pHBA for control of broadleaf weed, Rumex acetosa.