Pattern-reversal visual evoked potentials in migraineurs with or without visual aura.
To determine the possible electrophysiologic changes in migraineurs with or without visual aura, we investigated pattern-reversal visual evoked potentials in 39 patients. We compared the mean P100 latency and amplitude of 16 patients with aura, 23 patients without aura, and 17 age- and sex-matched normal subjects. There were no significant differences between groups. There was no correlation between age and the parameters in any group. However, in 7 of 23 patients without aura, the P100 latency was longer than the mean control value +2 SD. The mean disease duration in this subgroup was significantly longer than the means of the remaining 16 patients without aura or the patients with aura (P < 0.05 for each). This suggests the possibility that P100 latency prolongation is a consequence, but not an entity caused by the pathogenetic mechanism of the disease from the beginning.


Human papillomavirus and p16INK4a in oropharyngeal squamous cell carcinomas: A systematic review and meta-analysis.
We intended to update human papillomavirus (HPV) prevalence and p16INK4a positivity in oropharyngeal squamous cell carcinomars (SCC), and calculate HPV attributable fraction (AF) for oropharyngeal SCC by geographic region. We searched Medline, Embase, and the Cochrane Library to identify published studies of HPV prevalence and p16INK4a positivity alone or together in oropharyngeal SCC before December 28, 2021. Studies that reported type-specific HPV DNA prevalence using broad-spectrum PCR-based testing methods were included. We estimated pooled HPV prevalence, type-specific HPV prevalence, and p16INK4a positivity. AF of HPV was calculated by geographic region. One hundred and thirty-four studies including 12 139 cases were included in our analysis. The pooled HPV prevalence estimate for oropharyngeal SCC was 48.1% (95% confidence interval [CI] 43.2-53.0). HPV prevalence varied significantly by geographic region, and the highest HPV prevalence in oropharyngeal SCC was noted in North America (72.6%, 95% CI 63.8-80.6). Among HPV positive cases, HPV 16 was the most common type with a prevalence of 40.2% (95% CI 35.7-44.7). The pooled p16INK4a positivity in HPV positive and HPV16 positive oropharyngeal SCC cases was 87.2% (95% CI 81.6-91.2) and 91.7% (84.3-97.2). The highest AFs of HPV and HPV16 were noted in North America at 69.6% (95% CI 53.0-91.5) and 63.0% (48.0-82.7). [Correction added on 31 October 2023, after first online publication: the percentage symbol (%) was missing and has been added to 63.0% (48.0-82.7) in the Abstract and Conclusion.] A significant proportion of oropharyngeal SCC was attributable to HPV. HPV16 accounts for the majority of HPV positive oropharyngeal SCC cases. These findings highlight the importance of HPV vaccination in the prevention of a substantial proportion of oropharyngeal SCC cases.


A syndrome of depression and mutism in the Oglala Sioux.
The wacinko syndrome in the Oglala Sioux varies from a nonclinical reaction to pathological degrees of anger, pouting, withdrawal, depression, psychomotor retardation, mutism, immobility, and even to suicide. Although indigenous proctitioners recognize the syndrome as a distinctive disorder, it has not been described by non-Indian practitioners. The author presents a case report and suggests that most cases are diagnosable as reactive depressive illness.


Designing Videos With and for Adults With ADHD for an Online Intervention: Participatory Design Study and Thematic Analysis of Evaluation.
Adults with attention deficit hyperactivity disorder (ADHD) represent a heterogeneous group with both strengths and difficulties associated with the diagnosis. An online intervention attuned to their needs may improve their everyday functioning. When designing online interventions, it is important to adapt the therapeutic content to the values and needs of the target group. This paper describes and evaluates a participatory process used to produce content for an online intervention for adults with ADHD by producing video vignettes clarifying core training principles grounded in the participants' everyday experiences. We report on the qualitative data from 2 research phases: the design and evaluation of video vignettes for an online intervention. In the first phase, 12 adults with ADHD, 2 clinicians, and 2 research assistants participated in the production of video vignettes for the online intervention. In the second phase, participants (n=109) gave feedback on the videos as part of a clinical trial of the intervention. A subgroup (n=7) was interviewed in-depth regarding their experiences with the videos. The qualitative data were analyzed using thematic analysis. In the first phase, the participants with ADHD contributed with experiences from challenging everyday situations. In the process, we navigated between therapeutic principles and the participants' experiential perspectives to create content relevant and consistent with the target group's values and experiences. In the second phase, we identified 3 themes related to the participants' experiences and interpretation of the video vignettes: (1) recognition of ADHD-related challenges, (2) connection with the characters and the situations, and (3) video protagonists as companions and role models for change. A participatory design process for designing online mental health interventions can be used to probe and balance between the therapeutic principles defined by clinicians and the participants' experiences with mental health issues in the production of therapeutic content. In our study, the inclusion of video vignettes in an online intervention enabled a contextualized and relevant presentation of everyday experiences and psychosocial factors in the life of an adult with ADHD. ClinicalTrials.gov NCT04511169; https://clinicaltrials.gov/ct2/show/NCT04511169.


Untapped potential of commercial drivers in providing post-crash care to road traffic accident victims: A cross-sectional study from fast urbanizing city of Jodhpur, India.
Most road traffic accident (RTA) deaths occur before victim reaches a definitive trauma care facility. The aim of the study was to determine the role of commercial drivers toward providing post-crash care to RTA victims in Jodhpur, Rajasthan. This cross-sectional study assessed the role of commercial auto-rickshaw and cab drivers for providing post-crash care in urban Jodhpur during 2019-2020. Eligible participants volunteering for the study were included from taxi and auto stands in urban Jodhpur. A pre-tested questionnaire was administered by a trained interviewer. Data analysis was done using SPSS v23.0. Summary measures in terms of frequencies, means, and range are reported. Chi-square test, Fisher's Exact test, and Multivariate Logistic Regression analysis were done for statistical associations. Two hundred male participants completed the study with a mean age of 37.74 (8.96) years having an average work experience as commercial drivers of more than 10 years. Over 70% of participants witnessed RTA in the past year and 52% provided care to victims. The knowledge of post-crash care was most affected by their education level (adjusted odds ratio [aOR]: 1.778, 95% confidence interval [CI]: 0.958, 3.301), whereas the intended post-crash care practices were significantly better among participants with previous training (aOR: 15.376, 95% CI: 2.149, 110.017). The current study establishes the role of commercial drivers as first responders at accident sites in the fast urbanizing city of Jodhpur, Rajasthan. Systematic capacity building initiatives of commercial drivers to salvage RTA victims have potential to strengthen pre-hospital trauma care continuum in non-metro districts of India experiencing high burden of accidents.


Accuracy and reproducibility of artemis central flap thickness and visual outcomes of LASIK with the Carl Zeiss Meditec VisuMax femtosecond laser and MEL 80 excimer laser platforms.
To quantify the accuracy and reproducibility of central flap thickness for flaps created with the VisuMax femtosecond laser system. This was a prospective study of 24 eyes of 12 myopic LASIK patients. The VisuMax femtosecond laser was used to create flaps with an intended central flap thickness of 110 microm. Artemis 1 very high-frequency digital ultrasound scans were performed preoperatively and 3 months postoperatively. Central flap thickness was calculated as the addition of the preoperative epithelial thickness and the postoperative stromal component of the flap. Descriptive statistics (mean, standard deviation, minimum, maximum, and range) of central Reinstein Flap Thickness were calculated for all flaps. Central flap thickness accuracy was calculated as the difference between the mean and intended flap thickness. Reproducibility was evaluated as the flap thickness standard deviation between eyes. At 3 months, mean central Reinstein Flap Thickness was 112.3+/-7.9 microm (range: 102.6 to 132.9 microm). The accuracy was +2.3 microm and reproducibility was 7.9 microm. On average, the flap diameter was 0.47+/-0.21 mm greater than the intended flap diameter. The VisuMax femtosecond laser system was found to create flaps accurate to the intended thickness in the center with a low standard deviation, which will help reduce the risk of obtaining an excessively thick flap.


Immunochemical detection of a common antigen among Streptococcus uberis isolates.
Fifty-three isolates of Streptococcus uberis from various sources were examined for the presence of a common antigen. Initially, a serum was produced in rabbits which, by using rocket line immunoelectrophoresis, proved to react with identity to all of the S. uberis crude extracts as well as group B and E streptococcal extracts. The antigen(s) responsible for this cross-reactivity was partially purified by Sephacryl S-200 gel chromatography and analyzed by fused rocket immunoelectrophoresis. Further analysis by immunodiffusion showed that probably two antigens in the gel chromatography-consolidated fractions were common to the S. uberis and group B and E isolates, but that one of the antigens present was unique to S. uberis. Trypsin destroyed the immunoreactivity of this antigen. Isolation of this common antigen could possibly alleviate some of the tedium associated with the identification of this organism.


PET/MR in Head and Neck Cancer - An Update.
In academic centers, PET/MR has taken the road to clinical nuclear medicine in the past 6 years since the last review on its applications in head and neck cancer patients in this journal. Meanwhile, older sequential PET + MR machines have largely vanished from clinical sites, being replaced by integrated simultaneous PET/MR scanners. Evidence from several studies suggests that PET/MR overall performs equally well as PET/CT in the staging and restaging of head and neck cancer and in radiation therapy planning. PET/MR appears to offer advantages in the characterization and prognostication of head and neck malignancies through multiparametric imaging, which demands an exact preparation and validation of imaging modalities, however. The majority of available clinical PET/MR studies today covers FDG imaging of squamous cell carcinoma arising from a broad spectrum of locations in the upper aerodigestive tract. In the future, specific PET/MR studies are desired that address specific histopathological tumor entities, nonepithelial malignancies, such as major salivary gland tumors, squamous cell carcinomas arising in specific locations, and malignancies imaged with non-FDG radiotracers. With the advent of digital PET/CT scanners, PET/MR is expected to partake in future technical developments, such as novel iterative reconstruction techniques and deviceless motion correction for respiration and gross movement in the head and neck region. Owing to the still comparably high costs of PET/MR scanners and facility requirements on the one hand, and the concentration of multidisciplinary head and neck cancer treatment mainly at academic centers on the other hand, a more widespread use of this imaging modality outside major hospitals is currently limited.


Postnatal development of the area centralis of the kitten retina: an electron microscopic study.
The postnatal development of the area centralis of the kitten retina was followed with the electron microscope. After birth, small but well developed photoreceptor outer segments were observed. Cone pedicles formed triads and bipolar cells formed dyads; so, potentially, cone pathways to the ganglion cell were present at this time. By the start of the second week, rod spherules formed shallow invaginations containing both central and lateral processes and rod bipolar cells formed dyads. Thus, potentially, rod pathways to the ganglion cell were present. By the end of the third week, the area centralis was sufficiently well developed to take advantage of the clearing of the optical media which occurs in postnatal development. Maturity was attained during the fifth week.


[Medicines and the body: what is it consumers think and know about medicines].
Little is known about what patients think of the medicines they take. Such knowledge could be of importance for health results. In a primary care setting, the knowledge about pharmacokinetics, pharmacodynamics and about how medicines work in the body were addressed through a validated questionnaire for self fulfillment, in anonymity, to be returned by mail. 272 questionnaires were received representing the population in study in gender and age. As main results knowledge about pharmacokinetics, pharmacodynamics is scarce and there is good knowledge about drug adverse events even though patients don't know how it is medicines work in the body and show very good knowledge about safety medicine's issues. As main conclusions there is little knowledge about how medicines work in the body, much information work being needed to upgrade what patients know in order to ameliorate health results, when medicines are needed.


Factors Associated With Intention and Use of e-Mental Health by Mental Health Counselors in General Practices: Web-Based Survey.
Mental health care counselors have a high intention to use e-mental health (EMH), whereas actual use is limited. Facilitating future use requires insight into underlying factors as well as eligibility criteria that mental health care counselors use in their decision to apply EMH. The aim of this study was to unfold the intention and underlying reasons for mental health counselors to use EMH and to unveil the criteria they use to estimate patient eligibility for EMH. The theoretical framework was based on the reasoned action approach model, the Unified Theory of Acceptance and Use of Technology, and the Measurement Instrument for Determinants of Innovation model. To empirically validate our theoretical model, a web-based survey was conducted among mental health care counselors (n=132). To unveil the eligibility criteria, participants were asked to rank their reasons for considering EMH suitable or unsuitable for a patient. The mean intention to use EMH was positive (mean 4.04, SD 0.64). The mean use of EMH before the COVID-19 pandemic was 38% (mean 0.38, SD 0.22), and it was 49% (mean 0.49, SD 0.25) during the pandemic. In total, 57% of the patient population was considered eligible for EMH. Usefulness and benefits (β=.440; P<.001), Task perception (β=.306; P=.001), and Accessibility (β=.140; P=.02) explained the intention to use EMH (F3,131=54.151; P<.001; R2=0.559). In turn, intention explained patient eligibility (F1,130=34.716; P<.001; R2=0.211), whereas intention and patient eligibility explained EMH use (F2,129=41.047; P<.001; R2=0.389). Patient eligibility partially mediated the relationship between intention to use EMH and EMH use, with a larger direct effect (c'=0.116; P<.001) than indirect effect (c=0.065, 95% CI 0.035-0.099; P<.001). Mental health counselors assessed patients' eligibility for EMH mainly through the availability of computers and the internet and patient motivation. To stimulate the use of EMH, intention and patient eligibility need to be influenced. Intention, in turn, can be enhanced by addressing the perceived usefulness and benefits of EMH, perceived accessibility, and task perception. Access to a computer and patients' motivation to use EMH are important in facilitating patient eligibility. To cause an impact with EMH in general practice, mental health counselors need to be convinced of the benefits of EMH and transfer this enthusiasm to the patient. It is recommended to involve mental health counselors in the development of EMH to increase the (perceived) added value and use.


Modeling pupil responses to rapid sequential events.
Pupil size is an easily accessible, noninvasive online indicator of various perceptual and cognitive processes. Pupil measurements have the potential to reveal continuous processing dynamics throughout an experimental trial, including anticipatory responses. However, the relatively sluggish (~2 s) response dynamics of pupil dilation make it challenging to connect changes in pupil size to events occurring close together in time. Researchers have used models to link changes in pupil size to specific trial events, but such methods have not been systematically evaluated. Here we developed and evaluated a general linear model (GLM) pipeline that estimates pupillary responses to multiple rapid events within an experimental trial. We evaluated the modeling approach using a sample dataset in which multiple sequential stimuli were presented within 2-s trials. We found: (1) Model fits improved when the pupil impulse response function (PuRF) was fit for each observer. PuRFs varied substantially across individuals but were consistent for each individual. (2) Model fits also improved when pupil responses were not assumed to occur simultaneously with their associated trial events, but could have non-zero latencies. For example, pupil responses could anticipate predictable trial events. (3) Parameter recovery confirmed the validity of the fitting procedures, and we quantified the reliability of the parameter estimates for our sample dataset. (4) A cognitive task manipulation modulated pupil response amplitude. We provide our pupil analysis pipeline as open-source software (Pupil Response Estimation Toolbox: PRET) to facilitate the estimation of pupil responses and the evaluation of the estimates in other datasets.


Functional complexity can mitigate performance trade-offs.
Trade-offs are believed to impose major constraints on adaptive evolution, and they arise when modification of a trait improves one aspect of performance but incurs a cost in another. Here we show that performance costs that result from competing demands on one trait can be mitigated by compensatory changes in other traits, so long as performance has a complex basis. Numerical simulations indicate that increases in the number of traits that determine performance decrease the strength of performance trade-offs. In centrarchid fishes, multiple traits underlie suction feeding performance, and experimental data and hydrodynamic modeling show that combinations of traits evolve to increase the ability to feed on attached prey while mitigating costs to performance on evasive prey. Diet data for centrarchid species reveal a weak trade-off between these prey types, corroborating the results based on hydrodynamic modeling and suggesting that complexity in the functional basis of suction feeding performance enhances trophic diversification. Complexity may thus permit the evolution of combinations of high-performance behaviors that appear to violate underlying trade-offs, such as the ability to exert high suction forces with large gape. This phenomenon may promote morphological, functional, and ecological diversification in the face of the myriad selective demands organisms encounter.


Do women with fragile X syndrome have problems in switching attention: preliminary findings from ERP and fMRI.
Fragile X syndrome (FXS) is a neurodevelopmental disorder that represents the most common known cause of developmental delay. Recent neuropsychological findings indicate that females with FXS present with a specific pattern of cognitive deficits and that these difficulties primarily involve skills requiring executive control. The present study is the first to examine the extent to which neural activity of females with FXS can be observed on a task that specifically taps two core deficits, namely switching and response inhibition. Brain activity was measured using both event-related electrical potentials (ERPs) and event-related functional MRI (fMRI) neuroimaging in separate studies using the same cognitive paradigm. Compared to controls, females with FXS were significantly slower and made more errors on trials that required an immediate response (Go) to stimulus onset but were comparable on trials that required a delayed response (Wait) to stimulus onset. At the brain level, several areas showed significantly greater activation for females with FXS compared with controls, including the cingulate cortex and left and right ventral prefrontal areas. In contrast, no areas were found to show significantly greater activation for controls compared with females with FXS.


[Distribution of melanoma-associated antigens (HMB 45 and S 100) in benign and malignant melanocytic tumors of the conjunctiva].
The reactivity of the monoclonal antibody HMB 45 was evaluated in melanocytic tumors of the conjunctiva. Among these are 10 acquired melanoses, 19 nevi and 34 melanomas. Results were compared with the presence of the S 100 antigen. Especially the intraepithelial and junctional components of primarily benign lesions were stained with HMB 45. Within malignant melanoma this antibody reacts with melanocytes in the epithelial, junctional and subepithelial areas. The polyclonal antibody S 100 stains all melanocytes in pigmented lesions of the conjunctiva. Intraepithelial or subepithelial malignant infiltrating tumor cells show very intense staining with HMB 45. HMB 45 has therefore high specificity for stimulated melanocytes, but it does not distinguish benign and malignant proliferating melanocytic cells.


Child safety from the perspective of essential needs.
to characterize the maternal care for children under one year of age with a view to child health promotion at home. exploratory study with qualitative data analysis, thematic mode, based on the conceptual framework of the essential needs of children, based on interviews recorded with 16 mothers. the analysis of the maternal narratives showed elements that facilitate the promotion of child safety: presence and involvement of the parents, constant surveillance for physical and emotional protection, experiences to stimulate child development, support networks for childcare at home; and inhibiting elements of child safety: limited perception of characteristics of child development and of children's singularities, overprotection and difficulties to set limits. the study enhances the understanding of home care in child health promotion, directing professional actions to guarantee ongoing nurturing relationships, protection, respect for individual differences, experiences appropriate to child development, limit setting and construction of stable and supportive social networks. In addition, the relevance of considering the maternal perspective in child health care is considered, as a strategy to apprehend aspects related to the attendance of the growth and development needs, particularly for child health promotion at home.


Hepatitis B immunity in United States military recruits.
In 2002, the US Department of Defense (DoD) mandated hepatitis B immunization for military recruits. A DoD study reported that screening for immunity with selective immunization would be cost-effective at a prevalence of immunity of >12%. The prevalence of hepatitis B immunity in the military recruit population was unknown. We studied a random sample of Army, Navy, and Marine Corps new recruits (2400 men and women from all 50 states, Puerto Rico, and US territories). Banked serum samples collected in 2001 were tested for antibody to hepatitis B surface antigen (anti-HBs) by AUSAB enzyme-linked immunoassay (EIA). Results were evaluated by military service branch, age, sex, race, level of education, geographic region of origin, and presence of state immunization laws. The overall prevalence of anti-HBs seropositivity, adjusted to the age distribution of the recruit population in 2001, was 31.5% (95% confidence interval [CI], 29.6%-33.4%). The prevalence of anti-HBs seropositivity, directly adjusted to the 18-35-year-old US population in 2000, was 23.0% (95% CI, 20.7%-25.3%). Anti-HBs seropositivity prevalence was highest among the young, decreased with increasing age, and was higher in women, recruits from the Northeast and West, and recruits from states with laws mandating hepatitis B immunization before entry into elementary and middle school. Screening new recruits for evidence of immunity before hepatitis B immunization is indicated. The prevalence of immunity increased with successive birth cohorts and may reflect the success of childhood immunization programs.


New evidence on the persistence of health spending.
Surprisingly little is known about long-term spending patterns in the under-65 population. Such information could inform efforts to improve coverage and control costs. Using the MarketScan claims database, we characterize the persistence of health care spending in the privately insured, under-65 population. Over a 6-year period, 69.8% of enrollees never had annual spending in the top 10% of the distribution and the bottom 50% of spenders accounted for less than 10% of spending. Those in the top 10% in 2003 were almost as likely (34.4%) to be in the top 10% five years later as one year later (43.4%). Many comorbid conditions retained much of their predictive power even 5 years later. The persistence at both ends of the spending distribution indicates the potential for adverse selection and cream skimming and supports the use of disease management, particularly for those with the conditions that remained strong predictors of high spending throughout the follow-up period.


Causality and functional relevance of BRCA1 and BRCA2 pathogenic variants in non-high-grade serous ovarian carcinomas.
The identification of causal BRCA1/2 pathogenic variants (PVs) in epithelial ovarian carcinoma (EOC) aids the selection of patients for genetic counselling and treatment decision-making. Current recommendations therefore stress sequencing of all EOCs, regardless of histotype. Although it is recognised that BRCA1/2 PVs cluster in high-grade serous ovarian carcinomas (HGSOC), this view is largely unsubstantiated by detailed analysis. Here, we aimed to analyse the results of BRCA1/2 tumour sequencing in a centrally revised, consecutive, prospective series including all EOC histotypes. Sequencing of n = 946 EOCs revealed BRCA1/2 PVs in 125 samples (13%), only eight of which were found in non-HGSOC histotypes. Specifically, BRCA1/2 PVs were identified in high-grade endometrioid (3/20; 15%), low-grade endometrioid (1/40; 2.5%), low-grade serous (3/67; 4.5%), and clear cell (1/64; 1.6%) EOCs. No PVs were identified in any mucinous ovarian carcinomas tested. By re-evaluation and using loss of heterozygosity and homologous recombination deficiency analyses, we then assessed: (1) whether the eight 'anomalous' cases were potentially histologically misclassified and (2) whether the identified variants were likely causal in carcinogenesis. The first 'anomalous' non-HGSOC with a BRCA1/2 PV proved to be a misdiagnosed HGSOC. Next, germline BRCA2 variants, found in two p53-abnormal high-grade endometrioid tumours, showed substantial evidence supporting causality. One additional, likely causal variant, found in a p53-wildtype low-grade serous ovarian carcinoma, was of somatic origin. The remaining cases showed retention of the BRCA1/2 wildtype allele, suggestive of non-causal secondary passenger variants. We conclude that likely causal BRCA1/2 variants are present in high-grade endometrioid tumours but are absent from the other EOC histotypes tested. Although the findings require validation, these results seem to justify a transition from universal to histotype-directed sequencing. Furthermore, in-depth functional analysis of tumours harbouring BRCA1/2 variants combined with detailed revision of cancer histotypes can serve as a model in other BRCA1/2-related cancers. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


Diagnostic value of antibodies against ribosomal phosphoproteins. A cross sectional and longitudinal study.
Antibodies against ribosomal phosphoproteins (anti-P antibodies) are found in about 10% of patients with systemic lupus erythematosus (SLE). Using an ELISA with a synthetic peptide for screening and an immunoblotting technique as a confirmation test for detection of these antibodies, we found 16 positive patients among 946 sera sent to our reference laboratory for anti-DNA determination. All 12 patients on which we could obtain clinical data had clearcut SLE, fulfilling 6 ARA criteria on average. Skin symptoms were observed more frequently in anti-P positive than in anti-P negative patients with SLE. We also tested 56 sera from 54 patients with well defined SLE during monosymptomatic exacerbations and found an identical frequency of about 10% of anti-P antibodies in groups of patients with different types of exacerbation, including psychosis. A retrospective analysis of 9 patients followed 3-10 years showed that they all were already positive for anti-P at the onset of disease. In total these patients showed 15 major peaks in anti-P levels (defined as at least a 4-fold rise in titer in a period of 3 months). Five of the fluctuations in anti-P levels were paralleled by fluctuations in anti-DNA levels. In 6/15 cases, peaks of anti-P levels were accompanied by an exacerbation of SLE, but only 2 peaks of anti-P levels were already detectable before the onset of the exacerbation. In addition, 6 other exacerbations occurred in the absence of major anti-P rises in the preceding 3 months. Therefore, quantitative determinations of anti-P have at most a limited practical value in the followup of patients with SLE.


Opioids in Gastroenterology: Treating Adverse Effects and Creating Therapeutic Benefits.
The use of opioid medications on both an acute and chronic basis is ubiquitous in the United States. As opioid receptors densely populate the gastrointestinal tract, symptoms and side effects can be expected in these patients. In the esophagus, dysmotility may result, manifesting with dysphagia and a syndrome indistinguishable from primary achalasia. In the stomach, a marked delay in gastric emptying may occur with postprandial nausea and early satiety. Postoperatively, particularly with abdominal surgery, opioid-induced ileus may ensue. In the colon, opioid-induced constipation is common. A unique syndrome termed narcotic bowel syndrome is characterized by chronic abdominal pain often accompanied by nausea and vomiting in the absence of other identifiable causes. With the recognition of the important role of opioids on gastrointestinal function, novel drugs have been developed that use this physiology. These medications include peripheral acting opioid agonists to treat opioid-induced constipation and combination agonist and antagonists used for diarrhea-predominant irritable bowel syndrome. This review summarizes the most recent data in these areas.


To what extent is joint and muscle mechanics predicted by musculoskeletal models sensitive to soft tissue artefacts?
Musculoskeletal models are widely used to estimate joint kinematics, intersegmental loads, and muscle and joint contact forces during movement. These estimates can be heavily affected by the soft tissue artefact (STA) when input positional data are obtained using stereophotogrammetry, but this aspect has not yet been fully characterised for muscle and joint forces. This study aims to assess the sensitivity to the STA of three open-source musculoskeletal models, implemented in OpenSim. A baseline dataset of marker trajectories was created for each model from experimental data of one healthy volunteer. Five hundred STA realizations were then statistically generated using a marker-dependent model of the pelvis and lower limb artefact and added to the baseline data. The STA׳s impact on the musculoskeletal model estimates was finally quantified using a Monte Carlo analysis. The modelled STA distributions were in line with the literature. Observed output variations were comparable across the three models, and sensitivity to the STA was evident for most investigated quantities. Shape, magnitude and timing of the joint angle and moment time histories were not significantly affected throughout the entire gait cycle, whereas magnitude variations were observed for muscle and joint forces. Ranges of contact force variations differed between joints, with hip variations up to 1.8 times body weight observed. Variations of more than 30% were observed for some of the muscle forces. In conclusion, musculoskeletal simulations using stereophotogrammetry may be safely run when only interested in overall output patterns. Caution should be paid when more accurate estimated values are needed.


Ceftolozane/Tazobactam Resistance and Mechanisms in Carbapenem-Nonsusceptible Pseudomonas aeruginosa.
This study established the in vitro activity of ceftolozane/tazobactam (C/T) and its genotypic resistance mechanisms by whole-genome sequencing (WGS) in 195 carbapenem-nonsusceptible Pseudomonas aeruginosa (CNSPA) clinical isolates recovered from Singapore between 2009 and 2020. C/T susceptibility rates were low, at 37.9%. Cross-resistance to ceftazidime/avibactam was observed, although susceptibility to the agent was slightly higher, at 41.0%. Whole-genome sequencing revealed that C/T resistance was largely mediated by the presence of horizontally acquired β-lactamases, especially metallo-β-lactamases. These were primarily disseminated in well-recognized high-risk clones belonging to sequence types (ST) 235, 308, and 179. C/T resistance was also observed in several non-carbapenemase-producing isolates, in which resistance was likely mediated by β-lactamases and, to a smaller extent, mutations in AmpC-related genes. There was no obvious mechanism of resistance observed in five isolates. The high C/T resistance highlights the limited utility of the agent as an empirical agent in our setting. Knowledge of local molecular epidemiology is crucial in determining the potential of therapy with novel agents.IMPORTANCEPseudomonas aeruginosa infection is one of the most difficult health care-associated infections to treat due to the ability of the organism to acquire a multitude of resistance mechanisms and express the multidrug resistance phenotype. Ceftolozane/tazobactam (C/T), a novel β-lactam/β-lactamase inhibitor combination, addresses an unmet medical need in patients with these multidrug-resistant P. aeruginosa infections. Our findings demonstrate geographical variation in C/T susceptibility owing to the distinct local molecular epidemiology. This study adds on to the growing knowledge of C/T resistance, particularly mutational resistance, and will aid in the design of future β-lactams and β-lactamase inhibitors. WGS proved to be a useful tool to understand the P. aeruginosa resistome and its contribution to emerging resistance in novel antimicrobial agents.


Spatial Transcriptomics-Based Identification of Molecular Markers for Nanomedicine Distribution in Tumor Tissue.
The intratumoral accumulation of nanomedicine has been considered a passive process, referred to as the enhanced permeability and retention effect. Recent studies have suggested that the tumor uptake of nanomedicines follows an energy-dependent pathway rather than being a passive process. Herein, to explore the factor candidates that are associated with nanomedicine tumor uptake, a molecular marker identification platform is developed by integrating microscopic fluorescence images of a nanomedicine distribution with spatial transcriptomics information. When this approach is applied to PEGylated liposomes, molecular markers related to hypoxia, glycolysis, and apoptosis can be identified as being related to the intratumoral distribution of the nanomedicine. It is expected that the method can be applied to explain the distribution of a wide range of nanomedicines and that the data obtained from this analysis can enhance the precise utilization of nanomedicines.


Genetic deletion of IL-17A reduces cigarette smoke-induced inflammation and alveolar type II cell apoptosis.
Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder marked by relative resistance to steroids. Inflammation and apoptosis have been suggested to be important mechanisms for COPD. Interleukin (IL)-17 superfamily has been associated with chronic inflammation and diminished responses to steroids. It is reasonable to consider that IL-17 may play a role in the pathogenesis of COPD. In this study, we examined IL-17 expression in mice exposed to cigarette smoke (CS) and investigated the contribution of IL-17 to CS-induced inflammation and alveolar cell apoptosis in IL-17(-/-) mice. After exposing wild-type and IL-17(-/-) mice to mainstream CS for 4 wk, IL-17A, but not IL-17F, expression was increased in mice upon CS exposure. Neutrophil infiltration in the lungs of IL-17(-/-) mice was significantly decreased. In IL-17(-/-) mice, there is reduced expression of IL-6, macrophage inflammatory protein-2, and matrix metalloproteinase-12 compared with wild-type mice after CS exposure. The number of apoptotic type II alveolar cells was significantly increased in CS-exposed wild-type mice but not in IL-17(-/-) mice. The effect of IL-17A on type II alveolar cell apoptosis was confirmed in vitro through either addition of IL-17A or transient knockdown of IL-17A by small-interfering RNA transfection in type II alveolar cells. These findings suggest that IL-17A plays an important role in the inflammatory response to CS exposure through increased multiple inflammatory mediators. Moreover, IL-17 may also contribute to type II alveolar cell apoptosis. This study opens a new option in targeting IL-17A to modulate inflammatory response to CS and may be the bases for new therapy for COPD.


Impact of the Timing of Enzyme Replacement Therapy Initiation and Cognitive Impairment Status on Outcomes for Patients with Mucopolysaccharidosis II (MPS II) in the United States: A Retrospective Chart Review.
Background: Mucopolysaccharidosis II (MPS II; Hunter syndrome; OMIM 309900) is a rare, X-linked, lysosomal storage disease caused by deficient iduronate-2-sulfatase activity. Accumulation of glycosaminoglycans results in multisystemic disease manifestations, which may include central nervous system involvement and cognitive impairment (CI). Patients with MPS II experience a high disease burden, leading to extensive healthcare resource utilization (HRU) and reduced quality of life. Objectives: This study aimed to assess the impact of timing of enzyme replacement therapy (ERT) initiation and CI status on the clinical characteristics and HRU of patients with MPS II. Methods: A retrospective medical chart review of 140 male patients who received a diagnosis of MPS II between 1997 and 2017 was performed at 19 US sites; data on disease manifestations and HRU stratified by age at ERT initiation or CI status were analyzed for the full study population and a subgroup of patients who received a diagnosis of MPS II before the age of 6 years. Results: In patients initiating ERT before 3 years of age, there was a trend toward lower symptom burden and HRU compared with patients who initiated ERT at an older age. Evaluation of developmental and behavioral signs and symptoms in the full study population showed that communication delay (70.0% of patients), cognitive delay (62.1%), behavioral problems (52.9%), and toileting delay (50.0%) were particularly common; earliest documented signs and symptoms were motor delay (median [range] age at first documentation: 4.2 [0.9-18.7] years) and behavioral problems (4.4 [0.6-13.7] years). Patients with CI generally experienced greater symptom burden and higher HRU than those without CI, with the most notable differences documented for communication and toileting delays. Formal cognitive testing was documented in <30% of cognitively impaired patients diagnosed with MPS II before the age of 6 years. Conclusions: Our findings reinforce previous recommendations for ERT to be initiated early to maximally benefit patients with MPS II, especially those younger than 3 years old. Cognitively impaired patients experience a particularly high disease burden and HRU. Patient care could be improved with early cognitive assessments and the development of treatments that address cognitive decline.


Immunisation: the views of parents and health professionals in Ireland.
A knowledge, attitude and practice study on vaccinations was undertaken among Irish parents and healthcare professionals between May and August 2001. Parents expressed fear of vaccine side effects, mistrust of health services, and felt poorly informed on the vaccination issues. According to group discussions, health professionals felt they lack time and user-friendly materials to properly inform the parents.


Influence of heat processing on the bioaccessibility of zinc and iron from cereals and pulses consumed in India.
Influence of heat processing on the bioaccessibility of zinc and iron from food grains consumed in India was evaluated. Cereals - rice (Oryza sativa), finger millet (Eleusine coracana), sorghum (Sorghum vulgare), wheat (Triticum aestivum), and maize (Zea mays), and pulses - chickpea (Cicer arietinum) - whole and decorticated, green gram (Phaseolus aureus) - whole and decorticated, decorticated black gram (Phaseolus mungo), decorticated red gram (Cajanus cajan), cowpea (Vigna catjang), and French bean (Phaseolus vulgaris) were examined for zinc and iron bioaccessibility by employing an in vitro dialysability procedure. Both pressure-cooking and microwave heating were tested for their influence on mineral bioaccessibility. Zinc bioaccessibility from food grains was considerably reduced upon pressure-cooking, especially in pulses. Among cereals, pressure-cooking decreased zinc bioaccessibility by 63% and 57% in finger millet and rice, respectively. All the pressure-cooked cereals showed similar percent zinc bioaccessibility with the exception of finger millet. Bioaccessibility of zinc from pulses was generally lower as a result of pressure-cooking or microwave heating. The decrease in bioaccessibility of zinc caused by microwave heating ranged from 11.4% in chickpea (whole) to 63% in cowpea. Decrease in zinc bioaccessibility was 48% in pressure-cooked whole chickpea, 45% and 55% in pressure-cooked or microwave-heated whole green gram, 32% and 22% in pressure-cooked or microwave-heated decorticated green gram, and 45% in microwave-heated black gram. Iron bioaccessibility, on the other hand, was significantly enhanced generally from all the food grains studied upon heat treatment. Thus, heat treatment of grains produced contrasting effect on zinc and iron bioaccessibility.


Re-evaluation for systematic reviews of traditional Chinese medicine in the treatment of chronic bronchitis.
Chronic bronchitis (CB) is a common clinical chronic respiratory disease, which has a high incidence in the middle aged and elderly population. With the development of the disease, the number of acute attacks becomes more and more frequent, which leads to the continuous decrease of lung function. If not treated in time, it will lead to a variety of complications and seriously affect the quality of life of patients. Traditional Chinese medicine (TCM) or TCM combined with western medicine is highly effective in the treatment of CB disease. In recent years, there are many systematic reviews on the use of TCM therapy in the treatment of CB, and the efficacy and safety of TCM in the treatment of CB diseases are evaluated. The aim of this study was to re-evaluate the Meta analysis/Systematic reviews (MAs/SRs) of TCM for the treatment of CB, aiming to provide a clinical basis for the treatment of CB by TCM. Retrieval among Chinese and English databases such as China National Knowledge Infrastructure, Wanfang database, China Scientific Journals Database, SinoMed, PubMed, Web of Science, The Cochrane Library and EMbase, etc. were conducted within the duration from database establish Tion date to March 2023.The included research was independently conducted by 2 researchers for literature screening, data extraction, and quality evaluation. The AMSTAR 2 scale was used to evaluate the quality of the report, the PRISMA 2020 statement evaluated the quality of the report, the ROBIS tool evaluated the risk of bias, and the GRADE quality evaluation tool evaluated the quality of the evidence. Fifteen MAs/SRs were included, for a total of 224 studies involving 20,710 patients with CB. The 15 studies included in AMSTAR 2 are of very low quality. The ROBIS evaluation results showed that 8 MAs/SRs were considered to have high risk and 7 with low risk. The PRISMA 2020 report quality showed evaluation results of the included studies scores between 24 and 30, among them 13 with high quality and 2 with low quality. The GRADE system results showed that, within 70 outcome indicators, only 14 of them have moderate quality for evidence, with 31 for low quality, 25 for very low quality, and none for high quality. The MAs/SRs methodological quality of using TCM for treatment CB is generally poor, the quality of reports as well as evidence are generally low, and the risk of bias is high, therefore we should treat these results with caution.


The PropeR way to support medical doctors in daily practice. Developing the protocol based DSS.
This paper describes the first phase of the development of a Protocol based Decision Support System (PDSS) that will be linked to an Electronic Patient Record system (EPR system). The protocol system will be pro-active: the physician will be automatically prompted from the EPR of a particular patient if the protocol that applies for that patient defines it necessary. The PropeR project studies the impact of a PDSS that is linked to an EPR on daily care processes. There are two areas of research: hospital and home care. This paper describes the application in the hospital. The protocol that is being computerized is a treatment protocol for Acute Myelogenous Leukaemia (AML) that also studies treatment alternatives (conventional versus experimental treatment). This paper based AML protocol has been translated into a formal representation. The KA-tool Gaston is used to make this representation. Twenty-eight subprotocols have been organized in a hierarchical structure with three levels. One of the aims of the project is to make a representation of the AML protocol that can be used in other organizations as well. The main problem we encountered is that the representation not only contains the content of the protocol, but also aspects of application of that protocol in daily care of the hospital and aspects of support. The solution to this problem is the creation of two layers of representation: the first layer is an exact copy of the protocol and thus sharable and the second layer focuses on the support of the protocol in the daily working processes and is mainly domain specific: for the University Hospital Maastricht. At the moment, this division into two layers is being discussed.


[Tobacco smoking and obesity as risk factors of polyvascular atherosclerosis].
The polyvascular disease is the disease that includes the simultaneous existence of atherosclerotic process on coronary, carotid and lower extremities peripheral arteries. It is very difficult, if not impossible to determine the prevalence of atherosclerosis, because it is one predominant asymptomatic illness. There is no correct information related to atherosclerosis clinical readings, that is to it's most important consequences: coronary heart disease, cerebrovascular disease and peripheral blood vessels obstruction. Atherosclerosis is a complex disease with numerous predisposing factors that we call the risk factors. We divide all atherosclerotic risk factors on changeable and unchangeable (age, sex and heredity). The risk factors can further be divided on classical (conventional) and non-traditional (raised oxidative stress, endothelium disfunction and inflammation). Tobacco smoking can result by the sevenfold risk increase of peripheral arteries disease and at least the double risk increase of coronary arteries disease beginning. These two main forms of cardiovascular diseases, related with tobacco smoking, are the main atherothrombosis consequences. Obesity has overcome the global epidemical proportions with more than one million people with excessively body mass and, at least, 300 millions of clinical obese people. Obesity is considered as chronic inflammation disease that leads towards the chronic mass non-inflammation diseases as atherosclerosis, Diabetes type 2, non-alcohol stetosis of liver, cancer (of prostate, of breast) and osteoarthrosis.


Anthropogenic disturbance driving population decline of a dominant tree in East Asia evergreen broadleaved forests over the last 11, 000 years.
Current biodiversity loss is generally considered to have been caused by anthropogenic disturbance, but it is unclear when anthropogenic activities began to affect biodiversity loss. One hypothesis suggests it began with the Industrial Revolution, whereas others propose that anthropogenic disturbance has been associated with biodiversity decline since the early Holocene. To test these hypotheses, we examined the unique vegetation of evergreen broadleaved forests (EBLFs) in East Asia, where humans have affected landscapes since the early Holocene. We adopted a genomic approach to infer the demographic history of a dominant tree (Litsea elongata) of EBLFs. We used Holocene temperature and anthropogenic disturbance factors to calculate the correlation between these variables and historical effective population size of L. elongata with Spearman statistics, and integrated the maximum-entropy niche model to determine the impact of climate change and anthropogenic disturbance on fluctuation in its effective population size. We identified 9 well-defined geographic clades for the populations of L. elongata. Based on the estimated historical population sizes of these clades, all the populations contracted, indicating persistent population decline over the last 11,000 years. Demographic history of L. elongata and human population change, change in cropland use, and change in irrigated rice area were significantly negatively correlated, whereas climate change in the Holocene was not correlated with demographic history. Our results support the early human impact hypothesis and provide comprehensive evidence of that early anthropogenic disturbance may contribute to the current biodiversity crisis in East Asia. :11,000 , 。, ; , 。, , 、。, (EBLFs), (Litsea elongata), 。, , (, , )。, , 9, 911,000。, 11,000, , , 。, 。 :, , , , , This article is protected by copyright. All rights reserved.


INTRAVITREAL AFLIBERCEPT AND RANIBIZUMAB INJECTIONS FOR TYPE 3 NEOVASCULARIZATION.
To compare the effectiveness of intravitreal injection of aflibercept with ranibizumab in patients with Type 3 neovascularization. Sixty-three treatment-naive eyes with Type 3 neovascularization (58 patients) were retrospectively analyzed. The eyes had received intravitreal aflibercept or ranibizumab injections. All patients were treated using an initial series of three monthly loading injections, followed by further injections as required. The visual and anatomical outcomes of treatment were evaluated after 12 months. The mean best-corrected visual acuity in the aflibercept-treated group (21 eyes), expressed as the logarithm of the minimum angle of resolution, improved from 0.71 ± 0.42 (Snellen equivalent; 20/102) to 0.54 ± 0.39 (20/69) after 12 months of treatment (P = 0.022). Similarly, in the ranibizumab-treated group (42 eyes), the best-corrected visual acuity improved from 0.68 ± 0.38 (20/95) to 0.53 ± 0.36 (20/67) (P = 0.013) at 12 months. The central foveal thickness decreased in the aflibercept-treated group from 356 ± 139 μm to 212 ± 155 μm and in the ranibizumab-treated group from 348 ± 177 μm to 208 ± 161 μm (P = 0.014 and P = 0.017, respectively). There was no significant difference between the groups about improvement in best-corrected visual acuity or decrease in central foveal thickness. However, geographic atrophy was significantly more frequent in the aflibercept-treated group, occurring in 42.9% of eyes, than in the ranibizumab-treated group (19.0% of eyes; P = 0.045). There was no difference between the aflibercept and ranibizumab treatments in terms of visual acuity improvement after 12 months in patients with Type 3 neovascularization. However, geographic atrophy developed more frequently in the aflibercept-treated group.


Transient dystonias revisited: a comparative study of preterm and term children at 2 1/2 years of age.
Minor neurological dysfunctions (MND) have frequently been reported as an outcome of preterm birth. Behavioural and learning difficulties are a known feature, but coordination problems are especially described in preterm infants at later ages. All preterm infants in our study were born with a gestational age of <32 weeks and a birthweight of <1500 g. The aim of the study was to determine if in a normal clinical situation, children at risk for developing coordination problems could be detected by focusing particularly on their spontaneous, although elicited, motor performance. Forty-two children of 2 years 6 months of age were studied of whom 25 were 'low-risk' preterm and 17 were born at term. All children had been followed up since birth. In a structured, free-field situation the quality of body rotation, spontaneous reaching-out, and manipulation during parts of the Bayley Developmental Test were observed and videotaped. Body rotations were scored on a 2-point scale, and arm and hand functions on a 3-point scale. Most preterm infants showed non-optimal body rotations and borderline or non-optimal arm and hand functions in contrast to most term children. A clear connection was found between less optimal body rotations and poor arm and hand functions. Retrospectively, poor arm and hand functions at 2 years 6 months seemed to be related to those at 39 weeks. At the age of 39 weeks a clear relation had been found between poor postural control (many preterm infants could not sit independently) and earlier hyperextension of the trunk at 18 weeks and quality of arm-hand functions. In the present study at 2 years 6 months a correlation with the former hyperextension could no longer be found, but there was a significant relation between poor trunk rotation and arm and hand function and the earlier arm and hand functions at 39 weeks.


Evolution of carotid stenting: indications.
While carotid angioplasty and stenting has been clearly established as a minimally invasive alternative to endarterectomy for patients with carotid occlusive disease, its indications continue to evolve, being refined as more controlled data of large studies are being accumulated. The purpose of this article is to review the current evidence supporting the application of the technique in certain subsets of patients, and the relative contraindications for its use.


Short term dynamics of the sputum microbiome among COPD patients.
Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder characterized by incompletely reversible airflow obstruction. The complexity of the lung microbial community in COPD patients has been highlighted in recent years. Evidence suggests that transplantation, medications, age, and disease severity influence microbial community membership. However, the dynamics of the lung microbiome in stable COPD patients remain poorly understood. In this study, we completed a longitudinal 16S ribosomal RNA survey of the lung microbiome on replicate sputum samples collected from 4 former smokers with COPD (Stage 2) within a 2-day time period. Samples from each individual over the two-day period were similar based on α-diversity, principle component analysis and taxonomy at the phyla and genera level. Sputum samples from COPD patients were also collected between 2-9 months of follow-up. Data suggest an increased variability of the sputum microbiota when comparing samples collected ≤ 3 months compared to those collected ≥ 4 months; however, no statistically significant shifts in the abundance (>2-fold) of taxa between the two time points was observed. Bacterial composition and the number of operational taxonomic units (OTUs) remained similar over time. Results from this study suggest that the sputum microbiome is relatively stable in clinically stable COPD patients (Stage 2). This study furthers our understanding of the dynamics of the lung microbiome in COPD patients.


[Effects of asthma on nutritional status in children: a systematic review].
Asthma is a chronic inflammatory disease of high prevalence, considered a public health problem and is thought to be one cause of low birth weight and growth retardation. The purpose of this article was to review in literature the effects of asthma on the nutritional status in children. A systematic review was made by searching for articles in PubMed, SciELO and LILACS databases. Review articles, studies with adults or research that did not evaluate the effects of asthma in children were excluded. Hence original articles in humans were included. In the systematic review we found 901 articles in MEDLINE (1966-1996), 47 in LILACS and SciELO in the 16 - Brazil, totaling 964 articles. Of these, 17 articles were selected. Evidence that asthma interferes in nutritional status can not be proven in this study.


[Growth and body composition changes in late preterm infants in the first months of life].
The aim of this study was to compare growth and body composition of late preterm infants to that of extremely preterm and full-term infants. Observational longitudinal study. Forty-nine late preterm infants and 63 extremely preterm infants were included in the study. Forty healthy, full-term, breast-fed infants were enrolled as a reference group. Anthropometric parameters and body composition by an air displacement plethysmography system were assessed at 36th week, at term, at 1 and 3 months of corrected age in all groups. Late preterm infants were also assessed on the fifth day of life. Late preterm infants showed higher weight, length and head circumference values than those of very low birth weight infants but lower fat mass values on the fifth day of life and at 36th week of corrected age. However, at 3 months of corrected age, percentage of fat mass in late preterm infants reached values comparable with those of very low birth weight infants, probably because of the fast catch-up fat recorded between the fifth day of life and term corrected age. Moreover, percentage of fat mass in the first month of corrected age in preterm infants was higher as compared with full-term infants. This difference was no longer found at 3 months of corrected age. Further studies are needed to investigate whether this rapid increase in fat mass may modulate the risk of chronic diseases.


Low serum allopregnanolone is associated with symptoms of depression in late pregnancy.
Allopregnanolone (3α-hydroxy-5α-pregnan-20-one) is a neurosteroid which has an inhibitory function through interaction with the GABAA receptor. This progesterone metabolite has strong sedative and anxiolytic properties, and low endogenous levels have been associated with depressed mood. This study aimed to investigate whether the very high serum allopregnanolone levels in late pregnancy covary with concurrent self-rated symptoms of depression and anxiety. Ninety-six women in pregnancy weeks 37-40 rated symptoms of depression and anxiety with the Montgomery-Åsberg Depression Rating Scale (MADRS-S) and Spielberger State-Trait Anxiety Inventory. Their serum allopregnanolone was analyzed by Celite chromatography and radioimmunoassay. Ten women had elevated depression scores (MADRS-S ≥ 13), and this group had significantly lower allopregnanolone levels compared to women with MADRS-S scores in the normal range (39.0 ± 17.9 vs. 54.6 ± 18.7 nmol/l, p = 0.014). A significant negative correlation was found between self-rated depression scores and allopregnanolone concentrations (Pearson's correlation coefficient = -0.220, p = 0.031). The linear association between self-rated depression scores and allopregnanolone serum concentrations remained significant when adjusted for gestational length, progesterone levels, and parity. Self-rated anxiety, however, was not associated with allopregnanolone serum concentrations during pregnancy. High allopregnanolone serum concentrations may protect against depressed mood during pregnancy.


THE MAGIC OF PLAY: LOW-INCOME MOTHERS' AND FATHERS' PLAYFULNESS AND CHILDREN'S EMOTION REGULATION AND VOCABULARY SKILLS.
Using data from a diverse sample of low-income families who participated in the Early Head Start Research Evaluation Project (n = 73), we explored the association between mothers' and fathers' playfulness with toddlers, toddler's affect during play, and children's language and emotion regulation at prekindergarten. There were two main findings. First, fathers' playfulness in toddlerhood was associated with children's vocabulary skills in prekindergarten whereas mothers' playfulness was related to children's emotion regulation. Cross-parental effects were found only for mothers. The association between mothers' playfulness and children's vocabulary and emotion regulation was strengthened when fathers engaged in more pretend play and when children were affectively positive during the play. These findings show that playfulness is an important source of variation in the vocabulary and emotion regulation of children growing up in low-income families. They also point to domain-specific ways that mothers and fathers promote children's regulatory and vocabulary skills, and highlight the importance of children's positive engagement in play.


The public health control of scabies: priorities for research and action.
Scabies is a parasitic disease of the skin that disproportionately affects disadvantaged populations. The disease causes considerable morbidity and leads to severe bacterial infection and immune-mediated disease. Scientific advances from the past 5 years suggest that scabies is amenable to population-level control, particularly through mass drug administration. In recognition of these issues, WHO added scabies to the list of neglected tropical diseases in 2017. To develop a global control programme, key operational research questions must now be addressed. Standardised approaches to diagnosis and methods for mapping are required to further understand the burden of disease. The safety of treatments for young children, including with ivermectin and moxidectin, should be investigated. Studies are needed to inform optimum implementation of mass treatment, including the threshold for intervention, target, dosing, and frequency. Frameworks for surveillance, monitoring, and evaluation of control strategies are also necessary.


Phase unwrapping for noisy phase maps using rotational compensator with virtual singular points.
In the process of phase unwrapping for an image obtained by an interferometer or in-line holography, noisy image data may pose difficulties. Traditional phase unwrapping algorithms used to estimate a two-dimensional phase distribution include much estimation error, due to the effect of singular points. This paper introduces an accurate phase-unwrapping algorithm based on three techniques: a rotational compensator, unconstrained singular point positioning, and virtual singular points. The new algorithm can confine the effect of singularities to the local region around each singular point. The phase-unwrapped result demonstrates that accuracy is improved, compared with past methods based on the least-squares approach.


Efficacy of antiglaucoma fixed combination therapy versus unfixed components in reducing intraocular pressure: a systematic review.
To evaluate the efficacy of the fixed combination ocular hypotensive therapies compared with their non-fixed components used concomitantly for lowering intraocular pressure (IOP) in glaucoma and ocular hypertension. A systematic review of the literature, up to May 2007, without limits on year or language of publication was performed. Seven randomised controlled trials (n = 2,083 eyes) were identified. Assessment of methodological quality was made using standardised criteria. Results were pooled quantitatively using meta-analysis methods, and statistical analysis was performed using STATA software. The difference in mean intraocular pressure (mm Hg) from baseline between the fixed combination and non-fixed component therapies was compared. Non-inferiority in terms of efficacy was set at an upper confidence limit of < or =1.5 mm Hg for all time points (hour (Hr)0, Hr2 and Hr8) and evaluated at 12 weeks. Safety was evaluated from data on adverse events as reported in the included studies. Of the 679 abstracts identified, seven randomised controlled trials met the selection criteria. The quality scores of included studies were high (mean of 29.4, maximum score 30). The mean differences (95% CI) and p values at 12 weeks were as follows: 0.200 mm Hg, (CI -0.106 to 0.507), p = 0.20 for Hr0, 0.393 mm Hg (CI 0.038 to 0.747), p = 0.03 for Hr2 and 0.501 mm Hg (CI 0.156 to 0.846), p = 0.004 for Hr8. Although both Hr2 and Hr8 showed statistical significance favouring the non-fixed combinations, the non-inferiority measure < or =1.5 mm Hg upper confidence limit was not exceeded. Fixed combination therapies are equally safe and effective at lowering IOP as their non-fixed components administered concomitantly.


Feasibility of accelerated partial breast irradiation with strut-adjusted volume implant brachytherapy in Japan focusing on dosimetry and acute toxicity: a Japanese multi-institutional prospective study.
A Japanese multi-institutional prospective study was initiated to investigate the effectiveness and safety of accelerated partial breast irradiation (APBI) using strut-adjusted volume implant (SAVI) brachytherapy, with subjects registered between 2016 and 2021. Herein, we report the preliminary results on the feasibility of this treatment modality in Japan, focusing on the registration process, dosimetry, and acute toxicities. Primary registration was conducted before breast-conserving surgery (BCS) and the eligibility criteria included the following: age ≥ 40 years, tumor unifocal and unicentric, ≤ 3 cm in diameter, cN0M0, proven ductal, mucinous, tubular, medullary, or lobular carcinoma by needle biopsy. Secondary registration was conducted after BCS had been performed leaving a cavity for device implantation and pathological evaluations, and the eligibility criteria were as follows: negative surgical margin, tumor ≤ 3 cm in diameter on gross pathological examination, histologically confirmed ductal, mucinous, tubular medullary, colloid, or lobular carcinoma, pN0, L0V0, no extensive ductal component, no initiation of chemotherapy within 2 weeks of the brachytherapy APBI planning with SAVI was performed for the patients successfully entered in the study by the secondary registration process, and the treatment was administered at the dose of 34 Gy in 10 fractions administered twice daily. Between 2016 and 2021, 64 women were enrolled in the study through primary registration, of which 19 were excluded from the secondary registration process, and in one, it was deemed impossible to comply with the dose constraints established during treatment planning. After the exclusion of these latter 20 patients, we treated the remaining 44 patients by APBI with SAVI. The dose constraints could be adhered to in all the patients, but re-planning was necessitated in 3 patients because of applicator movement during the treatment period. Grade 2 acute toxicities were observed in 18% of all patients, but more severe acute toxicities than Grade 2 were not observed in any of the patients. APBI with SAVI brachytherapy is feasible in Japan from the aspects of compliance with dose constraints and frequency of acute toxicities.


Recent advances in parapneumonic effusion and empyema.
Complicated parapneumonic effusion and empyema continue to account for significant morbidity and mortality, and uncertainties remain regarding their optimal management. This review describes recent advances in this field, as well as areas for future research. Recent advances have addressed the pathogenesis, bacteriology, and treatment of pleural infection. Key areas for research in the development of empyema include the interplay between inflammatory and coagulation cascades and development of fibrosis within the pleural space. The varied bacteriology of empyema has been more clearly defined, and in particular the differences between community- and hospital-acquired infection highlighted. Studies of treatment have focused particularly on the roles of intrapleural fibrinolytics and surgery. Increased understanding of the pathogenesis of empyema may ultimately yield novel therapeutic targets. Comprehensive descriptions of the bacteriology of empyema aids antibiotic choice, and the use of intrapleural DNase shows promise in facilitating drainage of infected pleural fluid. Uncertainties remain, such as the role of intrapleural fibrinolytics and the optimal timing of surgical intervention.


[Use of the integral parameter of dermatoglyphic differences for determining the type of zygosity of twins].
A method is described increasing the reliability of twin zygosity diagnosis in cases when the possibility of using a large number of mendelian markers is restricted. The method is based on the determination of generalized index of dermatoglyphic differences between members of twin pair for 18 characteris of finger and palm dermatoglyphics and on principles of multivariate genetic analysis, which is worked out to determine the degree of heritability of multifactorial character and to study the structure of hereditary predisposition to multifactorial diseases. The efficiency of the method with respect to determinating the type of twin zygosity is approximately equivalent to the efficiency of using 5--6 mendelian marker systems.


Delineating SPTAN1 associated phenotypes: from isolated epilepsy to encephalopathy with progressive brain atrophy.
De novo in-frame deletions and duplications in the SPTAN1 gene, encoding the non-erythrocyte αII spectrin, have been associated with severe West syndrome with hypomyelination and pontocerebellar atrophy. We aimed at comprehensively delineating the phenotypic spectrum associated with SPTAN1 mutations. Using different molecular genetic techniques, we identified 20 patients with a pathogenic or likely pathogenic SPTAN1 variant and reviewed their clinical, genetic and imaging data. SPTAN1 de novo alterations included seven unique missense variants and nine in-frame deletions/duplications of which 12 were novel. The recurrent three-amino acid duplication p.(Asp2303_Leu2305dup) occurred in five patients. Our patient cohort exhibited a broad spectrum of neurodevelopmental phenotypes, comprising six patients with mild to moderate intellectual disability, with or without epilepsy and behavioural disorders, and 14 patients with infantile epileptic encephalopathy, of which 13 had severe neurodevelopmental impairment and four died in early childhood. Imaging studies suggested that the severity of neurological impairment and epilepsy correlates with that of structural abnormalities as well as the mutation type and location. Out of seven patients harbouring mutations outside the α/β spectrin heterodimerization domain, four had normal brain imaging and three exhibited moderately progressive brain and/or cerebellar atrophy. Twelve of 13 patients with mutations located within the spectrin heterodimer contact site exhibited severe and progressive brain, brainstem and cerebellar atrophy, with hypomyelination in most. We used fibroblasts from five patients to study spectrin aggregate formation by Triton-X extraction and immunocytochemistry followed by fluorescence microscopy. αII/βII aggregates and αII spectrin in the insoluble protein fraction were observed in fibroblasts derived from patients with the mutations p.(Glu2207del), p.(Asp2303_Leu2305dup) and p.(Arg2308_Met2309dup), all falling in the nucleation site of the α/β spectrin heterodimer region. Molecular modelling of the seven SPTAN1 amino acid changes provided preliminary evidence for structural alterations of the A-, B- and/or C-helices within each of the mutated spectrin repeats. We conclude that SPTAN1-related disorders comprise a wide spectrum of neurodevelopmental phenotypes ranging from mild to severe and progressive. Spectrin aggregate formation in fibroblasts with mutations in the α/β heterodimerization domain seems to be associated with a severe neurodegenerative course and suggests that the amino acid stretch from Asp2303 to Met2309 in the α20 repeat is important for α/β spectrin heterodimer formation and/or αII spectrin function.


Opioid and non-opioid stress analgesia: assessment of tolerance and cross-tolerance with morphine.
Opioid and non-opioid mechanisms of analgesia elicited by two kinds of footshock stress that differ only in temporal characteristics previously have been inferred on the basis of susceptibility to naloxone blockade. The present study sought further evidence on this point by comparing these two kinds of footshock analgesia for possible tolerance development and cross-tolerance with morphine. It was found that, with repeated exposure to stress, tolerance developed to naloxone-sensitive, but not naloxone-insensitive, stress analgesia. Furthermore, morphine-tolerant rats displayed cross-tolerance to only the naloxone-sensitive form of footshock analgesia. Although prior exposure to both footshock paradigms potentiated morphine analgesia, less potentiation occurred in rats tolerant to the naloxone-sensitive footshock stress. Thus, cross-tolerance between morphine and this type of stress analgesia appears to occur in both directions. These findings are consistent with those using naloxone antagonism as a criterion for opioid mediation and support the conclusion that separate opioid and non-opioid mechanisms of stress analgesia exist.


Analysis of a homologous series of perfluorocarboxylates from American Red Cross adult blood donors, 2000-2001 and 2006.
The purpose of this study was to determine the concentration trends of a nine-target-analyte homologous series of perfluorocarboxylates from six American Red Cross adult blood donor centers. A total of 645 serum and 600 plasma samples were obtained in 2000-2001 and 2006, respectively, with samples stratified for each 10-year (20-69) age- and sex-group per each location. Samples were extracted by protein precipitation and quantified by using tandem mass spectrometry. The nine perfluorocarboxylates were perfluorobutanoate (PFBA, C(3)F(7)CO(2)(-)), perfluoropentanoate (PFPeA, C(4)F(9)CO(2)(-)), perfluorohexanoate (PFHxA, C(5)F(11)CO(2)(-)), perfluoroheptanoate (PFHpA, C(6)F(13)CO(2)(-)), perfluorooctanoate (PFOA, C(7)F(15)CO(2)(-)), perfluorononanoate (PFNA, C(8)F(17)CO(2)(-)), perfluorodecanoate (PFDA, C(9)F(19)CO(2)(-)), perfluoroundecanoate (PFUnA,C(10)F(21)CO(2)(-)), and perfluorododecanoate (PFDoA, C(11)F(23)CO(2)(-)). The majority of measurements were less than the lower limit of quantitation for PFPeA, PFHxA, and PFDoA. For the remaining targeted analytes, the geometric mean serum and plasma concentrations (ng/mL) for 2000-2001 and 2006 were, respectively, as follows: PFBA 2.61 vs 0.33, PFHpA 0.13 vs 0.09, PFOA 4.70 vs 3.44, PFNA 0.57 vs 0.97, PFDA 0.16 vs 0.34, and PFUnA 0.10 vs 0.18. Estimates of the 95th percent tolerance limits (ng/mL) were as follows: PFBA 5.3 vs 1.4, PFHpA 0.4 vs 0.4, PFOA 12.3 vs 7.7, PFNA 1.4 vs 2.2, PFDA 0.4 vs 0.8, and PFUnA 0.3 vs 0.5. Important observations were the decline in PFBA and increase in PFNA, PFDA, and PFUnA concentrations between 2000-2001 and 2006. The longer chain length perfluorocarboxylates were also highly correlated with each other.


Thermal stability engineering of Glomerella cingulata cutinase.
Cutinase has been ascertained as a biocatalyst for biotechnological and industrial bioprocesses. The Glomerella cingulata cutinase was genetically modified to enhance its enzymatic performance to fulfill industrial requirements. Two sites were selected for mutagenesis with the aim of altering the surface electrostatics as well as removing a potentially deamidation-prone asparagine residue. The N177D cutinase variant was affirmed to be more resilient to temperature increase with a 2.7-fold increase in half-life at 50°C as compared with wild-type enzyme, while, the activity at 25°C is not compromised. Furthermore, the increase in thermal tolerance of this variant is accompanied by an increase in optimal temperature. Another variant, the L172K, however, exhibited higher enzymatic performance towards phenyl ester substrates of longer carbon chain length, yet its thermal stability is inversely affected. In order to restore the thermal stability of L172K, we constructed a L172K/N177D double variant and showed that these two mutations yield an improved variant with enhanced activity towards phenyl ester substrates and enhanced thermal stability. Taken together, our study may provide valuable information for enhancing catalytic performance and thermal stability in future engineering endeavors.


Near-Infrared Laser-Triggered In Situ Dimorphic Transformation of BF2-Azadipyrromethene Nanoaggregates for Enhanced Solid Tumor Penetration.
The shape of a drug delivery system impacts its in vivo behavior such as circulation time, accumulation, and penetration. Considering the advantages of functional dyes in bioapplications, we synthesize a class of nanoaggregates based on BF2-azadipyrromethene (aza-BODIPY) dyes, which can realize long blood circulation and deep tumor penetration simultaneously in vivo through morphological transformation modulated by a near-infrared (NIR) laser. First, when the temperature increases, the wormlike nanofibers of the aza-BODIPY-1 aggregate, possessing a long blood circulation time, can be transformed into spherical nanoparticles, which are conducive to increasing the penetration in the solid tumor. Second, without any postmodification, the nanofibers exhibit an outstandingly narrow absorption band in the NIR spectral range, so that they possess ideal photothermal properties. Through 655 nm laser irradiation, the intrinsic photothermal effect causes a local temperature increase to ∼48 °C, realizing the transformation of 1-NFs to 1-NPs. Third, the morphological transformation is real-time detected by photoacoustic (PA) imaging. By monitoring the change of the PA signal at a specific wavelength, the in vivo deformation process of nanomaterials can be traced. Consequently, the in situ morphology transformation of aza-BODIPY-based nanomaterials can simultaneously realize long blood circulation and deep penetration, resulting in the enhanced antitumor outcome.


The effects of phenotypic plasticity on genetic correlations.
Recent theory suggests that genetic correlations should help to predict the simultaneous response to selection of two or more traits, and much recent research has been directed towards understanding the sources of variation in genetic correlations. Genetic correlations can change from sample to sample, from species to species, from population to population, during the course of development and - within a population, at a fixed stage of development - from one environment to another. These are changes not only in magnitude but also in sign. Theory suggests that genetic correlations should not change sign when the two traits are tightly integrated by physiology or development. Patterns of change of genetic correlations are caused by differences in development and physiology, an understanding of which appears to be necessary to predict the response to selection in natural, heterogeneous environments.


Genetic diversity and genomic distribution of homologs encoding NBS-LRR disease resistance proteins in sunflower.
Three-fourths of the recognition-dependent disease resistance genes (R-genes) identified in plants encode nucleotide binding site (NBS) leucine-rich repeat (LRR) proteins. NBS-LRR homologs have only been isolated on a limited scale from sunflower (Helianthus annuus L.), and most of the previously identified homologs are members of two large NBS-LRR clusters harboring downy mildew R-genes. We mined the sunflower EST database and used comparative genomics approaches to develop a deeper understanding of the diversity and distribution of NBS-LRR homologs in the sunflower genome. Collectively, 630 NBS-LRR homologs were identified, 88 by mining a database of 284,241 sunflower ESTs and 542 by sequencing 1,248 genomic DNA amplicons isolated from common and wild sunflower species. DNA markers were developed from 196 unique NBS-LRR sequences and facilitated genetic mapping of 167 NBS-LRR loci. The latter were distributed throughout the sunflower genome in 44 clusters or singletons. Wild species ESTs were a particularly rich source of novel NBS-LRR homologs, many of which were tightly linked to previously mapped downy mildew, rust, and broomrape R-genes. The DNA sequence and mapping resources described here should facilitate the discovery and isolation of recognition-dependent R-genes guarding sunflower from a broad spectrum of economically important diseases. Sunflower nucleotide and amino acid sequences have been deposited in DDBJ/EMBL/GenBank under accession numbers EF 560168-EF 559378 and ABQ 58077-ABQ 57529.


Arbuscular Mycorrhizal Fungi Drive Organo-Mineral Association in Iron Ore Tailings: Unravelling Microstructure at the Submicron Scale by Synchrotron-Based FTIR and STXM-NEXAFS.
Arbuscular mycorrhizal (AM) fungi play an important role in organic matter (OM) stabilization in Fe ore tailings for eco-engineered soil formation. However, little has been understood about the AM fungi-derived organic signature and organo-mineral interactions in situ at the submicron scale. In this study, a compartmentalized cultivation system was used to investigate the role of AM fungi in OM formation and stabilization in tailings. Particularly, microspectroscopic analyses including synchrotron-based transmission Fourier transform infrared (FTIR) and scanning transmission X-ray microspectroscopy combined with near-edge X-ray absorption fine structure spectroscopy (STXM-NEXAFS) were employed to characterize the chemical signatures at the AM fungal-mineral and mineral-OM interfaces at the submicron scale. The results indicated that AM fungal mycelia developed well in the tailings and entangled mineral particles for aggregation. AM fungal colonization enhanced N-rich OM stabilization through organo-mineral association. Bulk spectroscopic analysis together with FTIR mapping revealed that fungi-derived lipids, proteins, and carbohydrates were associated with Fe/Si minerals. Furthermore, STXM-NEXAFS analysis revealed that AM fungi-derived aromatic, aliphatic, and carboxylic/amide compounds were heterogeneously distributed and trapped by Fe(II)/Fe(III)-bearing minerals originating from biotite-like minerals weathering. These findings imply that AM fungi can stimulate mineral weathering and provide organic substances to associate with minerals, contributing to OM stabilization and aggregate formation as key processes for eco-engineered soil formation in tailings.


Gene expression profiling reveals transcription factor networks and subgenome bias during Brassica napus seed development.
We profiled the global gene expression landscape across the reproductive lifecycle of Brassica napus. Comparative analysis of this nascent amphidiploid revealed the contribution of each subgenome to plant reproduction. Whole-genome transcription factor networks identified BZIP11 as a transcriptional regulator of early B. napus seed development. Knockdown of BZIP11 using RNA interference resulted in a similar reduction in gene activity of predicted gene targets, and a reproductive-lethal phenotype. Global mRNA profiling revealed lower accumulation of Cn subgenome transcripts relative to the An subgenome. Subgenome-specific transcription factor networks identified distinct transcription factor families enriched in each of the An and Cn subgenomes early in seed development. Analysis of laser-microdissected seed subregions further reveal subgenome expression dynamics in the embryo, endosperm and seed coat of early stage seeds. Transcription factors predicted to be regulators encoded by the An subgenome are expressed primarily in the seed coat, whereas regulators encoded by the Cn subgenome were expressed primarily in the embryo. Data suggest subgenome bias are characteristic features of the B. napus seed throughout development, and that such bias might not be universal across the embryo, endosperm and seed coat of the developing seed. Transcriptional networks spanning both the An and Cn genomes of the whole B. napus seed can identify valuable targets for seed development research and that -omics level approaches to studying gene regulation in B. napus can benefit from both broad and high-resolution analyses.


Exocytosis of secretory organelles from blood platelets incubated with cationic polypeptides.
The blood platelet release reaction involves the secretion, in parallel, of specific chemical constituents stored in intracellular organelles to the plasma without loss of substances suggestive of cell damage. The present investigation has employed an unusual effect of cationic polypeptides to follow the platelet secretory process. When platelets were incubated with polybrene and polylysine, the agents were taken up and deposited in cytoplasmic organelles. The matrix of granules developed a lattice-like substructure not produced by other chemical agents, and dark zones of granules and dense bodies became more electron opaque. Subsequently, the platelets exposed to cationic polypeptides underwent the shape change and internal transformation similar to that produced by potent aggregating agents. Granules and dense bodies appeared in the open canalicular system and were extruded in a relatively intact state from the altered platelets. No differences were observed in the response of normal, afibrinogenemic or thrombasthenic platelets to incubation with polybrene and polylysine. The results indicate that cationic polypeptides can stimulate the extrusion of secretory organelles, and support the previous reports suggesting that channels of the open canalicular system serve as conduits for discharging the products of the release reaction.


Prevalence and genetic characterization of Cryptosporidium isolates from common brushtail possums (Trichosurus vulpecula) adapted to urban settings.
The common brushtail possum (Trichosurus vulpecula) is one of the most abundant native marsupials in urban Australia, having successfully adapted to utilize anthropogenic resources. The habituation of possums to food and shelter available in human settlements has facilitated interaction with people, pets, and zoo animals, increasing the potential for transmission of zoonotic Cryptosporidium pathogens. This study sought to examine the identity and prevalence of Cryptosporidium species occurring in possums adapted to urban settings compared to possums inhabiting remote woodlands far from urban areas and to characterize the health of the host in response to oocyst shedding. Findings indicated that both populations were shedding oocysts of the same genotype (brushtail possum 1 [BTP1]) that were genetically and morphologically distinct from zoonotic species and genotypes and most closely related to Cryptosporidium species from marsupials. The urban population was shedding an additional five Cryptosporidium isolates that were genetically distinct from BTP1 and formed a sister clade with Cryptosporidium parvum and Cryptosporidium hominis. Possums that were shedding oocysts showed no evidence of pathogenic changes, including elevated levels of white blood cells, diminished body condition (body mass divided by skeletal body length), or reduced nutritional state, suggesting a stable host-parasite relationship typical of Cryptosporidium species that are adapted to the host. Overall, Cryptosporidium occurred with a higher prevalence in possums from urban habitat (11.3%) than in possums from woodland habitat (5.6%); however, the host-specific nature of the genotypes may limit spillover infection in the urban setting. This study determined that the coexistence of possums with sympatric populations of humans, pets, and zoo animals in the urban Australian environment is unlikely to present a threat to public health safety.


Understanding the experiences of doctors who undertake elective surgery on HIV/AIDS patients in an area of high incidence in South Africa.
This study investigates the experiences of doctors who perform elective surgical procedures in an area of South Africa with a high incidence of HIV and AIDS. A qualitative study approach was adopted. Interviews were individually conducted with 15 doctors. The transcribed interviews were read four times, each with a different data-collection purpose, and follow-up interviews were carried out when it was necessary to complete the data set. Surgical doctors from two semi-urban hospitals and one rural hospital in northern KwaZulu-Natal province took part in the study. The analysis of the interviews rendered four areas of concern in the experiences of doctors who perform surgery on HIV/ AIDS patients. These were: personal factors, patient factors, factors relating to the structure of the health system, and factors concerning protocols for the treatment of patients with HIV or AIDS. Although the doctors were altruistic in their approaches to operating on HIV/AIDS patients, they commonly mentioned the increased levels of stress they experience as a result of a multiplicity of issues surrounding the treatment and care of an HIV/AIDS patient specifically. The public health system has not made special arrangements to deal with the increased patient loads in hospitals as a result of the HIV epidemic, and this will have to be addressed as the number of HIV/AIDS patients increases.


Comparative analysis on genome-wide DNA methylation in longissimus dorsi muscle between Small Tailed Han and Dorper×Small Tailed Han crossbred sheep.
The objective of this study was to compare the DNA methylation profile in the longissimus dorsi muscle between Small Tailed Han and Dorper×Small Tailed Han crossbred sheep which were known to exhibit significant difference in meat-production. Six samples (three in each group) were subjected to the methylated DNA immunoprecipitation sequencing (MeDIP-seq) and subsequent bioinformatics analyses to detect differentially methylated regions (DMRs) between the two groups. 23.08 Gb clean data from six samples were generated and 808 DMRs were identified in gene body or their neighboring up/downstream regions. Compared with Small Tailed Han sheep, we observed a tendency toward a global loss of DNA methylation in these DMRs in the crossbred group. Gene ontology enrichment analysis found several gene sets which were hypo-methylated in gene-body region, including nucleoside binding, motor activity, phospholipid binding and cell junction. Numerous genes were found to be differentially methylated between the two groups with several genes significantly differentially methylated, including transforming growth factor beta 3 (TGFB3), acyl-CoA synthetase long chain family member 1 (ACSL1), ryanodine receptor 1 (RYR1), acyl-CoA oxidase 2 (ACOX2), peroxisome proliferator activated receptor-gamma2 (PPARG2), netrin 1 (NTN1), ras and rab interactor 2 (RIN2), microtubule associated protein RP/EB family member 1 (MAPRE1), ADAM metallopeptidase with thrombospondin type 1 motif 2 (ADAMTS2), myomesin 1 (MYOM1), zinc finger, DHHC type containing 13 (ZDHHC13), and SH3 and PX domains 2B (SH3PXD2B). The real-time quantitative polymerase chain reaction validation showed that the 12 genes are differentially expressed between the two groups. In the current study, a tendency to a global loss of DNA methylation in these DMRs in the crossbred group was found. Twelve genes, TGFB3, ACSL1, RYR1, ACOX2, PPARG2, NTN1, RIN2, MAPRE1, ADAMTS2, MYOM1, ZDHHC13, and SH3PXD2B, were found to be differentially methylated between the two groups by gene ontology enrichment analysis. There are differences in the expression of 12 genes, of which ACSL1, RIN2, and ADAMTS2 have a negative correlation with methylation levels and the data suggest that DNA methylation levels in DMRs of the 3 genes may have an influence on the expression. These results will serve as a valuable resource for DNA methylation investigations on screening candidate genes which might be related to meat production in sheep.


Differences in outcome in primary angioplasty in women.
In acute myocardial infarction (AMI), primary percutaneous transluminal coronary angioplasty (PTCA) has proved to be the best therapeutic approach. Several factors have been associated with worse outcome in AMI in females. Are there differences in outcome in women undergoing PTCA for AMI? To evaluate gender influence on clinical outcome and in-hospital mortality in patients with AMI who undergo primary percutaneous interventions. We studied 245 consecutive patients (72 women, 29.4 %), who underwent primary PTCA between January 2000 and December 2001. The following parameters were analyzed: risk factors for coronary artery disease including hypertension, diabetes, smoking, hypercholesterolemia and family history, previous AMI, PTCA or angina, pain-to-balloon time, extent of coronary disease and outcome. Female patients were older (67.9+/-11.6 vs. 59.6+/-13; p < 0.001) with a higher prevalence of hypertension (65.3 % vs. 47.4 %; p < 0.05) and angina (29.0 % vs. 16.0 %; p < 0.05) and lower prevalence of smoking (27.8 % vs. 54.3 %; p < 0.001). Pain-to-balloon time was longer in women (6.8+/-4.1 vs. 5.4+/-3.7 hours; p < 0.05). Extent of coronary disease was similar in both groups. Glycoprotein IIb/IIIa inhibitors were used in 84.7 % of women and 90.8 % of men. The frequency of hemorrhagic complications (5.6 % vs. 5.2 %) and arrhythmias (15.3 % vs. 10.4%) and in-hospital mortality (9.7 6.4 %) were higher in females, although without statistical significance (p = NS). Hospitalization time was similar in both groups. Despite the growing awareness of a gender bias in therapeutic approaches to AMI, there are still some differences in outcome, with a trend towards higher mortality rates in women. Older age and longer pain-to-balloon time could account for this.


Lessons Learned From an Evaluation of Serious Gaming as an Alternative to Mannequin-Based Simulation Technology: Randomized Controlled Trial.
The use of new technology like virtual reality, e-learning, and serious gaming can offer novel, more accessible options that have been demonstrated to improve learning outcomes. The aim of this study was to compare the educational effectiveness of serious game-based simulation training to traditional mannequin-based simulation training and to determine the perceptions of physicians and nurses. We used an obstetric use case, namely electronic fetal monitoring interpretation and decision making, for our assessment. This study utilized a mixed methods approach to evaluate the effectiveness of the new, serious game-based training method and assess participants' perceptions of the training. Participants were randomized to traditional simulation training in a center with mannequins or serious game training. They then participated in an obstetrical in-situ simulation scenario to assess their learning. Participants also completed a posttraining perceptions questionnaire. The primary outcome measure for this study was the participants' performance in an in-situ mannequin-based simulation scenario, which occurred posttraining following a washout period. No significant statistical differences were detected between the mannequin-based and serious game-based groups in overall performance, although the study was not sufficiently powered to conclude noninferiority. The survey questions were tested for significant differences in participant perceptions of the educational method, but none were found. Qualitative participant feedback revealed important areas for improvement, with a focus on game realism. The serious game training tool developed has potential utility in providing education to those without access to large simulation centers; however, further validation is needed to demonstrate if this tool is as effective as mannequin-based simulation.


Pathophysiologic Implications of Cytokines Secretion during Liver Transplantation Surgery.
We introduce the following issues of the cytokines secretion during liver transplantation surgery in this review article; 1) the aspect of cytokines secretion during liver transplantation surgery, 2) the evidences of association of cytokines concentration with post-transplantation graft survival, 3) a variety of factors that may influence the secretion of cytokines during liver transplantation, 4) pro-inflammatory and anti-inflammatory cytokine balance during the surgery, and 5) the issues of T helper 1 and T helper 2, and T helper 17 and regulatory T cell signature cytokines secretion and their ratio during liver transplantation surgery. Primary failure of the liver is associated with the secondary dysfunction of virtually all other organ systems, including the cardiovascular, pulmonary, renal, coagulation and central nervous systems. In addition, liver transplantation surgery itself is a major surgical procedure with accompanying life-threatening hemorrhage, massive transfusion, clamping and unclamping of great vessels and resulting ischemia-reperfusion injury and cardiovascular instability. Both the underlying liver failure and the surgical events act as stressors and promote the secretion of various cytokines. So it is clinically important to understand above issues regarding the cytokines secretion during liver transplantation surgery. As cytokines secretion has clear relationship with post-transplantation clinical outcomes, future study directions for artificially manipulating cytokines secretion is also suggested for enhancing outcomes of the patients.