Examining Cannabis, Tobacco, and Vaping Discourse on Reddit: An Exploratory Approach Using Natural Language Processing.
Background: Perceptions of tobacco, cannabis, and electronic nicotine delivery systems (ENDS) are continually evolving in the United States. Exploring these characteristics through user generated text sources may provide novel insights into product use behavior that are challenging to identify using survey-based methods. The objective of this study was to compare the topics frequently discussed among Reddit members in cannabis, tobacco, and ENDS-specific subreddits. Methods: We collected 643,070 posts on the social media site Reddit between January 2013 and December 2018. We developed and validated an annotation scheme, achieving a high level of agreement among annotators. We then manually coded a subset of 2,630 posts for their content with relation to experiences and use of the three products of interest, and further developed word cloud representations of the words contained in these posts. Finally, we applied Latent Dirichlet Allocation (LDA) topic modeling to the 643,070 posts to identify emerging themes related to cannabis, tobacco, and ENDS products being discussed on Reddit. Results: Our manual annotation process yielded 2,148 (81.6%) posts that contained a mention(s) of either cannabis, tobacco, or ENDS with 1,537 (71.5%) of these posts mentioning cannabis, 421 (19.5%) mentioning ENDS, and 264 (12.2%) mentioning tobacco. In cannabis-specific subreddits, personal experiences with cannabis, cannabis legislation, health effects of cannabis use, methods and forms of cannabis, and the cultivation of cannabis were commonly discussed topics. The discussion in tobacco-specific subreddits often focused on the discussion of brands and types of combustible tobacco, as well as smoking cessation experiences and advice. In ENDS-specific subreddits, topics often included ENDS accessories and parts, flavors and nicotine solutions, procurement of ENDS, and the use of ENDS for smoking cessation. Conclusion: Our findings highlight the posting and participation patterns of Reddit members in cannabis, tobacco, and ENDS-specific subreddits and provide novel insights into aspects of personal use regarding these products. These findings complement epidemiologic study designs and highlight the potential of using specific subreddits to explore personal experiences with cannabis, ENDS, and tobacco products.


Biotyping in psychosis: using multiple computational approaches with one data set.
Focusing on biomarker identification and using biomarkers individually or in clusters to define biological subgroups in psychiatry requires a re-orientation from behavioral phenomenology to quantifying brain features, requiring big data approaches for data integration. Much still needs to be accomplished, not only to refine but also to build support for the application and customization of such an analytical phenotypic approach. In this review, we present some of what Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) has learned so far to guide future applications of multivariate phenotyping and their analyses to understanding psychosis. This paper describes several B-SNIP projects that use phenotype data and big data computations to generate novel outcomes and glimpse what phenotypes contribute to disease understanding and, with aspiration, to treatment. The source of the phenotypes varies from genetic data, structural neuroanatomic localization, immune markers, brain physiology, and cognition. We aim to see guiding principles emerge and areas of commonality revealed. And, we will need to demonstrate not only data stability but also the usefulness of biomarker information for subgroup identification enhancing target identification and treatment development.


Accuracy of pepsinogens for early diagnosis of atrophic gastritis and gastric cancer in Iranian population.
Currently, non-invasive methods for screening atrophic gastritis and gastric cancer are lacking. The purpose of this study was to evaluate the value of serological parameters including serum pepsinogen I (PGI), pepsinogen II (PGII) and pepsinogen I: II ratio for the screening atrophic gastritis and gastric cancer. The study population consisted of 132 dyspeptic patients who had undergone upper endoscopy with biopsy. Blood samples for ELISA assays of serum PGI, PGII and IgG antibodies against Helicobacter pylori were drawn. Comparison between the two groups was done by Student's t- test, and Mann Whitney test. Cut-off points were calculated using receiver operating curves (ROC). Mean (±SD) age of the study population was 51.4 (±15.5) years. Values of PGI and PG ratio decreased significantly in the atrophic gastritis as compared with the control group (p<0.05). Values of PG and PG ratio didn't show any significant difference between the gastric cancer and control group (p>0.05). For patients with atrophic gastritis, the area under the ROC for PGI was 0.639 (95% CI:0.538-0.741, p=0.008) in which the best cut-off value was 40μg/L (sensitivity 90%, specificity 67%, accuracy 69%, negative predictive value 92%, YI : 0.429). The area under the ROC for PG ratio was 0.711 (95% CI: 0.617-0.806, p=0.0001) and the best cut-off value was 8 (sensitivity 71%, specificity 71%, accuracy 71%, negative predictive value 86%,YI : 0.431). It seems that PGI, PGI: PGII ratio is potential biomarkers for screening atrophic gastritis with high sensitivity, specificity, accuracy and negative predictive value. Serology could be used as a screening method for the detection of precancerous states due to its convenience, relative low cost and safety.


High speed low power optical detection of sub-wavelength scatterer.
Optical detection of scatterers on a flat substrate, generally done using dark field microscopy technique, is challenging since it requires high power illumination to obtain sufficient SNR (Signal to Noise Ratio) to be able to detect sub-wavelength particles. We developed a bright field technique, based on Fourier scatterometry, with special illumination and detection control to achieve this goal with a power level that can be sustained by most substrates including polymers. The performance of the system in a roll-to-roll line in production environment and strict throughput requirement is shown.


Theoretical discrimination index of postural instability in amyotrophic lateral sclerosis.
To assess the usefulness of a theoretical postural instability discrimination index (PIth) in amyotrophic lateral sclerosis (ALS). Prospective regression analyzes were performed to identify the biomechanical determinants of postural instability unrelated to lower limb motor deficits from gait initiation factors. PIth was constructed using a logit function of biomechanical determinants. Discriminatory performance and performance differences were tested. Backward displacement of the pression center (APAamplitude) and active vertical braking of the mass center (Braking-index) were the biomechanical determinants of postural instability. PIth = - 0.13 × APAamplitude - 0.12 × Braking-index + 5.67, (P < 0.0001, RSquare = 0.6119). OR (APAamplitude) and OR (Braking-index) were 0.878 and 0.887, respectively, i.e., for a decrease of 10 mm in APAamplitude or 10% in Braking-index, the postural instability risk was 11.391 or 11.274 times higher, respectively. PIth had the highest discriminatory performance (AUC 0.953) with a decision threshold value [Formula: see text] 0.587, a sensitivity of 90.91%, and a specificity of 83.87%, significantly increasing the sensitivity by 11.11%. PIth, as objective clinical integrator of gait initiation biomechanical processes significantly involved in dynamic postural control, was a reliable and performing discrimination index of postural instability with a significant increased sensitivity, and may be useful for a personalized approach to postural instability in ALS.


Neuro-ophthalmic manifestations of AIDS.
As the incidence of human immunodeficiency virus (HIV) infection increases throughout the world, there becomes a greater probability that the primary care clinician will be confronted by AIDS-related complications. Neuro-ophthalmic problems, including optic neuropathies, motility disturbances, and visual field defects, are an important and common part of the AIDS spectrum. However diverse and challenging to the clinician, they may be the initial presentation of HIV infection. While opportunistic infections and neoplasms comprise the major source of neuro-ophthalmic problems, HIV itself may also be included. This paper is a review of the common causes of AIDS-related neuro-ophthalmic disorders and their clinical manifestations.


Synthesis and Biological Activity of Novel (Z)- and (E)-Verbenone Oxime Esters.
Twenty-seven (Z)- and (E)-verbenone derivatives bearing an oxime ester moiety were designed and synthesized in search of novel bioactive molecules. Their structures were confirmed by UV-Vis, FTIR, NMR, ESI-MS, and elemental analysis. The antifungal and herbicidal activities of the target compounds were preliminarily evaluated. As a result, compound (E)-4n (R = β-pyridyl) exhibited excellent antifungal activity with growth inhibition percentages of 92.2%, 80.0% and 76.3% against Alternaria solani, Physalospora piricola, and Cercospora arachidicola at 50 µg/mL, showing comparable or better antifungal activity than the commercial fungicide chlorothalonil with growth inhibition of 96.1%, 75.0% and 73.3%, respectively, and 1.7-5.5-fold more growth inhibition than its stereoisomer (Z)-4n (R = β-pyridyl) with inhibition rates of 22.6%, 28.6% and 43.7%, respectively. In addition, seven compounds displayed significant growth inhibition activity of over 90% against the root of rape (Brassica campestris) at 100 µg/mL, exhibiting much better herbicidal activity than the commercial herbicide flumioxazin with a 63.0% growth inhibition. Among these seven compounds, compound (E)-4n (R = β-pyridyl) inhibited growth by 92.1%, which was 1.7-fold more than its stereoisomer (Z)-4n (R = β-pyridyl) which inhibited growth by 54.0%.


Use of a cell sorter for assays of cell clonogenicity.
A fluorescence-activated cell sorter has the capability of recognizing, categorizing, counting, and sorting cells, and it thus provides a convenient and rapid method for "micromanipulation" of known numbers of cells into appropriate vessels for cell viability or clonogenicity studies. Subsequent microscopic observation of the sorted cells allows discrimination between the separate processes of cell attachment (plating efficiency) and clonogenic growth (viability). Examples are presented showing the power of these techniques for studying the low-dose regions of radiation survival curves for Chinese hamster V79 cells grown as monolayers or spheroids, for cells irradiated under aerobic versus hypoxic conditions, and for cells of large spheroids exposed to Adriamycin, where the slow penetration of the drug results in a differential exposure to the various cell subpopulations.


[Persistent Genital Arousal Disorder Treated with Duloxetine: A Case Report].
Persistent Genital Arousal Disorder is characterized with unwanted, uncontrollable and persistent genital arousal symptoms that occur spontaneously in the absence of simultaneous sexual fantasy, sexual desire or sexual stimulation. The condition may last for hours or days. Patients often find it difficult to share this condition with their health care providers because they are afraid of being diagnosed with hypersexuality and they often get different psychiatric diagnoses such as Obsessive Compulsive Disorder and Major Depressive Disorder. Therefore, little is known about the real prevalence, pathophysiology or etiology of Persistent Genital Arousal Disorder. In addition, since there is no study conducted in this field, our information in this area is limited to case reports. Although there is no consensus about the treatment of Persistent Genital Arousal Disorder in the psychiatric literature, there are some case reports about the use of pregabaline, clomipramine, duloxetine, clonazepam, varenicline, olanzapine, risperidone in addition to the case reports on treatment with hypnotherapy, pelvic floor physiotherapy and electroconvulsive therapy (ECT). In this case report, we aimed to present the detailed description of a successful treatment procedure with duloxetine in a forty two years old female patient diagnosed with Persistent Genital Arousal Disorder. She had been using various antidepressants, antipsychotics, anxiolytics and mood stabilizers for sixteen years with different psychiatric misdiagnoses like Bipolar Disorder, Obsessive Compulsive Disorder, Anxiety Disorder and Major Depressive Disorder and yet, had not shared her symptoms of genital arousal with any psychiatrist previously.


An empirical method for establishing positional confidence intervals tailored for composite interval mapping of QTL.
Improved genetic resolution and availability of sequenced genomes have made positional cloning of moderate-effect QTL realistic in several systems, emphasizing the need for precise and accurate derivation of positional confidence intervals (CIs) for QTL. Support interval (SI) methods based on the shape of the QTL likelihood curve have proven adequate for standard interval mapping, but have not been shown to be appropriate for use with composite interval mapping (CIM), which is one of the most commonly used QTL mapping methods. Based on a non-parametric confidence interval (NPCI) method designed for use with the Haley-Knott regression method for mapping QTL, a CIM-specific method (CIM-NPCI) was developed to appropriately account for the selection of background markers during analysis of bootstrap-resampled data sets. Coverage probabilities and interval widths resulting from use of the NPCI, SI, and CIM-NPCI methods were compared in a series of simulations analyzed via CIM, wherein four genetic effects were simulated in chromosomal regions with distinct marker densities while heritability was fixed at 0.6 for a population of 200 isolines. CIM-NPCIs consistently capture the simulated QTL across these conditions while slightly narrower SIs and NPCIs fail at unacceptably high rates, especially in genomic regions where marker density is high, which is increasingly common for real studies. The effects of a known CIM bias toward locating QTL peaks at markers were also investigated for each marker density case. Evaluation of sub-simulations that varied according to the positions of simulated effects relative to the nearest markers showed that the CIM-NPCI method overcomes this bias, offering an explanation for the improved coverage probabilities when marker densities are high. Extensive simulation studies herein demonstrate that the QTL confidence interval methods typically used to positionally evaluate CIM results can be dramatically improved by accounting for the procedural complexity of CIM via an empirical approach, CIM-NPCI. Confidence intervals are a critical measure of QTL utility, but have received inadequate treatment due to a perception that QTL mapping is not sufficiently precise for procedural improvements to matter. Technological advances will continue to challenge this assumption, creating even more need for the current improvement to be refined.


Pro-apoptotic effect of the landrace Bangla Mahoba of Piper betle on Leishmania donovani may be due to the high content of eugenol.
In the absence of effective and safe treatment for visceral leishmaniasis or Kala-azar - a devastating parasitic disease caused by Leishmania donovani - the search for anti-leishmanial agents from natural resources in common use is imperative. Recently, the comparative in vitro anti-leishmanial activity of methanolic extracts from two landraces of Piper betle - P. betle landrace Bangla Mahoba (PB-BM) and P. betle landrace Kapoori Vellaikodi (PB-KV) - has been reported. Here, the putative pathway responsible for death induced by the effective extract of PB-BM methanolic extract in promastigotes, as well as the intracellular amastigote form of L. donovani, was assessed using various biochemical approaches. It was found that PB-BM was capable of selectively inhibiting both stages of Leishmania parasites by accelerating apoptotic events by generation of reactive oxygen species targeting the mitochondria without any cytotoxicity towards macrophages. The study was extended to determine the presence or absence of activity of the methanolic extract of PB-BM and PB-KV on the basis of differences in essential oil composition present in the extract assessed by GC and MS. The essential oil from PB-BM was found to be rich in eugenol compared with that from PB-KV. The anti-leishmanial efficacy of PB-BM methanolic extract mediated through apoptosis is probably due to the higher content of eugenol in the active landrace. This observation emphasizes the need to extend studies related to traditional medicines from bioactive plants below the species level to the gender/landrace level for better efficacy and reproducibility.


Noninvasive neuromodulation with ultrasound? A continuum mechanics hypothesis.
Deep brain stimulation and vagal nerve stimulation are therapeutically effective in treating some neurological diseases and psychiatric disorders. Optogenetic-based neurostimulation approaches are capable of activating individual synapses and yield the highest spatial control over brain circuit activity. Both electrical and light-based neurostimulation methods require intrusive procedures such as surgical implantation of electrodes or photon-emitting devices. Transcranial magnetic stimulation has also shown therapeutic effectiveness and represents a recent paradigm shift towards implementing less invasive brain stimulation methods. Magnetic-based stimulation, however, has a limited focusing capacity and lacks brain penetration power. Because ultrasound can be noninvasively transmitted through the skull to targeted deep brain circuits, it may offer alternative approaches to currently employed neuromodulation techniques. Encouraging this idea, literature spanning more than half a century indicates that ultrasound can modulate neuronal activity. In order to provide a comprehensive overview of potential mechanisms underlying the actions of ultrasound on neuronal excitability, here, I propose the continuum mechanics hypothesis of ultrasonic neuromodulation in which ultrasound produces effects on viscoelastic neurons and their surrounding fluid environments to alter membrane conductance. While further studies are required to test this hypothesis, experimental data indicate ultrasound represents a promising platform for developing future therapeutic neuromodulation approaches.


Residual groin pain at a minimum of two years after metal-on-metal THA with a twenty-eight-millimeter femoral head, THA with a large-diameter femoral head, and hip resurfacing.
Groin pain may persist in up to 4.3% of patients after total hip arthroplasty and up to 18% of patients one year after hip resurfacing. The incidence of this problem after total hip arthroplasty with a large-diameter femoral head is unknown. We analyzed the natural history of groin pain and its clinical consequences during the first two years after three types of hip arthroplasty. Data were collected prospectively on 279 patients. Eighty-five patients had a polyethylene sandwich metal-on-metal total hip arthroplasty with a 28-mm-diameter femoral head, 105 had hip resurfacing, and eighty-nine had a total hip arthroplasty with a large-diameter femoral head component with three other cup designs (forty-nine in this group had the same monoblock acetabular cup design as those who had hip resurfacing). At the twenty-four-month follow-up evaluation, seventy-seven patients (28%) reported at least one painful area around the hip and thirty-four patients (12.2%) had pain at more than one location. At three months, the incidence of groin discomfort was significantly increased in those who had hip resurfacing (30.5%) and in those who had total hip arthroplasty with a large-diameter femoral head (30%) compared with those who had total hip arthroplasty with a 28-mm femoral head (18.3%). This incidence decreased at two years (14.9%, 16.9%, and 12.9%, respectively). At twenty-four months postoperatively, eleven (four who had hip resurfacing, six who had total hip arthroplasty with the large-diameter head, and one who had total hip arthroplasty with the 28-mm head) of forty-one patients who had groin pain had not reported groin pain at previous follow-up evaluations. Of the forty-one patients reporting groin pain at the time of the last follow-up, twenty-three patients (56%) did not seek further evaluation or treatment, nine had revision surgery (22%), and the remaining nine patients thought the pain was substantial enough to warrant further evaluation and treatment. When the exact source of groin pain cannot be found after total hip arthroplasty, careful follow-up should be done as local reactions to metal-on-metal implants and component loosening may take time to become apparent clinically or on imaging studies.


Validation of a cadaveric model for comprehensive physiologic and anatomic evaluation of rhinoplastic techniques.
The physiologic effects of specific rhinoplasty maneuvers are incompletely understood, largely because of a limited ability to objectively examine such interventions. The purpose of this study was to develop and validate a cadaveric model for rhinoplasty testing. Ten cadaver heads were methodically prepared to simulate ventilatory conditions. Airway dimensions were measured with three-dimensional computed tomography and acoustic rhinometry. Airflow, pressure, and resistance were measured under conditions of both inhalation and exhalation. Resistance was determined using active anterior rhinomanometry and a continuously variable pressure gradient. Anatomic and physiologic properties were first compared against normative data. Measurements were then taken after application of an adhesive external midvault dilator (BreatheRight; GlaxoSmithKline). The average minimal cross-sectional areas by acoustic rhinometry and by computed tomography were 0.87 cm2 and 0.84 cm2 per nostril, respectively (n = 20). The average distance from the nostril to the internal nasal valve was 1.7 cm by acoustic rhinometry and 1.5 cm by computed tomography, consistent with published in vivo normative data at the internal nasal valve. The average resistance with simulated exhalation closely approximated known normative values. With the application of the adhesive nasal dilator, the average area (acoustic rhinometry) increased by 50 percent at the internal nasal valve. During inhalation, the resistance decreased by 21 percent following application of the adhesive dilator. The model provides an accurate representation of nasal anatomy and physiology suitable for objective analysis of rhinoplasty maneuvers. The objective modalities used herein may be applied to rhinoplasty study using this model with accuracy and reproducibility. The external dilator increased area at the internal valve (minimal cross-sectional area) and decreased resistance.


Possibility-based fuzzy neural networks and their application to image processing.
This paper describes the foundations for a class of fuzzy neural networks. Such a network is a composite or two-stage network consisting of a fuzzy network stage and a neural network stage. It exhibits the ability to classify complex feature set vectors with a configuration that is simpler than that needed by a standard neural network, Unlike a standard neural network, this network is able to accept as input a vector of scalar values, or a vector (set) of possibility functions. The first stage of the network is fuzzy based. It has two parts: a parameter computing network (PCN), followed by a converting layer. In the PCN the weights of the nodes are possibility functions, and hence, the output of this network is a fuzzy set. The second part of this stage, which is a single layer network, then converts this fuzzy set into a scalar vector for input to the second stage. The second stage of the network is a standard backpropagation based neural network. In addition to establishing the theoretical foundations for such a network, this paper presents sample applications of the network for classification problems in satellite image processing and seismic lithology pattern recognition.


The Hermansky-Pudlak syndrome 1 (HPS1) and HPS4 proteins are components of two complexes, BLOC-3 and BLOC-4, involved in the biogenesis of lysosome-related organelles.
Hermansky-Pudlak syndrome (HPS) is a genetic disease of lysosome, melanosome, and granule biogenesis. Mutations of six different loci have been associated with HPS in humans, the most frequent of which are mutations of the HPS1 and HPS4 genes. Here, we show that the HPS1 and HPS4 proteins are components of two novel protein complexes involved in biogenesis of melanosome and lysosome-related organelles: biogenesis of lysosome-related organelles complex-(BLOC) 3 and BLOC-4. The phenotypes of Hps1-mutant (pale-ear; ep) and Hps4-mutant (light-ear; le) mice and humans are very similar, and cells from ep and le mice exhibit similar abnormalities of melanosome morphology. HPS1 protein is absent from ep-mutant cells, and HPS4 from le-mutant cells, but le-mutant cells also lack HPS1 protein. HPS4 protein seems to be necessary for stabilization of HPS1, and the HPS1 and HPS4 proteins co-immunoprecipitate, indicating that they are in a complex. HPS1 and HPS4 do not interact directly in a yeast two-hybrid system, although HPS4 interacts with itself. In a partially purified vesicular/organellar fraction, HPS1 and HPS4 are both components of a complex with a molecular mass of approximately 500 kDa, termed BLOC-3. Within BLOC-3, HPS1 and HPS4 are components of a discrete approximately 200-kDa module termed BLOC-4. In the cytosol, HPS1 (but not HPS4) is part of yet another complex, termed BLOC-5. We propose that the BLOC-3 and BLOC-4 HPS1.HPS4 complexes play a central role in trafficking cargo proteins to newly formed cytoplasmic organelles.


Detection of Borrelia spp., Ehrlichia canis, Anaplasma phagocytophilum, and Dirofilaria immitis in Eastern Coyotes (Canis latrans) in Nova Scotia, Canada.
Borrelia burgdorferi and Borrelia miyamotoi are tickborne zoonotic pathogens in Canada. Both bacteria are vectored by ticks, Ixodes scapularis in Atlantic Canada, but require wildlife reservoir species to maintain the bacteria for retransmission to future generations of ticks. Coyotes (Canis latrans) are opportunistic feeders, resulting in frequent contact with other animals and with ticks. Because coyotes are closely related to domestic dogs (Canis lupus familiaris), it is probable that coyote susceptibility to Borrelia infection is similar to that of dogs. We collected livers and kidneys of eastern coyotes from licensed harvesters in Nova Scotia, Canada, and tested them using nested PCR for the presence of B. burgdorferi, B. miyamotoi, and Dirofilaria immitis. Blood obtained from coyote livers was also tested serologically for antibodies to B. burgdorferi, Ehrlichia canis, Anaplasma phagocytophilum, and D. immitis. Borrelia burgdorferi and D. immitis were detected by both nested PCR and serology tests. Seroreactivity to A. phagocytophilum was also found. Borrelia miyamotoi and E. canis were not detected. Our results show that coyotes in Nova Scotia have been exposed to a number of vectorborne pathogens.


The role of ecology in speciation by sexual selection: a systematic empirical review.
Theoretical and empirical research indicates that sexual selection interacts with the ecological context in which mate choice occurs, suggesting that sexual and natural selection act together during the evolution of premating reproductive isolation. However, the relative importance of natural and sexual selection to speciation remains poorly understood. Here, we applied a recent conceptual framework for examining interactions between mate choice divergence and ecological context to a review of the empirical literature on speciation by sexual selection. This framework defines two types of interactions between mate choice and ecology: internal interactions, wherein natural and sexual selection jointly influence divergence in sexual signal traits and preferences, and external interactions, wherein sexual selection alone acts on traits and preferences but ecological context shapes the transmission efficacy of sexual signals. The objectives of this synthesis were 3-fold: to summarize the traits, ecological factors, taxa, and geographic contexts involved in studies of mate choice divergence; to analyze patterns of association between these variables; and to identify the most common types of interactions between mate choice and ecological factors. Our analysis revealed that certain traits are consistently associated with certain ecological factors. Moreover, among studies that examined a divergent sexually selected trait and an ecological factor, internal interactions were more common than external interactions. Trait-preference associations may thus frequently be subject to both sexual and natural selection in cases of divergent mate choice. Our results highlight the importance of interactions between sexual selection and ecology in mate choice divergence and suggest areas for future research.


Four Weeks of Nordic Hamstring Exercise Reduce Muscle Injury Risk Factors in Young Adults.
Ribeiro-Alvares, JB, Marques, VB, Vaz, MA, and Baroni, BM. Four weeks of Nordic hamstring exercise reduce muscle injury risk factors in young adults. J Strength Cond Res 32(5): 1254-1262, 2018-The Nordic hamstring exercise (NHE) is a field-based exercise designed for knee-flexor eccentric strengthening, aimed at prevention of muscle strains. However, possible effects of NHE programs on other hamstring injury risk factors remain unclear. The purpose of this study was to investigate the effects of a NHE training program on multiple hamstring injury risk factors. Twenty physically active young adults were allocated into 2 equal-sized groups: control group (CG) and training group (TG). The TG was engaged in a 4-week NHE program, twice a week, 3 sets of 6-10 repetitions; while CG received no exercise intervention. The knee flexor and extensor strength were assessed through isokinetic dynamometry, the biceps femoris long head muscle architecture through ultrasound images, and the hamstring flexibility through sit-and-reach test. The results showed that CG subjects had no significant change in any outcome. TG presented higher percent changes than CG for hamstring isometric peak torque (9%; effect size [ES] = 0.27), eccentric peak torque (13%; ES = 0.60), eccentric work (18%; ES = 0.86), and functional hamstring-to-quadriceps torque ratio (13%; ES = 0.80). The NHE program led also to increased fascicle length (22%; ES = 2.77) and reduced pennation angle (-17%; ES = 1.27) in biceps femoris long head of the TG, without significant changes on muscle thickness. In conclusion, a short-term NHE training program (4 weeks; 8 training sessions) counteracts multiple hamstring injury risk factors in physically active young adults.


Evaluating the effectiveness of a multifaceted, multilevel continuous quality improvement program in primary health care: developing a realist theory of change.
Variation in effectiveness of continuous quality improvement (CQI) interventions between services is commonly reported, but with little explanation of how contextual and other factors may interact to produce this variation. Therefore, there is scant information available on which policy makers can draw to inform effective implementation in different settings. In this paper, we explore how patterns of change in delivery of services may have been achieved in a diverse range of health centers participating in a wide-scale program to achieve improvements in quality of care for Indigenous Australians. We elicited key informants' interpretations of factors explaining patterns of change in delivery of guideline-scheduled services over three or more years of a wide-scale CQI project, and inductively analyzed these interpretations to propose fine-grained realist hypotheses about what works for whom and in what circumstances. Data were derived from annual clinical audits from 36 health centers operating in diverse settings, quarterly project monitoring reports, and workshops with 12 key informants who had key roles in project implementation. We abstracted potential context-mechanism-outcome configurations from the data, and based on these, identified potential program-strengthening strategies. Several context-specific, mechanism-based explanations for effectiveness of this CQI project were identified. These were collective valuing of clinical data for improvement purposes; collective efficacy; and organizational change towards a population health orientation. Health centers with strong central management of CQI, and those in which CQI efforts were more dependent on local health center initiative and were adapted to resonate with local priorities were both favorable contexts for collective valuing of clinical data. Where health centers had prior positive experiences of collaboration, effects appeared to be achieved at least partly through the mechanism of collective efficacy. Strong community linkages, staff ability to identify with patients, and staff having the skills and support to take broad ranging action, were favorable contexts for the mechanism of increased population health orientation. Our study provides evidence to support strategies for program strengthening described in the literature, and extends the understanding of mechanisms through which strategies may be effective in achieving particular outcomes in different contexts.


Small nucleolar RNA and its potential role in breast cancer - A comprehensive review.
Small Nucleolar RNAs (snoRNAs) are known for their canonical functions, including ribosome biogenesis and RNA modification. snoRNAs act as endogenous sponges that regulate miRNA expression. Thus, precise snoRNA expression is critical for fine-tuning miRNA expression. snoRNAs processed into miRNA-like sequences play a crucial role in regulating the expression of protein-coding genes similar to that of miRNAs. Recent studies have linked snoRNA deregulation to breast cancer (BC). Inappropriate snoRNA expression contributes to BC pathology by facilitating breast cells to acquire cancer hallmarks. Since snoRNAs show significant differential expression in normal and cancer conditions, measuring snoRNA levels could be useful for BC prognosis and diagnosis. The present article provides a comprehensive overview of the role of snoRNAs in breast cancer pathology. More specifically, we have discussed the regulation, biological function, signaling pathways, and clinical utility of abnormally expressed snoRNAs in BC. Besides, we have also discussed the role of snoRNA host genes in breast tumorigenesis and emerging and future research directions in the field of snoRNA and cancer.


Divergent operons and the genetic structure of the maltose B region in Escherichia coli K12.
Complementation and polarity suppression data are interpreted in terms of the genetic structure of the maltose B region. It is proposed that this region comprises two divergent operons. One operon includes malK, a cistron involved in maltose permeation, and lamB the only known cistron specifically involved in lambda receptor synthesis. The other operon includes malJ(1) and malJ(2) which are most probably two different cistrons, both involved in maltose permeation*. It is further assumed that expression of the two operons is controlled by malT, the positive regulatory gene of the maltose system, located in the malA region. The target(s) for the action of the malT product is (are) most likely to be located between malJ(1) and malK. There is an indication that the two operons might overlap in the region of their promoters. The structure of such an overlap as well as the possible function of the products of the different cistrons in malB are briefly discussed.


Selection and use of content experts for instrument development.
Content experts frequently are used in the judgment-quantification stage of content validation of instruments. However, errors in instrumentation may arise when important steps in selecting and using these experts are not carefully planned. The systematic process of choosing, orienting, and using content experts in the judgment-qualification stage of instrument development is addressed, with particular attention to the often neglected, important step of familiarizing these experts with the conceptual underpinnings and measurement model of the instrument. An example using experts to validate content for a measure of caregiver burden is used to illustrate this stage of instrument review.


Northwick Park Care Needs Assessment: adaptation for inpatient neurological rehabilitation settings.
This paper is a report of a study to establish which timings and assumptions of the Northwick Park Dependency Scale and Care Needs Assessment are appropriate to the inpatient rehabilitation setting and which, if any, require adjustment. Cost-effective provision of nursing care relies on being able to adjust staffing levels in accordance with patient dependency. The Northwick Park Dependency Scale and Care Needs Assessment enables direct assessment of nursing care needs in community settings. An observational study was conducted in 2004 to record the time taken to complete direct nursing care interventions in a rehabilitation ward and to compare these times with simultaneously recorded time-estimates provided by the Care Needs Assessment. A total of 1168 nursing interactions were timed for 50 care episodes. There was considerable variation in the time taken for each nursing intervention, depending on overall patient dependency and the number of nurses required. Although there was good correlation between observed care times and those estimated by the Care Needs Assessment, observation confirmed that most interventions took substantially less time than the estimates. There was also a very different pattern of care in hospital compared with the community, with shorter, more frequent interactions as nurses distribute their time between different patients, and activities other than direct patient care. The Northwick Park Care Needs Assessment tool already has widespread application in other countries and its continued use for estimating community care needs remains relevant. The tool, once fully developed, will have the potential to contribute to international rehabilitation nursing workforce planning and research.


Effect of stearic acid on enalapril stability and dissolution from multiparticulate solid dosage forms.
Enalapril maleate (EM) is a widely used anti-hypertensive drug which is unstable when mixed with excipients. Enalaprilate and diketopiperazine (DPK) are the main degradation products of enalapril. The in situ preparation of enalapril sodium salt (NaE) has been used to improve drug stability in dosage forms; however, gas release and product rejection ensue when the chemical reaction for obtaining the sodium salt is not completely finished before packaging. This study evaluated the effect of stearic acid (SA) on enalapril stability in microcrystalline cellulose (MCC) pellets containing EM or NaE. MCC pellets containing SA were prepared by the extrusion-spheronization technique and characterized. Enalapril stability and dissolution were then evaluated. DPK and enalaprilate formation were reduced by the addition of SA in pellets containing EM. The overall enalapril degradation in these formulations was lower when compared with pellets containing EM or even NaE prepared without SA. The immediate-release characteristic was maintained by the addition of 5% crospovidone to all the formulations tested. The incorporation of SA into NaE pellets resulted in unexpected enalapril degradation, caused by the interaction of these compounds, as suggested by a thermal analysis of the SA-NaE binary mixture. The findings presented here showed that formulations containing SA could substitute the formation of NaE, since they provide better enalapril stability in solid dosage forms. In addition, it is suggested that the stabilization effects would be observed for other N-carboxyalkyl dipeptide analogs with angiotensin converting enzyme inhibition activity, since these new entities share the same degradation pathway of enalapril.


Pediatric Weight Management Through mHealth Compared to Face-to-Face Care: Cost Analysis of a Randomized Control Trial.
Mobile health (mHealth) may improve pediatric weight management capacity and the geographical reach of services, and overcome barriers to attending physical appointments using ubiquitous devices such as smartphones and tablets. This field remains an emerging research area with some evidence of its effectiveness; however, there is a scarcity of literature describing economic evaluations of mHealth interventions. We aimed to assess the economic viability of using an mHealth approach as an alternative to standard multidisciplinary care by evaluating the direct costs incurred within treatment arms during a noninferiority randomized controlled trial (RCT). A digitally delivered (via a smartphone app) maintenance phase of a pediatric weight management program was developed iteratively with patients and families using evidence-based approaches. We undertook a microcosting exercise and budget impact analysis to assess the costs of delivery from the perspective of the publicly funded health care system. Resource use was analyzed alongside the RCT, and we estimated the costs associated with the staff time and resources for service delivery per participant. In total, 109 adolescents participated in the trial, and 84 participants completed the trial (25 withdrew from the trial). We estimated the mean direct cost per adolescent attending usual care at €142 (SD 23.7), whereas the cost per adolescent in the mHealth group was €722 (SD 221.1), with variations depending on the number of weeks of treatment completion. The conversion rate for the reference year 2013 was $1=€0.7525. The costs incurred for those who withdrew from the study ranged from €35 to €681, depending on the point of dropout and study arm. The main driver of the costs in the mHealth arm was the need for health professional monitoring and support for patients on a weekly basis. The budget impact for offering the mHealth intervention to all newly referred patients in a 1-year period was estimated at €59,046 using the assessed approach. This mHealth approach was substantially more expensive than usual care, although modifications to the intervention may offer opportunities to reduce the mHealth costs. The need for monitoring and support from health care professionals (HCPs) was not eliminated using this delivery model. Further research is needed to explore the cost-effectiveness and economic impact on families and from a wider societal perspective. ClinicalTrials.gov NCT01804855; https://clinicaltrials.gov/ct2/show/NCT01804855.


Control of zinc oxide nanowire array properties with electron-beam lithography templating for photovoltaic applications.
Hydrothermally synthesized zinc oxide nanowire arrays have been used as nanostructured acceptors in emerging photovoltaic (PV) devices. The nanoscale dimensions of such arrays allow for enhanced charge extraction from PV active layers, but the device performance critically depends on the nanowire array pitch and alignment. In this study, we templated hydrothermally-grown ZnO nanowire arrays via high-resolution electron-beam-lithography defined masks, achieving the dual requirements of high-resolution patterning at a pitch of several hundred nanometers, while maintaining hole sizes small enough to control nanowire array morphology. We investigated several process conditions, including the effect of annealing sputtered and spincoated ZnO seed layers on nanowire growth, to optimize array property metrics-branching from individual template holes and off-normal alignment. We found that decreasing template hole size decreased branching prevalence but also reduced alignment. Annealing seed layers typically improved alignment, and sputtered seed layers yielded nanowire arrays superior to spincoated seed layers. We show that these effects arose from variation in the size of the template holes relative to the ZnO grain size in the seed layer. The quantitative control of branching and alignment of the nanowire array that is achieved in this study will open new paths toward engineering more efficient electrodes to increase photocurrent in nanostructured PVs. This control is also applicable to inorganic nanowire growth in general, nanomechanical generators, nanowire transistors, and surface-energy engineering.


Active Solid-State Nanopores: Self-Driven Flows/Chaos at the Liquid-Gas Nanofluidic Interface.
Here, we present a comprehensive study of self-driven flow dynamics at the liquid-gas interface within nanofluidic pores in the absence of external driving forces. The investigation focuses on the Rayleigh-Taylor instability phenomena that occur in sub-100 nm scale fluidic pores interfacing between 2 μm scale water and air reservoir. We obtain a flow velocity equation, and we validate it using simulations, concentrating on the mass transfer efficiency of these flow structures. Furthermore, we introduce the concept─"active solid-state nanopore"─that exhibits a self-driven flow switching behavior, transitioning between active and passive states without the need for mechanical components. We found a unique state of chaos at the nanoscale resembling the chaotic motion of fluid. This study contributes to the preliminary understanding of fluid dynamics at the classical-quantum interface. Implications of self-driven nanofluidics extend across diverse fields from biosensing and healthcare applications to advancing net-zero sustainable energy production and contributing to the fundamental understanding of fluid dynamics in confined spaces.


Effects of WNT/beta-catenin pathway activation on signaling through T-cell factor and androgen receptor in prostate cancer cell lines.
Dysregulation of the WNT/beta-catenin pathway is thought to contribute to prostate cancer progression. Mutations of beta-catenin occurring in 5-7% of advanced prostate cancers may act by stimulating TCF-dependent and/or androgen receptor (AR)-dependent transcription. Using a reporter gene approach we found overexpressed mutated beta-catenin to enhance AR-regulated probasin-promoter activity in the AR-positive prostate cancer cell line 22Rv1, particularly at low androgen levels. In 22Rv1 cells mutated beta-catenin was able to stimulate TCF-dependent transcription but was unable to do so in LNCaP cells where it activates the AR. Since beta-catenin mutations are rare in vivo, we studied further possible routes of WNT-pathway modulation. Higher concentrations of LiCl, a GSK3beta-inhibitor, were required to activate TCF-dependent rather than AR-dependent reporter constructs. In 22Rv1 overexpression of E-cadherin repressed androgen-dependent transcription, but did not inhibit transcription of TCF-dependent reporter genes as in bladder cancer cell lines. Interestingly, Wnt-3a stimulated proliferation selectively in the AR-positive prostate cancer cell lines 22Rv1 and LNCaP, even though TCF-dependent reporter gene transcription was not induced in LNCaP cells. In summary, the data from our study support the idea that activation of WNT/beta-catenin signaling in AR-positive prostate cancer cells may predominantly act through AR-dependent mechanisms rather than classical TCF-dependent mechanisms.


Diverging taxonomic and functional trajectories following disturbance in a Neotropical forest.
In the current global change context, it is urgent to anticipate the fate of tropical forests. This means understanding tree community response to disturbance and the underlying processes. In that respect, we aim here to clarify taxonomic and functional post-disturbance trajectories, and determine the scope of the Intermediate Disturbance Hypothesis (IDH) that remains debated in tropical forests. We analyzed community trajectories following a disturbance gradient from 10 to 60% of above-ground biomass loss in a Neotropical forest over 30 years. We considered trajectories along time of community taxonomic and functional trajectories in terms of richness, evenness, composition, and redundancy. We based on the annual botanical inventories of 75 ha of a Neotropical forest and on large trait datasets comprising seven leaf, stem, and life-history traits. We identified a decoupling between taxonomic composition, differing among communities, and functional composition, similar among communities and convergent in the functional space. The taxonomic diversity followed humped-shaped trajectories along time after disturbance depending on the initial disturbance intensity, which validated the IDH (Intermediate Disturbance Hypothesis). The functional diversity trajectories, however, were homogeneous among plots and dismissed the IDH. We explained this decoupling by the variations in community functional redundancy that mitigated the functional impact of disturbance. Although consistent, the recovery of community composition, diversity, and redundancy remained divergent from the initial state after 30 years. These results acknowledged the need of decades-long cycles without disturbance to ensure community complete recovery.


Design of kallidin-releasing tissue kallikrein inhibitors based on the specificities of the enzyme's binding subsites.
The tissue kallikrein inhibitors reported in the present work were derived by selectively replacing residues in Nalpha-substituted arginine- or phenylalanine-pNA (where pNA is p-nitroanilide), and in peptide substrates for these enzymes. Phenylacetyl-Arg-pNA was found to be an efficient inhibitor of human tissue kallikrein (Ki 0.4 microM) and was neither a substrate nor an inhibitor of plasma kallikrein. The peptide inhibitors having phenylalanine as the P1 residue behaved as specific inhibitors for kallidin-releasing tissue kallikreins, while plasma kallikrein showed high affinity for inhibitors containing (p-nitro)phenylalanine at the same position. The Ki value of the most potent inhibitor developed, Abz-Phe-Arg-Arg-Pro-Arg-EDDnp [where Abz is o-aminobenzoyl and EDDnp is N-(2,4-dinitrophenyl)-ethylenediamine], was 0.08 microM for human tissue kallikrein. Progress curve analyses of the inhibition of human tissue kallikrein by benzoyl-Arg-pNA and phenylacetyl-Phe-Ser-Arg-EDDnp indicated a single-step mechanism for reversible formation of the enzyme-inhibitor complex.


Flucytosine and cryptococcosis: time to urgently address the worldwide accessibility of a 50-year-old antifungal.
Current, widely accepted guidelines for the management of HIV-associated cryptococcal meningoencephalitis (CM) recommend amphotericin B combined with flucytosine (5-FC) for ≥2 weeks as the initial induction treatment of choice. However, access to flucytosine in Africa and Asia, where disease burden is greatest, is inadequate at present. While research into identifying effective and well-tolerated antifungal combinations that do not contain flucytosine continues, an ever-increasing body of evidence from in vitro, in vivo and clinical studies points to the benefits of flucytosine in the treatment of CM in both intravenous combinations with amphotericin B and oral combinations with high-dose fluconazole. This article provides an up-to-date review of this evidence, and the current issues and challenges regarding increasing access to this key component of combination antifungal therapy for cryptococcosis.


Insulin-like growth factor-I analogue protects muscles of dystrophic mdx mice from contraction-mediated damage.
Contraction-mediated injury is a major contributing factor to the pathophysiology of muscular dystrophy and therefore therapies that can attenuate this type of injury have clinical relevance. Systemic administration of insulin-like growth factor-I (IGF-I) has been shown to improve muscle function in dystrophic mdx mice, an effect associated with a shift towards a more oxidative muscle phenotype and a reduced susceptibility to contraction-mediated damage. The actions of IGF-I in vivo are modulated by IGF binding proteins (IGFBPs), which generally act to inhibit IGF-I signalling. We tested the hypothesis that an analogue of IGF-I (LR IGF-I), which has significantly reduced binding affinity for IGFBPs, would improve the dystrophic pathology by reducing the susceptibility to muscle injury. Dystrophic mdx and wild-type (C57BL/10) mice were administered LR IGF-I continuously ( approximately 1.5 mg kg(-1) day(-1)) via osmotic mini-pump for 4 weeks. Administration of LR IGF-I reduced the susceptibility of extensor digitorum longus, soleus and diaphragm muscles to contraction damage, as evident from lower force deficits after a protocol of lengthening contractions. In contrast to the mechanism of protection conferred by administration of IGF-I, the protection conferred by LR IGF-I was independent of changes in muscle fatigue and oxidative metabolism. This study further indicates that modulation of IGF-I signalling has therapeutic potential for muscular diseases.


Differences of immune disorders between Alzheimer's disease and breast cancer based on transcriptional regulation.
Although chronic inflammation and immune disorders are of great importance to the pathogenesis of both dementia and cancer, the pathophysiological mechanisms are not clearly understood. In recent years, growing epidemiological evidence and meta-analysis data suggest an inverse association between Alzheimer's disease (AD), which is the most common form of dementia, and cancer. It has been revealed that some common genes and biological processes play opposite roles in AD and cancer; however, the biological immune mechanism for the inverse association is not clearly defined. An unsupervised matrix decomposition two-stage bioinformatics procedure was adopted to investigate the opposite behaviors of the immune response in AD and breast cancer (BC) and to discover the underlying transcriptional regulatory mechanisms. Fast independent component analysis (FastICA) was applied to extract significant genes from AD and BC microarray gene expression data. Based on the extracted data, the shared transcription factors (TFs) from AD and BC were captured. Second, the network component analysis (NCA) algorithm in this study was presented to quantitatively deduce the TF activities and regulatory influences because quantitative dynamic regulatory information for TFs is not available via microarray techniques. Based on the NCA results and reconstructed transcriptional regulatory networks, inverse regulatory processes and some known innate immune responses were described in detail. Many of the shared TFs and their regulatory processes were found to be closely related to the adaptive immune response from dramatically different directions and to play crucial roles in both AD and BC pathogenesis. From the above findings, the opposing cellular behaviors demonstrate an invaluable opportunity to gain insights into the pathogenesis of these two types of diseases and to aid in developing new treatments.


The mental health of populations directly and indirectly exposed to violent conflict in Indonesia.
Large disasters affect people who live both near and far from the areas in which they occur. The mental health impact is expected to be similar to a ripple effect, where the risk of mental health consequences generally decreases with increasing distance from the disaster center. However, we have not been able to identify studies of the ripple effect of man-made disaster on mental health in low-income countries. The objective was to examine the hypothesis of a ripple effect on the mental health consequences in populations exposed to man-made disasters in a developing country context, through a comparison of two different populations living in different proximities from the center of disaster in Mollucas. Cross-sectional longitudinal data were collected from 510 Internally Displaced Persons (IDPs) living in Ambon, who were directly exposed to the violence, and non-IDPs living in remote villages in Mollucas, Indonesia, who had never been directly exposed to violence in Mollucas. Data were collected during home visits and statistical comparisons were conducted by using chi square tests, t-test and logistic regression. There was significantly more psychological distress "caseness" in IDPs than non-IDPs. The mental health consequences of the violent conflict in Ambon supported the ripple effect hypothesis as displacement status appears to be a strong risk factor for distress, both as a main effect and interaction effect. Significantly higher percentages of IDPs experienced traumatic events than non-IDPs in all six event types reported. This study indicates that the conflict had an impact on mental health and economic conditions far beyond the area where the actual violent events took place, in a diminishing pattern in line with the hypothesis of a ripple effect.


Scanning Tunneling Spectroscopy of Proximity Superconductivity in Epitaxial Multilayer Graphene.
We report on spatial measurements of the superconducting proximity effect in epitaxial graphene induced by a graphene-superconductor interface. Superconducting aluminum films were grown on epitaxial multilayer graphene on SiC. The aluminum films were discontinuous with networks of trenches in the film morphology reaching down to exposed graphene terraces. Scanning tunneling spectra measured on the graphene terraces show a clear decay of the superconducting energy gap with increasing separation from the graphene-aluminum edges. The spectra were well described by Bardeen-Cooper-Schrieffer (BCS) theory. The decay length for the superconducting energy gap in graphene was determined to be greater than 400 nm. Deviations in the exponentially decaying energy gap were also observed on a much smaller length scale of tens of nanometers.


Eating and hypothalamus changes in behavioral-variant frontotemporal dementia.
Behavioral-variant frontotemporal dementia (bvFTD) is a progressive neurodegenerative brain disorder, clinically characterized by changes in cognition, personality, and behavior. Marked disturbances in eating behavior, such as overeating and preference for sweet foods, are also commonly reported. The hypothalamus plays a critical role in feeding regulation, yet the relation between pathology in this region and eating behavior in FTD is unknown. This study aimed to address this issue using 2 complementary approaches. First, 18 early stage bvFTD patients and 16 healthy controls underwent high-resolution structural magnetic resonance imaging and assessment of eating behavior. Hypothalamic volumes were traced manually on coronal images. Second, postmortem analyses of 12 bvFTD cases and 6 matched controls were performed. Fixed hypothalamic tissue sections were stained for a cell marker and for peptides regulating feeding behaviors using immunohistochemistry. Stereological estimates of the hypothalamic volume and the number of neurons and glia were performed. Significant atrophy of the hypothalamus in bvFTD was present in both analyses. Patients with high feeding disturbance exhibited significant atrophy of the posterior hypothalamus. Neuronal loss, which was observed only in bvFTD cases with Tar DNA protein-43 deposition, was also predominant posteriorly. In contrast, orexin (hypocretin), neuropeptide Y, cocaine- and amphetamine-regulating transcript, and vasopressin-containing neurons that regulate appetite were spared in posterior nuclei known to participate in feeding regulation. Degeneration and consequent dysregulation within the hypothalamus relates to significant feeding disturbance in bvFTD. These findings provide a basis for the development of therapeutic models.


The hydrophilic domain of Tic110, an inner envelope membrane component of the chloroplastic protein translocation apparatus, faces the stromal compartment.
It has previously been found that Tic110, an integral protein of the chloroplast inner envelope membrane, is a component of the chloroplastic protein import apparatus. However, conflicting reports exist concerning the topology of this protein within the inner envelope membrane. In this report, we provide evidence that indicates that the large (>90-kDa) hydrophilic domain of Tic110 is localized within the chloroplast stroma. Trypsin, a protease that cannot penetrate the permeability barrier of the inner envelope membrane, degrades neither Tic110 nor other proteins exposed to the stromal compartment but is able to digest proteins exposed to the intermembrane space between the two envelope membranes. Previous reports indicating that trypsin is able to degrade Tic110 were influenced by incomplete quenching of protease activity. When trypsin is not sufficiently quenched, it is able to digest Tic110, but only after chloroplasts have been ruptured. It is therefore necessary to employ adequate quenching protocols, such as the one reported here, whenever trypsin is utilized as an analytical tool. Based on a stromal localization for the majority of Tic110, we propose that this protein may be involved in the recruitment of stromal factors, possibly molecular chaperones, to the translocation apparatus during protein import.


Deficiency of FAM3D (Family With Sequence Similarity 3, Member D), A Novel Chemokine, Attenuates Neutrophil Recruitment and Ameliorates Abdominal Aortic Aneurysm Development.
Chemokine-mediated neutrophil recruitment contributes to the pathogenesis of abdominal aortic aneurysm (AAA) and may serve as a promising therapeutic target. FAM3D (family with sequence similarity 3, member D) is a recently identified novel chemokine. Here, we aimed to explore the role of FAM3D in neutrophil recruitment and AAA development. FAM3D was markedly upregulated in human AAA tissues, as well as both elastase- and CaPO4-induced mouse aneurysmal aortas. FAM3D deficiency significantly attenuated the development of AAA in both mouse models. Flow cytometry analysis indicated that FAM3D-/- mice exhibited decreased neutrophil infiltration in the aorta during the early stage of AAA formation compared with their wild-type littermates. Moreover, application of FAM3D-neutralizing antibody 6D7 through intraperitoneal injection markedly ameliorated elastase-induced AAA formation and neutrophil infiltration. Further, in vitro coculture experiments with FAM3D-neutralizing antibody 6D7 and in vivo intravital microscopic analysis indicated that endothelial cell-derived FAM3D induced neutrophil recruitment. Mechanistically, FAM3D upregulated and activated Mac-1 (macrophage-1 antigen) in neutrophils, whereas inhibition of FPR1 (formyl peptide receptor 1) or FPR2 significantly blocked FAM3D-induced Mac-1 activation, indicating that the effect of FAM3D was dependent on both FPRs. Moreover, specific inhibitors of FPR signaling related to Gi protein or β-arrestin inhibited FAM3D-activated Mac-1 in vitro, whereas FAM3D deficiency decreased the activation of both FPR-Gi protein and β-arrestin signaling in neutrophils in vivo. FAM3D, as a dual agonist of FPR1 and FPR2, induced Mac-1-mediated neutrophil recruitment and aggravated AAA development through FPR-related Gi protein and β-arrestin signaling.


An Ancient Lineage of Highly Divergent Parvoviruses Infects both Vertebrate and Invertebrate Hosts.
Chapparvoviruses (ChPVs) comprise a divergent, recently identified group of parvoviruses (family Parvoviridae), associated with nephropathy in immunocompromised laboratory mice and with prevalence in deep sequencing results of livestock showing diarrhea. Here, we investigate the biological and evolutionary characteristics of ChPVs via comparative in silico analyses, incorporating sequences derived from endogenous parvoviral elements (EPVs) as well as exogenous parvoviruses. We show that ChPVs are an ancient lineage within the Parvoviridae, clustering separately from members of both currently established subfamilies. Consistent with this, they exhibit a number of characteristic features, including several putative auxiliary protein-encoding genes, and capsid proteins with no sequence-level homology to those of other parvoviruses. Homology modeling indicates the absence of a β-A strand, normally part of the luminal side of the parvoviral capsid protein core. Our findings demonstrate that the ChPV lineage infects an exceptionally broad range of host species, including both vertebrates and invertebrates. Furthermore, we observe that ChPVs found in fish are more closely related to those from invertebrates than they are to those of amniote vertebrates. This suggests that transmission between distantly related host species may have occurred in the past and that the Parvoviridae family can no longer be divided based on host affiliation.


[Aeroallergens, skin tests and allergic diseases in 1091 patients].
To know the frequency of positively of several skin tests, data cards from patients, of the Allergy and Clinic Immunology Service of the Hospital de Especialidades del Centro Medico Nacional Siglo XXI (Mexico City), between January, 1989 and March, 1995, were reviewed. Aqueous extracts manufactures by our laboratory were applied, in a dilution of 1:1000 weight-volume. 1091 from 5,651 skin tests patients were positive. Asthma and rhinitis were diagnosed in 492, allergic rhinitis in 289, allergic asthma in 111, and other diagnosis in 199 cases. The most frequent inhalable aeroallergens were house dust and perennial Dermatophagoides p and f1 with predominance in the rainy season, followed by pollens from Fraxinus a. Quercus a and Capriola, with predominance in the rainy season. The most frequent fungi were Candida and Fusarium, with predominance in the dry season.


Challenges of virtual interviewing for surgical fellowships: a qualitative analysis of applicant experiences.
The COVID-19 pandemic forced surgical fellowship programs to transition from in-person to remote applicant interviews; the virtual interviewing format presented new and unique challenges. We sought to understand applicants' perceived challenges to virtual interviewing for a surgical fellowship program. A grounded theory-based qualitative study was performed utilizing semi-structured interviews with fellowship applicants from the 2020 fellowship match. All Fellowship Council-registered applicants were eligible. We purposefully sampled participants to balance across gender, specialty-choice, and academic versus community-program affiliation. Interviews were inductively analyzed by two researchers for prominent themes. Fifteen interviews were conducted. Participants were 60% male (n = 9), with 33% (n = 5) from non-academic institutions. They applied for the following fellowships: Advanced Gastrointestinal/Minimal Invasive (55%), Bariatric (30%), Hepatopancreatobiliary (10%) and Surgical Oncology (5%). Four main themes emerged to describe virtual interview process challenges: (1) perceived data deficiency, (2) superficial personal connections, (3) magnification of non-professionalism, and (4) logistical frustrations. Applicants recommend program directors provide more information about the fellowship prior to interview day and offer informal independent interactions with current and previous fellows. According to fellowship applicants, virtual interviews resulted in a lack of information for rank-list decision making ultimately requiring them to rely on other information avenues to base their decisions. These applicants have offered advice to fellowship program directors and future applicants to better optimize this process.


[Mercury strain gauge plethysmography. A noninvasive exploration method for monitoring the efficacy of treatment of deep venous thrombosis].
The plethysmographic tracings of a patient presenting a deep venous thrombosis, give information about the functional evolution of the affected limb. The plethysmographic parameters which are used to estimate the efficacy of the treatment of the deep venous thrombosis are: the venous capacitance, the venous outflow and the venous pressure. These values are always compared with the contralateral limb. The decision to stop an anticoagulant treatment is made after observing an increase of the venous capacitance and outflow and, simultaneously, a decrease of the venous pressure. During the last three years, we have followed up 200 patients with this method. It allows a rational therapeutic management which is based on the objective monitoring of the functional potentialities of the venous system.


Computational analysis to repurpose drugs for COVID-19 based on transcriptional response of host cells to SARS-CoV-2.
The Coronavirus Disease 2019 (COVID-19) pandemic has infected over 10 million people globally with a relatively high mortality rate. There are many therapeutics undergoing clinical trials, but there is no effective vaccine or therapy for treatment thus far. After affected by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), molecular signaling pathways of host cells play critical roles during the life cycle of SARS-CoV-2. Thus, it is significant to identify the involved molecular signaling pathways within the host cells. Drugs targeting these molecular signaling pathways could be potentially effective for COVID-19 treatment. In this study, we developed a novel integrative analysis approach to identify the related molecular signaling pathways within host cells, and repurposed drugs as potentially effective treatments for COVID-19, based on the transcriptional response of host cells. We identified activated signaling pathways associated with the infection caused SARS-CoV-2 in human lung epithelial cells through integrative analysis. Then, the activated gene ontologies (GOs) and super GOs were identified. Signaling pathways and GOs such as MAPK, JNK, STAT, ERK, JAK-STAT, IRF7-NFkB signaling, and MYD88/CXCR6 immune signaling were particularly activated. Based on the identified signaling pathways and GOs, a set of potentially effective drugs were repurposed by integrating the drug-target and reverse gene expression data resources. In addition to many drugs being evaluated in clinical trials, the dexamethasone was top-ranked in the prediction, which was the first reported drug to be able to significantly reduce the death rate of COVID-19 patients receiving respiratory support. The integrative genomics data analysis and results can be helpful to understand the associated molecular signaling pathways within host cells, and facilitate the discovery of effective drugs for COVID-19 treatment.


Eating-related problems among 13-15 year old Swedish adolescents: frequency and stability over a one-year period.
The frequency of eating-related problems in young adolescents, and their stability over a one-year period, was studied by the RiBED-8 (Risk Behaviours related to Eating Disorders, 8 items) in a community sample of 13-15 year old adolescents who took part in a prospective study with a 2-wave longitudinal design. The RiBED-8 was found to have good reliability and construct validity among the girls, although it did not show equally convincing psychometric properties among boys. With a cut-off of at least three critical answers on the RiBED-8, 28.5-31.0% of the girls were seen as risk cases for the development of eating disorder. Of those girls who were risk cases at Time 1, a majority (68.8%) remained so at Time 2; of those girls who were not risk cases at Time 1, 16.1% became risk cases at Time 2. It is suggested that the RiBED-8 is a brief, easily administered instrument that may be potentially useful in screening for eating-related problems among girls.


A mathematical model for designing networks of C-Reactive Protein point of care testing.
One approach to improving antibiotic stewardship in primary care may be to support all General Practitioners (GPs) to have access to point of care C-Reactive Protein tests to guide their prescribing decisions in patients presenting with symptoms of lower respiratory tract infection. However, to date there has been no work to understand how clinical commissioning groups might approach the practicalities of system-wide implementation. We aimed to develop an accessible service delivery modelling tool that, based on open data, could generate a layout of the geographical distribution of point of care facilities that minimised the cost and travel distance for patients across a given region. We considered different implementation models where point of care tests were placed at either GP surgeries, pharmacies or both. We analysed the trade-offs between cost and travel found by running the model under different configurations and analysing the model results in four regions of England (two urban, two rural). Our model suggests that even under assumptions of short travel distances for patients (e.g. under 500m), it is possible to achieve a meaningful reduction in the number of necessary point of care testing facilities to serve a region by referring some patients to be tested at nearby GP surgeries or pharmacies. In our test cases pharmacy-led implementation models resulted in some patients having to travel long distances to obtain a test, beyond the desired travel limits. These results indicate that an efficient implementation strategy for point of care tests over a geographic region, potentially building on primary care networks, might lead to significant cost reduction in equipment and associated personnel training, maintenance and quality control costs; as well as achieving fair access to testing facilities.


The phosphatidylinositol 4,5-biphosphate and TORC2 binding proteins Slm1 and Slm2 function in sphingolipid regulation.
The Stt4 phosphatidylinositol 4-kinase has been shown to generate a pool of phosphatidylinositol 4-phosphate (PI4P) at the plasma membrane, critical for actin cytoskeleton organization and cell viability. To further understand the essential role of Stt4-mediated PI4P production, we performed a genetic screen using the stt4(ts) mutation to identify candidate regulators and effectors of PI4P. From this analysis, we identified several genes that have been previously implicated in lipid metabolism. In particular, we observed synthetic lethality when both sphingolipid and PI4P synthesis were modestly diminished. Consistent with these data, we show that the previously characterized phosphoinositide effectors, Slm1 and Slm2, which regulate actin organization, are also necessary for normal sphingolipid metabolism, at least in part through regulation of the calcium/calmodulin-dependent phosphatase calcineurin, which binds directly to both proteins. Additionally, we identify Isc1, an inositol phosphosphingolipid phospholipase C, as an additional target of Slm1 and Slm2 negative regulation. Together, our data suggest that Slm1 and Slm2 define a molecular link between phosphoinositide and sphingolipid signaling and thereby regulate actin cytoskeleton organization.


In-vivo protection of group A beta-haemolytic streptococci from penicillin by beta-lactamase-producing Bacteroides species.
The incidence of persistent group A beta-haemolytic streptococci in tonsils, despite penicillin therapy, has increased in recent years. beta-Lactamase-producing organisms have previously been recovered from 74% of patients with persisting group A streptococci. We investigated the possibility that beta-lactamase-producing strains of Bacteroides spp. can protect streptococci from penicillin. A mixed infection was induced in mice in the form of a subcutaneous abscess involving a penicillin-susceptible group A streptococcus, and a beta-lactamase-producing strain of either Bact. melaninogenicus or Bact. fragilis. The infected animals were treated for seven days with parenteral penicillin, penicillin and clavulanic acid or clindamycin. Penicillin treatment prevented the formation of abscesses in animals inoculated with group A streptococci alone, but not in those inoculated with group A streptococci and Bacteroides spp. We attributed this resistance to penicillin therapy, and the subsequent formation of abscesses in mice, to protection of the streptococci from penicillin by beta-lactamase-producing strains of Bacteroides spp. Effective therapy for mixed infections was achieved when clavulanic acid, a beta-lactamase inhibitor, was administered with penicillin. A similar effect was noted with clindamycin, which is active against both group A streptococci and Bacteroides spp.


Microbial adherence to cosmetic contact lenses.
To investigate whether cosmetic contact lenses (CCL) with surface pigments affect microbial adherence. Fifteen brands of CCL were purchased from optical, non-optical retail outlets, and via the Internet. A standardized rub-off test was performed on each CCL (five lenses per brand) to confirm the location of the pigments. The rub-off test comprised gentle rubbing on the surfaces of each CCL with wetted cotton buds for a maximum of 20 rubs per surface. A new set of CCL (five lenses per brand) were incubated in Pseudomonas aeruginosa overnight. Viable counts of adhered bacteria were determined by the number of colony-forming units (CFU) on agar media on each lens. The adherence of P. aeruginosa as well as Staphylococcus aureus and Serratia marcescens to three brands of CCL (A-C) (five lenses per brand) were also compared to their adherences on their clear counterparts. Only two of the 15 brands of CCL tested (brands B and C) had pigments that did not detach with the rub-off test. The remaining 13 brands of CCL all failed the rub-off test and these lenses showed higher P. aeruginosa adherence (8.7 × 10(5)-1.9 × 10(6) CFU/lens). Brands B and C lenses showed at least six times less bacterial adhesion than the other 13 brands. Compared to their clear counterparts, bacterial adherence to brands B and C lenses did not differ significantly, whereas brand A lenses showed significantly higher adherence. Surface pigments on CCL resulted in significantly higher bacterial adherence.


Patients with ERCC1-negative locally advanced esophageal cancers may benefit from preoperative chemoradiotherapy.
To assess the significance of excision repair cross-complementation group 1 (ERCC1) expression as a predictive marker, we analyzed the effects of preoperative chemoradiotherapy on survival relative to ERCC1 status in patients with locally advanced operable esophageal cancer. Paraffin-embedded pretreatment tumor specimens, collected by endoscopic biopsy from patients treated with surgery alone or with preoperative chemoradiotherapy followed by surgery, were immunohistochemically assayed for ERCC1 expression. Of the 175 patients, 152 biopsy specimens were available for immunohistochemical analysis. Based on a median ERCC1 expression score of 1, we divided the samples into ERCC1-positive (score >1; 71 patients, 47%) and ERCC1-negative (score </=1; 81 patients, 53%) groups. No differences in patient and disease characteristics were observed between the two groups. However, among patients with ERCC1-negative tumors, those who received preoperative chemoradiotherapy had longer overall survival (OS) and event-free survival (EFS) than those treated with esophagectomy alone (median OS, 59.2 versus 25.4 months, P = 0.057; median EFS, 50.7 versus 19.7 months, P = 0.042). This difference was not observed among patients with ERCC1-positive tumors. In multivariate analysis, treatment modality was the major determinant of both EFS (P = 0.006) and OS (P = 0.008) for patients with ERCC1-negative tumors, whereas Eastern Cooperative Oncology Group performance status was the only significant predictor of outcome among ERCC1-positive patients. Among patients who received esophagectomy alone, those with ERCC1-positive tumors had a tendency toward longer OS and EFS (P = 0.085 and 0.094, respectively). Patients with ERCC1-negative operable esophageal tumors show a greater benefit from preoperative chemoradiotherapy followed by esophagectomy than those who undergo esophagectomy alone.


Endogenous regulator of G-protein signaling proteins modify N-type calcium channel modulation in rat sympathetic neurons.
Experiments using heterologous overexpression indicate that regulator of G-protein signaling (RGS) proteins play important roles in Gbetagamma-mediated ion channel modulation. However, the roles subserved by endogenous RGS proteins have not been extensively examined because tools for functionally inhibiting natively expressed RGS proteins are lacking. To address this void, we used a strategy in which Galpha(oA) was rendered insensitive to pertussis toxin (PTX) and RGS proteins by site-directed mutagenesis. Either PTX-insensitive (PTX-i) or both PTX- and RGS-insensitive (PTX/RGS-i) mutants of Galpha(oA) were expressed along with Gbeta(1) and Ggamma(2) subunits in rat sympathetic neurons. After overnight treatment with PTX to suppress natively expressed Galpha subunits, voltage-dependent Ca(2+) current inhibition by norepinephrine (NE) (10 microm) was reconstituted in neurons expressing either PTX-i or PTX/RGS-i Galpha(oA). When compared with neurons expressing PTX-i Galpha(oA), the steady-state concentration-response relationships for NE-induced Ca(2+) current inhibition were shifted to lower concentrations in neurons expressing PTX/RGS-i Galpha(oA). In addition to an increase in agonist potency, the expression of PTX/RGS-i Galpha(oA) dramatically retarded the current recovery after agonist removal. Interestingly, the alteration in current recovery was accompanied by a slowing in the onset of current inhibition. Together, our data suggest that endogenous RGS proteins contribute to membrane-delimited Ca(2+) channel modulation by regulating agonist potency and kinetics of G-protein-mediated signaling in neuronal cells.


Tendencies and outcomes in endoscopic biliary sphincterotomies among people with or without type 2 diabetes mellitus in Spain, 2003-2013.
We aimed to compare incidence and outcomes for endoscopic biliary sphincterotomies in people with or without type 2 diabetes mellitus (T2DM) in Spain (2003-2013). We collected all cases of endoscopic biliary sphincterotomies using national hospital discharge data and evaluated annual incident rates stratified by T2DM status. We analyzed trends over time for in-hospital mortality (IHM) as the primary outcome and a composite of IHM or procedure-related complications (key secondary outcome). In multivariate analyses, we tested T2DM as an independent factor of IHM and IHM or complications. We identified 126,885 endoscopic biliary sphincterotomies (23,002 [18.1%] in T2DM people). Crude incidence rates of endoscopic biliary sphincterotomies were > 3-fold higher in people with vs without T2DM (85.5/105 vs 26.9/105 population, respectively). Annual incidence rates of endoscopic biliary sphincterotomies showed 11-year relative increments of 77.5% (from 60.0 to 106.5/105) in T2DM, and 53.7% (from 21.6 to 33.2/105) in non-T2DM people (p < 0.001). We found no significant changes in mortality trends over time for the populations with or without T2DM (p = 0.15 and p = 0.21, respectively). Rates of procedural pancreatitis decreased in people without T2DM (p < 0.001). In the multivariate analysis, older age, higher comorbidity and endoscopic biliary sphincterotomy during urgent admission were associated with a higher IHM. T2DM was associated with a lower IHM after an endoscopic biliary sphincterotomy (OR = 0.82 [0.74-0.92]). Time trend multivariate analyses 2003-2013 showed significant reductions in IHM over time only in people with T2DM (OR = 0.97 [0.94-1.00]). Further studies are needed to confirm a lower IHM for endoscopic biliary sphincterotomies in people with T2DM.


Lactobacillus acidophilus suppresses intestinal inflammation by inhibiting endoplasmic reticulum stress.
Nuclear factor kappa B (NF-κB) activation and endoplasmic reticulum (ER) stress signaling play significant roles in the pathogenesis of inflammatory bowel disease (IBD). Thus, we evaluated whether new therapeutic probiotics have anti-colitic effects, and we investigated their mechanisms related to NF-κB and ER-stress pathways. Luciferase, nitric oxide, and cytokine assays using HT-29 or RAW264.7 cells were conducted. Mouse colitis was induced using dextran sulfate sodium and confirmed by disease activity index and histology. Macrophages and T-cell subsets in isolated peritoneal cavity cells and splenocytes were analyzed by flow cytometry. Gene and cytokine expression profiles were determined using reverse-transcription polymerase chain reaction. Lactobacillus acidophilus (LA1) and Pediococcus pentosaceus inhibited nitric oxide production in RAW264.7 cells, but only LA1 inhibited Tnfa and induced Il10 expression. LA1 increased the lifespan of dextran sulfate sodium-treated mice and attenuated the severity of colitis by inducing M2 macrophages in peritoneal cavity cells and Th2 and Treg cells in splenocytes. The restoration of goblet cells in the colon was accompanied by the induction of Il10 expression and the suppression of pro-inflammatory cytokines. Additionally, we found that LA1 exerts an anti-colitic effect by improving ER stress in HT-29 cells as well as in vivo. We showed that LA1 significantly interferes with ER stress and suppresses NF-κB activation. Our findings suggest that LA1 can be used as a potent immunomodulator in IBD treatment, and the regulation of ER stress may have significant implications in treating IBD.


Calmodulin mediates Ca2+ sensitivity of sodium channels.
Ca2+ has been proposed to regulate Na+ channels through the action of calmodulin (CaM) bound to an IQ motif or through direct binding to a paired EF hand motif in the Nav1 C terminus. Mutations within these sites cause cardiac arrhythmias or autism, but details about how Ca2+ confers sensitivity are poorly understood. Studies on the homologous Cav1.2 channel revealed non-canonical CaM interactions, providing a framework for exploring Na+ channels. In contrast to previous reports, we found that Ca2+ does not bind directly to Na+ channel C termini. Rather, Ca2+ sensitivity appears to be mediated by CaM bound to the C termini in a manner that differs significantly from CaM regulation of Cav1.2. In Nav1.2 or Nav1.5, CaM bound to a localized region containing the IQ motif and did not support the large Ca(2+)-dependent conformational change seen in the Cav1.2.CaM complex. Furthermore, CaM binding to Nav1 C termini lowered Ca2+ binding affinity and cooperativity among the CaM-binding sites compared with CaM alone. Nonetheless, we found suggestive evidence for Ca2+/CaM-dependent effects upon Nav1 channels. The R1902C autism mutation conferred a Ca(2+)-dependent conformational change in Nav1.2 C terminus.CaM complex that was absent in the wild-type complex. In Nav1.5, CaM modulates the Cterminal interaction with the III-IV linker, which has been suggested as necessary to stabilize the inactivation gate, to minimize sustained channel activity during depolarization, and to prevent cardiac arrhythmias that lead to sudden death. Together, these data offer new biochemical evidence for Ca2+/CaM modulation of Na+ channel function.


Enzyme Databases in the Era of Omics and Artificial Intelligence.
Enzyme research is important for the development of various scientific fields such as medicine and biotechnology. Enzyme databases facilitate this research by providing a wide range of information relevant to research planning and data analysis. Over the years, various databases that cover different aspects of enzyme biology (e.g., kinetic parameters, enzyme occurrence, and reaction mechanisms) have been developed. Most of the databases are curated manually, which improves reliability of the information; however, such curation cannot keep pace with the exponential growth in published data. Lack of data standardization is another obstacle for data extraction and analysis. Improving machine readability of databases is especially important in the light of recent advances in deep learning algorithms that require big training datasets. This review provides information regarding the current state of enzyme databases, especially in relation to the ever-increasing amount of generated research data and recent advancements in artificial intelligence algorithms. Furthermore, it describes several enzyme databases, providing the reader with necessary information for their use.


Sequence homology and immunologic cross-reactivity of human cytomegalovirus with HLA-DR beta chain: a means for graft rejection and immunosuppression.
A peptide (Leu-Gly-Arg-Pro-Asp-Glu-Asp-Ser-Ser-Ser-Ser-Ser-Ser-Ser-Cys) that was identical to residues 82 through 96 of a predicted protein of 208 amino acids from the immediate-early region (IE-2) nucleic acid sequence of human cytomegalovirus was chemically synthesized. By computer analysis, the first five amino acids of this peptide showed sequence homology to the beta chain of the human histocompatibility complex HLA-DR. The homologous amino acids, 53 through 57, were located in a region that is conserved between the human DR beta chain and the beta chain of the H-2 class II histocompatibility antigen for mice. The shared region between the IE-2 protein and DR beta chain were similar in both hydrophilicity and predicted beta-turn potential. The IE-2 viral peptide induced antibodies that specifically recognized the human DR beta chain. These observations describe a protein encoded by the IE-2 region of human cytomegalovirus that contains sequence homology and shows immunologic cross-reactivity with a conserved domain of HLA-DR and suggest a mechanism to explain how human cytomegalovirus infection contributes to graft rejection after transplantation.


Health Characteristics Associated With Hot Flashes in Women With HIV During Menopause: An Integrative Review.
Hot flashes (HFs) are a prominent symptom of menopause known to unfavorably influence mood, sleep, and quality of life. More women living with HIV are entering menopause and may experience a greater prevalence of HFs and more severe HFs compared with uninfected women. This integrative review evaluated existing evidence on potential health characteristics associated with HFs in women living with HIV during menopause. A search strategy was conducted within 6 databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guided the review, and the Johns Hopkins Nursing Evidence-Based Practice model was used to evaluate methodological quality and appraisal of the evidence. Five articles met the review eligibility criteria. Three content categories emerged from the key findings of the 5 articles: HIV-specific characteristics, mental health and cognitive characteristics, and quality of life and social characteristics. Implications for research and clinical care were identified.


Current Insights.
The Current Insights feature is designed to introduce life science educators and researchers to current articles of interest in other social science and education journals. In this installment, I highlight three recent studies from the fields of psychology and higher education that can inform practices in the life sciences. The first is a synthesis paper that builds a unifying framework for the diverse activities that fall under the umbrella term "active learning." This paper emphasizes a novel aspect of the active-learning classroom: student agency. The second paper employs an underutilized framework in biology education research, quantitative critical theory, to explore why faculty-student interactions may not be universally beneficial. The third paper explores how valuing relationships can keep first-generation college students from reaching out for help when they need it. Together, these last two papers help researchers understand the perceived costs and benefits of seeking help from faculty.


Measurements of intraocular pressure throughout the pregnancy in Pakistani women.
Decrease in intraocular pressure (IOP) during pregnancy has been reported by previous studies, but amount of decrease varies from study to study. Moreover, previous studies have concentrated on the last trimester of pregnancy or one reading per trimester. IOP changes throughout the pregnancy have never been described. Therefore, the present study was planned to determine IOP throughout the pregnancy, after placing control on IOP affecting factors. Thirty-six pregnant and same numbers of non-pregnant women of the same age group were studied. IOP measurements were taken at four week intervals throughout the pregnancy, with the Goldmann applanation tonometer. As compared to control subjects, up to 8th week, IOP remained the same. At 12th week, it becomes significantly lower. The IOP differences between first and second (P < 0.05), and second and third (P < 0.001) trimesters of pregnancy were significant. In every subject, IOP decreased during pregnancy. However, there were variations among individuals in the extent of IOP decrease. With advancing pregnancy, intraocular pressure decreases. Knowledge of the normal level of intraocular pressure in various stages of pregnancy may help glaucoma screeners.


[Phosphorescence analysis of the chlorophyll triplet state in preparations of photosystem II].
The low-temperature (77 K) phosphorescence of chlorophyll (Chl) in the reaction centres (D1D2-cyt b559-particles) and the core complexes of photosystem II isolated from higher plants was studied. Two phosphorescence spectral bands with the emission maxima at 950 and 977 nm, excitation maxima at 666 and 675-680 nm, and the lifetimes equal to 2 and 1.5 ms, respectively, were registered. The data indicate that the phosphorescence corresponds to the triplet Chl a molecules spatially separated from carotenoids. In samples treated by potassium ferricyanide and frozen under illumination by red light, the intensities of both bands were reduced, but the decrease of the short-wavelength 950-nm band was much more pronounced. This allows an assumption that the short-wavelength phosphorescence belongs to Chl a molecules, which are more accessible for ferricyanide because they are located on the surface of the chlorophyll-protein complexes, whereas the long-wavelength phosphorescence is emitted by the Chl molecules located inside the D1D2 heterodimer and therefore, is more protected by protein macromolecules.


Shared versus separate processes for letter and digit identification.
Letters and digits, although similar in many respects, also differ in potentially significant ways. Most importantly, letters are elements of an alphabetic writing system, whereas digits are logographs. In this article, we explore whether letters and digits are identified by a single character identification process that makes no fundamental distinction between the two types of characters, or whether instead letter and digit identification processes diverge at least in some respects. We present evidence from an acquired dyslexic patient, L.H.D., who is impaired in both letter and digit identification. Working within a theoretical framework specifying the levels of representation implicated in letter identification, we systematically compare L.H.D.'s letter and digit processing. The results provide evidence that letter and digit identification implicate the same levels of representation, and further that L.H.D.'s identification errors for both letters and digits arise at the same point in processing. On the basis of these results, we argue for a shared process that mediates identification of both letters and digits. Finally, we discuss relevant previous results in light of this conclusion.


Expression of KISS1 and MMP-9 in non-small cell lung cancer and their relations to metastasis and survival.
KISS1 and matrix metalloproteinase-9 (MMP-9) may play important roles as metastasis suppressor and metastasis promoter genes, respectively, in a variety of malignancies. However, there is little information about their possible roles in non-small cell lung cancer (NSCLC). The goals of this study were to determine the mRNA and protein expressions of KISS1 and MMP-9 in NSCLC and their relations to metastasis and prognosis. The mRNA and protein expressions of KISS1 and of MMP-9 protein were detected by in situ hybridization and immunohistochemistry respectively in 85 cases of NSCLC, and their matched lymph node metastases. Expressions of KISS1 mRNA and protein were significantly higher in low TNM stages of NSCLC (I-II) compared to more advanced stages (III-IV) (p<0.05). Moreover, in advanced TNM stages, cases without metastasis had higher KISS1 gene expression compared to those with lymph node metastasis (p<0.05). In contrast, MMP-9 expression was higher in stage III-IV NSCLC cases compared to stage I-II tumors (p<0.05) and higher in NSCLC cases with metastasis than those without metastasis (p<0.05). There was negative correction between KISS1 and MMP-9 protein expression (p<0.01). The 5-year survival rate in cases with higher KISS1 protein expression was significantly higher than in those with low expression (20.9 vs. 2.4%, p<0.01). However, the 5-year survival rate of patients with high MMP-9 protein expression were lower than those with low expression (19 vs. 4.7%, p<0.05). Our data suggest that KISS1 and MMP-9 may serve as potential prognostic and therapeutic markers in lung cancer.