The Influence of Caffeine Expectancies on Sport, Exercise, and Cognitive Performance.
Caffeine (CAF) is widely consumed across sport and exercise for its reputed ergogenic properties, including central nervous stimulation and enhanced muscular force development. However, expectancy and the related psychological permutations that are associated with oral CAF ingestion are generally not considered in most experimental designs and these could be important in understanding if/how CAF elicits an ergogenic effect. The present paper reviews 17 intervention studies across sport, exercise, and cognitive performance. All explore CAF expectancies, in conjunction with/without CAF pharmacology. Thirteen out of 17 studies indicated expectancy effects of varying magnitudes across a range of exercise tasks and cognitive skills inclusive off but not limited to; endurance capacity, weightlifting performance, simple reaction time and memory. Factors, such as motivation, belief, and habitual CAF consumption habits influenced the response. In many instances, these effects were comparable to CAF pharmacology. Given these findings and the lack of consistency in the experimental design, future research acknowledging factors, such as habitual CAF consumption habits, habituated expectations, and the importance of subjective post-hoc analysis will help to advance knowledge within this area.


Primary charge separation within the structurally symmetric tetrameric Chl2APAPBChl2B chlorophyll exciplex in photosystem I.
In Photosystem I (PS I), the role of the accessory chlorophyll (Chl) molecules, Chl2A and Chl2B (also termed A-1A and A-1B), which are directly adjacent to the special pair P700 and fork into the A- and B-branches of electron carriers, is incompletely understood. In this work, the Chl2A and Chl2B transient absorption ΔA0(λ) at a time delay of 100 fs was identified by ultrafast pump-probe spectroscopy in three pairs of PS I complexes from Synechocystis sp. PCC 6803 with residues PsaA-N600 or PsaB-N582 (which ligate Chl2B or Chl2A through a H2O molecule) substituted by Met, His, and Leu. The ΔA0(λ) spectra were quantified using principal component analysis, the main component of which was interpreted as a mutation-induced shift of the equilibrium between the excited state of primary donor P700⁎ and the primary charge-separated state P700+Chl2-. This equilibrium is shifted to the charge-separated state in wild-type PS I and to the excited P700 in the PS I complexes with the substituted ligands to the Chl2A and Chl2B monomers. The results can be rationalized within the framework of an adiabatic model in which the P700 is electronically coupled with the symmetrically arranged monomers Chl2A and Chl2B; such a structure can be considered a symmetric tetrameric exciplex Chl2APAPBChl2B, in which the excited state (Chl2APAPBChl2B)* is mixed with two charge-transfer states P700+Chl2A- and P700+Chl2B-. The electron redistribution between the two branches in favor of the A-branch apparently takes place in the picosecond time scale after reduction of the Chl2A and Chl2B monomers.


The three-layer concentric model of glioblastoma: cancer stem cells, microenvironmental regulation, and therapeutic implications.
Tumors arising in the central nervous system are thought to originate from a sub-population of cells named cancer stem cells (CSCs) or tumor initiating cells (TICs) that possess an immature phenotype, combined with self-renewal and chemotherapy resistance capacity. Moreover, in the last years, these cells have been identified in particular brain tumor niches fundamental for supporting their characteristics. In this paper, we report studies from many authors demonstrating that hypoxia or the so called "hypoxic niche" plays a crucial role in controlling CSC molecular and phenotypic profile. We recently investigated the relationship existing between Glioblastoma (GBM) stem cells and their niche, defining the theory of three-concentric layers model for GBM mass. According to this model, GBM stem cells reside preferentially within the hypoxic core of the tumour mass, while more differentiated cells are mainly localized along the peripheral and vascularized part of the tumour. This GBM model provides explanation of the effects mediated by the tumour microenvironment on the phenotypic and molecular regulation of GBM stem cells, describing their spatial distribution in the tumor bulk. Moreover, we discuss the possible clinical implications of the creation of this model for future GBM patient management and novel therapeutic strategies development.


Multiple conductance states of the light-activated channel of Limulus ventral photoreceptors. Alteration of conductance state during light.
The properties of light-dependent channels in Limulus ventral photoreceptors have been studied in cell-attached patches. Two sizes of single-channel events are seen during illumination. Previous work has characterized the large (40 pS) events; the goal of the current work was to characterize the small (15 pS) events and determine their relationship to the large events. The small events are activated by light rather than as a secondary result of the change in membrane voltage during light. The mean open time of the small events is 1.34 +/- 0.49 ms (mean +/- SD, n = 15), approximately 50% of that of the large events. The large and small events have the same reversal potential and a similar dependence of open-state probability on voltage. Evidence that these events are due to different conductance states of the same channel comes from analysis of relatively infrequent events showing a direct transition between the 15 and 40-pS levels. Furthermore, large and small events do not superpose, even at positive voltages when the probability of being open is very high, as would be predicted if the two-sized events were due to independent channels. Expression of the different conductance states is not random; during steady illumination there are alternating periods of several hundred milliseconds in which there are consecutive, sequential large events followed by periods in which there are consecutive, sequential small events. At early times during the response to a step of light, the large conductance state is preferentially expressed. At later times, there is an increase in the relative contribution of the low conductance state. These findings indicate that there is a process that changes the preferred conductance state of the channel. This alteration has functional importance in the process of light adaptation.


Molecular cloning and sequencing of the gene encoding the fimbrial subunit protein of Bacteroides gingivalis.
The gene encoding the fimbrial subunit protein of Bacteroides gingivalis 381, fimbrilin, has been cloned and sequenced. The gene was present as a single copy on the bacterial chromosome, and the codon usage in the gene conformed closely to that expected for an abundant protein. The predicted size of the mature protein was 35,924 daltons, and the secretory form may have had a 10-amino-acid, hydrophilic leader sequence similar to the leader sequences of the MePhe fimbriae family. The protein sequence had no marked similarity to known fimbrial sequences, and no homologous sequences could be found in other black-pigmented Bacteroides species, suggesting that fimbrillin represents a class of fimbrial subunit protein of limited distribution.


Comparison of Three Ultrasound Views for Internal Jugular Venous Cannulation in Patients Undergoing Cardiac Surgery: A Randomized Trial.
The quality of needle visualization during ultrasound-guided internal jugular vein (IJV) cannulation determines the ease of procedure, whereas posterior IJV wall puncture is the most common risk associated. The IJV can be imaged in different views, which offer certain advantages over each other. We compared three different ultrasound views for IJV cannulation short axis (SAX), long axis (LAX), and oblique axis (OAX) with respect to the quality of needle visualization, first pass success rate, and posterior IJV wall puncture. Two hundred ten patients undergoing elective cardiac surgery were analyzed in this prospective randomized clinical trial. Patients were randomly assigned to one of the three groups: SAX (n = 70), LAX (n = 70), and OAX (n = 70). The quality of needle visualization, first pass success rate, and incidence of posterior IJV wall puncture in each of the three ultrasound views were studied. The Chi-square test and ANOVA were used for the comparison of means and proportion between the groups. The quality of needle visualization was graded as good in 90% patients in OAX group, 81.4% patients in LAX group, and 14.2% patients in SAX group, respectively (P < 0.0001). OAX group had the highest first pass success rate (94.2%) followed by SAX (88.5%), and then, LAX (82.8%), but it was statistically insignificant among the groups (P = 0.105). The mean IJV access time was longer in LAX group when compared to OAX and SAX group (P < 0.0001).The incidence of IJV posterior wall puncture was 14.2% patients in SAX group and none in other groups (P = 0.0011). The results suggest that OAX view can be adopted as standard approach during ultrasound-guided IJV cannulation as it safe and reliable.


Cognitive-motor intervention in Alzheimer's disease: long-term results from the Maria Wolff trial.
Little is known about the long-term acceptance and effects of cognitive and motor stimulation interventions (CMSI) in Alzheimer's disease (AD). To evaluate a replicable CMSI program for mild cognitive impairment (MCI) and mild-to-moderate AD persons. Eighty-four non-institutionalized subjects with AD were randomized to receive either CMSI, administered by a single care provider, or standard support. Cognition, activities of daily living (ADL), mood, and study partner's subjective burden were assessed by blinded raters. Data on institutionalization, psychiatric medications, and demise were collected by the study physicians. Random effects model and survival analyses were conducted, after 2 and 3 years of study. Three-year assessments could be performed by the physician in 85% and by the blinded rater in 66% of subjects. Significant benefits were observed in basic ADL at the 2- and 3-year assessments, whereas instrumental ADL showed benefits only up to the second year of intervention (p < 0.05). Long-term cognitive-motor stimulation is well accepted and produces functional benefits in subjects with AD, with no extra subjective burden in the partner.


Pharmacogenomic panel testing provides insight and enhances medication management in people with HIV.
Our study aimed to assess the impact of pharmacogenomic panel testing in people with HIV (PWH). Prospective, observational intervention assessment. One hundred PWH were provided a comprehensive pharmacogenomic panel during routine care visits within the HIV specialty clinic of a large academic medical center. The panel determined the presence of specific genetic variants that could predict response or toxicity to commonly prescribed antiretroviral therapy (ART) and non-ART medications. An HIV specialty pharmacist reviewed the results with participants and the care team. The pharmacist (1) recommended clinically actionable interventions based on the participants' current drug therapy, (2) assessed for genetic explanations for prior medication failures, adverse effects, or intolerances, and (3) advised on potential future clinically actionable care interventions based on individual genetic phenotypes. Ninety-six participants (median age 53 years, 74% white, 84% men, 89% viral load <50 copies/ml) completed panel testing, yielding 682 clinically relevant pharmacogenomic results (133 major, 549 mild-moderate). Ninety participants (89 on ART) completed follow-up visits with 65 (72%) receiving clinical recommendations based on current medication profiles. Of the 105 clinical recommendations, 70% advised additional monitoring for efficacy or toxicity, and 10% advised alteration of drug therapy. Panel results offered explanation for prior ART inefficacy in one participant and ART intolerance in 29%. Genetic explanation for non-ART toxicity was seen in 21% of participants, with genetic contributors to inefficacy of non-ART therapy identified in 39% of participants. Preliminary data in a small cohort of PWH demonstrates benefit of routine pharmacogenomic panel testing.


Assessment of an Innovative Voluntary Substance Abuse Treatment Program Designed to Replace Compulsory Drug Detention Centers in Malaysia.
As part of an ongoing initiative by the Malaysian government to implement alternative approaches to involuntary detention of people who use drugs, the National Anti-Drug Agency has created new voluntary drug treatment programs known as Cure and Care (C&C) Centers that provide free access to addiction treatment services, including methadone maintenance therapy, integrated with social and health services. We evaluated early treatment outcomes and client satisfaction among patients accessing C&C treatment and ancillary services at Malaysia's second C&C Center located in Kota Bharu, Kelantan. In June-July 2012, a cross-sectional convenience survey of 96 C&C inpatients and outpatients who entered treatment >30 days previously was conducted to assess drug use, criminal justice experience, medical co-morbidities, motivation for seeking treatment, and attitudes towards the C&C. Drug use was compared for the 30-day-period before C&C entry and the 30-day-period before the interview. Self-reported drug use levels decreased significantly among both inpatient and outpatient clients after enrolling in C&C treatment. Higher levels of past drug use, lower levels of social support, and more severe mental health issues were reported by participants who were previously imprisoned. Self-reported satisfaction with C&C treatment services was high. Conclusions/Importance: Preliminary evidence of reduced drug use and high levels of client satisfaction among C&C clients provide support for Malaysia's ongoing transition from compulsory drug detention centers (CDDCs) to these voluntary drug treatment centers. If C&C centers are successful, Malaysia plans to gradually transition away from CDDCs entirely.


A string correction algorithm for cursive script recognition.
This paper deals with a method of estimating a correct string X from its noisy version Y produced by a cursive script recognition system. An accurate channel model that allows for splitting, merging, and substitution of symbols is introduced. The best estimate X is obtained by using a dynamic programming search which combines a known search strategy (stack decoding) with a trie structure representation of a dictionary. The computational complexity of the algorithm is derived and compared with that of a method based on the generalized Levenshtein metric. Experimental results with the algorithm on English text based on a dictionary of the 1027 most commonly occurring words are described.


Physiological and Neuromuscular Response to a Simulated Sprint-Distance Triathlon: Effect of Age Differences and Ability Level.
This study aimed to describe the acute impact of a simulated sprint-distance triathlon at physiological and neuromuscular levels and to determine whether age and athletic performance influenced the response in triathletes. Nineteen triathletes performed a sprint-distance triathlon under simulated conditions. Cardiovascular response was monitored during the race. Rate of perceived exertion along with muscular performance parameters (countermovement jump [CMJ], squat jump [SJ], and handgrip strength test [HS]) were tested at pre- and posttest and during every transition, while a 20-m sprint test (S20m) was performed before and after the race. Blood lactate was recorded postrace. A repeated measures analysis of variance showed that the neuromuscular response-in terms of CMJ, SJ, and HS-was unchanged (p ≥ 0.05), while S20m performance was impaired at posttest (p < 0.001). A linear regression analysis showed that ΔCMJ predicted the overall race time (R = 0.226; p = 0.046). In addition, 2 cluster analyses (k-means) were performed by grouping according to athletic performance and age. Between-group comparison showed no significant differences in the impact of the race at either the physiological or the neuromuscular level. The results showed that muscular performance parameters were not impaired throughout the race despite high levels of fatigue reported. However, despite maintaining initial levels of muscle force after the race, the fatigue-induced changes in S20m were significant, which could reinforce the need to train sprint ability in endurance athletes. Finally, despite the differences in ability level or in age, the acute physiological and neuromuscular responses to a simulated sprint-distance triathlon were similar.


Revealing humans' sensorimotor functions with electrical cortical stimulation.
Direct electrical stimulation (DES) of the human brain has been used by neurosurgeons for almost a century. Although this procedure serves only clinical purposes, it generates data that have a great scientific interest. Had DES not been employed, our comprehension of the organization of the sensorimotor systems involved in movement execution, language production, the emergence of action intentionality or the subjective feeling of movement awareness would have been greatly undermined. This does not mean, of course, that DES is a gold standard devoid of limitations and that other approaches are not of primary importance, including electrophysiology, modelling, neuroimaging or psychophysics in patients and healthy subjects. Rather, this indicates that the contribution of DES cannot be restricted, in humans, to the ubiquitous concepts of homunculus and somatotopy. DES is a fundamental tool in our attempt to understand the human brain because it represents a unique method for mapping sensorimotor pathways and interfering with the functioning of localized neural populations during the performance of well-defined behavioural tasks.


Pnictogen-Bonding Catalysis and Transport Combined: Polyether Transporters Made In Situ.
The combination of catalysis and transport across lipid bilayer membranes promises directional access to a solvent-free and structured nanospace that could accelerate, modulate, and, at best, enable new chemical reactions. To elaborate on these expectations, anion transport and catalysis with pnictogen and tetrel bonds are combined with polyether cascade cyclizations into bioinspired cation transporters. Characterized separately, synergistic anion and cation transporters of very high activity are identified. Combined for catalysis in membranes, cascade cyclizations are found to occur with a formal rate enhancement beyond one million compared to bulk solution and product formation is detected in situ as an increase in transport activity. With this operational system in place, intriguing perspectives open up to exploit all aspects of this unique nanospace for important chemical transformations.


Activity-dependent structural dynamics of insect sensory fibers.
This report analyses the role of neuronal activity in shaping the axonal arborizations of sensory neurons from individually identified filiform hairs on the prosternum of locusts (Locusta migratoria), and their connections with a pair of identified interneurons (A4I1). Afferents from lateral filiform hairs terminate in the ipsilateral neuropil and connect only with the ipsilateral interneuron in all instars. Afferents from ventral filiform hairs possesses ipsi- and contralateral branches and make monosynaptic connections with both interneurons in first instars. In later instars, the ipsilateral branch, and its synaptic connection to the ipsilateral interneuron, is gradually reduced until it is lost in the adult, whereas the contralateral branch, and its synaptic connection with the contralateral interneuron, is strengthened. Therefore, after an initial overgrowth of fibers and synapses, segregation of fibers occurs involving the loss of synaptic connections. This loss of branches and synapses was prevented by immobilizing a subpopulation of ventral and lateral filiform hairs, or each group independently, so that their normal activity was blocked. In such treated animals afferents from ventral filiform hairs retain their ipsi- and contralateral branches until adulthood. We therefore conclude that afferent activity plays an important role in shaping the final structure and connectivity of afferents, as neither the peripheral position of the receptors nor the hormonal environment was changed by these manipulations.


Impact of Anticoagulants in Reducing Mortality and Disability in Cardioembolic Stroke Patients.
Background and Objectives: Stroke is currently the second most common cause of death and disability-adjusted life years worldwide. Previous studies have determined that cardioembolic stroke is associated with higher mortality. Our aim is to compare the long-term outcome and mortality of atherothrombotic, cardioembolic stroke patients and patients taking direct oral anticoagulants (DOACs), and to demonstrate that adequate treatment with DOACs is associated with better results. Materials and Methods: In our retrospective study, we collected the data of ischemic stroke patients who were treated at P. Stradins Clinical University Hospital, Riga, Latvia, Stroke Unit, in the year 2017. In the present study, we analyzed this information to assess the patients' demographic and clinical data, vascular risk factors, functional and neurological evaluation results, and the use of anticoagulant therapy. Stroke survivors were followed-up via telephone at 30/90/180/365 days and 4 years after being discharged from the hospital. The Latvian version of the National Institutes of Health Stroke Scale (NIHSS-LV) was used to evaluate patients' neurological outcomes at discharge, and patients' functional outcomes were evaluated using the modified Rankin scale (mRS). The collected data of the patients were separated into three groups according to the stroke subtype and use of direct oral anticoagulants. Results: A total of 654 ischemic stroke patients were admitted to the hospital in the year 2017. Of all the strokes included in the study, 262 presented an atherothrombotic etiology and 392 presented a cardioembolic etiology. The median age of the patients in the study was 76 years (IQR: 67-83). The median age of patients in the atherothrombotic stroke group was 71 years (IQR = 64-79), in the cardioembolic stroke group it was 79 (IQR = 72-84), and in the DOAC group it was 75 years (IQR = 69-82), respectively. At the period of four years, of all the atherothrombotic stroke survivors 14 (10.5%) had a severe disability, and 64 (48.1%) did not survive. However, 12 (4.1%) of the cardioembolic stroke survivors were severely disabled and 37 (12.5%) had died. In the group of patients taking DOACs 6 (4.5%) had a severe disability and 17 (12.9%) did not survive. In all the patient groups, the leading cause of death was due to severe disability (22%), followed by recurrent cardioembolic events (8%). Conclusions: Previous studies until now have concluded that cardioembolic stroke is associated with higher mortality and an unfavorable functional outcome. In our study, the cardioembolic stroke group and the DOAC group had a statistically significant higher percentage of patients with congestive heart failure and older age, but their long-term mortality was lower and they achieved independence more often than the atherothrombotic stroke patients. The proper use of anticoagulants shows great improvement in long-term survival rate and functional outcome.


A natural vaccine candidate strain against cholera.
E1 Tor Vibrio cholerae (EVC) strains may be classified into two kinds-epidemigenic (EEVC) strains and non-epidemigenic (NEEVC) strains-based on a phage-biotyping system. A large number of EEVC strains have been screened for toxigenic and putative colonization attributes. One such naturally occurring strains (designated IEM101) has been found which is devoid of genes encoding cholera toxin (CT), accessory cholera enterotoxin (ACE), zonula occludens toxin (ZOT), but possesses RS1 sequences and toxin-coregulated pilus A gene (icpA) although icpA is poorly expressed. It expresses type B pili but does not possess type C pili. It is an E1 Tor Ogawa strain and does not cause fluid accumulation in rabbit ilcal loop tests. Active immunization of rabbits with strain IEM101 elicited good protection against challenge with virulent strains of V. cholerae O1. Oral administration caused no side effects in 15 human volunteers, colonized the gut for four to ten days and elicited good immune responses.


Phenotypic analysis of outer surface protein C (OspC) of Borrelia burgdorferi sensu lato by monoclonal antibodies: relationship to genospecies and OspA serotype.
Molecular analyses of the genes encoding OspC, a major immunodominant protein of Borrelia burgdorferi sensu lato, revealed a considerable degree of heterogeneity. In the present study, we investigated whether a similar heterogeneity of the OspC phenotype can be shown by analysis with monoclonal antibodies (MAbs). Thirteen OspC-specific MAbs (L22 MAbs) were produced by immunizing mice with either different combinations of whole-cell antigens or recombinantly expressed OspCs cloned from strains belonging to different Borrelia spp. Ten of them differed in their reactivities with various strains. Western blot (immunoblot) analyses of 38 B. burgdorferi sensu lato strains resulted in 13 different reactivity patterns. These 13 different patterns were observed among only six different OspA serotypes, indicating that OspC is more heterogeneous than OspA. Patterns 1 to 4 were present only in B. burgdorferi sensu stricto, patterns 5 to 7 were present only in Borrelia afzelii, and patterns 9 to 13 were present only in Borrelia garinii. Pattern 8 was observed among B. afzelii and B. garinii strains but not among B. burgdorferi sensu stricto strains. One L22 MAb (2B8) recognized a common OspC-specific epitope of all 38 B. burgdorferi sensu lato strains analyzed, and another one (22C11) recognized a common epitope of OspC from both B. afzelii and B. garinii and was not reactive with OspC from B. burgdorferi sensu stricto. Western blot and sequence analysis of truncated OspCs located the 22C11 epitope as well as a species-specific sequence motif between amino acids 20 and 35. Other broadly reactive L22 MAbs were 10D3, 1F8, and 7G5. Some L22 MAbs (1C3, 1C3, 12E5, 1B11, 1F10, and 6C8) bound to epitopes present only in a few strains. Relapsing fever borreliae (Borrelia hermsii, Borrelia turicatae, and Borrelia duttoni) were nonreactive, with the following exception: three L22 MAbs (2B8, 6C4, and 10C5) recognized an abundantly expressed 20-kDa-range protein of B. turicatae. Because OspC is an immunodominant protein during the early immune response in Lyme borreliosis and has been shown to be effective as a vaccine in an animal model, our findings have important implications for the development of diagnostic reagents as well as vaccine research.


Validation of a Satisfaction Scale with a Telemedicine COVID-19 Service: Satis-COVID.
Objectives: Despite being a widespread tool, telehealth was significantly incorporated during the COVID-19 pandemic period, but it still lacks analysis methodologies, greater digital security, and satisfaction assessment instruments that are still little explored and validated. The objective is to assess user satisfaction through the validation of a satisfaction scale with a telemedicine COVID-19 service (TeleCOVID). Methods: Cross-sectional study of a cohort of confirmed COVID-19 cases evaluated and monitored by the TeleCOVID team. To study the scale's measurement qualities, a factorial analysis was performed to test the validity of the construct. Correlation between items and the global scale was assessed using Spearman's correlation coefficient, and the instrument's internal consistency was assessed using Cronbach's alpha coefficient. Results: There were 1,181 respondents evaluating the care received from the TeleCOVID project. A total of 61.6% were female, and 62.4% aged between 30 and 59 years. The correlation coefficients indicated a good correlation between the items present in the instrument. The internal consistency of the global scale was high (Cronbach's alpha = 0.903) and the item-total correlations for the scale ranged from 0.563 to 0.820. The average overall user satisfaction was 4.58, based upon a 5-point Likert scale where 5 is the highest level of satisfaction. Conclusions: The results presented here show how much telehealth can contribute to improving access, resolutibility, and quality of care to the population in general in Public Health Care. In view of the results found, it can be said that the TeleCOVID team offered excellent care and fulfilled its proposed objectives. The scale fulfills its objective of evaluating the quality of teleservice, bringing good results in terms of validity and reliability, in addition to showing high levels of user satisfaction.


Mitosis domain generalization in histopathology images - The MIDOG challenge.
The density of mitotic figures (MF) within tumor tissue is known to be highly correlated with tumor proliferation and thus is an important marker in tumor grading. Recognition of MF by pathologists is subject to a strong inter-rater bias, limiting its prognostic value. State-of-the-art deep learning methods can support experts but have been observed to strongly deteriorate when applied in a different clinical environment. The variability caused by using different whole slide scanners has been identified as one decisive component in the underlying domain shift. The goal of the MICCAI MIDOG 2021 challenge was the creation of scanner-agnostic MF detection algorithms. The challenge used a training set of 200 cases, split across four scanning systems. As test set, an additional 100 cases split across four scanning systems, including two previously unseen scanners, were provided. In this paper, we evaluate and compare the approaches that were submitted to the challenge and identify methodological factors contributing to better performance. The winning algorithm yielded an F1 score of 0.748 (CI95: 0.704-0.781), exceeding the performance of six experts on the same task.


The Effect of Individual and Group Education Done by Nurses on Smoking Dependency and Smoking Cessation Motivation in Patients with Coronary Artery Disease.
This study was carried out to reveal the effect of individual and group education done by a nurse on smoking dependency and smoking cessation motivation in patients with coronary artery disease (CAD). The present randomized controlled trial study was conducted in Iran. A total of 255 patients were randomly divided into three groups: 1) individual education, 2) group education, and 3) control. Data were collected using the Fagerstrom Test of Nicotine Dependence (FTND) and Smoking Cessation Motivation Questionnaire (Q-MAT) one time before the intervention and two times after intervention (1st and 3rd months). The mean scores of motivation for smoking cessation and smoking dependency in patients in the individual and group education were significantly better than the control group after the intervention (1st and 3rd months) (P < 0.05). Although there was no significant difference in the mean scores of smoking cessation motivation and smoking dependency in patients in the individual education and group education groups after education, the status of the patients in the group education was slightly better. Education by nurses might have a significant impact on smoking cessation motivation and smoking dependency in patients with CAD. Further studies are recommended.


Use of a lactic acid plus lactoserum intimate liquid soap for external hygiene in the prevention of bacterial vaginosis recurrence after metronidazole oral treatment.
To determine the recurrence of bacterial vaginosis (BV) after the use of a lactic acid plus lactoserum liquid soap starting immediately after the treatment with oral metronidazole and the quality of life of the participants. A total of 123 women with diagnosis of BV with at least three of the following criteria: 1) homogeneous vaginal discharge without inflammation of the vagina or vulva; 2) vaginal pH ≥ 4.5; 3) positive Whiff test; and 4) "clue cells" in more than 20% of the epithelial cells in the vagina. A Nugent score ≥ 4 in the vaginal bacterioscopy was also used. After BV diagnosis, metronidazole 500 mg was administered orally bid during 7 days. Patients cured of BV were then instructed to use 7.5 to 10 mL of a lactic acid plus lactoserum liquid soap once-a-day for hygiene of the external genital region. Three subsequent control visits after starting the hygiene treatment (30, 60, and 90 days; ± 5 days) were scheduled. A questionnaire was applied in the form of visual analogue scale (VAS) in all the visits regarding: 1) level of comfort at the genital region; 2) malodorous external genitalia; 3) comfort in sexual intercourse; 4) satisfaction with intimate hygiene; and 5) self-esteem. Ninety two (74.8%) women initiated the use of a lactic acid plus lactoserum liquid soap at visit 1. At visit 2, 3, and 4 there were 84, 62 and 42 women available for evaluation, respectively. The rate of recurrence of BV was 19.0%, 24.2% and 7.1%, respectively in the three visits and vaginal candidiasis was observed in five treated women. Quality of life was evaluated in the 42 women who completed the four visits schedule and there were significant improvement in the five domains assessed. A lactic acid plus lactoserum liquid soap for external intimate hygiene may be an option for the prevention of BV recurrence after treatment and cure with oral metronidazole.


Prediction of fasted and fed bioequivalence for immediate release drug products using physiologically based biopharmaceutics modeling (PBBM).
Bioequivalence studies are an integral part of clinical pharmacology strategy for drug development. Physiologically based biopharmaceutics modeling (PBBM) can be a helpful tool to assess potential bioequivalence risks and predict the outcome of bioequivalence studies. In this study, GastroPlus™ was used for virtual bioequivalence (VBE) assessment of 6 case studies which includes four BCS 2, and one each of BCS 1 and 3 molecules. The purpose was to investigate if bioequivalence in fed state can be accurately predicted based on model developed on data from bioequivalence study in fasted state and known food effect from clinical studies. Our results show that we were able to successfully predict passing (5 cases) and failed (1 case) bioequivalence studies. Ultimately, if there is confidence in such models, a case can be made to waive fed bioequivalence study, on a case-by-case basis (e.g. for BCS class 1 and 2 molecules with known food effect mechanism, reliable estimate of human pharmacokinetic parameters, and available in vivo data in fasted state for model verification). This has the potential to reduce clinical burden in drug development, increase confidence in pivotal BE studies and support regulatory applications such as justify waiving of BE study for Scale-Up and Post Approval Changes (SUPAC). Hence VBE can significantly reduce time and cost of drug development, as well as minimize drug exposure to healthy volunteers.


Traditional beliefs as forgotten influencing factors on breast-feeding performance in Turkey.
The aim of this cross-sectional study was to identify the infant feeding practices and to evaluate the attitudes and beliefs of mothers on breast-feeding in Turkey. This study was established in 10 provinces of Turkey between December 2000 and March 2001 and the study group was comprised of 1,767 women between the ages of 15-49 years (mean 27.6 +/- 6.4 years). Questionnaires were self-filled by mothers in the waiting rooms of the health centers. One hundred seventy-three women (9.9%) were illiterate, 829 (47.7%) had < or =5 years of schooling, and 83.4% were housewives. A significant number of women have traditional beliefs related to breast-feeding practices. According to 23.4% of the women at least 3 calls to prayer (average 12 hours) should be waited before the first breast-feeding postpartum and more than 30% of the mothers believe that colostrum should not be given to the newborn, some mothers breast milk could harm their babies, and an evil eye could harm their breast milk. The traditional belief status and educational status of the women differed significantly between provinces, lower educational status and higher rates of women with traditional beliefs were observed in less developed eastern provinces. Overall, 60.6% of the women were knowledgeable on breast-feeding practices, whereas only 13.5% were scored as good in attitudes. Among all women with breast-feed babies, 35.8% started supplementary feeding in the first 3 months of life. Mother's age, education, occupation and traditional beliefs did not have a significant effect on supplementation time. As a result, these findings suggest the importance of taking into account the customs, local beliefs and family influences in planning community health programs.


Disturbances of postural sway components in cannabis users.
A prominent effect of acute cannabis use is impaired motor coordination and driving performance. However, few studies have evaluated balance in chronic cannabis users, even though density of the CB1 receptor, which mediates the psychoactive effects of cannabis, is extremely high in brain regions critically involved in this fundamental behavior. The present study measured postural sway in regular cannabis users and used rambling and trembling analysis to quantify the integrity of central and peripheral nervous system contributions to the sway signal. Postural sway was measured in 42 regular cannabis users (CB group) and 36 non-cannabis users (N-CB group) by asking participants to stand as still as possible on a force platform in the presence and absence of motor and sensory challenges. Center of pressure (COP) path length was measured, and the COP signal was decomposed into rambling and trembling components. Exploratory correlational analyses were conducted between sway variables, cannabis use history, and neurocognitive function. The CB group had significantly increased path length and increased trembling in the anterior-posterior (AP) direction. Exploratory correlational analyses suggested that AP rambling was significantly inversely associated with visuo-motor processing speed. Regular cannabis use is associated with increased postural sway, and this appears to be predominantly due to the trembling component, which is believed to reflect the peripheral nervous system's contribution to the sway signal.


Introduction of the YTE mutation into the non-immunogenic HIV bnAb PGT121 induces anti-drug antibodies in macaques.
Recombinant antibodies play increasingly important roles as immunotherapeutic treatments for human cancers as well as inflammatory and infectious diseases and have revolutionized their management. In addition, their therapeutic potential may be enhanced by the introduction of defined mutations in the crystallizable fragment (Fc) domains eg YTE (M252Y/S254T/T256E) and LS (M428L/N434S), as a consequence of increased half-lives and prolonged duration of protection. However, the functional properties of any biologic may be compromised by unanticipated immunogenicity in humans, rendering them ineffective. Several potent broadly neutralizing HIV monoclonal antibodies (bnAbs) have been identified that protect against SHIV challenge in macaque models and reduce HIV viremia in HIV-infected individuals. In the present study, the pharmacokinetics and immunogenicity of one or more 5mg/kg subcutaneous (SC) injections in naïve macaques of the HIV bnAb PGT121 and its PGT121-YTE mutant, both produced in plants, have been compared towards prolonging efficacy. Induction of anti-drug/anti-idiotypic antibodies (ADA, anti-id) has been monitored using both binding ELISAs and more functional inhibition of virus neutralization (ID50) assays. Timing of the anti-Id responses and their impact on pharmacokinetic profiles (clearance) and efficacy (protection) have also been assessed. The results indicate that ADA induction in naïve macaques may result both from injection of the previously non-immunogenic PGT121 into pre-primed animals and also by the introduction of the YTE mutation. Binding ADA antibody levels, induced in 7/10 macaques within two weeks of a first or second PGT121-YTE injection, were closely associated with both reduced pharmacokinetic profiles and loss of protection. However no correlation was observed with inhibitory ADA activity. These studies provide insights into both the structural features of bnAb and the immune status of the host which may contribute to the development of ADA in macaques and describe possible YTE-mediated changes in structure/orientation of HIV bnAbs that trigger such responses.


Al3+ selective colorimetric and fluorescent red shifting chemosensor: application in living cell imaging.
We report the development of a fluorescent probe based on the benzothiazole unit to monitor intracellular Al(3+) levels in living cells. The fluorescent probe exhibits a fluorescence response towards Al(3+) under physiological conditions with high sensitivity and selectivity and even facilitates naked-eye detection of Al(3+). The fluorescence intensity was significantly quenched with red shifting upon addition of 0.5 equiv. of Al(3+). The simple and cost effective receptor avails rapid detection of Al(3+) ions at concentrations as low as 0.42 μM and is expected to be effective for the design of efficient biological sensor.


Cell biology. TAPping into mRNA export.
There seem to be numerous pathways for exporting mRNAs from the nucleus to the cytoplasm. But working out which set of export adaptors and receptors transport individual mRNAs has been very difficult. In a Perspective, Moore and Rosbash discuss a new strategy using cell-penetrating peptide inhibitors for unraveling the routes of mRNA export in living cells (Gallouzi and Steitz).


Place-pitch and vowel-pitch comparisons in cochlear implant patients using the Melbourne-Nucleus cochlear implant.
Results of place-pitch and vowel-pitch comparisons are presented in 21 cochlear implant patients using the Melbourne-Nucleus cochlear implant. Vowel-pitch comparisons were also carried out in 10 normal hearing subjects. A technique for the place-pitch ranking test has been developed. A graphic representation of the results shows the well-ranked electrodes in sequential pitch-order, and reveals any indication of abnormal place-pitch perception. It aids the selection of correctly place-pitch ranked electrodes. The vowel-pitch comparisons showed that both normal hearing subjects and cochlear implant patients are able to rank vowels according to 'vowel-pitch'. In normal hearing subjects, three main types of vowel-pitch processing have been found. Results indicate that an information selection and reduction process occurs at higher levels along the auditory pathway. Cochlear implant patients test results showed the limited contribution of the first and the virtual lack of the second formant's contribution to pitch-ranking the voiced vowels. These results indicate that fundamental frequency converted to pulse rate may not be adequate at certain segments along the cochlear partition. Vowels are not perceived by cochlear implant patients according to their first or second formant frequency converted to place-pitch. There would seem to be a need for alternative speech processing strategies in the Melbourne-Nucleus implant.


Systematic review of patient-reported outcome measures in the surgical treatment of patients with esophageal cancer.
Esophageal cancer is currently the eighth most common cancer worldwide. Improvements in operative techniques and neoadjuvant therapies have led to improved outcomes. Resection of the esophagus carries a high risk of severe complications and has a negative impact on health-related quality of life (QOL). The aim of this study was to assess which patient-reported outcome measures (PROMs) are used to measure QOL after esophagectomy for cancer. A comprehensive search of original articles was conducted investigating QOL after surgery for esophageal carcinoma. Two authors independently selected relevant articles, conducted clinical appraisal, and extracted data (PJ and JS). Out of 5893 articles, 58 studies were included, consisting of 41 prospective and 17 retrospective cohort studies, including a total of 6964 patients. These studies included 11 different PROMs. The existing PROMs could be divided into generic, symptom-specific, and disease-specific questionnaires. The European Organisation for Research and Treatment of Cancer (EORTC) QOL Questionnaire Core 30 (QLQ C-30) along with the EORTC QLQ-OESophagus module OES18 was the most widely used; in 42 and 32 studies, respectively. The EORTC and the Functional Assessment of Cancer Therapy (FACT) questionnaires use an oncological module and an organ-specific module. One validation study was available, which compared the FACT and EORTC, showing moderate to poor correlation between the questionnaires. A great variety of PROMs are being used in the measurement of QOL after surgery for esophageal cancer. A questionnaire with a general module along with a disease-specific module for assessment of QOL of different treatment modalities seem to be the most desirable, such as the EORTC and the FACT with their specific modules (EORTC QLQ-OES18 and FACT-E). Both are developed in different treatment modalities, such as in surgical patients. With regard to reproducibility of current results, the EORTC is recommended.


Spring mass characteristics of the fastest men on Earth.
The spring mass model has widely been used to characterize the whole body during running and sprinting. However the spring mass characteristics of the world's fastest men are still unknown. Thus the aim of this study was to model these characteristics for currently the 3 fastest men on earth (Usain Bolt, Tyson Gay and Asafa Powell). This was done by using data collected during the 2009 World championships in Berlin and the modelling method of Morin et al. 21. Even though Bolt achieved the greatest velocity (12.3 m.s - 1) over the 60-80 m split compared to his competitors, his estimated vertical stiffness (355.8 kN.m - 1) and leg stiffness (21.0 kN.m - 1) were significantly lower than his competitors. This reduction in stiffness is a consequence of Bolt's longer contact time (0.091 s) [corrected] and lower step frequency (4.49 Hz).Thus Bolt is able to run at a greater velocity but with lower stiffness compared to his competitors.


Sertoli Cells Loaded with Doxorubicin in Lipid Micelles Reduced Tumor Burden and Dox-Induced Toxicity.
The toxic side effects of doxorubicin (Dox) limit its long-term use as a lung cancer chemotherapeutic. Additionally, drug delivery to the deep lung is challenging. To address these challenges, isolated rat Sertoli cells (SCs) were preloaded with Dox conjugated to lipid micelle nanoparticles (SC-DLMNs) and delivered to mouse lungs. These immunocompetent cells, when injected intravenously, travel to the lung, deliver the payload, and get cleared by the system quickly without causing any adverse reaction. We observed that SC-DLMNs effectively treated Lewis lung carcinoma 1-induced lung tumors in mice and the drug efficacy was comparable to SC-Dox treatment. Mice treated with SC-DLMNs also showed significantly less toxicity compared to those treated with SC-Dox. The encapsulation of Dox in lipid micelle nanoparticles reduced the toxicity of Dox and the SC-based delivery method ensured drug delivery to the deep lung without evoking any immune response. Taken together, these results provide a novel SC-based nanoparticle drug delivery method for improved therapeutic outcome of cardiotoxic antilung cancer drugs.


The development, retention and decay rates of strength and power in elite rugby union, rugby league and American football: a systematic review.
Strength and power are crucial components to excelling in all contact sports; and understanding how a player's strength and power levels fluctuate in response to various resistance training loads is of great interest, as it will inevitably dictate the loading parameters throughout a competitive season. This is a systematic review of training, maintenance and detraining studies, focusing on the development, retention and decay rates of strength and power measures in elite rugby union, rugby league and American football players. A literature search using MEDLINE, EBSCO Host, Google Scholar, IngentaConnect, Ovid LWW, ProQuest Central, ScienceDirect Journals, SPORTDiscus and Wiley InterScience was conducted. References were also identified from other review articles and relevant textbooks. From 300 articles, 27 met the inclusion criteria and were retained for further analysis. STUDY QUALITY: Study quality was assessed via a modified 20-point scale created to evaluate research conducted in athletic-based training environments. The mean ± standard deviation (SD) quality rating of the included studies was 16.2 ± 1.9; the rating system revealed that the quality of future studies can be improved by randomly allocating subjects to training groups, providing greater description and detail of the interventions, and including control groups where possible. Percent change, effect size (ES = [Post-Xmean - Pre-Xmean)/Pre-SD) calculations and SDs were used to assess the magnitude and spread of strength and power changes in the included studies. The studies were grouped according to (1) mean intensity relative volume (IRV = sets × repetitions × intensity; (2) weekly training frequency per muscle group; and (3) detraining duration. IRV is the product of the number of sets, repetitions and intensity performed during a training set and session. The effects of weekly training frequencies were assessed by normalizing the percent change values to represent the weekly changes in strength and power. During the IRV analysis, the percent change values were normalized to represent the percent change per training session. The long-term periodized training effects (12, 24 and 48 months) on strength and power were also investigated. Across the 27 studies (n = 1,015), 234 percent change and 230 ES calculations were performed. IRVs of 11-30 (i.e., 3-6 sets of 4-10 repetitions at 74-88% one-repetition maximum [1RM]) elicited strength and power increases of 0.42% and 0.07% per training session, respectively. The following weekly strength changes were observed for two, three and four training sessions per muscle region/week: 0.9%, 1.8 % and 1.3 %, respectively. Similarly, the weekly power changes for two, three and four training sessions per muscle group/week were 0.1%, 0.3% and 0.7 %, respectively. Mean decreases of 14.5% (ES = -0.64) and 0.4 (ES = -0.10) were observed in strength and power across mean detraining periods of 7.2 ± 5.8 and 7.6 ± 5.1 weeks, respectively. The long-term training studies found strength increases of 7.1 ± 1.0% (ES = 0.55), 8.5 ± 3.3% (ES = 0.81) and 12.5 ± 6.8% (ES = 1.39) over 12, 24 and 48 months, respectively; they also found power increases of 14.6% (ES = 1.30) and 12.2% (ES = 1.06) at 24 and 48 months. Based on current findings, training frequencies of two to four resistance training sessions per muscle group/week can be prescribed to develop upper and lower body strength and power. IRVs ranging from 11 to 30 (i.e., 3-6 sets of 4-10 repetitions of 70-88% 1RM) can be prescribed in a periodized manner to retain power and develop strength in the upper and lower body. Strength levels can be maintained for up to 3 weeks of detraining, but decay rates will increase thereafter (i.e. 5-16 weeks). The effect of explosive-ballistic training and detraining on pure power development and decay in elite rugby and American football players remain inconclusive. The long-term effects of periodized resistance training programmes on strength and power seem to follow the law of diminishing returns, as training exposure increases beyond 12-24 months, adaptation rates are reduced.


Mating system of Brazilian Oryza glumaepatula populations studied with microsatellite markers.
A knowledge of natural populations' breeding systems is important in order to implement in situ and ex situ management and conservation practices. Using microsatellite markers, three Oryza glumaepatula populations from Brazil were studied to determine the breeding system and genetic structure parameters of this species. Each population represented by ten families with ten individuals per family was studied using eight microsatellite primers. Families of the Rio Xingu population (XI) were obtained from the greenhouse, whereas families from Rio Solimoes (SO) and Rio Paraguay (PG) were collected from the wild. Amplified products electrophoresed on non-denaturing polyacrylamide gels were visualized with a silver staining procedure. The mating system parameters were analysed based on the mixed mating model (software MLTR) while genetic structure analyses of the three populations and their families were performed using the FSTAT software. The mean numbers of alleles per loci were 2.5, 3.9 and 2.5, respectively for the XI, PG and SO populations. Compared with their families, higher values for the observed heterozygosity and gene diversity were estimated for the parental populations. The subdivision (based on R(ST)) and inbreeding (F(IS)) in the SO and PG populations had similar effects, while inbreeding was the main effect in the families. Multilocus outcrossing rates varied from 0.011 to 0.223 in the three populations, indicating divergence in the outcrossing rates among O. glumaepatula populations. For the species (considering SO and PG populations together) an intermediate value was observed (tm = 0.116). Biparental inbreeding varied from 0.008 to 0.123, contributing to the selfing rate in these populations. More than 50 % of the outcrossing occurred between related individuals. The results indicated divergence in the mating system among O. glumaepatula populations, with consequences for conservation practices. The mating system of this species was classified as mixed with a predominance of self-fertilization.


Exogenous methyl jasmonate induces volatile emissions in cotton plants.
We investigated the effect of exogenous methyl jasmonate (MeJA) on the emission of herbivore-induced volatiles; these volatile chemicals can signal natural enemies of the herbivore to the damaged plant. Exogenous treatment of cotton cv. Deltapine 5415 plants with MeJA induced the emission of the same volatile compounds as observed for herbivore-damaged plants. Cotton plants treated with MeJA emitted elevated levels of the terpenes (E)-beta-ocimene, linalool, (3E)-4,8-dimethyl-1,3,7-nonatriene, (E,E)-alpha-farnesene, (E)-beta-farnesene, and (E,E)-4,8,12-trimethyl-1,3,7,11-tridecatetraene compared to untreated controls. Other induced components included (Z)-3-hexenyl acetate, methyl salicylate, and indole. Methyl jasmonate treatment did not cause the release of any of the stored terpenes such as alpha-pinene, beta-pinene, alpha-humulene, and (E)-beta-caryophyllene. In contrast, these compounds were emitted in relatively large amounts from cotton due to physical disruption of glands by the herbivores. The timing of volatile release from plants treated with MeJA or herbivores followed a diurnal pattern, with maximal volatile release during the middle of the photoperiod. Similar to herbivore-treated plants, MeJA treatment led to the systemic induction of (Z)-3-hexenyl acetate, (E)-beta-ocimene, linalool, (3E)-4,8-dimethyl-1,3,7-nonatriene, (E,E)-alpha-farnesene, (E)-beta-farnesene, and (E,E)-4,8,12-trimethyl-1,3,7,11-tridecatetraene. Our results indicate that treatment of cotton with MeJA can directly and systemically induce the emission of volatiles that may serve as odor cues in the host-search behavior of natural enemies.


Chloride channels in the apical membrane of cortical collecting duct cells.
Ion channels in the apical membrane of cortical collecting duct (CCD) cells in culture were studied by the patch-clamp technique. CCD cells from rabbit kidney were isolated by solid-phase immunoadsorption with a monoclonal antibody. The majority of CCD cells (93%) had phenotypic characteristics similar to intercalated cells (ICC). Although Cl- channels were present in the apical membrane of the ICC cells, they were rarely active in cell-attached patches; however, channels were activated after patch excision. In inside-out patches, the channels exhibited rapid flickering, substrates, and large unitary currents. The single-channel conductance was 303 pS, the Cl(-)-to-Na+ permeability ratio was 10:1 and the Cl(-)-to-HCO3- permeability ratio was 1.5:1. The channel was inhibited by the Cl- channel blockers 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, diphenylamine carboxylic acid, and 5-nitro-2-(3-phenylpropylamino)-benzoic acid. Although a reduction in the cytoplasmic Ca2+ concentration inhibited channel activity in both inside-out patches and cell-attached patches, alterations of Ca2+ within the physiological range did not change the channel open probability. Finally, changing the cytoplasmic pH (6.5 to 8.0) did not alter the open probability. Thus a large conductance anion channel is present in the apical membrane of CCD cells in culture. This channel may be involved in cell volume regulation or in Cl- and HCO3- secretion.


Nasal Staphylococcus aureus and Methicillin-Resistant S. aureus Carriage among Janitors Working in Hospitals in Northern Taiwan.
Staphylococcus aureus is an important cause of infection, and brings additional concern with methicillin resistance. In addition, nasal methicillin-resistant Staphylococcus aureus (MRSA) colonization rates among health care workers are higher than that for general population. To determine the prevalence rate and risk factors for the colonization of S. aureus, including MRSA, among janitors working in hospitals in northern Taiwan, we conducted this study. Between June and August, 2014, a total of 186 janitors, 111 working in hospitals and 75 working in non-medical institutions, were recruited. Specimens were obtained from the nares of the subjects for the detection of S. aureus, with a questionnaire completed for each subject. All the S. aureus isolates, including MRSA and methicillin-susceptible S. aureus (MSSA), were further molecularly characterized. The nasal carriage rate of S. aureus was 15.3% for hospital janitors and 13.3% for non-medical janitors. The carriage rate of MRSA was 3.6% for hospital janitors and 1.3% for non-medical janitors. No statistically significant difference was found in the nasal carriage rate of S. aureus (p = 0.707) and MRSA (p = 0.65) between hospital janitors and non-medical janitors. Hospital janitors working in hospital more than 6 years and cleaning microbiologic laboratories were significantly associated with nasal S. aureus colonization. All 5 MRSA isolates carried either staphylococcal cassette chromosome type IV or V and three of them belonged to sequence type (ST) 59, the community clone prevailing in Taiwan. Of the 22 MSSA isolates, six pulsotypes were identified, with one major type for 14 isolates (shared by five STs) and another type for 4 isolates (all belonged to ST 188). Exposure to the hospital environment may not increase the nasal carriage rate of S. aureus, including MRSA, among janitors in hospitals in Taiwan. However, for janitors in the hospital setting, working for more than six years in hospital and cleaning laboratories may be risks factors for carrying S. aureus.


Homology-independent discovery of replicating pathogenic circular RNAs by deep sequencing and a new computational algorithm.
A common challenge in pathogen discovery by deep sequencing approaches is to recognize viral or subviral pathogens in samples of diseased tissue that share no significant homology with a known pathogen. Here we report a homology-independent approach for discovering viroids, a distinct class of free circular RNA subviral pathogens that encode no protein and are known to infect plants only. Our approach involves analyzing the sequences of the total small RNAs of the infected plants obtained by deep sequencing with a unique computational algorithm, progressive filtering of overlapping small RNAs (PFOR). Viroid infection triggers production of viroid-derived overlapping siRNAs that cover the entire genome with high densities. PFOR retains viroid-specific siRNAs for genome assembly by progressively eliminating nonoverlapping small RNAs and those that overlap but cannot be assembled into a direct repeat RNA, which is synthesized from circular or multimeric repeated-sequence templates during viroid replication. We show that viroids from the two known families are readily identified and their full-length sequences assembled by PFOR from small RNAs sequenced from infected plants. PFOR analysis of a grapevine library further identified a viroid-like circular RNA 375 nt long that shared no significant sequence homology with known molecules and encoded active hammerhead ribozymes in RNAs of both plus and minus polarities, which presumably self-cleave to release monomer from multimeric replicative intermediates. A potential application of the homology-independent approach for viroid discovery in plant and animal species where RNA replication triggers the biogenesis of siRNAs is discussed.


Bottom-Up Interventions Effective in Promoting Work Engagement: A Systematic Review and Meta-Analysis.
Background: Promoting work engagement is of interest to organizations across sectors due to the associated positive outcomes. This interest warrants research on the evidence of work engagement interventions. Intervention research increasingly advocates a bottom-up approach, highlighting the role of employees themselves. These workplace interventions often encourage employees to identify, develop, and make use of workplace resources. The aim of this systematic review and meta-analysis is to investigate the effectiveness and potential underlying mechanisms of these bottom-up, resource-developing interventions. Method: Systematic searches were conducted in the online databases Web of Science, Academic Search Complete, Business Source Ultimate, PsycInfo, PsycArticles, SCOPUS, and Google Scholar. Publication year range was 2000-2020. Eligibility criteria were defined using PICOS. To be eligible for the systematic review, the intervention study identified had to aim at promoting working individuals' work engagement by developing workplace resources from bottom-up. Work engagement had to be measured using the Utrecht Work Engagement Scale. The systematic review included one-, two-, or multiple-armed - randomized or non-randomized - intervention studies with various study designs. Further, a meta-analysis was conducted on a sub-set of the studies included in the systematic review. To be eligible for the meta-analysis, the studies had to be two- or multiple-armed and provide the information necessary to compute effect sizes. Results: Thirty-one studies were included in the systematic review. The majority reported that overall work engagement increased as an effect of the intervention. The evidence regarding the sub-components of work engagement was scattered. Potential underlying mechanisms explored were intervention foci, approach, and format. Dimensions of satisfaction and performance were identified as secondary outcomes. Participant experiences were generally described as positive in most of the studies applying mixed methods. The meta-analysis showed a small but promising intervention effect on work engagement (24 studies, SMD: -0.22, 95% CI: -0.34 to -0.11, with I 2=53%, indicating moderate inconsistency in the evidence). Conclusion: The synthesized evidence suggests that bottom-up, resource-developing interventions are effective in the promotion of work engagement. The meta-analysis suggests that focusing on strengths use or mobilizing ego resources and adopting a universal approach increase intervention effectiveness.


Non-suicidal Self-Injury Among Adolescents From Diverse Ethnocultural Groups in Israel: The Association With Sleep Problems and Internet Addiction.
Although Non-suicidal Self-Injury (NSSI) has received more attention in recent years, most of these studies focused on samples from North American and European countries; consequently, little is known about its patterns and frequency in other cultures as well as its relation to sleep problems and internet addiction. As one of the few studies that aim to fill this gap, the current study examined the prevalence, characteristics, and types of NSSI behaviors among adolescents from diverse ethnocultural groups. A sample of 642 adolescents, aged 12-18 years, were randomly recruited from different middle and high schools in Israel, employing a snowball sampling technique. The sample included the following: 50% Jews and 34.7% Muslims born in Israel, 9.7% immigrants from the former Soviet Union (FSU), and 4.4% immigrants from Ethiopia. The participants completed self-report questionnaires that assessed their NSSI, sleep problems, internet addictions, and depressive symptoms. Almost one-third of the sample had engaged in NSSI, while 6% frequently injured themselves. More than half of the FSU immigrants and one-third of the Muslim participants indicated that they engaged in NSSI. These two population groups also exhibited severe depressive symptoms, sleep problems, and internet addictions. The most parsimonious correlations with NSSI included being male, an immigrant/Muslim minority who exhibited severe depressive symptoms and internet addictions. These results emphasize the need for routine NSSI assessments to prevent long-term sequelae, including any forms of suicidal thoughts and behaviors and adult borderline personality disorder (BPD). Primary preventive programs that include adaptive coping skills may eliminate the social contagion effect of NSSI.


Promoted megakaryocytic differentiation of K562 cells through oxidative stress caused by near ultraviolet irradiation.
Reactive oxygen species (ROS) have been proven to be important activators for various cellular activities, including cell differentiation. Several reports showed the necessity of ROS during cell differentiation of the megakaryocytic (MK) lineage. In this study, we employed near ultraviolet (near-UV) irradiation to generate endogenous oxidative stress in an MK differentiation process of K562 cells with phorbol 12-myristate 13-acetate (PMA) induction. A significant increase in the intracellular ROS level was detected on day 1 after near-UV irradiation. In the initial stage of differentiation, a shifted fraction of G1 and G2 phase cells was obtained using near-UV irradiation, giving an increased percentage of G2 phase cells (up from 31.1 to 68.7%). The near-UV irradiation-induced upregulation of the p21 gene, which is a cell cycle inhibitor, suggested that the G2 phase cells were prevented from undergoing cell division. It was found that the percentage of high ploidy (8N and 16N) cells was enhanced significantly at the later stage of the K562 cell culture with near-UV irradiation. Moreover, time-lapse analysis showed that near-UV irradiation encouraged the expression of CD41, a specific surface marker of megakaryocytes. This is the first report that the elevated oxidative stress through the near-UV irradiation promoted the MK differentiation of PMA-induced K562 cells.


Drug-coated balloons for the treatment of symptomatic intracranial atherosclerosis: initial experience and follow-up outcome.
The optimal treatment for patients with symptomatic severe intracranial atherosclerotic disease is not well established. Angioplasty and stenting have been attempted, with controversial results, mainly attributed to perioperative complications and a high incidence of restenosis or in-stent restenosis. Drug-coated balloons (DCBs) have shown encouraging results for coronary and peripheral artery disease, without convincing data for intracranial vasculature. To assess the feasibility, clinical and angiographic outcomes of DCBs for patients with intracranial de novo atherosclerotic disease. Between September 2016 and September 2017, details of 30 patients with 31 arteries treated with DCBs for symptomatic severe intracranial atherosclerotic disease (≥70% stenosis or chronic total occlusion) were retrospectively collected in our centre. All lesions were predilated with conventional balloons. Periprocedural complications and clinical and vascular imaging follow-up outcomes were analysed. All arteries were successfully dilated with DCBs and 29 (93.5%) arteries achieved good antegrade perfusion, with remedial stenting for two arteries. Two patients presented with new ischemic stroke after the procedure. Over a mean follow-up of 9.8±2.6 months, no patient had recurrent ischemic symptoms. Repeat vascular imaging was performed at 7.0±1.1 months, with cerebral angiography in 24 patients (25 arteries) and MR angiography in six patients (six arteries). Only one (3.2%) artery presented with angiographic asymptomatic restenosis. This study suggests that DCB dilatation may be a safe and effective alternative for intracranial de novo atherosclerotic disease.


A qualitative analysis of the coping reservoir model of pre-clinical medical student well-being: human connection as making it 'worth it'.
By all indications, well-being among physicians is poor, which manifests in various outcomes, including burnout, depression/anxiety, low life satisfaction, alcohol/substance misuse, suicide ideation, and suicide. Despite the vast literature on physician burnout, there is relatively little research on how pre-clinical experiences in medical school may be an antecedent to subsequent poor health among physicians. Here we focus on two neglected areas within the literature by focusing on the pre-clinical stage of medical school and the positive, as opposed to exclusively the negative, aspects of the medical school experience as it affects well-being. This study utilizes the metaphor of the Coping Reservoir Model as a theoretical and analytical framework for understanding medical student well-being by identify the 'depleting' and 'replenishing' inputs that are deposited into students' coping reservoirs. We analyze 105 medical students' reflective writings using a data analytic process consistent with an interpretive description approach, engaging in a hierarchical 3-step coding process to identify the main replenishing inputs deposited into students' coping reservoirs. The main depleting inputs that we identify are consistent with those identified by The Coping Reservoir Model. In addressing our main research question regarding the replenishing inputs, results show the main positive factors are psycho-social resources, intellectual stimulation, and social support/relationships. Most importantly, relationships with patients shape all three of these positive factors and provide the main source of hope that the stress of medical school will get better. What allows students to frame their experiences with hope and optimism are the connections they form with each other and with patients. The prolonged stress of medical school is made "worth it" in hopes that it will "get better" with more meaningful patient interaction in the future. These results that emphasize the positive aspects of medical school are discussed in context of their theoretical contributions to The Coping Reservoir Model and the practical implications for medical education to improve medical student well-being by facilitating human connection.


Regulation of CD14 expression during monocytic differentiation induced with 1 alpha,25-dihydroxyvitamin D3.
CD14, a monocyte/macrophage receptor for the complex of LPS and LPS binding protein, is a differentiation marker for the monocyte/macrophage lineage. We have analyzed the regulation of CD14 expression during 1 alpha,25-dihydroxyvitamin D3 (VitD3)-induced monocytic differentiation. Using FACS, Northern blotting, and nuclear run-on analyses, we demonstrate that the up-regulation of CD14 expression during monocytic cell maturation is regulated mainly at the level of gene transcription, and that new protein synthesis is required for CD14 induction. We have recently cloned the CD14 5' upstream sequence and demonstrated its tissue-specific promoter activity. Using stable transfection of the monocytoid U937 cell line with a series of deletion mutants of the CD14 5' upstream sequence coupled to a reporter gene construct, we show that bp -128 to -70 is the critical region for the induction of CD14 expression. This region contains two binding sites for the Sp1 transcription factor. A 3-bp mutation at the distal Sp1-binding site not only eliminates Sp1 interaction, but also abolishes most of the VitD3 induction of CD14 expression. Electrophoretic mobility shift analysis does not detect a direct interaction of the CD14 distal Sp1-binding site with the vitamin D3 receptor and its partner, the retinoid X receptor. These data demonstrate that VitD3 induces CD14 indirectly through some intermediary factor, and suggest a critical role for Sp1 in this process.


Passive CAP-VAC: a simple and safe technique to clean the posterior capsule.
To describe a new and less risky technique for the cleaning of posterior capsule during phacoemulsification called passive cap vac. Passive cap vac consisted in the removal of residual posterior capsule opacities using a disconnected 0.3 mm aspiration cannula. The hole of the aspiration cannula was faced toward posterior capsule and gently rubbed against it to achieve a complete cleaning of posterior capsule. The video of the technique is available online. With this new technique, the aspiration was ruled by the gravity and by the height of the balanced saline solution (BSS), in addition the Venturi's effect and the absence of active aspiration beyond the cannula avoided an excessive aspiration of posterior capsule. Passive cap vac allowed to clean posterior capsule using softer forces than traditional way, minimizing the risk of capsular tear.


Prognostic factors in metastatic breast cancer.
Modern polychemotherapy has decisively changed the spontaneous course and median survival in metastatic stages of breast cancer. The prognosis for patients with the rather unfavorable type of visceral metastatic spread is definitely better now than 10 years ago. The influence of modern polychemotherapy on the survival and course of cases with mainly osseous metastases, however, is more limited. It seems that, in contrast to hormonal therapy, modern polychemotherapy alters the course of more aggressive types of metastases with a poor prognosis into a more favorable form of disease.


Leukemia stem cells and new strategies to overcome resistance to therapy.
Acute leukemias are the result of aberrant hematopoietic processes initiated by rare leukemia stem cells that have maintained or acquired the capacity of indefinite proliferation through accumulated mutations and/or epigenetic changes. The most likely view of hematopoietic cell lineage organization is that of complex reactive or adaptative systems. The properties of leukemia stem cells indicate that current chemotherapy will not be effective. Furthermore, recent advances indicate that stem cell microenvironment directly affects cell fate decisions. Because they are quiescent, leukemia stem cells do not respond to cell cycle-specific cytotoxic agents used in treating leukemia, which contribute to treatment failure. New strategies are required that specifically target the malignant stem cell population.


Feasibility study: Proposed alternative to N95 respirator during the personal protective equipment shortage from COVID-19 pandemic.
Having an adequate supply of personal protective equipment during the COVID-19 pandemic has been a constant challenge for hospitals across the United States. In the event of shortages, our assembled mask might offer noninferior protection compared to an N95 respirator. To study the ability of an assembled mask to pass a quantitative fit testing. We conducted a feasibility study at the Oklahoma City Veteran Affairs Health Care System. Volunteers were fitted with an assembled mask made of either a Hans Rudolph half-face mask or a Respironics Performax full-face mask, attached to an Iso-Gard HEPA light Filter 28022 through a Performax SE elbow hinge. Quantitative fit testing was conducted using the Occupation Safety and Health Administration fit testing protocol. The primary outcome was the percentage of participants who pass the quantitative fit test. Secondary outcomes included the overall fit factor (FF), average FF for different exercises, changes in pulse oximetry and end-tidal CO2 at 0 and 15 minutes, willingness to use the mask, and visibility assessment. Twenty participants completed the study, and all (100 percent) passed the quantitative fit testing. The overall FF had a geometric mean of 2,317 (range: 208-16,613) and a geometric standard deviation of 3.8. The lowest FF was recorded while the subjects were talking. Between time 0 and 15 minutes, there was no clinically significant change in pulse oximetry and end-tidal CO2 levels. Most participants reported "very good" visibility and were "highly likely" to use the Hans Rudolph half-face mask in the case of shortage. Our assembled respirator offers noninferior protection to N95 respirators in the setting of hypothetical protective equipment shortage.


Control of renal handling of potassium loads in ducks with active salt glands.
Domestic ducks adapted to saline of 400 mosmol/kgH2O as their only water supply received intravenous loads of 100 mM KCl for 2 h while being intravenously infused with 200 mM NaCl at 1.0 ml/min to produce simultaneous salt gland secretion and diuresis-natriuresis. K+ loading did not alter the plasma levels of the osmoregulatory hormones arginine vasotocin, angiotensin II, aldosterone, and atrial natriuretic factor but promptly evoked kaliuresis because of a rise from 17 to 155 mM in urinary K+, with a proportional decrease in urinary Na+. Continuous infusion of amiloride (0.04 mg.min.-1.kg body wt-1 iv) further enhanced diuresis and natriuresis and lowered urinary K+, but the kaliuretic response to K+ loading was only moderately reduced because of enhanced diuresis and a rise in urinary K+ from 3 to 33 mM, with a slight decrease in urinary Na+. Changes in plasma hormone levels reflected dehydration due to excessive diuresis but were not related to kaliuresis. Salt gland secretion was not affected directly by amiloride but was secondarily reduced by the induced dehydration. In amiloride-treated ducks, hyperkalemia in response to K+ loading was exaggerated relative to the modest reduction in K+ excretion and may be attributed to moderate metabolic acidosis and/or general effects of amiloride on K+ metabolism. It is concluded that none of the established osmoregulatory hormones is involved in short-term control of renal K+ handling in ducks and that distal tubular K+ excretion involving amiloride-sensitive Na+ channels is quantitatively unimportant in this avian species.


Bacterial quorum sensing molecule N-3-oxo-dodecanoyl-L-homoserine lactone causes direct cytotoxicity and reduced cell motility in human pancreatic carcinoma cells.
In spite of chemotherapeutic and surgical advances, pancreatic cancer continues to have a dismal prognosis. Metastasis due to tumor cell migration remains the most critical challenge in treating pancreatic cancer, and conventional chemotherapy is rarely curative. In the quest for more novel molecules to fight this disease, we tested the hypothesis that the Pseudomonas aeruginosa quorum sensing signal molecule N-3-oxo-dodecanoyl-L-homoserine lactone (O-DDHSL) would be cytotoxic to and reduce mobility of pancreatic carcinoma cells (Panc-1 and Aspc-1). Results showed a decrease in cell viability from apoptosis, diminished colony formation, and inhibition of migration of the evaluated pancreatic carcinoma cell lines. Also, cell viability decreased in the presence of O-DDHSL when cells were grown in matrigel basement membrane matrix. While messenger RNA for IQGAP-1 decreased in Panc-1 and HPDE cells upon exposure to O-DDHSL, no change was observed in Aspc-1 cells. Cofilin mRNA expression was found to be increased in both HPDE and Panc-1 cells with marginal decrease in Aspc-1 cells. RhoC, a Rho-family GTPase involved in cell motility, increased in the presence of O-DDHSL, suggesting a possible compensatory response to alteration in other migration associated genes. Our results indicate that O-DDHSL could be an effective biomolecule in eukaryotic systems with multimodal function for essential molecular targeting in pancreatic cancer.


The role of the precuneus in metaphor comprehension: evidence from an fMRI study in people with schizophrenia and healthy participants.
Comprehension of conventional and novel metaphors involves traditional language-related cortical regions as well as non-language related regions. While semantic processing is crucial for understanding metaphors, it is not sufficient. Recently the precuneus has been identified as a region that mediates complex and highly integrated tasks, including retrieval of episodic memory and mental imagery. Although the understanding of non-literal language is relatively easy for healthy individuals, people with schizophrenia exhibit deficits in this domain. The present study aims to examine whether people with schizophrenia differentially recruit the precuneus, extending to the superior parietal (SP) cortex (SPL), to support their deficit in metaphor comprehension. We also examine interregional associations between the precuneus/SPL and language-related brain regions. Twelve people with schizophrenia and twelve healthy controls were scanned while silently reading literal word pairs, conventional metaphors, and novel metaphors. People with schizophrenia showed reduced comprehension of both conventional and novel metaphors. Analysis of functional connectivity found that the correlations between activation in the left precuneus/SPL and activation in the left posterior superior temporal sulcus (PSTS) were significant for both literal word pairs and novel metaphors, and significant correlations were found between activation in the right precuneus/SPL and activation in the right PSTS for the three types of semantic relations. These results were found in the schizophrenia group alone. Furthermore, relative to controls, people with schizophrenia demonstrated increased activation in the right precuneus/SPL. Our results may suggest that individuals with schizophrenia use mental imagery to support comprehension of both literal and metaphoric language. In particular, our findings indicate over-integration of language and non-language brain regions during more effortful processes of novel metaphor comprehension.


Alcohol use amongst learners in rural high school in South Africa.
Drinking behaviour by adolescents is a significant public health challenge nationally and internationally. Alcohol use has serious challenges that continue to deprive adolescents of their normal child growth and development. Drinking is associated with dangers that include fighting, crime, unintentional accidents, unprotected sex, violence and others. The aim of the study is to investigate drinking patterns, and factors contributing to drinking, amongst secondary school learners in South Africa. The sample included 177 male (46.6%) and 206 female (53.4%) respondents in the age range from 15–23 years, selected by stratified random sampling. The results indicated that 35.5% of male and 29.7% of female respondents used alcohol. Both male and female respondents consumed six or more alcohol units (binge drinking) within 30 days; on one occasion the consumption was 17.5% and 15.9% respectively. It was found that alcohol consumption increases with age, 32.2% of 15–17 year-olds and 53.2% of 18–20 year-olds consumed different types of alcohol. It was deduced that 28.9% respondents reported that one of the adults at home drank alcohol regularly, and 9.3% reported that both their parents drank alcohol daily. It was found that 27.6% of the respondents agreed that friends made them conform to drinking. The tenth and eleventh grade reported 15.2% of male and 13.9% of female respondents were aware that alcohol can be addictive. This study found that age, gender, parental alcohol use and peer pressure were found to be the major contributing factors to alcohol use amongst learners Prevention campaigns such as introducing the harmful effects of alcohol use amongst learners are of utmost importance in reducing alcohol use amongst learners in South Africa.


Cardiovascular health--behaviour of medical students in Karachi.
To assess the health behaviour and perceptions of medical students towards cardiovascular disease. This descriptive cross-sectional survey was conducted on 203 Pakistani medical students enrolled in a private medical college in Karachi, Pakistan using systematic random sampling. It was based on a self-administered questionnaire. Eight percent smoked, 9% were overweight, 33% had a family history of coronary artery disease, 32% regulated dietary fat intake, 28% exercised regularly, 62.1% knew personal blood pressure and 5.4% personal cholesterol levels. Regarding developing cardiovascular disease in the future, 62% showed concern but only 54% of these adopted preventive practices. About 46% believed medical college life had a harmful effect on their health. Gender, family history and personal health status perception were behavior modifying influences (p<0.05). Reasons reported for their behavior were: no need of prevention at their age (38.3%) and never thinking about these issues (37.0%). The study shows a high prevalence of coronary artery disease family history, inappropriate dietary intake, physical inactivity; poor screening practices and lack of awareness. The results underscore the urgent need to promote preventive knowledge and practices among medical students, if they are to become prevention oriented physicians and counsel patients on preventive strategies to counter the rapidly increasing burden of cardiovascular diseases effectively.


Politics on the brain: an FMRI investigation.
We assessed political attitudes using the Implicit Association Test (IAT) in which participants were presented faces and names of well-known Democrat and Republican politicians along with positive and negative words while undergoing functional MRI. We found a significant behavioral IAT effect for the face, but not the name, condition. The fMRI face condition results indicated that ventromedial and anterior prefrontal cortices were activated during political attitude inducement. Amygdala and fusiform gyrus were activated during perceptual processing of familiar faces. Amygdala activation also was associated with measures of strength of emotion. Frontopolar activation was positively correlated with an implicit measure of bias and valence strength (how strongly the participants felt about the politicians), while strength of affiliation with political party was negatively correlated with lateral PFC, lending support to the idea that two distinct but interacting networks-one emphasizing rapid, stereotypic, and emotional associative knowledge and the other emphasizing more deliberative and factual knowledge-cooperate in the processing of politicians. Our findings of ventromedial PFC activation suggests that when processing the associative knowledge concerned with politicians, stereotypic knowledge is activated, but in addition, the anterior prefrontal activations indicate that more elaborative, reflective knowledge about the politician is activated.


On the role of flavonoids in the integrated mechanisms of response of Ligustrum vulgare and Phillyrea latifolia to high solar radiation.
The role of flavonoids in mechanisms of acclimation to high solar radiation was analysed in Ligustrum vulgare and Phillyrea latifolia, two Mediterranean shrubs that have the same flavonoid composition but differ strikingly in their leaf morpho-anatomical traits. In plants exposed to 12 or 100% solar radiation, measurements were made for surface morphology and leaf anatomy; optical properties, photosynthetic pigments, and photosystem II efficiency; antioxidant enzymes, lipid peroxidation and phenylalanine ammonia lyase; synthesis of hydroxycinnamates and flavonoids; and the tissue-specific distribution of flavonoid aglycones and ortho-dihydroxylated B-ring flavonoid glycosides. A denser indumentum of glandular trichomes, coupled with both a thicker cuticle and a larger amount of cuticular flavonoids, allowed P. latifolia to prevent highly damaging solar wavelengths from reaching sensitive targets to a greater degree than L. vulgare. Antioxidant enzymes in P. latifolia were also more effective in countering light-induced oxidative load than those in L. vulgare. Consistently, light-induced accumulation of flavonoids in L. vulgare, particularly ortho-dihydroxylated flavonoids in the leaf mesophyll, greatly exceeded that in P. latifolia. We conclude that the accumulation of flavonoid glycosides associated with high solar radiation-induced oxidative stress and, hence, biosynthesis of flavonoids appear to be unrelated to 'tolerance' to high solar radiation in the species examined.


Difelikefalin suppresses itch and reduces scratching independent of inflammation in a murine model of atopic dermatitis.
Therapies specifically targeting nonhistaminergic pruritus are largely lacking. Difelikefalin (DFK) has been found to reduce itch in various chronic pruritic conditions, including atopic dermatitis (AD). We sought to investigate the ability of DFK to impact scratching behavior, inflammatory mediators, and neuronal signaling in a murine model of AD. The ears of C57BL/6 mice were topically treated with MC903 for 12 consecutive days to induce AD-like inflammation and itch. Before MC903 treatment, mice were treated with either DFK (0.5 mg/kg, intraperitoneal injection twice daily) or vehicle (saline). Skin ear thickness, histological analysis, flow cytometry, RNA-sequencing, and differential gene expression analyses of mouse ear skin were used to examine the effect of DFK on skin inflammation. Scratching behavior was quantified to measure itch behavior in mice that were topically treated with MC903 for 6 consecutive days; then, mice received a single injection of either DFK (1.0 mg/kg, intraperitoneal injection) or saline. Calcium imaging and single-cell RNA-sequencing were used in mouse dorsal root ganglia neurons to determine the size of the neurons activated with DFK treatment. Statistical significance was determined by Mann-Whitney test, unless otherwise noted. DFK rapidly suppressed itch without altering AD-like skin inflammation in MC903 (calcipotriol)-treated mice. In vitro Ca2+ influx trace of dorsal root ganglia suggested that a major target for DFK is the larger-diameter mechanoreceptors (eg, Aꞵ-fibers), rather than small-diameter pruriceptive C-fibers. These studies support a potential neuromodulatory role of DFK for reducing itch associated with AD in mice.


Technetium-99m spiperone dithiocarbamate: a potential radiopharmaceutical for dopamine receptor imaging with SPECT.
Spiperone dithiocarbamate (SPDC) was prepared by reacting spiperone with carbon disulfide followed by sodium hydroxide. SPDC was labelled with 99mTc by reduction of pertechnetate with formamidine sulfinic acid or sodium dithionite at alkaline pH, resulting in approximately 40% incorporation of 99mTc. The lipophilic complex was conveniently isolated at high specific activity and high radiochemical purity by extraction into dichloromethane, which was then evaporated and the residue was redissolved in a 1:3 mixture of ethanol and saline containing 0.1 mg/mL gentisic acid. Biodistribution studies following i.p. injection in rats showed low uptake of radioactivity in the brain, but striatum/cortex and striatum/cerebellum ratios were reduced by pretreatment with haloperidol. This agent may allow imaging of dopamine D-2 receptors using single-photon emission computed tomography (SPECT).


What are the key leadership competencies required by medical school deans in Uganda? A qualitative cross-sectional study.
Effective leadership is vital for organizational growth and sustainability. Globally, medical schools are faced with leadership challenges due to the pace of globalization, technological advances, reduced funding and changed funding cycles, increasing student enrolment, demands of accreditation, academic collaboration, innovations and research. This makes identification and selection for the right leadership competencies a priority. To investigate the key leadership competencies required by deans of medical schools in Uganda. A qualitative study using semi-structured interviews with the current deans and purposively selected former deans of medical schools in Uganda was conducted between March and June, 2020. We analysed the data using Grounded theory. Thirteen (13) deans (9 of the 12 current deans and 4 former deans) participated in the study. We established ten (10) key roles of a dean of a medical school categorised as academic leadership, administrative leadership and professional leadership. Eleven (11) key competencies were identified as necessary for effective leadership of medical schools in Uganda, and categorized as personality-related competencies, organizational management competencies and medical/health expertise. A dean of a medical school in Uganda should possess a combination of personality, medical expertise, health professions training and organizational management competencies and have training in leadership, financial and resources management.


Interspecific gene flow in a multispecies oak hybrid zone in the Sierra Tarahumara of Mexico.
Interspecific gene flow can occur in many combinations among species within the genus Quercus, but simultaneous hybridization among more than two species has been rarely analysed. The present study addresses the genetic structure and morphological variation in a triple hybrid zone formed by Q. hypoleucoides, Q. scytophylla and Q. sideroxyla in north-western Mexico. A total of 247 trees from ten reference and 13 presumed intermediate populations were characterized using leaf shape variation and geometric morphometrics, and seven nuclear microsatellites as genetic markers. Discriminant function analysis was performed for leaf shape variation, and estimates of genetic diversity and structure, and individual Bayesian genetic assignments were obtained. Reference populations formed three completely distinct groups according to discriminant function analysis based on the morphological data, and showed low, but significant, genetic differentiation. Populations from the zone of contact contained individuals morphologically intermediate between pairs of species in different combinations, or even among the three species. The Bayesian admixture analysis found that three main genetic clusters best fitted the data, with good correspondence of reference populations of each species to one of the genetic clusters, but various degrees of admixture evidenced in populations from the contact area. The three oak species have formed a complex hybrid zone that is geographically structured as a mosaic, and comprising a wide range of genotypes, including hybrids between different species pairs, backcrosses and probable triple hybrids.


Urinary tract infection in patients with chronic kidney disease.
Chronic kidney disease (CKD) has become a burden of health care globally. However, data on epidemiology, clinical features, and outcomes of urinary tract infection (UTI) in this population are scarce. This study aims to retrospectively review such data. A retrospective cohort study was conducted from 1 January 2005 to 31 December 2011 in patients with CKD requiring hospitalization. Patients who had upper and lower UTIs were compared for demography and clinical data. Logistic regressior was used to assess which variables were associated with upper UTI. A total of 276 bacteriuria patients were admitted to our ward with upper and lower UTIs. The average ages of the upper and lower UTI patients were 59.21 +/- 16.54 and 71.18 +/- 14.77 years, respectively. The results of logistic regression analysis showed that age (OR 0.946, P < 0.001), female sex (OR 4.695, P < 0.001), and renal stones (OR 8.232, P < 0.001) were independently associated with upper UTI. This study shows that patients with CKD and UTIs were elderly, and that females were prone to have more bacteriuria and upper UTIs than males. In addition, patients who had renal stones were more prone to have upper UTI than other bacteriuria patients Aggressive treatment of renal stones should be considered in these patients.