Female Sexual Health Training for Oncology Providers: New Applications.
Sexual health care remains an unmet need for women with cancer. Many barriers are described, such as provider discomfort and lack of training; however, there is little evidence-based guidance regarding how to effectively address these obstacles. This pilot study was performed to determine whether brief, targeted sexual health training for oncology providers results in improved provider comfort level and frequency of addressing female cancer-related sexual issues. A brief (30-45 minute), targeted sexual health training program focused on improving comfort level, knowledge and communication skills when addressing breast cancer-related sexual issues was developed by the primary author. Using a pretest-posttest format, this educational program was provided to oncology providers (physicians and nurses/other allied health) from a suburban health-care system. Surveys based on 5-point Likert scales were provided before and 3-6 month post training. Primary endpoints were changes in mean Likert scores for provider comfort level and self-reported frequency of addressing sexual issues. A secondary endpoint was change in mean Likert scores for perception of access to sexual health resources/referrals. Eligible respondents included 8 oncologists, 4 surgeons, and 62 nurses/other allied health. For total respondents, comparison of mean Likert scores for survey 1 (n = 71) and survey 2 (n = 36) demonstrated statistically significant increases for all parameters queried, including provider comfort level with bringing up (Pre mean Likert score = 3.4, Post = 4.3, P < 0.0001) and coordinating care (Pre = 3.5, Post = 4.6, P < 0.0001), and frequency of addressing sexual issues for both diagnosis/treatment and surveillance phase (Pre = 2.4, Post = 3.3, P ≤ 0.0052). Brief, targeted sexual health training for oncology providers positively correlated with improved provider comfort level and frequency of addressing female cancer-related sexual issues.


SNAP: A General Purpose Network Analysis and Graph Mining Library.
Large networks are becoming a widely used abstraction for studying complex systems in a broad set of disciplines, ranging from social network analysis to molecular biology and neuroscience. Despite an increasing need to analyze and manipulate large networks, only a limited number of tools are available for this task. Here, we describe Stanford Network Analysis Platform (SNAP), a general-purpose, high-performance system that provides easy to use, high-level operations for analysis and manipulation of large networks. We present SNAP functionality, describe its implementational details, and give performance benchmarks. SNAP has been developed for single big-memory machines and it balances the trade-off between maximum performance, compact in-memory graph representation, and the ability to handle dynamic graphs where nodes and edges are being added or removed over time. SNAP can process massive networks with hundreds of millions of nodes and billions of edges. SNAP offers over 140 different graph algorithms that can efficiently manipulate large graphs, calculate structural properties, generate regular and random graphs, and handle attributes and meta-data on nodes and edges. Besides being able to handle large graphs, an additional strength of SNAP is that networks and their attributes are fully dynamic, they can be modified during the computation at low cost. SNAP is provided as an open source library in C++ as well as a module in Python. We also describe the Stanford Large Network Dataset, a set of social and information real-world networks and datasets, which we make publicly available. The collection is a complementary resource to our SNAP software and is widely used for development and benchmarking of graph analytics algorithms.


Large global effective population sizes in Paramecium.
The genetic effective population size (N(e)) of a species is an important parameter for understanding evolutionary dynamics because it mediates the relative effects of selection. However, because most N(e) estimates for unicellular organisms are derived either from taxa with poorly understood species boundaries or from host-restricted pathogens and most unicellular species have prominent phases of clonal propagation potentially subject to strong selective sweeps, the hypothesis that N(e) is elevated in single-celled organisms remains controversial. Drawing from observations on well-defined species within the genus Paramecium, we report exceptionally high levels of silent-site polymorphism, which appear to be a reflection of large N(e).


[Adherence to recommendations to prevent falls in the elderly, Albacete, Spain, 2009].
There are recommendations to prevent falls. Our goal is to determine, in older people, the knowledge and adherence to these recommendations, and to analyze the demographic characteristics and associated morbidity. Observational study of prevalence and crossed association. The target population are older people living in the community. The subjects were randomly selected (n = 919) and interviewed about their knowledge and level of adherence to existing recommendations to prevent falls in older people, we also gathered information about their health problems and their demographic characteristics. A descriptive analysis was performed and compared the "more compliant" subjects with the rest of the participants. Using a multivariate analysis the association of adhesion with possible factors was found. 50.8% were unaware that there are physical exercises recommended to prevent falls and 22.0% that taking care of your feet can contribute to this end. The recommendations with greater adherence are those related to the bathroom, where 62.2% used the shower for personal hygiene and 83.5% use non-slip floor mat in the shower or bathtub. Variables associated with increased compliance are: presence of 3 or more health problems (OR: 1.6), age over 80 years (OR: 1.4), higher level of schooling (OR: 1.5) and unmarried individuals, widowed or divorced (OR: 1.4).


High Oxygen Shocking Reduces Postharvest Disease and Maintains Satisfying Quality in Fresh Goji Berries during Cold Storage by Affecting Fungi Community Composition.
Fresh goji (Lycium barbarum L.) berries were treated with high-concentration (50% and 90%) oxygen shocking for 30 min and then stored at 0 ± 0.5 °C for 30 d. Decay, aerobic plate count, firmness, weight loss, total soluble solid (TSS), and titratable acidity (TA) were evaluated during storage. A total of 90% O2 shocking more effectively reduced decay and maintained the weight loss and firmness of goji berries. Subsequently, changes in fungi communities were analyzed using high-throughput sequencing (HTS) in the 90% O2-shocking and control groups. The results showed that 90% O2 shocking retained the richness and diversity of fungi communities and the microbiome was related to the quality properties of the fruit. Thus, we inferred that high oxygen shocking inhibited the development of natural decay and maintained the satisfying quality of goji berries by affecting the fungi community composition, which reduced the growth of pathogenic fungi and harmful saprotrophic fungi in the genera, such as Filobasidium sp., Alternaria sp., and Cladosporium sp. We provide a new insight into the disease development and quality changes during the storage of postharvest goji berries.


Does the recruitment of excitation and inhibition in the motor cortex differ?
The level of excitability within the motor cortex can be described as a balance between excitation and inhibition, but it is unknown how well both processes correlate. To address this question, the authors measured motor cortical excitability and inhibition in healthy human subjects, comparing the recruitment of motor evoked potentials (MEPs) and the duration of the cortical silent period (CSP) after transcranial magnetic stimulation (TMS). Single-pulse "focal" TMS was applied at intensities varying between 90% and 200% of motor thresholds to the right motor cortex of 15 healthy volunteers. The peak-to peak size of MEP responses and the duration of the CSP were measured in small hand muscles. Stimulus-response (S-R) curves were constructed by plotting the MEP size and CSP duration against stimulus intensities. The absolute duration of CSP and the size MEPs correlated significantly and to a similar extent with stimulus intensity (r = 0.60 and 0.53, respectively). The slope of the MEP-S-R was steeper compared with CSP-S-R, particularly at low stimulation intensities. CSP duration saturated earlier and CSP-S-Rs were shifted upwards at a given stimulus intensity compared with MEP-S-Rs. The findings suggest that recruitment of inhibition and excitation within the sensorimotor cortex correlate. However, inhibitory effects are recruited at lower intensities and saturate earlier than excitation.


Complete breakup of the helium atom by proton and antiproton impact.
We present a fully ab initio, nonperturbative, time-dependent approach to describe single and double ionization of helium by proton and antiproton impact. The problem is discretized by a flexible finite-element discrete-variable representation on the radial grid. Good agreement with the most recent experimental data for absolute angle-integrated cross sections is obtained for projectile energies between 3 keV and 6 MeV. Also, angle-differential cross sections for two-electron ejection are predicted for a proton impact energy of 6 MeV. The time evaluation of the ionization process is portrayed by displaying the electron density as a function of the projectile location.


Learning from Katrina: environmental health observations from the SWCPHP response team in Houston.
Hurricane Katrina provided an opportunity to observe the public health and medical care response system in practice and provided vital lessons about identifying and learning critical response measures as well as about ineffective investments of time and effort. The Southwest Center for Public Health Preparedness (SWCPHP) response team, while working among evacuees housed at Reliant Park in Houston, Texas, made a number of observations related to environmental public health. This summary reports firsthand observations which are, to a great extent, supported by the Federal Response to Hurricane Katrina: Lessons Learned report, and it provides a contextual backdrop for improvement in the areas of volunteer and citizen preparedness training and education. Katrina provided an opportunity to see public health in a highly stressed practice setting and to identify and reinforce the fundamental tenets of public health with which all individuals responding to an event should be familiar. Knowledge gained from Katrina should be integrated into future efforts related to disaster response planning; specifically, it is imperative that volunteers receive standardized training in the areas of incident command systems (ICS), basic hygiene, transmission of disease, and food and water safety principles.


Multicopy suppression underpins metabolic evolvability.
Our understanding of the origins of new metabolic functions is based upon anecdotal genetic and biochemical evidence. Some auxotrophies can be suppressed by overexpressing substrate-ambiguous enzymes (i.e., those that catalyze the same chemical transformation on different substrates). Other enzymes exhibit weak but detectable catalytic promiscuity in vitro (i.e., they catalyze different transformations on similar substrates). Cells adapt to novel environments through the evolution of these secondary activities, but neither their chemical natures nor their frequencies of occurrence have been characterized en bloc. Here, we systematically identified multifunctional genes within the Escherichia coli genome. We screened 104 single-gene knockout strains and discovered that many (20%) of these auxotrophs were rescued by the overexpression of at least one noncognate E. coli gene. The deleted gene and its suppressor were generally unrelated, suggesting that promiscuity is a product of contingency. This genome-wide survey demonstrates that multifunctional genes are common and illustrates the mechanistic diversity by which their products enhance metabolic robustness and evolvability.


[Early diagnosis of pulmonary embolism by means of scintigraphy].
The occasions on which lung embolism is likely to occur and proceed with or without initial clinical symptoms are described. Lung scintiscanning technique, complemented by special expedients and personal experience, is explained. It is felt that the method helps in the early detection of suspect or clinically silent forms, as well as in the corroboration or ruling out of a clinical diagnosis as soon as this is possible. Scintiscanning is also of assistance in showing the anatomopathological features and extent of the process. The technique is simple and readily tolerated, even by patients with slight respiratory or circulatory disturbances. On the other hand, it is not competitive with conventional and well-tried angiopneumography.


SRY-positive 46, XY male with vanishing testis syndrome, feminization and gynecomastia.
The vanishing testis with maleness is a rare syndrome with frequency of 1 in 20,000 males. Here, we report about a 30 years old male subject with vanishing testis syndrome, feminization and gynecomastia. Follicle stimulating hormone (FSH) and Leutinizing hormone (LH) levels were elevated whereas testosterone was below normal and anti-mullerian-hormone level was undetectable in the patient. The chromosomal analysis and DNA analysis of SRY and ZFY, DAX-I, AZFa, AZFb, AZFc and heterochromatic region of Y chromosome with STS primer (sY160) were done to detect any genetic changes at specified sites (both at chromosomal and molecular level). Karyotyping confirmed patient as 46, XY male, with no evidence of mosaicism in blood cells. PCR amplification of SRY gene indicated that the SRY gene of the patient was normal. PCR amplification of SRY, ZFY, DAX-I, AZFa, AZFb, AZFc gene and Y chromosome heterochromatic region using STS primer sY(160) did not reveal any microdeletions. The anti-mullerian-hormone level was undetectable indicating that the patient didn't have any testicular tissue in scrotum. Increased levels of FSH, LH and reversed androgen: estrogen ratio might have given rise to gynecomastia in the patient. SRY-positive 46,XY male with vanishing testis might be due to torsion of testis during descent in fetal period. The torsion of testis might have caused vascular occlusion and thereby regression of testicular tissue occurred, but the exact genetic condition yet to understand.


[Effects of rotation and fallowing on the microbial communities and enzyme activities in a solar greenhouse soil under continuous cucumber cropping].
A pot experiment was conducted to study the effects of rotation and fallowing on the microbial communities and enzyme activities in a greenhouse soil continuously cropped with cucumber and on the growth and yield of followed cucumber. Comparing with continuous cropping, rotation improved the components of soil microbial communities, which was manifested in the increase of bacteria and actinomycetes and the decrease of fungi. Rotation and fallowing enhanced the activities of soil invertase, urease, catalase, and polyphenol oxidase significantly. The quantities of soil bacteria and actinomycetes and the activity of soil invertase increased at the fruiting stage of cucumber plants, being the maximum at harvest stage, but decreased thereafter. In contrast, the quantity of soil fungi had a linear increase, and the activities of soil urease, catalase, and polyphenol oxidase decreased gradually during fruit development. Welsh onion and waxy maize promoted the growth and fruiting of the followed cucumber plants significantly, being the optimal rotation crops for cucumber.


Prophylactic and therapeutic effects of small interfering RNA targeting SARS-coronavirus.
To identify and characterize the siRNA duplexes that are effective for inhibition of SARS-CoV infection and replication in the non-human primate cells. This in vitro study will serve as the foundation for development of novel anti-SARS therapeutics. 48 siRNA sequences were designed for targeting regions throughout entire SARS-CoV genome RNA including open-reading frames for several key proteins. Chemically synthesized siRNA duplexes were transfected into foetal rhesus kidney (FRhK-4) cells prior to or after SARS-CoV infection. The inhibitory effects of the siRNAs were evaluated for reductions of intracellular viral genome copy number and viral titres in the cell culture medium measured by Q-RT-PCR and CPE-based titration, respectively. Four siRNA duplexes were found to achieve potent inhibition of SARS-CoV infection and replication. A prolonged prophylactic effect of siRNA duplexes with up to 90% inhibition that lasted for at least 72 h was observed. Combination of active siRNA duplexes targeting different regions of the viral genome resulted in therapeutic activity of up to 80% inhibition. Chemically synthesized siRNA duplexes targeting SARS-CoV genomic RNA are potent agents for inhibition of the viral infection and replication. The location effects of siRNAs were revealed at both genome sequence and open-reading frame levels. The rapid development of siRNA-based SARS-CoV inhibitors marked a novel approach for combating newly emergent infectious diseases.


A widely conserved bacterial cytoskeletal component influences unique helical shape and motility of the spirochete Leptospira biflexa.
Leptospires and other members of the evolutionarily ancient phylum of Spirochaetes are bacteria often characterized by long, highly motile spiral- or wave-shaped cells. Morphology and motility are critical factors in spirochete physiology, contributing to the ability of these bacteria to successfully colonize diverse environments. However, the mechanisms conferring the helical structure of Leptospira spp. have yet to be fully elucidated. We have identified five Leptospira biflexa bactofilin proteins, a recently characterized protein family with cytoskeletal properties. These five bactofilins are conserved in all species of the Leptospiraceae, indicating that these proteins arose early in the evolution of this family. One member of this protein family, LbbD, confers the optimal pitch distance in the helical structure of L. biflexa. Mutants lacking lbbD display a unique compressed helical morphology, a reduced motility and a decreased ability to tolerate cell wall stressors. The change in the helical spacing, combined with the motility and cell wall integrity defects, showcases the intimate relationship and coevolution between shape and motility in these spirochetes.


Thalamic projections to sensorimotor cortex in the newborn macaque.
In the present experiments thalamocortical projections to different functional areas of the newborn (or prematurely delivered) macaque's sensorimotor cortex were labeled using retrogradely transported fluorescent dyes. Several dyes were used in each animal to (1) enable the direct comparison of the soma distributions of different thalamocortical projections within thalamic space, and (2) identify by double labeling neurons shared between these distributions. The projection patterns in the newborn macaque were compared with those of the mature animal reported by Darian-Smith et al. (J. Comp. Neurol. 1990;298:000-000). The main observations were (1) all thalamocortical projections to the sensorimotor cortex of the mature macaque are well established by embryonic days 146-150, as was shown by labeling these pathways in infants delivered by cesarean section, (2) a significant number of thalamocortical neurons in the newborn were double-labeled following dye injections into different pre- or postcentral areas, and where the margins of the dye uptake zones were separated by 3-8 mm, and (3) extensive projections from the anterior pulvinar nucleus to the motor and premotor cortex, and to the supplementary motor cortex were labeled in the newborn macaque. Both the exuberant terminal arborizations, and the precentral pulvinar projections were diminished by the 6th postnatal month, and absent in the mature macaque. The role of epigenetic determinants of these postnatal events is briefly considered.


A clinical prediction model identifies a subgroup with inferior survival within intermediate risk acute myeloid leukemia.
Intermediate risk acute myeloid leukemia (AML) comprises around 50% of AML patients and is featured with heterogeneous clinical outcomes. The study aimed to generate a prediction model to identify intermediate risk AML patients with an inferior survival. We performed targeted next generation sequencing analysis for 121 patients with 2017 European LeukemiaNet-defined intermediate risk AML, revealing 122 mutated genes, with 24 genes mutated in > 10% of patients. A prognostic nomogram characterized by white blood cell count ≥10×109/L at diagnosis, mutated DNMT3A and genes involved in signaling pathways was developed for 110 patients who were with clinical outcomes. Two subgroups were identified: intermediate low risk (ILR; 43.6%, 48/110) and intermediate high risk (IHR; 56.4%, 62/110). The model was prognostic of overall survival (OS) and relapse-free survival (RFS) (OS: Concordance index [C-index]: 0.703, 95%CI: 0.643-0.763; RFS: C-index: 0.681, 95%CI 0.620-0.741), and was successfully validated with two independent cohorts. Allogeneic hematopoietic stem cell transplantation (alloHSCT) reduced the relapse risk of IHR patients (3-year RFS: alloHSCT: 40.0±12.8% vs. chemotherapy: 8.6±5.8%, P= 0.010). The prediction model can help identify patients with an unfavorable prognosis and refine risk-adapted therapy for intermediate risk AML patients.


Effects of repeated attachment security priming in outpatients with primary depressive disorders.
The aim of this study was to assess the potential effectiveness of secure attachment priming in outpatients with depressive disorders. Forty-eight participants engaged in secure attachment priming or neutral priming in the laboratory (Time 1), after which they received three daily consecutive primes via text message (Times 2-4), aimed at maintaining the effects from Time 1. A follow-up one day later (Time 5) was also included. Dependent measures were assessed at Times 1, 4 and 5. Participants in the secure attachment priming condition experienced higher felt-security than the control group at all time-points, indicating that the felt-security benefit was maintained through repeated priming. Secure priming had a greater impact on reducing symptoms of anxiety and depression in comparison to the control prime, though the differences were only significant at Time 4. The moderate sample size limited our statistical power. This study was the first experiment using repeated secure attachment priming within a clinical sample. Our findings have potential clinical implications; security priming could be used alongside other treatments to improve outcome. Recommendations for further research are discussed.


Probe for evaluating the absorbing and transport scattering properties of turbid fluids using low-cost time-of-flight technology.
A probe is described that when immersed into a highly scattering fluid provides a measurement of its scattering and absorbing properties at a single optical wavelength. It uses recently available low-cost proximity sensor modules to estimate the mean flight times of photons diffusely transmitted between near-infrared sources and detectors at two different separations. The probe has been designed with a specific application for enabling the rapid and efficient production of fluids, which mimic the optical properties of biological tissues. The potential of the device is demonstrated using precalibrated solutions of intralipid, an intravenous nutrient, and absorbing dye. It is shown that a combination of time-of-flight measurements at two source–detector separations can uniquely specify the absorption coefficient and the transport scattering coefficient.


[Reproductive cycle and index of condition used for Melongena corona (Mollusca: Gastropoda)].
Melongena corona bispinosa was studied in Yucatán, México (21 degrees 16' N, 89 degrees 49' W) for a year. Males have reproductive peaks in February and December, and a post-copulation peak in June. Female peaks are in March and May, plus oviposition peaks in April and January. Males and females differ in the mean gonadosom ic index (F=13.79, p<0.05) but not in the dry tissue/shell weight (F=0.0902, p<0.05), dry tissue and total weight (F=0.2466, p<0.05) and dry tissue weight/internal shell volume (F=1.0565, p<0.05).


Hypomagnesaemia due to proton-pump inhibitor therapy: a clinical case series.
Reports since 2006 have identified proton-pump inhibitor (PPI) therapy as a cause of hypomagnesaemia, in a total of 13 cases. To summarize the clinical course of 10 patients (one male, nine female) identified with severe hypomagnesaemia, all of whom were on PPI therapy. A case report illustrates the experience of a severely affected patient. Clinical and biochemical review. Severe hypomagnesaemia was defined as 0.54 mmol/l or less, >4 SD below the mean. Patients were 68.8 +/- 8.6 years old when they presented with severe hypomagnesaemia, having been on PPI therapy for a mean of 8.3 +/- 3.5 years. Eight patients were on diuretics at initial presentation. There was significant morbidity as eight patients remained on PPI therapy after presentation for a mean of 2.75 +/- 1.54 years. There were 18 emergency hospital admissions with severe hypomagnesaemia. Oral and parenteral magnesium supplements were relatively ineffective at correcting the problem, but stopping PPI therapy lead to prompt resolution of the hypomagnesaemia (within 2 weeks in five carefully monitored patients), with symptomatic benefit. Hypomagnesaemia recurred if PPI therapy was re-introduced because of troublesome dyspepsia. However, pantoprazole, the least potent PPI, largely relieved dyspepsia and hypomagnesaemia did not inevitably develop when combined with oral magnesium supplements. These cases confirm that long-term PPI therapy can cause severe, symptomatic hypomagnesaemia, which resolves when PPI therapy is withdrawn. The serum magnesium should be checked annually in patients on long-term PPI therapy, or if they feel unwell.


Olfactory detection of ozone and D-limonene: reactants in indoor spaces.
Young adult subjects who occupied a well-ventilated space with low background of level of ozone achieved via carbon-filtration could detect ozone odor at 7 ppb, lower than expected from archival compilations. The outcome was not inconsistent, however, with some observations of recognition, beyond mere detection, at about 15-20 ppb. Individual differences in sensitivity lay at or just below an order of magnitude, rare in olfactory testing and indicative of precision. In a study of d-limonene, subjects again showed high sensitivity and small individual differences. The subjects could detect the odor at 8 and 15 ppb, depending upon whether they occupied a space with or without carbon filtration, respectively. The results argue for use of carbon filtration to measure sensitivity most stringently, although absence of filtration seems not to incur a large penalty. The protocol used here, with collection of hundreds of judgments in a day, yet with little net exposure of the subject to odorant; with verifiably stable delivery; and with analytical confirmation of level should reduce tolerance for outcomes of large differences among subjects and among studies. Humans manifested much higher sensitivity to ozone and D-limonene than commonly thought, a pattern revealing itself more broadly in olfactory studies as testing improves and analytical confirmation of delivery becomes more common. Published databases, with errors of +/-1000%, often badly underestimate sensitivity and can thereby encourage use of higher concentrations of compounds, particularly VOCs, than relevant in studies of reactive indoor chemistry.


Liquid level interferometer.
An inexpensive field instrument has been built to measure changes in water level to an accuracy of lambda/8. A novel magnetic suspension is used to position the floating retroreflector of a laser interferometer. Direction sensing is achieved by dual optical channels phased near quadrature by means of an absorbing beam splitter.


Chronic Road Salt Exposure Across Life Stages and The Interactive Effects of Warming and Salinity in a Semiaquatic Insect.
The salinization of freshwater habitats from winter road salt application is a growing concern. Understanding how taxa exposed to road salt run-off respond to this salinity exposure across life history transitions will be important for predicting the impacts of increasing salinity. We show that Leucorrhinia intacta Hagen, 1861 (Odonata: Libellulidae) dragonflies are robust to environmentally relevant levels of salt pollution across intrinsically stressful life history transitions (hatching, growth, and metamorphosis). Additionally, we observed no carry-over effects into adult dragonfly morphology. However, in a multiple-stressor setting, we see negative interactive effects of warming and salinity on activity, and we found that chronically warmed dragonfly larvae consumed fewer mosquitoes. Despite showing relatively high tolerance to salinity individually, we expect that decreased dragonfly performance in multiple-stressor environments could limit dragonflies' contribution to ecosystem services such as mosquito pest control in urban freshwater environments.


Impact of SARS-CoV-2 infection on clinical outcomes of in vitro fertilization treatments: a systematic review and meta-analysis.
The influence of SARS-CoV-2 infection on clinical outcomes in patients undergoing in vitro fertilization has been uncertain. Therefore, this systematic review and meta-analysis aimed to evaluate the impact of past SARS-CoV-2 infection on IVF outcomes. A comprehensive search of PubMed, EMBASE, and Cochrane Library databases was conducted from December 2019 to January 2023. Included studies comparing IVF outcomes between patients with prior SARS-CoV-2 infection and controls without previous infection were analyzed. Study quality was assessed using the Newcastle-Ottawa Quality Assessment Scale. Sensitivity analysis, publication bias, and heterogeneity were also examined. The review protocol was registered with PROSPERO (CRD42023392007). A total of eight studies, involving 317 patients with past SARS-CoV-2 infection and 904 controls, met the inclusion criteria. The meta-analysis revealed no significant differences between the infection group and controls in terms of clinical pregnancy rate (OR 0.97, 95% CI 0.73-1.29; P = 0.82), implantation rate (OR 0.99, 95% CI 0.67-1.46; P = 0.96), or miscarriage rate (OR 0.64, 95% CI 0.15-2.65; P = 0.53). Subgroup analyses based on transfer type demonstrated comparable clinical pregnancy rates between the two groups in both fresh embryo transfer (OR 0.97, 95% CI 0.69-1.36; P = 0.86) and frozen embryo transfer (OR 0.96, 95% CI 0.38-2.44; P = 0.94). In conclusion, this meta-analysis suggests that previous SARS-CoV-2 infection does not have a detrimental impact on clinical outcomes in IVF patients. These findings provide valuable insights into assessing the influence of prior SARS-CoV-2 infection on successful pregnancy outcomes in IVF treatment. The systematic review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. This review was prospectively registered with the International Prospective Register of Systematic Reviews (ID CRD42023392007) on January 16, 2023.


Generation and characterization of monoclonal antibodies to NIAM: a nuclear interactor of ARF and Mdm2.
Nuclear interactor of ARF and Mdm2 (NIAM) is a newly discovered growth inhibitor that helps maintain chromosomal stability. It is functionally linked to the ARF-Mdm2-p53 tumor suppressor pathway and is predicted to be a tumor suppressor, but the lack of antibodies capable of detecting the endogenous human protein has delayed efforts to define its role in human tumorigenesis. This study reports the development, screening, and characterization of several monoclonal antibodies (MAbs) that specifically recognize endogenous human NIAM protein by Western blotting, immunoprecipitation, immunofluorescence, and immunohistochemistry. These MAbs are predicted to be important tools for evaluating the expression and physiological function of NIAM in normal versus neoplastic human cells and tissues.


Development and validation of novel multimorbidity indices for older adults.
Measuring multimorbidity in claims data is used for risk adjustment and identifying populations at high risk for adverse events. Multimorbidity indices such as Charlson and Elixhauser scores have important limitations. We sought to create a better method of measuring multimorbidity using claims data by incorporating geriatric conditions, markers of disease severity, and disease-disease interactions, and by tailoring measures to different outcomes. Health conditions were assessed using Medicare inpatient and outpatient claims from subjects age 67 and older in the Health and Retirement Study. Separate indices were developed for ADL decline, IADL decline, hospitalization, and death, each over 2 years of follow-up. We validated these indices using data from Medicare claims linked to the National Health and Aging Trends Study. The development cohort included 5012 subjects with median age 76 years; 58% were female. Claims-based markers of disease severity and disease-disease interactions yielded minimal gains in predictive power and were not included in the final indices. In the validation cohort, after adjusting for age and sex, c-statistics for the new multimorbidity indices were 0.72 for ADL decline, 0.69 for IADL decline, 0.72 for hospitalization, and 0.77 for death. These c-statistics were 0.02-0.03 higher than c-statistics from Charlson and Elixhauser indices for predicting ADL decline, IADL decline, and hospitalization, and <0.01 higher for death (p < 0.05 for each outcome except death), and were similar to those from the CMS-HCC model. On decision curve analysis, the new indices provided minimal benefit compared with legacy approaches. C-statistics for both new and legacy indices varied substantially across derivation and validation cohorts. A new series of claims-based multimorbidity measures were modestly better at predicting hospitalization and functional decline than several legacy indices, and no better at predicting death. There may be limited opportunity in claims data to measure multimorbidity better than older methods.


Writing Histone Monoubiquitination in Human Malignancy-The Role of RING Finger E3 Ubiquitin Ligases.
There is growing evidence highlighting the importance of monoubiquitination as part of the histone code. Monoubiquitination, the covalent attachment of a single ubiquitin molecule at specific lysines of histone tails, has been associated with transcriptional elongation and the DNA damage response. Sites function as scaffolds or docking platforms for proteins involved in transcription or DNA repair; however, not all sites are equal, with some sites resulting in actively transcribed chromatin and others associated with gene silencing. All events are written by E3 ubiquitin ligases, predominantly of the RING (really interesting new gene) finger type. One of the most well-studied events is monoubiquitination of histone H2B at lysine 120 (H2Bub1), written predominantly by the RING finger complex RNF20-RNF40 and generally associated with active transcription. Monoubiquitination of histone H2A at lysine 119 (H2AK119ub1) is also well-studied, its E3 ubiquitin ligase constituting part of thePolycomb Repressor Complex 1 (PRC1), RING1B-BMI1, associated with transcriptional silencing. Both modifications are activated as part of the DNA damage response. Histone monoubiquitination is a key epigenomic event shaping the chromatin landscape of malignancy and influencing how cells respond to DNA damage. This review discusses a number of these sites and the E3 RING finger ubiquitin ligases that write them.


Three-dimensional alteration of constricted alveolar ridge affected by root thrusting with and without open-flap decortication.
To investigate the morphometric and histological alterations of the constricted alveolar ridge when affected by root thrusting with and without open-flap decortication. Eight beagles were divided into three groups: C, control without root thrusting; R, root thrusting only; RD, root thrusting with alveolar decortication. The ridge constriction model was prepared in 16 mandibular quadrants after extraction of the third premolars. Reciprocal root thrusting of the second and fourth premolars was performed toward the constricted ridge for 10 weeks, having a moment of 900 g-mm. Open-flap decortication was conducted on the constricted bone surface in group RD. Micro-CT-based histomorphometric analysis and trichrome-staining-based tissue fractional analysis were performed to evaluate morphometric and microstructural changes on the ridge. Group R revealed a higher percentage of bone volume (P < .001), lower bone mineral density (P < .01), and higher trabecular number (P < .001) than did group C, which was supported by a higher bone fraction woven to lamellar bone (P < .05) resulting from histologic fractional analysis. However, group RD showed no significant difference from group C. Root thrusting toward the constricted ridge induced hypertrophic bone modeling with a high trabecular fraction on the ridge. However, combined open-flap decortication with root thrusting did not improve the volume or quality of the constricted ridge.


Burnout and Emotional Intelligence in Neurosurgical Advanced Practice Providers Across the United States: A Cross-Sectional Analysis.
Although much research has examined nursing and physician burnout, the advanced practice provider (APP) population has not yet been studied. The goal of the present study was to survey APPs in neurosurgery to determine whether greater emotional intelligence (EI) is protective against burnout. An 80-item survey was created that incorporated the Maslach Burnout Inventory Human Services Survey for Medical Personnel, the Trait Emotional Intelligence Questionnaire-short form, and original questions developed by us. The collective survey was distributed, administered, and collected using the web-based REDCap (Research Electronic Data Capture) platform. Statistical analyses were completed using a comparison between participants with and without burnout. A total of 106 neurosurgical APPs (26 men, 80 women) completed the survey, of whom, 57 (54%) reported current burnout. High average scores for personal accomplishment and global EI were inversely related to burnout (P = 0.034 and P = 0.003, respectively). In addition, the following factors were associated with burnout: inadequate support staff in the work place (P = 0.008), inadequate time off work (P < 0.001), inadequate administrative time (P = 0.009), not experiencing support from one's supervisor (P = 0.017), insufficient time for continuing medical education (P < 0.001), an inability to separate work from personal time (P < 0.001), and an inability to advance within one's professional field (P = 0.043). For neurosurgical APPs, EI is protective against burnout. Many opportunities exist at the individual and organizational level to alleviate burnout among neurosurgical APPs. Targeted strategies to improve work-life balance, EI, support systems, and opportunities for career development among neurosurgical APPs might enhance employment satisfaction and reduce burnout.


Acquired pachydermatoglyphy. A cutaneous sign of internal malignancy.
A 70-year-old man with hypertrophic osteoartropathy secondary to a squamous cell carcinoma of the lung presented a distinctive pattern of late-onset bilateral palmar keratoderma. A yellowish rugose appearance with accentuation of normal ridges and sulci (pachydermatoglyphy) involving the palms was observed. The differential diagnosis and the clinical relevance of acquired pachydermatoglyphy as a cutaneous marker of internal malignancy are discussed.


Advanced paternal age and risk of schizophrenia in offspring - Review of epidemiological findings and potential mechanisms.
A large number of studies have examined the association between advanced paternal age (APA) and risk of schizophrenia in offspring. Here we present an overview of epidemiological studies on this subject published since 2000, and systematically summarize their methodologies and results. Next, we discuss evidence to elucidate the potential mechanisms contributing to the association between APA and offspring schizophrenia, considering paternal psychiatric morbidity and genetic liability, maternal factors, and findings from family design studies. We propose that multiple mechanisms, including causal and non-causal pathways, contribute to the observed relationship between APA and schizophrenia in offspring, and conclude by highlighting the need for multi-disciplinary studies in disentangling these complex, non-mutually exclusive mechanisms.


Surgical treatment for congenital occlusion of the inferior vena cava in its diaphragmatic portion.
This is a case report on a congenital occlusion of the inferior vena cava in its diaphragmatic part. Additionally, the proximal 10 cm within the retrohepatic portion of the vessel were highly stenotic. With exception of the vena hepatica brevis all larger hepatic veins were occluded. Correction was achieved using a 14 mm Gore-Tex (Polytetrafluoroethylene) graft, which connected the abdominal part of the inferior vena cava to the right atrium.


Adaptive divergence generates distinct plastic responses in two closely related Senecio species.
The evolution of plastic responses to external cues allows species to maintain fitness in response to the environmental variations they regularly experience. However, it remains unclear how plasticity evolves during adaptation. To test whether distinct patterns of plasticity are associated with adaptive divergence, we quantified plasticity for two closely related but ecologically divergent Sicilian daisy species (Senecio, Asteraceae). We sampled 40 representative genotypes of each species from their native range on Mt. Etna and then reciprocally transplanted multiple clones of each genotype into four field sites along an elevational gradient that included the native elevational range of each species, and two intermediate elevations. At each elevation, we quantified survival and measured leaf traits that included investment (specific leaf area), morphology, chlorophyll fluorescence, pigment content, and gene expression. Traits and differentially expressed genes that changed with elevation in one species often showed little changes in the other species, or changed in the opposite direction. As evidence of adaptive divergence, both species performed better at their native site and better than the species from the other habitat. Adaptive divergence is, therefore, associated with the evolution of distinct plastic responses to environmental variation, despite these two species sharing a recent common ancestor.


A case of chronic neutrophilic leukemia with original chromosomal abnormalities.
We report a new case of the unusual myeloproliferative syndrome chronic neutrophilic leukemia (CNL) that met all the criteria generally required for the diagnosis of this entity. The patient presented abnormalities in platelet function not previously reported that may explain the bleeding tendency observed in these patients. The study of neutrophil function suggested also defective mobility and intracellular bactericidal activity. The chromosomal study revealed original abnormalities consisting of multiple chromosomal ruptures and figures. The disease was controlled with busulfan. After 20 months, the patient died of sepsis. An autopsy was performed confirming the diagnosis and ruling out the existence of a cause of a leukemoid reaction, such as cancer or granulomatous disease.


Effects of aspirin on distortion product otoacoustic emission suppression in human adults: a comparison with neonatal data.
One of the distortion product otoacoustic emission (DPOAE) paradigms used to study cochlear function is DPOAE (2f1-f2) ipsilateral suppression. Newborns do not have adultlike DPOAE suppression. At 6000 Hz, infants show excessively narrow DPOAE suppression tuning and shallow growth of suppression for low-frequency suppressor tones. The source of this immaturity is not known but the outer hair cell (OHC) is one possible locus. In the present study, DPOAE suppression was measured at f2 = 1500 and 6000 Hz from two groups with impaired OHC function in an attempt to model the observed immaturity in neonates: adults with aspirin-induced OHC dysfunction and subjects with sensorineural hearing loss (SNHL). Their DPOAE suppression results were compared to those obtained from a group of term newborns to address whether infant DPOAE suppression resembles suppression from individuals with known OHC dysfunction. Results indicate that aspirin systematically alters DPOAE suppression in adults at f2 = 6000 Hz, but not 1500 Hz. However, neither aspirin-induced OHC dysfunction nor naturally occurring SNHL produces "neonatal-like" DPOAE suppression at either test frequency. This finding does not support the hypothesis that non-adultlike DPOAE suppression characterizing newborns can be explained by minor impairments or alterations of OHC function.


Bacillus cabrialesii: Five Years of Research on a Novel Species of Biological Control and Plant Growth-Promoting Bacteria.
Bacillus cabrialesii is a novel bacterial species isolated from wheat (Triticum turgidum L. subsp. durum) plants in the Yaqui Valley, Mexico, by our research team. Over years of research studying this strain at the cutting-edge level, it has shown different mechanisms of action. B. cabrialesii is strongly reported as a plant-growth-promoting bacterium and a biological control agent on wheat crops. Knowing this, B. cabrialesii has been brought from lab to field as part of a bacterial consortium, not to mention that there are ongoing investigations into formulating a cost-effective bioinoculant to increase the yield and/or quality of wheat. Moreover, studies of this novel species as a biocontrol agent in other crops (pepper, tomato, cucumber, and potato) are being carried out, with preliminary results that make B. cabrialesii a promising biological control agent, inhibiting the growth of phytopathogens. However, research into this bacterium has not only been reported in our country; there are many studies around the world in which promising native Bacillus strains end up being identified as B. cabrialesii, which reaffirms the fact that this bacterial species can promote plant growth and combat phytopathogens, showing great agrobiotechnological potential.


Step-up approach for the management of pancreatic necrosis: a review of the literature.
Infected necrotizing pancreatitis is a challenging condition to treat because of the profound inflammatory response these patients undergo which can then be exacerbated by interventions. Treatment of this condition has evolved in timing of intervention as well as method of intervention and includes less invasive options for treatment such as percutaneous drainage and endoscopic drainage, in addition to less invasive endoscopic and video-assisted or laparoscopic debridements. The precise optimal treatment strategy for these patients is an ongoing topic of discussion and may be different for each patient as this is a heterogenous condition.


Childhood bullying: implications for physicians.
Childhood bullying has potentially serious implications for bullies and their targets. Bullying involves a pattern of repeated aggression, a deliberate intent to harm or disturb a victim despite the victim's apparent distress, and a real or perceived imbalance of power. Bullying can lead to serious academic, social, emotional, and legal problems. Studies of successful antibullying programs suggest that a comprehensive approach in schools can change student behaviors and attitudes, and increase adults' willingness to intervene. Efforts to prevent bullying must address individual, familial, and community risk factors, as well as promote an understanding of the severity of the problem. Parents, teachers, and health care professionals must become more adept at identifying possible victims and bullies. Physicians have important roles in identifying at-risk patients, screening for psychiatric comorbidities, counseling families about the problem, and advocating for bullying prevention in their communities.


Ocular filariasis: not strictly tropical.
A 65-year-old man consulted for a discomfort in the right eye that had suddenly appeared the evening before. The examination revealed a white worm localized under the temporal bulbar conjunctiva. After extraction, the parasitological characteristics identified the worm as Dirofilaria repens (Nochtiella subgenus). This is a parasite of canids and felids, usually nonpathogenic to humans, but which can be transmitted through mosquito bites, especially around the Mediterranean basin. The simple extraction of the worm, encysted under the skin or under the conjunctiva, cures the patient.


An immunodominant site of gamma-zein1 is in the region of tandem hexapeptide repeats.
The immunochemical data from studies with polyclonal antisera to gamma-zein1, the 27 kD component of the maize prolamin, indicated that the region containing 8 tandem repeats of the sequence PPPVHL is an immunodominant site. In one case, the entire antibody repertoire of an antiserum recognized epitope(s) within this region. Three 17-mer oligopeptides corresponding to the predicted antigenic epitopes of gamma-zein1 were synthesized and reacted with three different anti-gamma-zein1 sera in order to map antigenic sites in the intact protein. These antisera yielded positive reactions with a 17-mer peptide (peptide 37), which was not in a hydrophilic maximum but derived from the repeat region. The same antisera gave little or no reaction with other peptides (peptides 38 and 39), both of which were in a hydrophilic maximum. In addition, an antiserum to peptide 37 reacted strongly with both the homologous antigen and the intact gamma-zein1. Peptide 37 also blocked the binding of antisera to gamma-zein1 in competition assays. Subsequently, the shorter 6-mer (peptide 82) and 12-mer (peptide 80) versions of peptide 37 were synthesized, and both reacted with anti-peptide 37 serum and also with each of the three anti-gamma-zein1 sera. In these reactions and in competition assays, the reactivity and the blocking ability increased in proportion to the length of the peptide. Based on these data, it was concluded that the repeat region of gamma-zein1 is the site of one or more continuous immunodominant epitopes. The data also suggest that the repeat region is exposed on the surface of the folded protein and probably occur as a mobile, random coil.


Postural control in healthy adults: Determinants of trunk sway assessed with a chest-worn accelerometer in 12 quiet standing tasks.
Many diseases and conditions decrease the ability to control balance. In clinical settings, there is therefore a major interest in the assessment of postural control. Trunk accelerometry is an easy, low-cost method used for balance testing and constitutes an alternative method to the posturography using force platforms. The objective was to assess the responsiveness of accelerometry in a battery of 12 quiet standing tasks. We evaluated the balance of 100 healthy adults with an accelerometer fixed onto the sternum. We used the average amplitude of acceleration as an indirect measure of postural sways. The tasks of increased difficulty were realized with or without vision. The battery of tasks was repeated four times on two different days to assess reliability. We analyzed the extent to which the task difficulty and the absence of vision affected the trunk sway. The influence of individual characteristics (age, height, mass, sex, and physical activity level) was also assessed. The reliability analysis revealed that four repetitions of the battery of tasks are needed to reach a high accuracy level (mean ICC = 0.85). The results showed that task difficulty had a very large effect on trunk sways and that the removal of vision further increased sways. Concerning the effects of individual characteristics, we observed that women tended to oscillate more than men did in tasks of low difficulty. Age and physical activity level also had significant effects, whereas height and mass did not. In conclusion, age, sex, and physical fitness are confounders that should be considered when assessing patients' balance. A battery of simple postural tasks measured by upper-trunk accelerometry can be a useful method for simple balance evaluation in clinical settings.


Lethal multiple pterygium syndrome in a newborn, a case report.
Lethal multiple pterygium syndrome is a very rare genetic disorder. The manifestations of this condition include growth deficiency of the fetus, craniofacial anomalies, joint contracture, and skin webbing (pterygia). This disorder is fatal before birth or shortly after birth. We reported a case of lethal multiple pterygium syndrome with multiple anomalies including pterygia involving the axilla, bilateral antecubital fossa, and groin. Arthrogryposis involving multiple lower and upper extremities joints. Cleft palate, microstomia and limitation of mouth opening, webbed neck, asymmetric small and narrow chest, ambiguous genitalia, depressed and wide nasal bridge, antemongoloid slant, low-set, malformed, and posteriorly rotated ears, pterygia, syndactyly and camptodactyly of hands and rocket bottom feet. LMPS is a congenital genetic disease with multiple anomalies that is fatal in the second and third trimesters of pregnancy or shortly after birth. With genetic testing and counseling, it can be prevented from recurring in subsequent pregnancies.


Assessment of clinically relevant bleeding as a surrogate outcome for major bleeding: validation by meta-analysis of randomized controlled trials.
Essentials Surrogacy of clinically relevant bleeding (CRB) for major bleeding has never been validated. Our meta-analysis evaluated CRB surrogacy in trials of new versus traditional anticoagulants. Surrogacy was not validated in orthopedic surgery, venous thromboembolism or atrial fibrillation The difficulty in demonstrating the surrogacy may reflect a lack of homogeneity in its definition SUMMARY: Background Clinically relevant bleeding (CRB), comprising major bleeding and clinically relevant non-major bleeding, has been used as a surrogate for major bleeding in most anticoagulant trials. The validity of this surrogate to estimate trade-off between thrombotic and bleeding events in clinical trials was never assessed. Methods We systematically reviewed randomized phase III trials comparing new anticoagulants with the standard of care for venous thromboembolism prevention following major orthopedic surgery, venous thromboembolism (VTE) treatment, or stroke and systemic embolism prevention in atrial fibrillation (AF), and reporting both major bleeding and CRB rates. The validity of CRB as a surrogate for major bleeding was assessed according to the strength of the association between the relative risks of major bleeding and CRB, measured by the use of R2trial and its 95% confidence interval (CI). Results In the postoperative prophylactic setting (13 studies), major bleeding and CRB rates were 1.12% and 3.56%, respectively, and R2trial was 0.69 (95% CI 0.34-0.93). For acute VTE studies (n = 12), major bleeding and CRB rates were 1.87% and 9.07%; the corresponding R2trial values were 0.28 (95% CI 0.01-0.80) and 0.68 (95% CI 0.09-1.00) when only double-blind studies were considered (n = 7). For AF studies (n = 7; 22 strata), major bleeding and CRB rates were 4.82% and 15.3%, and R2trial was 0.59 (95% CI 0.15-0.82). Conclusion Despite an apparent correlation between CRB and major bleeding in major orthopedic surgery, AF, and double-blind acute VTE studies, the wide CIs suggest that CRB might not be an acceptable surrogate outcome in any of these settings.


Diagnosis and treatment of malignant eyelid tumors.
Malignant tumors of the eyelid are much less frequent than benign eyelid alterations. These are frequently incidental findings without symptoms which are often overlooked or misinterpreted by patients. This article gives an overview of clinical aspects, diagnostics and treatment of the five most common malignant eyelid tumors and exemplarily explains the essential principles of evidence-based treatment of malignant eyelid tumors. This narrative review was prepared based on a selective literature search. The depiction of the treatment of eyelid tumors is supported by illustrations of clinical cases. The medical history and inspection provide initial indications of malignancy. Every eyelid change suspected of being malignant should be examined histologically to confirm a diagnosis. By far the most common malignant eyelid tumor in Europe is basal cell carcinoma, which metastasizes only in exceptional cases. Squamous cell carcinomas, sebaceous adenocarcinomas, melanomas and Merkel cell carcinomas occur much less frequently. In these cases, potential metastasis in particular must be considered when making the diagnosis and staging has to be initiated. Surgical excision into healthy tissue with tumor-free margins is the gold standard for malignant eyelid tumors. Non-surgical adjuvant or neoadjuvant forms of evidence-based treatment can be initiated based on the individual case to minimize the risk of recurrence and metastasis. It is essential to recognize eyelid changes at an early stage, to classify them correctly and to initiate the appropriate treatment. The interaction between the general condition and the personal needs of a patient as well as state of the art medicine are the keys to a good personalized treatment.


Connecting structure to infrared spectra of molecular and autodissociated HCl--water aggregates.
The properties of perdeuterated HCl(H2O)n aggregates with n=1, 2, ..., 6 water molecules are studied by means of ab initio molecular dynamics simulations. The specific focus is on the phenomenon of autodissociation of the acid HCl as a function of the microsolvation environment size. The calculations provide a basis for characterization in terms of autodissociation energetics as well as in terms of the impact of thermal fluctuations on structure including proton fluxionality and in terms of anharmonic infrared vibrational spectra. Structure stabilization is dominated by strong hydrogen bonds resulting in distinct topologies, which, in turn, heavily influence acid dissociation. The latter is favored for the first time when n = 4. In that case, three hydrogen bonds can be donated toward the chlorine while at the same time a hydronium core is perfectly solvated according to the eigencomplex motif. Hydrogen-bonding interactions between DCl and its solvating molecules affect the dynamical behavior of the D-Cl bond significantly. This can be seen by the onset of fluxionality and an emerging tendency toward proton transfer for the larger clusters. Connecting IR spectra to structural information is possible by exploiting the following observations. Zwitterionic species show characteristic differences in the hydronium region, whereas the D-Cl stretching regime is useful to distinguish neutral aggregates. Furthermore, in the case of fluxional protons large-amplitude motion leads to characteristic band shifts and significant band broadening effects.


Diastereoselective and enantioselective reduction of tetralin-1,4-dione.
The chemistry of tetralin-1,4-dione, the stable tautomer of 1,4-dihydroxynaphthalene, has not been explored previously. It is readily accessible and offers interesting opportunities for synthesis. The title reactions were explored. L-Selectride reduced the diketone to give preferentially the cis-diol (d.r. 84 : 16). Red-Al gave preferentially the trans-diol (d.r. 13 : 87). NaBH(4), LiAlH(4), and BH(3) gave lower diastereoselectivities (yields: 76-98%). Fractional crystallization allowed isolation of the cis-diol and the trans-diol (55% and 66% yield, respectively). Borane was used to cleanly give the mono-reduction product. Highly enantioselective CBS reductions afforded the trans-diol (72% yield, 99% ee) and the mono-reduction product (81%, 95% ee). Diastereoselective and enantioselective reductions of the unexplored tetralin-1,4-dione provides a very convenient entry into a number of synthetically highly attractive 1,4-tetralindiols and 4-hydroxy-1-tetralone.


Heterogeneity in Autonomic Arousal Level in Perseverative Worry: The Role of Cognitive Control and Verbal Thought.
One puzzle in high worry and generalized anxiety disorder (GAD) is the heterogeneity in the level of autonomic arousal symptoms seen among affected individuals. While current models agree that worry persists, in part, because it fosters avoidance of unpleasant internal experiences, they disagree as to whether worry does so by suppressing activation of autonomic arousal or by fostering persistent autonomic hyperarousal. Our Cognitive Control Model predicts that which pattern of autonomic arousal occurs depends on whether or not a worrier has sufficient cognitive control capacity to worry primarily in a verbal versus imagery-based manner. Because this model has been supported by only one study to date, the present study sought to replicate and extend that study's findings. Results from an online survey in an unselected sample of over 900 college students provide further support for our model's central tenet and initial support for its prediction that higher effortful control is associated with a higher percentage of verbal thought during worry. Finally, we report tentative evidence that autonomic arousal symptoms in worry and GAD vary as a function of individual differences in cognitive control capacity because higher capacity is linked to a greater predominance of verbal thought during worry.


[Usefulness of echocardiography in the diagnosis of infectious endocarditis].
Thirty-four patients with clinical diagnosis of infective endocarditis were studied with M mode and/or two-dimensional echocardiography. of them. Twenty-two were men; their ages ranged from 9 to 67 years. In 23 cases surgical or post mortem confirmation of the echocardiographic diagnosis was obtained. The clinical features as well as history of previous cardiopathy (94.1%) and its type (congenital 38.2%, rheumatic 29.4%, rheumatic with valvular prosthesis 23.5%) were analyzed. In the 23 patients with proven endocarditis, the echocardiographic diagnosis was positive in 19 (82%); vegetations were evident in 13. In 6 patients vegetations were not found. There were 3 false positive cases and one false negative, giving a sensitivity of 0.81 and a specificity of 0.85. The causes of false negative and false positive findings were analyzed. These were closely related to the duration of the disease and time which elapsed between the echocardiographic study and confirmation in surgery or necropsy as well as the size of the vegetations. The echocardiographic diagnosis was difficult when a valvular prosthesis was present. Echocardiography is a useful technique for diagnosis and follow up of patients with infective endocarditis.


Physiology of rat-liver polysomes. The stability of messenger ribonucleic acid and ribosomes.
Starvation of rats for several days led to marked decrease in cytoplasmic polysomes and accumulation of breakdown products having S values less than 200s. Re-feeding of the starved animals induced a rapid reassembly of polysomes. These newly formed polysomes, in the presence of actinomycin D, decayed in a biphasic fashion: about two-thirds decayed with an apparent half-life of 3-3(1/2)hr. but the other one-third were much more stable. Evidence that polysome decay is an accurate reflexion of messenger RNA stability is presented, and it is concluded that in the presence of large doses of actinomycin D, rat-liver cytoplasm contains messenger RNA classes of widely varying stability, the more stable class having a half-life of at least 80hr. The half-life of liver ribosomes was also determined and was found to be 110-127hr.


[Sonographic diagnosis of solid space-occupying abdominal lesions in childhood].
Between 1981 and May 1986 31 children with solid abdominal tumor masses were observed in our clinic. The first diagnostic procedure was a sonographic examination, followed by further radiological investigations if necessary. 30 cases were examined histologically; in one case the sonographic findings were confirmed by an angiography. The most frequent abdominal masses were neuroblastomas and Wilms tumors (7 cases each). A mesoblastic nephroma was diagnosed in 3 cases, a lymphoma, a hepatoblastoma and a rhabdomyosarcoma 2 times each. One time we found a pancreas carcinoma, a teratoma, a hemangiomatosis of the liver, a malignant Schwannoma, a Ewing sarcoma, an adenoma of the adrenal gland, a pheochromocytoma and an osteosarcoma. According to our own experience and recent reports in the literature it seems possible in most cases, to predict the correct diagnosis of solid abdominal masses using the informations of sonographic imaging. Sonography is a highly specific non-invasive diagnostic tool for planning treatment (e.g. early surgery, cytostatic therapy and/or radiation) of solid abdominal masses. Nevertheless the histological examination should be performed in every case to confirm the definitive diagnosis.


The potentially insecticidal Narcissus pseudonarcissus lectin demonstrates age-related mitogenicity.
Lectins from monocotyledonous plants such as Narcissus pseudonarcissus (NPA) possess insecticidal properties and have the potential to increase pest resistance in transgenic crops. Therefore it is of interest to investigate the mitogenic properties of such lectins. Mononuclear cells purified from human umbilical cord and adult peripheral blood samples were stimulated with NPA and compared to phytohaemagglutinin as an example of a lectin from a dicotyledonous plant. Here we report that NPA is slightly mitogenic for adult human lymphocytes but mitogenicity is increased more than sevenfold for lymphocytes from umbilical cord blood. Similarly, NPA was found to be mitogenic for peripheral blood mononuclear cells (PBMC) from lambs and not adult sheep, supporting the age-related mitogenicity and indicating that further examination of the younger human population is warranted.


[Synthesis of alpha-fetoprotein in primary cultures of hepatocytes from adult mice].
Alpha-fetoprotein (AFP) and albumin synthesis in primary hepatocyte cultures of adult mice was studied by the immunoperoxidase techniques. Albumin was detectable in all hepatocytes during the cultivation period (from day 1 to day 8). AFP could be found regularly beginning from days 3-4 up to day 8. Attempts to obtain hepatocytes surviving for a longer period of time ended in failure. The number of AFP-containing hepatocytes in the culture ranged within single cells to about half of all the hepatocytes. The proliferating hepatocytes that contained both AFP and albumin were found in some of the experiments.


Alpha1D-adrenergic receptors and mitogen-activated protein kinase mediate increased protein synthesis by arterial smooth muscle.
Catecholamines may influence vascular smooth muscle cell (SMC) growth and vascular hypertrophic diseases. We previously demonstrated that stimulation of alpha1-adrenoceptors (AR) causes hypertrophy of vascular SMCs in vitro and in situ. Here, we used adult rat aorta SMCs that express alpha1D- and alpha1B-ARs (but not alpha1A-ARs) in vitro to examine the mechanisms and alpha1-AR subtypes involved. Norepinephrine (NE) increased protein synthesis and content in a time- and dose-dependent manner. To identify the responsible alpha1-AR subtype, we first documented the selectivity of two alpha1-AR subtype antagonists, BMY 7378 (alpha1D-AR antagonist) and chloroethylclonidine (CEC; alpha1B-AR antagonist), using Rat-1 fibroblasts stably transfected with the three different rodent alpha1-AR cDNAs. NE dose-dependently increased protein synthesis in each cell line. In alpha1D fibroblasts, BMY 7378 inhibited growth and protected alpha1D-ARs from CEC alkylation while having little blocking or protecting effect on the growth induced by stimulation of fibroblasts that express alpha1A- or alpha1B-ARs. In rat aorta SMCs, pretreatment with CEC in the presence of BMY 7378 to protect alpha1D-ARs had no effect on NE-induced protein synthesis. BMY 7378 inhibited the SMC growth response with a pKb of 8.4. NE caused rapid and transient p42-p44 mitogen-activated protein kinase (MAPK) activation that was alpha1D-AR dependent. Furthermore, NE caused tyrosine phosphorylation of multiple cellular proteins, phosphorylation of Raf-1, and stimulation of c-fos mRNA expression in aorta SMCs. The selective MAPK kinase inhibitor PD 98059 inhibited NE-induced protein synthesis and MAPK activation with IC50 values of 2.3 and 1.6 microM, respectively. These data demonstrate that SMC growth induced by NE is mediated by alpha1D-ARs that couple to activation of the MAPK cascade.


Simultaneous application of combination of three surgical techniques for treatment of gingival recession: a case report.
The treatment of Miller class III gingival recession is considered a challenge in periodontal practice, and among the different techniques used, autogenous connective tissue graft has shown the most favorable results. In some cases, more than one procedure may be necessary. In this case report, we describe the simultaneous application of a combination of three techniques (the tunnel technique, a connective tissue graft and a laterally positioned flap) to treat a Miller class III gingival recession localized in the lower anterior region. Twelve months after surgical procedures, partial root coverage, favorable esthetic results and a gain in clinical attachment level were observed, with no periodontal pockets or bleeding on probing.


Human Gingival Crevicular Fluids (GCF) Proteomics: An Overview.
Like other fluids of the human body, a gingival crevicular fluid (GCF) contains proteins, a diverse population of cells, desquamated epithelial cells, and bacteria from adjacent plaque. Proteomic tools have revolutionized the characterization of proteins and peptides and the detection of early disease changes in the human body. Gingival crevicular fluids (GCFs) are a very specific oral cavity fluid that represents periodontal health. Due to their non-invasive sampling, they have attracted proteome research and are used as diagnostic fluids for periodontal diseases and drug analysis. The aim of this review is to explore the proteomic science of gingival crevicular fluids (GCFs), their physiology, and their role in disease detection.


Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer: An early exploratory analysis of real-world data.
The TOPAZ-1 phase III trial reported a survival benefit with the anti-programmed death cell ligand 1 (anti-PD-L1) durvalumab in combination with gemcitabine and cisplatin in patients with advanced biliary tract cancer. The present study investigated the efficacy and safety of this new standard treatment in a real-world setting. The analysed population included patients with unresectable, locally advanced or metastatic adenocarcinoma of the biliary tract treated with durvalumab in combination with gemcitabine and cisplatin at 17 Italian centres. The primary endpoint of the study was progression-free survival (PFS), whereas secondary endpoints included overall survival (OS), overall response rate (ORR) and safety. Unadjusted and adjusted hazard ratios (HRs) by baseline characteristics were calculated using the Cox proportional hazards model. From February 2022 to November 2022, 145 patients were enrolled. After a median follow-up of 8.5 months (95% CI: 7.9-13.6), the median PFS was 8.9 months (95% CI: 7.4-11.7). Median OS was 12.9 months (95% CI: 10.9-12.9). The investigator-assessed confirmed ORR was 34.5%, and the disease control rate was 87.6%. Any grade adverse events (AEs) occurred in 137 patients (94.5%). Grades 3-4 AEs occurred in 51 patients (35.2%). The rate of immune-mediated AEs (imAEs) was 22.7%. Grades 3-4 imAEs occurred in 2.1% of the patients. In univariate analysis, non-viral aetiology, ECOG PS >0 and NLR ≥3 correlated with shorter PFS. The results reported in this first real-world analysis mostly confirmed the results achieved in the TOPAZ-1 trial in terms of PFS, ORR and safety.


[Influenza in the 1993/'94 season; composition of the vaccine for the 1994/'95 season].
The influenza season 1993/'94 in the Netherlands and the rest of Northwestern Europe was marked by an influenza A/H3N2 epidemic. The morbidity of this epidemic was moderate, but a high mortality rate was observed. The epidemic viruses, represented by A/Netherlands/241/93 (H3N2), were characterised by haemagglutination inhibition assays and nucleotide sequence analysis. The viruses were related to A/Beijing/32/92 (H3N2), the vaccine strain for 1993/'94, but clear antigenic differences were detected. Therefore, the WHO has recommended a new A/H3N2 component, A/Shangdong/9/93, for the vaccine of 1994/'95. The onset of the epidemic was unusually early in the influenza season. An increase in the influenza activity was already noticed in the second week of November and it reached its peak in week 49. As a result of the early epidemic, the influenza vaccination programme had not been completed yet. Therefore, the point of time for vaccinating people at risk may have to be reconsidered and moved up in order to complete the vaccination programme earlier.


Sequential Salinomycin Treatment Results in Resistance Formation through Clonal Selection of Epithelial-Like Tumor Cells.
Acquiring therapy resistance is one of the major obstacles in the treatment of patients with cancer. The discovery of the cancer stem cell (CSC)-specific drug salinomycin raised hope for improved treatment options by targeting therapy-refractory CSCs and mesenchymal cancer cells. However, the occurrence of an acquired salinomycin resistance in tumor cells remains elusive. To study the formation of salinomycin resistance, mesenchymal breast cancer cells were sequentially treated with salinomycin in an in vitro cell culture assay, and the resulting differences in gene expression and salinomycin susceptibility were analyzed. We demonstrated that long-term salinomycin treatment of mesenchymal cancer cells resulted in salinomycin-resistant cells with elevated levels of epithelial markers, such as E-cadherin and miR-200c, a decreased migratory capability, and a higher susceptibility to the classic chemotherapeutic drug doxorubicin. The formation of salinomycin resistance through the acquisition of epithelial traits was further validated by inducing mesenchymal-epithelial transition through an overexpression of miR-200c. The transition from a mesenchymal to a more epithelial-like phenotype of salinomycin-treated tumor cells was moreover confirmed in vivo, using syngeneic and, for the first time, transgenic mouse tumor models. These results suggest that the acquisition of salinomycin resistance through the clonal selection of epithelial-like cancer cells could become exploited for improved cancer therapies by antagonizing the tumor-progressive effects of epithelial-mesenchymal transition.


Evaluation of the National Cervical Cancer Screening Programme in Singapore.
A retrospective observational study was performed to evaluate the effectiveness of CervicalScreen Singapore (CSS), a National Cervical Cancer Screening Programme. National trends on incidence, mortality of cervical cancer and carcinoma in situ of the cervix before and after the launch of CSS were examined. Linear regression was used to calculate the average annual percentage change in age-standardised incidence and mortality rates. We also examined the operational measures of CSS, such as the women who joined the CSS programme and the diagnostic accuracy of Pap smears. The study was confined to women who consented to join CSS at government-funded polyclinics. Nationally, there was a greater decline in the age-standardised incidence and mortality rates in the period 2004-2008 as compared to the period 1987-2003. Under CSS, a total of 99,759 Pap smears were performed on 81,087 women in the period 2004-2008. However, the number of first screens decreased from 18,434 in 2004 to 11,624 in 2008. Among women aged 25-69 years who had their first Pap smear screening and who were recommended for routine rescreen in three years, 10% had a subsequent rescreen within three years. Overall, the CSS programme was able to detect 0.37 invasive cancers per 1,000 screens in women aged 25-69 years. The CSS programme has contributed to a decline in the mortality and incidence of cervical cancer in Singapore. However, the challenges of increasing the screening uptake among eligible women need to be addressed.


History cleans up messes: The impact of time in driving divergence and introgression in a tropical suture zone.
Contact zones provide an excellent arena in which to address questions about how genomic divergence evolves during lineage divergence. They allow us to both infer patterns of genomic divergence in allopatric populations isolated from introgression and to characterize patterns of introgression after lineages meet. Thusly motivated, we analyze genome-wide introgression data from four contact zones in three genera of lizards endemic to the Australian Wet Tropics. These contact zones all formed between morphologically cryptic lineage-pairs within morphologically defined species, and the lineage-pairs meeting in the contact zones diverged anywhere from 3.1 to 5.8 million years ago. By characterizing patterns of molecular divergence across an average of 11K genes and fitting geographic clines to an average of 7.5K variants, we characterize how patterns of genomic differentiation and introgression change through time. Across this range of divergences, we find that genome-wide differentiation increases but becomes no less heterogeneous. In contrast, we find that introgression heterogeneity decreases dramatically, suggesting that time helps isolated genomes "congeal." Thus, this work emphasizes the pivotal role that history plays in driving lineage divergence.


Limits of historical and scientific knowledge.
The purpose of this paper is to suggest that subtle and essential uncertainties in language determine the limits of science and history, and thereby define the boundaries of research in the history of science. Historical research, in the strict sense of history as opposed to prehistory, begins with the examination of written records. There is a host of problems in the interpretation of the historical record, but underlying all of these is the simply stated yet complex question of the meaning of words in historical documents. Since this is where the practice of history begins, this problem delimits the boundaries of historical knowledge. In this paper, I will examine structural ambiguities in the meaning of words, explain how they arise, and provide independent evidence for the validity of the analysis.


The Validity and Reliability of the Turkish Version of Miller Forensic Assessment of Symptoms Test (M-FAST).
The aim of this study was to show the validity and reliability of the M-FAST Turkish Version. Translation and back-translation of the M-FAST was done, then the M-FAST Turkish Version was created with linguistic equivalence. The study was performed with 97 detainees and convicts sent from penal institutions who were internalized at our hospital forensic psychiatry service. M-FAST Turkish Version was applied to evaluees and as a result of clinical interview according to DSM-IV-TR diagnostic criteria and various data explorations the evaluee was examined for malingering. To investigate the internal consistency of the scale, Cronbach's alpha and test-retest methods were used. In order to check the validity of the scale, in addition to the clinician's diagnosis, participants were requested to fill the Minnesota Multiphasic Personality Inventory (MMPI) F and K validity scales. The mean age of participants was 31.8±9.3 (SD) years. 47 evaluees (48.5%) were diagnosed as malingering. In the internal consistency analysis, Cronbach's alpha Coefficient was found to be .93. Test-retest relationship that was applied to 22 evaluees was found to be highly significant and strong (r=.89, p<.001). M-FAST scores were significantly high at the malingering group (n=47) (z=-8.02, p<.001). ROC curve analysis suggested a score of ≥7 points as the optimal cut-off for a malingering level for the M-FAST. Kappa coefficients of malingering ± groups were found to be, M-FAST≥7 Kappa: .83; F>16 Kappa: .29; F-K>16 Kappa: .30. For diagnosis of malingering, M-FAST Scale and the MMPI inventory scales were evaluated with the Binary Logistic Regression analysis and only M-FAST scores were found to be significant in prediction of malingering. The findings of this study support that, M-FAST Turkish Form represents the structure of the original scale and can be used as a reliable and valid instrument.


Structure of nonuniform polymer melts: density functional perturbation approach.
A density functional perturbation approximation for polyatomic molecules, which is based on the fundamental-measure theory for hard-core repulsion and the hybrid weighted-density approximation for chain connectivity, was proposed to clarify the structure of polymer melts at interfaces. It was applied to predict the local density distributions, adsorption isotherms, and surface excess of a freely jointed tangent hard-sphere chain in hard slit pores. Wertheim's first-order perturbation theory extended by J. Chem. Phys. 112, 2368 (2002)] was used to calculate the weight function and second-order direct correlation function due to the chain connectivity. The theoretical results are in excellent agreement with the computer simulations.


Shifting cardiovascular care to nurses results in structured chronic care.
To explore nurse involvement in cardiovascular risk management (CVRM) in primary care and how this involvement was associated with the degree of structured chronic illness care. A cross-sectional observational study in 7 European countries. Five aspects of nurse involvement in CVRM and 35 specific components of structured chronic illness care were documented in 202 primary care practices in Austria, Belgium, Germany, the Netherlands, Slovenia, Spain, and Switzerland. An overall measure for chronic care management, range 0 to 5, was constructed, derived from elements of the Chronic Care Model (CCM). Random coefficient regression modeling was used to explore associations. A majority of practices involved nurses for organization of CVRM in administrative tasks (82.2 %), risk factor monitoring (78.5%) and patient education (57.1%). Fewer practices involved nurses in defining protocol and the organization for CVRM (45%) or diagnosis and treatment (34.6%). With an increasing number of tasks handled by nurses, overall median adoption of CCM increased from 2.7 (95% CI, 1.5-3.6) to 4.2 (95% CI, 3.8-4.1). When the number of nurse tasks increased by 1, the adoption of CCM increased by 0.13 (P <.05; 95% CI, 0.03-0.22). Some practices with low nurse involvement had high adoption of CCM, while variation of adoption of CCM across practices reduced substantially with an increasing level of nurse involvement. Nurses were involved in the delivery of CVRM in varying degrees. Higher involvement of nurses was associated with higher degree of structured chronic illness care, with less variation.


Development of proteinase-activated receptor 1 antagonists as therapeutic agents for thrombosis, restenosis and inflammatory diseases.
Thrombin, a plasma serine protease, plays a key role not only in coagulation and hemostasis but in thrombosis, restenosis and atherosclerosis. Thrombin activates platelets, endothelium, inflammatory cells and smooth muscle cells. The cellular action of thrombin is mediated by specific G-protein coupled thrombin receptors called proteinase-activated receptors (protease-activated receptor or PARs). Among the three thrombin receptors, PAR1 is the primary thrombin receptor in human and animal cells with an exception of non-primate platelets. An increased thrombin generation and PAR1 expression are observed on cells within atherosclerotic plaque and thrombus and following vascular injury. Animal studies with PAR1 deficient mice and small molecule antagonists indicate an important role of PAR1 in thrombosis and restenosis and thus the therapeutic potential of a PAR1 antagonist in treating these diseases. Development of a thrombin receptor tethered ligand analog binding assay led to the discovery of several different series of potent, nonpeptide small molecular antagonists of PAR1. These antagonists are PAR1 selective and inhibit most of the cellular effects of thrombin. A PAR1 antagonist has an advantage over a direct thrombin inhibitor since it does not inhibit enzymatic action of thrombin in the coagulation cascade with the consequent minimal bleeding side-effects, unlike a direct thrombin inhibitor. In addition, the emerging evidence for the role of PAR1 in various inflammatory diseases suggests as yet unexplored therapeutic potentials of PAR1 antagonists in various inflammatory diseases.


Role Of Symptomatic Treatment In Comparison To Antibiotics In Uncomplicated Urinary Tract Infections.
Uncomplicated urinary tract infections (UTIs) are the most common bacterial infections among women presenting to primary care causing rapidly increasing strains of resistant bacteria to the growing antibiotic industry. Restricting antibiotics to necessary indications is the only solution. The objectives of the study were to compare the efficacy of symptomatic treatment vs antibiotic in patients with uncomplicated UTI, in terms of individual symptom score, i.e., frequency, urgency, dysuria, supra pubic pain scores and total symptoms scores. A randomized control trial (RCT) in 100 women (15-50 years) with symptoms of urinary frequency, urgency, dysuria and pain supra pubic region, associated with uncomplicated UTI, at Urology department, AMI, Abbottabad. Two treatment strategies were compared in uncomplicated UTI patient). Patients were randomized to antibiotic or symptomatic treatment groups on consecutive non-probability basis (50 in each group) given for 05 days. Efficacy of medications was assessed by comparing pre and post treatment symptom scores along with the post treatment scores of both groups compared to see statistical significance of difference by independent samples t-test. There was a statistically significant difference in symptoms improvement in both treatment arms of all scores, i.e., p-value=0.000. Whereas only dysuria score was able to show a statistically significance of difference in post Rx scores comparison of both groups, p-value=0.004. Symptomatic treatment is not inferior to antibiotic treatment when proper patient selection is undertaken, resulting in decreased need for unnecessary antibiotics use.


Robotic Camera Assistance and Its Benefit in 1033 Traditional Laparoscopic Procedures: Prospective Clinical Trial Using a Joystick-guided Camera Holder.
Despite advances in instruments and techniques in laparoscopic surgery, one thing remains uncomfortable: the camera assistance. The aim of this study was to investigate the benefit of a joystick-guided camera holder (SoloAssist®, Aktormed, Barbing, Germany) for laparoscopic surgery and to compare the robotic assistance to human assistance. 1033 consecutive laparoscopic procedures were performed assisted by the SoloAssist®. Failures and aborts were documented and nine surgeons were interviewed by questionnaire regarding their experiences. In 71 of 1033 procedures, robotic assistance was aborted and the procedure was continued manually, mostly because of frequent changes of position, narrow spaces, and adverse angular degrees. One case of short circuit was reported. Emergency stop was necessary in three cases due to uncontrolled movement into the abdominal cavity. Eight of nine surgeons prefer robotic to human assistance, mostly because of a steady image and self-control. The SoloAssist® robot is a reliable system for laparoscopic procedures. Emergency shutdown was necessary in only three cases. Some minor weak spots could have been identified. Most surgeons prefer robotic assistance to human assistance. We feel that the SoloAssist® makes standard laparoscopic surgery more comfortable and further development is desirable, but it cannot fully replace a human assistant.


Palifermin in a hematopoietic stem cell transplant patient with osteonecrosis of the jaw.
This case report describes the use of palifermin in a multiple myeloma patient with a history of osteonecrosis of the jaw (ONJ) for the prevention of high-dose chemotherapy-induced mucositis. Following the day of autologous stem cell infusion, palifermin was discontinued secondary to adverse events. Specifically, palifermin-associated macroglossia seemed to exacerbate the pain localized in the oral cavity area affected by ONJ, necessitating escalated doses of narcotic analgesics. When contemplating palifermin as a mucosal protectant in a hematopoietic stem cell transplant patient with ONJ, a careful benefit-to-risk assessment is in order to ensure optimal effectiveness without undue harm.


A comparative approach for characterizing the relationship among morphology, range-of-motion and locomotor behaviour in the primate shoulder.
Shoulder shape directly impacts forelimb function by contributing to glenohumeral (GH) range-of-motion (ROM). However, identifying traits that contribute most to ROM and visualizing how they do so remains challenging, ultimately limiting our ability to reconstruct function and behaviour in fossil species. To address these limitations, we developed an in silico proximity-driven model to simulate and visualize three-dimensional (3D) GH rotations in living primate species with diverse locomotor profiles, identify those shapes that are most predictive of ROM using geometric morphometrics, and apply subsequent insights to interpret function and behaviour in the fossil hominin Australopithecus sediba. We found that ROM metrics that incorporated 3D rotations best discriminated locomotor groups, and the magnitude of ROM (mobility) was decoupled from the anatomical location of ROM (e.g. high abduction versus low abduction). Morphological traits that enhanced mobility were decoupled from those that enabled overhead positions, and all non-human apes possessed the latter but not necessarily the former. Model simulation in A. sediba predicted high mobility and a ROM centred at lower abduction levels than in living apes but higher than in modern humans. Together these results identify novel form-to-function relationships in the shoulder and enhance visualization tools to reconstruct past function and behaviour.


Error pattern and item order on Halstead's Speech Sounds Perception Test.
Examined the possibility that the previously reported pattern of errors on the Speech Sounds Perception Test could be explained on the basis of learning (N = 30). This possibility was examined by altering the order of presentation of subtests so that the series with the highest mean error scores in the previous study were moved to the positions in which fewest errors had been observed previously. It was found that in spite of the alteration of order of presentation, the subtests that had the greatest number of errors in the previous study again had the largest mean errors. Conversely, the subtests with the lowest mean errors previously again had the lowest mean errors. It was concluded that order of administration did not influence the number of errors on each subtest and that therefore the observed pattern could not be explained on the basis of learning. Further data were presented that suggested a relationship between the mean number of errors on each subtest and the number of items in each subtest with correct choices that were phonetically similar to real words.


Intercropping Walnut and Tea: Effects on Soil Nutrients, Enzyme Activity, and Microbial Communities.
The practice of intercropping, which involves growing more than one crop simultaneously during the same growing season, is becoming more important for increasing soil quality, land-use efficiency, and subsequently crop productivity. The present study examined changes in soil physicochemical properties, enzymatic activity, and microbial community composition when walnut (Juglans spp.) was intercropped with tea (Camellia sinensis L.) plants in a forest and compared with a walnut and tea monocropping system. The results showed that walnut-tea intercropping improved the soil nutrient profile and enzymatic activity. The soil available nitrogen (AN), available phosphorus (AP), available potassium (AK), organic matter (OM) content, and sucrase activity were significantly boosted in intercropped walnut and tea than in monocropping forests. The interaction between crops further increased bacterial and fungal diversity when compared to monoculture tea forests. Proteobacteria, Bacteroidetes, Firmicutes, Chlamydiae, Rozellomycota, and Zoopagomycota were found in greater abundance in an intercropping pattern than in monoculture walnut and tea forest plantations. The walnut-tea intercropping system also markedly impacted the abundance of several bacterial and fungal operational taxonomic units (OTUs), which were previously shown to support nutrient cycling, prevent diseases, and ameliorate abiotic stress. The results of this study suggest that intercropping walnut with tea increased host fitness and growth by positively influencing soil microbial populations.


Medical management of perianal Crohn's disease.
Perianal disease is a frequent complication necessitating both medical and surgical management in Crohn's disease. Fissures, fistulae, or abscesses are found in approximately 36% of patients; occur more often in the ileocolonic and colonic disease; and may precede the onset of intestinal symptoms (Farmer et al, Gastroenterology 68:627-635, 1975; Rankin et al, Gastroenterology 77:914-920, 1979; Gray et al, Gut 6:515-524, 1965; and Homan et al, Arch Surg 111:1333-1335, 1976). To approach perianal manifestations, the physician must identify the anatomic location of the disease, treat the suppurative complications, and consider a long-term approach to palliation of chronic inflammatory sequelae. This article will review the medical management of perianal Crohn's disease and indications for surgery.


The water extract of Radix scutellariae, its total flavonoids and baicalin inhibited CYP7A1 expression, improved bile acid, and glycolipid metabolism in T2DM mice.
Radix scutellariae (the root of Scutellaria baicalensis Georgi), is a traditional Chinese medicine (TCM) used to treat type 2 diabetes mellitus (T2DM). Abundant flavonoids are the antidiabetic components of Radix scutellariae, of which baicalin (Baicalein 7-O-glucuronide, BG) is the major bioactive component. Our previous studies found that the water extract of Radix scutellariae (WESB) could exert hypoglycemic and hypolipidemic efficacies by adjusting the ileum FXR-medicated interaction between gut microbiota and bile acid (BA) metabolism. However, it remains unclear whether WESB and its biologically active ingredients exert an antidiabetic effect through bile acid signaling mediated by FXR-CYP7A1. To explore the mechanism of WESB and its total flavonoids (TF) further and BG on BA signals and glycolipid metabolism in T2DM mice. The antidiabetic effects of WESB, TF and BG were evaluated by indexing the body weight, fasting blood glucose (FBG) and oral glucose tolerance test (OGTT) in HFD/STZ-induced (high-fat diet and streptozocin) diabetic mice, and comparing them with the positive control (metformin). The lipids in the mouse liver and the total bile acids (TBA) in the mouse liver and bile were detected by commercial kits. The concentration of BAs in the mouse feces was determined by liquid chromatography-tandem mass spectrometry. The protein expression levels of cholesterol 7α-hydroxylase (CYP7A1), farnesol X receptor (FXR), etc., in the liver and/or ileum, play a key role in the BAs metabolism of T2DM mice were evaluated by immunoblot analysis. The hyperglycemia and impaired glucose tolerance of T2DM mice were improved after WESB, TF and BG treatment. Especially after BG administration, the levels of low-density lipoprotein-cholesterol (LDL-c) and total glyceride (TG) in the T2DM mouse liver were significantly decreased (p < 0.05). While the level of high-density lipoprotein cholesterol (HDL-c) was significant increased (p < 0.001). Meanwhile, the levels of TBA in both the liver and bile of T2DM mice were significantly decreased by BG (p < 0.05). Moreover, the high expression of CYP7A1 in the liver of T2DM mice was significantly inhibited by WESB, TF and BG (p < 0.05), and the high expression of FXR in the ileum of T2DM mice was significantly inhibited by TF (p < 0.05). These results indicated that the hypoglycemic effects of WESB, TF and BG might be exerted by inhibiting the expression of CYP7A1 in T2DM mice, and TF inhibited expression of intestinal FXR by inducing changes in fecal BA profile. BG significantly improved hepatic lipid metabolism. Moreover, BG reduced lipid accumulation in the liver and bile by inhibiting the expression of CYP7A1 in T2DM mice. These findings provide useful explanations for the antidiabetic mechanism of Radix scutellariae.