Discerning patterns of human immunodeficiency virus risk in healthy young adults.
Previous research has questioned the effectiveness of existing methods to identify individuals at high risk for contracting and transmitting human immunodeficiency virus and other sexually transmitted diseases. Thus, new approaches are needed to provide these individuals with risk-reduction strategies. We review our research on young adults' sexual decision making by using theories and methods from social and cognitive sciences. Four patterns of condom use and associated levels of risks and beliefs were identified. These patterns suggest value in targeting intervention strategies to individuals at different levels of risk. The findings also imply that the monogamous population may be at higher risk for infection than they realize. Primary-care physicians are the first line of contact for many individuals in the health care system and may be in the best position to screen for at-risk individuals. Given the time demands and other barriers, easy-to-use, evidence-based guidelines for such screening are needed. We propose such guidelines for primary-care physicians to use in identifying an individual's risk, from which custom-tailored intervention strategies can be developed.


Spatial distribution of muscle fibers within the territory of a motor unit.
The spatial distribution of muscle fibers belonging to a motor unit was studied in the soleus (SOL) and tibialis anterior (TA) of adult cats to provide a detailed description of the spatial patterns which exist within the territory of a motor unit. Glycogen depletion of the motor unit was achieved through repetitive stimulation of either the intracellularly identified motoneuron or the functionally isolated motor axon. Muscle fibers belonging to the stimulated unit were identified in serial cross-sections, and in the cross-section which contained the most depleted fibers the centroid of each depleted fiber was determined. Subsequently, three spatial analyses, ie, a quadrat analysis, a point-to nearest neighbor analysis and an interfiber distance analysis, were used to determine if motor unit fibers were distributed randomly throughout the territory of the unit. Motor unit fibers tended to be localized within the muscle cross-section and were not evenly or homogeneously distributed throughout the territory. In general, the analyses suggested that motor unit fibers may be arranged in clusters or subgroups of varying size. The data demonstrate three different quantitative analyses for studying the organization of muscle fibers of normal motor units, which can be used for objective assessment and diagnosis of neuromuscular diseases.


Components of verbal working memory: evidence from neuroimaging.
We review research on the neural bases of verbal working memory, focusing on human neuroimaging studies. We first consider experiments that indicate that verbal working memory is composed of multiple components. One component involves the subvocal rehearsal of phonological information and is neurally implemented by left-hemisphere speech areas, including Broca's area, the premotor area, and the supplementary motor area. Other components of verbal working memory may be devoted to pure storage and to executive processing of the contents of memory. These studies rest on a subtraction logic, in which two tasks are imaged, differing only in that one task presumably has an extra process, and the difference image is taken to reflect that process. We then review studies that show that the previous results can be obtained with experimental methods other than subtraction. We focus on the method of parametric variation, in which a parameter that presumably reflects a single process is varied. In the last section, we consider the distinction between working memory tasks that require only storage of information vs. those that require that the stored items be processed in some way. These experiments provide some support for the hypothesis that, when a task requires processing the contents of working memory, the dorsolateral prefrontal cortex is disproportionately activated.


External validation of the Ferguson pulmonary risk score for predicting major pulmonary complications after oesophagectomy†.
Pulmonary complications remain a frequent cause of morbidity in patients undergoing oesophagectomy. Risk screening tools assist in patient stratification. Ferguson proposed a risk score system to predict major pulmonary complications after oesophagectomy. Our objective was to externally validate this risk score system. We analysed our institutional database for patients undergoing oesophagectomy for cancer from August 2009 to December 2012. We analysed patients who had complete documentation of variables used in the Ferguson risk score calculation: forced expiratory volume in the 1 s, diffusion capacity of the lung for carbon monoxide, performance status and age. One hundred and thirty-six patients qualified for analysis in the validation study. Outcome variables measured included major pulmonary complications, defined as need for reintubation for respiratory failure and pneumonia. The risk score was then calculated for each individual based on the model. Incidence of major pulmonary events was assessed in the five risk class groupings to assess the discriminative ability of the Ferguson score. Major pulmonary complications occurred in 35% of patients (47/136). Overall mortality was 6% (8/136). Patients were grouped into five risk categories according to their Ferguson pulmonary risk score: 0-2, 8 patients (6%); 3-4, 24 patients (18%); 5-6, 49 patients (36%); 29 patients (21%); 9-14, 26 patients (19%). The incidence of major pulmonary complications in these categories was 0, 17, 20, 41 and 77%, respectively. The accuracy of the risk score system for predicting major pulmonary complications was 76% (P < 0.0001). This pulmonary risk scoring system is a reliable instrument to be used during the preoperative phase to differentiate patients who may be at higher risk for pulmonary complications after oesophagectomy. These data can assist in patient selection, and in patient education/informed consent and can guide postoperative management.


Implementation of pre-exposure prophylaxis programme in Spain. Feasibility of four different delivery models.
Pre-exposure prophylaxis (PrEP) is an effective and cost-effective strategy for HIV prevention. Spain carried out an implementation study in order to assess the feasibility of implementing PrEP programmes within its heterogeneous health system. Observational longitudinal study conducted on four different types of health-care setting: a community centre (CC), a sexually transmitted infections clinic (STIC), a hospital-based HIV unit (HBHIVU) and a hospital-based STI unit (HBSTIU). We recruited gay, bisexual and other men who have sex with men (GBSM) and transgender women at risk of HIV infections, gave them PrEP and monitored clinical, behavioural PrEP-related and satisfaction information for 52 weeks. We collected perceptions on PrEP implementation feasibility from health-care professionals participating in the study. A total of 321 participants were recruited, with 99.1% being GBMSM. Overall retention was 87.2% and it was highest at the CC (92.6%). Condom use decreased during the study period, while STIs did not increase consistently. The percentage of people who did not miss any doses of PrEP during the previous week remained at over 93%. No HIV seroconversions occurred. We observed overall decreases in GHB (32.5% to 21.8%), cocaine (27.5% to 21.4%), MDMA (25.7% to 14.3%), speed (11.4% to 5.7%) and mephedrone use (10.7% to 5.0%). The overall participant satisfaction with PrEP was 98.6%. Health-care professionals' perceptions of PrEP feasibility were positive, except for the lack of personnel. PrEP implementation is feasible in four types of health-care settings. Local specificities have to be taken into consideration while implementing PrEP.


Myocardial Ablation of G Protein-Coupled Receptor Kinase 2 (GRK2) Decreases Ischemia/Reperfusion Injury through an Anti-Intrinsic Apoptotic Pathway.
Studies from our lab have shown that decreasing myocardial G protein-coupled receptor kinase 2 (GRK2) activity and expression can prevent heart failure progression after myocardial infarction. Since GRK2 appears to also act as a pro-death kinase in myocytes, we investigated the effect of cardiomyocyte-specific GRK2 ablation on the acute response to cardiac ischemia/reperfusion (I/R) injury. To do this we utilized two independent lines of GRK2 knockout (KO) mice where the GRK2 gene was deleted in only cardiomyocytes either constitutively at birth or in an inducible manner that occurred in adult mice prior to I/R. These GRK2 KO mice and appropriate control mice were subjected to a sham procedure or 30 min of myocardial ischemia via coronary artery ligation followed by 24 hrs reperfusion. Echocardiography and hemodynamic measurements showed significantly improved post-I/R cardiac function in both GRK2 KO lines, which correlated with smaller infarct sizes in GRK2 KO mice compared to controls. Moreover, there was significantly less TUNEL positive myocytes, less caspase-3, and -9 but not caspase-8 activities in GRK2 KO mice compared to control mice after I/R injury. Of note, we found that lowering cardiac GRK2 expression was associated with significantly lower cytosolic cytochrome C levels in both lines of GRK2 KO mice after I/R compared to corresponding control animals. Mechanistically, the anti-apoptotic effects of lowering GRK2 expression were accompanied by increased levels of Bcl-2, Bcl-xl, and increased activation of Akt after I/R injury. These findings were reproduced in vitro in cultured cardiomyocytes and GRK2 mRNA silencing. Therefore, lowering GRK2 expression in cardiomyocytes limits I/R-induced injury and improves post-ischemia recovery by decreasing myocyte apoptosis at least partially via Akt/Bcl-2 mediated mitochondrial protection and implicates mitochondrial-dependent actions, solidifying GRK2 as a pro-death kinase in the heart.


Nuts and bolts of salivary gland pathology in primary Sjögren's syndrome.
Primary Sjögren's syndrome (pSS) is a chronic, systemic, inflammatory autoimmune disease characterised by lymphocyte proliferation and progressive damage to exocrine glands. Salivary gland histopathology based on salivary gland biopsy is relevant for the diagnosis of pSS and therefore broadly applied in clinical practice. Tissue can be obtained from labial salivary glands (LSG) biopsy or from major salivary glands (MSG) biopsy, namely the parotid; in this latter scenario, the procedure can be either an open surgical biopsy or a US guided core needle biopsy.In this review we will: i) present the histopathological findings that may be encountered by pathologists on biopsies from pSS patients; ii) discuss the advantages and disadvantages of the surgical and/or imaging guided procedures to obtain tissues from LSG or MSG; iii) describe the histopathological features of lymphoma of MSG in pSS patients.


Predictive model of blood transfusion during CABG surgery in Pakistan.
To determine predictors of need for transfusion of blood and blood products and create a clinical predictive model to reduce indiscriminate use of blood products during surgery. We conducted a retrospective chart review of 485 patients who underwent coronary artery bypass surgery from January 2004 to December 2004 at a Tertiary Care Hospital in Karachi, Pakistan. Independent predictors associated with transfusion were identified and a clinical prediction model developed. The transfusion rate was 37.1%. A predictive model was created based on the presence of pulmonary disease, diabetes mellitus, low ejection fraction and recent/ongoing myocardial infarction. The study identifies some predictors of need for blood transfusion in patients undergoing Coronary Artery Bypass Grafting. However, prospective studies with a larger sample of patients are needed to determine other predictors and their applicability in patient selection across institutions.


[Perforation of gastric cancer].
An analysis of treatment of 85 patients with perforating cancerous tumor of the stomach is presented. Males--63, females--22. The patients' age ranged from 32 to 85 years. Sixty seven patients were operatd upon, 35 of them died. Eighteen patients were not subjected to surgery, all of them died. The following variants of complications associated with gastric cancer are noted: cancer perforation--in 32, hemorrhage and the perforation--in 35, perforation and hemorrhage occurred simultaneously--in 15, perforation followed by hemorrhage--in 3. High mortality rate was due to grave patients' condition, difficulties and errors of diagnosis, inadequacy of therapeutic measures, late operative interventions. The results obtained are described.


Lengths of the maxillary central incisor, the nasal bone, and the anterior cranial base in different skeletal malocclusions.
Based on the results of previous studies of osseous structures within the frontonasal field in patients with a known malformation in the frontonasal field, the aim of the present study was to clarify whether the same structures were malformed in patients with severe skeletal malocclusions. Incisor, nasal, and cranial base lengths were measured on lateral radiographs of adult patients with skeletal malocclusions, including open bite (n=35), mandibular overjet (n=56), maxillary overjet (n=31), deep bite (n=19), and compared with those of a control group with neutral occlusion and normal craniofacial morphology (n=39). Two-way ANOVA tests were used to evaluate differences in lengths between groups and gender. Statistically shorter maxillary central incisor length was found in the open bite group (p<0.05), the mandibular overjet group (p<0.001), and in the deep bite group (p<0.001) compared to the controls. Nasal bone length was shorter in the maxillary overjet group compared to controls (p<0.05). The lengths of the maxillary central incisor and nasal bone, both parameters located in the frontonasal field, are affected in different skeletal malocclusions. The present findings, especially the deviation of the upper incisor length in different skeletal malocclusions, are considered relevant for orthodontic diagnostics and treatment.


Mother-Infant Bonding and Emotional Availability at 12-Months of Age: The Role of Early Postnatal Bonding, Maternal Substance Use and Mental Health.
The quality of the mother-child relationship in the first year of life has far reaching implications across the life course (Bornstein in Annu Rev Psychol 65:121-158, 2014). Yet little is known about predictors of maternal bonding and emotional availability in early infancy. In this study we examined the extent to which postnatal bonding, maternal mental health, and substance use at 8-weeks postpartum predicted mother-infant bonding (self-report) and mother emotional availability (observational) at 12-months of age. Data were obtained from an Australian longitudinal cohort study of pregnancy (n = 308). Data were collected during pregnancy, at birth, and postnatally at 8-weeks and 12-months. The results show strong continuity between postnatal bonding at 8-weeks and 12-months. Early postpartum stress and depression were associated with bonding at 12-months; however, the effect did not persist after adjustment for bonding at 8-weeks. Tobacco use at 8-weeks, but no other indicators of mental health, predicted lower emotional availability scores at 12-months. Results suggest that the mother's felt bond to her child is stable across the first year of life and that early bonding is a more robust indicator of bonding at 12-months than a mother's mental health or substance use. These findings point to the importance of clinical and public health investments in establishing a strong bond between mother and child in the early postpartum period.


Arm retraction dynamics of entangled star polymers: A forward flux sampling method study.
The study of dynamics and rheology of well-entangled branched polymers remains a challenge for computer simulations due to the exponentially growing terminal relaxation times of these polymers with increasing molecular weights. We present an efficient simulation algorithm for studying the arm retraction dynamics of entangled star polymers by combining the coarse-grained slip-spring (SS) model with the forward flux sampling (FFS) method. This algorithm is first applied to simulate symmetric star polymers in the absence of constraint release (CR). The reaction coordinate for the FFS method is determined by finding good agreement of the simulation results on the terminal relaxation times of mildly entangled stars with those obtained from direct shooting SS model simulations with the relative difference between them less than 5%. The FFS simulations are then carried out for strongly entangled stars with arm lengths up to 16 entanglements that are far beyond the accessibility of brute force simulations in the non-CR condition. Apart from the terminal relaxation times, the same method can also be applied to generate the relaxation spectra of all entanglements along the arms which are desired for the development of quantitative theories of entangled branched polymers. Furthermore, we propose a numerical route to construct the experimentally measurable relaxation correlation functions by effectively linking the data stored at each interface during the FFS runs. The obtained star arm end-to-end vector relaxation functions Φ(t) and the stress relaxation function G(t) are found to be in reasonably good agreement with standard SS simulation results in the terminal regime. Finally, we demonstrate that this simulation method can be conveniently extended to study the arm-retraction problem in entangled star polymer melts with CR by modifying the definition of the reaction coordinate, while the computational efficiency will depend on the particular slip-spring or slip-link model employed.


Cyclosporine induces neuronal apoptosis and selective oligodendrocyte death in cortical cultures.
Cyclosporine is used clinically as an immunosuppressant, but carries a risk of central nervous system toxicity due to undefined mechanisms. We examined the ability of cyclosporine exposure to kill cultured mouse cortical neurons and glia. Mixed neuron/glial cultures exposed to 1 to 20 microM cyclosporine for 24 to 48 hours developed concentration-dependent neuronal death, with most neurons destroyed by 20 microM cyclosporine. This neuronal death was characterized by cell body shrinkage and blebbing, chromatin condensation, and internucleosomal DNA fragmentation, consistent with apoptosis. Neuronal death was reduced by addition of cycloheximide, brain-derived neurotrophic factor, or insulin-like growth factor I but not N-methyl-D-aspartate- or AMPA-type glutamate receptor antagonists. Oligodendrocytes were more sensitive to cyclosporine-induced damage than were neurons, but astrocytes were relatively resistant. Oligodendrocyte death was accompanied by positive TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling) staining and was attenuated by application of ciliary neurotrophic factor or insulin-like growth factor I but not glutamate receptor antagonists. Present observations raise the possibility that the central nervous system toxicity syndrome associated with cyclosporine may be caused by the drug-induced death of oligodendrocytes and neurons.


Defining Sepsis Mortality Clusters in the United States.
In the United States, sepsis is a major public health problem accounting for over 200,000 annual deaths. The aims of this study were to identify U.S. counties with high sepsis mortality and to assess the community characteristics associated with increased sepsis mortality. We performed a descriptive analysis of 2003 through 2012 Compressed Mortality File data. We defined sepsis deaths as deaths associated with an infection, classified according to the International Classification of Diseases, 10th Version. Three thousand one hundred and eight counties in the contiguous U.S. counties, excluding Hawaii and Alaska. Using geospatial autocorrelation methods, we defined county-level sepsis mortality as strongly clustered, moderately clustered, and nonclustered. We approximated the mean crude, age-adjusted, and community-adjusted sepsis mortality rates nationally and for clustering groups. We contrasted demographic and community characteristics between clustering groups. We performed logistic regression for the association between strongly clustered counties and community characteristics. Among 3,108 U.S. counties, the age-adjusted sepsis mortality rate was 59.6 deaths per 100,000 persons (95% CI, 58.9-60.4). Sepsis mortality was higher in the Southern U.S. and clustered in three major regions: Mississippi Valley, Middle Georgia, and Central Appalachia. Among 161 (5.2%) strongly clustered counties, age-adjusted sepsis mortality was 93.1 deaths per 100,000 persons (95% CI, 90.5-95.7). Strongly clustered sepsis counties were more likely to be located in the south (92.6%; p < 0.001), exhibit lower education, higher impoverished population, without medical insurance, higher medically uninsured rates, and had higher unemployment rates (p < 0.001). Sepsis mortality is higher in the Southern United States, with three regional clusters: "Mississippi Valley," "Middle Georgia," and "Central Appalachia": Regions of high sepsis mortality are characterized by lower education, income, employment, and insurance coverage.


Perlucidibaca aquatica sp. nov., isolated from fresh water.
A Gram-staining-negative, non-motile, non-pigmented, strictly aerobic and rod-shape bacterium, designated BK296T, was isolated from stream water originating from a limestone cave in Samcheok, Korea. Optimal growth of strain BK296T was observed at 30 °C, pH 7.0-8.0 and without NaCl. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain BK296T belonged to the genus Perlucidibaca, forming a robust clade with a member of the genus, and was most closely related to Perlucidibaca piscinae (97.8 %). The average nucleotide identity value between strain BK296T and Perlucidibacapiscinae IMCC1704T was 79.8 %, and the genome-to-genome distance was 17.5 % on mean. The G+C content of the DNA of strain BK296T was 55.7 mol%. The major fatty acids were summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), C16 : 0, C12 : 0 3-OH and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c). The major isoprenoid quinone was ubiquinone Q-8. On the basis of phenotypic, genotypic and phylogenetic analyses, strain BK296T (=KCTC 52162T=JCM 31377T) represents a novel species of the genus Perlucidibaca, for which the name Perlucidibaca aquatica sp. nov. is proposed.


Acute aortic dissection mimicking an acute coronary syndrome through occlusion of the right coronary artery.
Occlusion of the right coronary artery (RCA) is an uncommon complication of type A aortic dissection. Aortic dissection and acute coronary syndrome (ACS) share a similar pathogenesis in atherosclerosis and hypertension. Consequently a patient with ischaemic risk factors presenting with chest pain and dynamic ECG change may well be incorrectly treated for ACS if careful attention is not paid to the presenting symptoms and signs. This case report describes a 59-year-old man who presented with chest pain, confusion and an ischaemic ECG and was initially treated for ACS. He subsequently deteriorated clinically and imaging confirmed type A aortic dissection complicated by RCA occlusion. Following emergent surgery with aortic root replacement and coronary artery bypass grafting he later made a good recovery.


FLT3-ligand treatment of humanized mice results in the generation of large numbers of CD141+ and CD1c+ dendritic cells in vivo.
We established a humanized mouse model incorporating FLT3-ligand (FLT3-L) administration after hematopoietic cell reconstitution to investigate expansion, phenotype, and function of human dendritic cells (DC). FLT3-L increased numbers of human CD141(+) DC, CD1c(+) DC, and, to a lesser extent, plasmacytoid DC (pDC) in the blood, spleen, and bone marrow of humanized mice. CD1c(+) DC and CD141(+) DC subsets were expanded to a similar degree in blood and spleen, with a bias toward expansion of the CD1c(+) DC subset in the bone marrow. Importantly, the human DC subsets generated after FLT3-L treatment of humanized mice are phenotypically and functionally similar to their human blood counterparts. CD141(+) DC in humanized mice express C-type lectin-like receptor 9A, XCR1, CADM1, and TLR3 but lack TLR4 and TLR9. They are major producers of IFN-λ in response to polyinosinic-polycytidylic acid but are similar to CD1c(+) DC in their capacity to produce IL-12p70. Although all DC subsets in humanized mice are efficient at presenting peptide to CD8(+) T cells, CD141(+) DC are superior in their capacity to cross-present protein Ag to CD8(+) T cells following activation with polyinosinic-polycytidylic acid. CD141(+) DC can be targeted in vivo following injection of Abs against human DEC-205 or C-type lectin-like receptor 9A. This model provides a feasible and practical approach to dissect the function of human CD141(+) and CD1c(+) DC and evaluate adjuvants and DC-targeting strategies in vivo.


Comparing Two Computational Mechanisms for Explaining Functional Recovery in Robot-Therapy of Stroke Survivors.
In this paper we discuss two possible strategies of movement control that can be used by stroke survivors during rehabilitation robotics training. To perform a reaching task in a minimally assistive force field, subjects either can move following the trajectory provided by the assistive force or they can use an internal representation of a minimum jerk trajectory from their starting position to the target. We used the stiffness and damping values directly estimated from the experimental data to simulate the trajectories that result by taking into account both hypotheses. The comparison of the simulated results with the data collected on four hemiparetic subjects supports the hypothesis that the central nervous system (CNS) is still able to correctly plan the movement, although a normal execution is impaired.


Interleukin-1 family cytokines and their regulatory proteins in normal pregnancy and pre-eclampsia.
Maternal systemic inflammation is a feature of pre-eclampsia, a condition in pregnancy characterized by hypertension and proteinuria. Pre-eclampsia is caused by the placenta; many placental factors contribute to the syndrome's progression, and proinflammatory cytokines have been identified previously as one such mediator. The interleukin (IL)-1 family of cytokines are key regulators of the inflammatory network, and two naturally occurring regulatory molecules for IL-1 family cytokines, IL-1RA and sST2, have been found previously to be elevated in maternal blood from women with pre-eclampsia. Here we investigate more recently identified IL-1 family cytokines and regulatory molecules, IL-1RAcP, IL-37, IL-18BP, IL-36α/β/γ/Ra and IL-38 in pre-eclampsia. Pregnant women have more circulating IL-18BP and IL-36Ra than non-pregnant women, and sIL-1RAcP is elevated from women with pre-eclampsia compared to normal pregnancies. The placenta expresses all the molecules, and IL-37 and IL-18BP are up-regulated significantly in pre-eclampsia placentas compared to those from normal pregnancies. Together, these changes contribute to the required inhibition of maternal systemic cytotoxic immunity in normal pregnancy; however, in pre-eclampsia the same profile is not seen. Interestingly, the increased circulating levels of sIL-1RAcP and increased placental IL-18BP and IL-37, the latter of which we show to be induced by hypoxic damage to the placenta, are all factors which are anti-inflammatory. While the placenta is often held responsible for the damage and clinical symptoms of pre-eclampsia by the research community, here we show that the pre-eclampsia placenta is also trying to prevent inflammatory damage to the mother.


Does the Presence of Missing Data Affect the Performance of the SORG Machine-learning Algorithm for Patients With Spinal Metastasis? Development of an Internet Application Algorithm.
The Skeletal Oncology Research Group machine-learning algorithm (SORG-MLA) was developed to predict the survival of patients with spinal metastasis. The algorithm was successfully tested in five international institutions using 1101 patients from different continents. The incorporation of 18 prognostic factors strengthens its predictive ability but limits its clinical utility because some prognostic factors might not be clinically available when a clinician wishes to make a prediction. We performed this study to (1) evaluate the SORG-MLA's performance with data and (2) develop an internet-based application to impute the missing data. A total of 2768 patients were included in this study. The data of 617 patients who were treated surgically were intentionally erased, and the data of the other 2151 patients who were treated with radiotherapy and medical treatment were used to impute the artificially missing data. Compared with those who were treated nonsurgically, patients undergoing surgery were younger (median 59 years [IQR 51 to 67 years] versus median 62 years [IQR 53 to 71 years]) and had a higher proportion of patients with at least three spinal metastatic levels (77% [474 of 617] versus 72% [1547 of 2151]), more neurologic deficit (normal American Spinal Injury Association [E] 68% [301 of 443] versus 79% [1227 of 1561]), higher BMI (23 kg/m2 [IQR 20 to 25 kg/m2] versus 22 kg/m2 [IQR 20 to 25 kg/m2]), higher platelet count (240 × 103/µL [IQR 173 to 327 × 103/µL] versus 227 × 103/µL [IQR 165 to 302 × 103/µL], higher lymphocyte count (15 × 103/µL [IQR 9 to 21× 103/µL] versus 14 × 103/µL [IQR 8 to 21 × 103/µL]), lower serum creatinine level (0.7 mg/dL [IQR 0.6 to 0.9 mg/dL] versus 0.8 mg/dL [IQR 0.6 to 1.0 mg/dL]), less previous systemic therapy (19% [115 of 617] versus 24% [526 of 2151]), fewer Charlson comorbidities other than cancer (28% [170 of 617] versus 36% [770 of 2151]), and longer median survival. The two patient groups did not differ in other regards. These findings aligned with our institutional philosophy of selecting patients for surgical intervention based on their level of favorable prognostic factors such as BMI or lymphocyte counts and lower levels of unfavorable prognostic factors such as white blood cell counts or serum creatinine level, as well as the degree of spinal instability and severity of neurologic deficits. This approach aims to identify patients with better survival outcomes and prioritize their surgical intervention accordingly. Seven factors (serum albumin and alkaline phosphatase levels, international normalized ratio, lymphocyte and neutrophil counts, and the presence of visceral or brain metastases) were considered possible missing items based on five previous validation studies and clinical experience. Artificially missing data were imputed using the missForest imputation technique, which was previously applied and successfully tested to fit the SORG-MLA in validation studies. Discrimination, calibration, overall performance, and decision curve analysis were applied to evaluate the SORG-MLA's performance. The discrimination ability was measured with an area under the receiver operating characteristic curve. It ranges from 0.5 to 1.0, with 0.5 indicating the worst discrimination and 1.0 indicating perfect discrimination. An area under the curve of 0.7 is considered clinically acceptable discrimination. Calibration refers to the agreement between the predicted outcomes and actual outcomes. An ideal calibration model will yield predicted survival rates that are congruent with the observed survival rates. The Brier score measures the squared difference between the actual outcome and predicted probability, which captures calibration and discrimination ability simultaneously. A Brier score of 0 indicates perfect prediction, whereas a Brier score of 1 indicates the poorest prediction. A decision curve analysis was performed for the 6-week, 90-day, and 1-year prediction models to evaluate their net benefit across different threshold probabilities. Using the results from our analysis, we developed an internet-based application that facilitates real-time data imputation for clinical decision-making at the point of care. This tool allows healthcare professionals to efficiently and effectively address missing data, ensuring that patient care remains optimal at all times. Generally, the SORG-MLA demonstrated good discriminatory ability, with areas under the curve greater than 0.7 in most cases, and good overall performance, with up to 25% improvement in Brier scores in the presence of one to three missing items. The only exceptions were albumin level and lymphocyte count, because the SORG-MLA's performance was reduced when these two items were missing, indicating that the SORG-MLA might be unreliable without these values. The model tended to underestimate the patient survival rate. As the number of missing items increased, the model's discriminatory ability was progressively impaired, and a marked underestimation of patient survival rates was observed. Specifically, when three items were missing, the number of actual survivors was up to 1.3 times greater than the number of expected survivors, while only 10% discrepancy was observed when only one item was missing. When either two or three items were omitted, the decision curves exhibited substantial overlap, indicating a lack of consistent disparities in performance. This finding suggests that the SORG-MLA consistently generates accurate predictions, regardless of the two or three items that are omitted. We developed an internet application (https://sorg-spine-mets-missing-data-imputation.azurewebsites.net/) that allows the use of SORG-MLA with up to three missing items. The SORG-MLA generally performed well in the presence of one to three missing items, except for serum albumin level and lymphocyte count (which are essential for adequate predictions, even using our modified version of the SORG-MLA). We recommend that future studies should develop prediction models that allow for their use when there are missing data, or provide a means to impute those missing data, because some data are not available at the time a clinical decision must be made. The results suggested the algorithm could be helpful when a radiologic evaluation owing to a lengthy waiting period cannot be performed in time, especially in situations when an early operation could be beneficial. It could help orthopaedic surgeons to decide whether to intervene palliatively or extensively, even when the surgical indication is clear.


Early Cardiac Arrest Hemodynamics, End-Tidal Co2, and Outcome in Pediatric Extracorporeal Cardiopulmonary Resuscitation: Secondary Analysis of the ICU-RESUScitation Project Dataset (2016-2021).
Cannulation for extracorporeal membrane oxygenation during active extracorporeal cardiopulmonary resuscitation (ECPR) is a method to rescue patients refractory to standard resuscitation. We hypothesized that early arrest hemodynamics and end-tidal Co2 (ETco2) are associated with survival to hospital discharge with favorable neurologic outcome in pediatric ECPR patients. Preplanned, secondary analysis of pediatric Utstein, hemodynamic, and ventilatory data in ECPR patients collected during the 2016-2021 Improving Outcomes from Pediatric Cardiac Arrest study; the ICU-RESUScitation Project (ICU-RESUS; NCT02837497). Eighteen ICUs participated in ICU-RESUS. There were 97 ECPR patients with hemodynamic waveforms during cardiopulmonary resuscitation. None. Overall, 71 of 97 patients (73%) were younger than 1 year old, 82 of 97 (85%) had congenital heart disease, and 62 of 97 (64%) were postoperative cardiac surgical patients. Forty of 97 patients (41%) survived with favorable neurologic outcome. We failed to find differences in diastolic or systolic blood pressure, proportion achieving age-based target diastolic or systolic blood pressure, or chest compression rate during the initial 10 minutes of CPR between patients who survived with favorable neurologic outcome and those who did not. Thirty-five patients had ETco2 data; of 17 survivors with favorable neurologic outcome, four of 17 (24%) had an average ETco2 less than 10 mm Hg and two (12%) had a maximum ETco2 less than 10 mm Hg during the initial 10 minutes of resuscitation. We did not identify an association between early hemodynamics achieved by high-quality CPR and survival to hospital discharge with favorable neurologic outcome after pediatric ECPR. Candidates for ECPR with ETco2 less than 10 mm Hg may survive with favorable neurologic outcome.


Exercise and global well-being in community-dwelling adults with fibromyalgia: a systematic review with meta-analysis.
Exercise has been recommended for improving global-well being in adults with fibromyalgia. However, no meta-analysis has determined the effects of exercise on global well-being using a single instrument and when analyzed separately according to intention-to-treat and per-protocol analyses. The purpose of this study was to fill that gap. Studies were derived from six electronic sources, cross-referencing from retrieved studies and expert review. Dual selection of randomized controlled exercise training studies published between January 1, 1980 and January 1, 2008 and in which global well-being was assessed using the Fibromyalgia Impact Questionnaire (FIQ) were included. Dual abstraction of data for study, subject and exercise program characteristics as well as assessment of changes in global well-being using the total score from the FIQ was conducted. Risk of bias was assessed using the Cochrane bias assessment tool. Random-effects models and Hedge's standardized effect size (g) were used to pool results according to per-protocol and intention-to-treat analyses. Of 1,025 studies screened, 7 representing 5 per-protocol and 5 intention-to-treat outcomes in 473 (280 exercise, 193 control) primarily female (99%) participants 18-73 years of age were included. Small, statistically significant improvements in global well-being were observed for per-protocol (g and 95% confidence interval, -0.39, -0.69 to -0.08) and intention-to-treat (-0.34, -0.53 to -0.14) analyses. No statistically significant within-group heterogeneity was found (per-protocol, Qw = 6.04, p = 0.20, I2 = 33.8%; intention-to-treat, Qw = 3.19, p = 0.53, I2 = 0%) and no between-group differences for per-protocol and intention-to-treat outcomes were observed (Qb = 0.07, p = 0.80). Changes were equivalent to improvements of 8.2% for per-protocol analyses and 7.3% for intention-to-treat analyses. The results of this study suggest that exercise improves global well-being in community-dwelling women with fibromyalgia. However, additional research on this topic is needed, including research in men as well as optimal exercise programs for improving global well-being in adults.


Stoichiometric analysis of the specific interaction of the glucocorticoid receptor with DNA.
Purified preparations of activated glucocorticoid X receptor complex (GR) contain a Mr 94,000 hormone-binding polypeptide co-purifying together with a Mr 72,000 non-hormone-binding polypeptide (Wrange, O., Okret, S., Radojcic, M., Carlstedt-Duke, J., and Gustafsson, J.-A. (1984) J. Biol. Chem. 259, 4534-4541). GR binds selectively to discrete regions of DNA in mouse mammary tumor virus (Payvar, F., DeFranco, D., Firestone, G.L., Edgar, B., Wrange, O., Okret, S., Gustafsson, J.-A., and Yamamoto, K. R. (1983) Cell 35, 381-392). Such GR-binding DNA fragments were used to measure the stoichiometry of GR to DNA. Quantitative DNaseI protection "footprinting" analysis was used to ensure that saturation conditions for specific DNA-binding were achieved. Glycerol density gradient centrifugation was used to quantitate Mr 94,000 binding to specific and nonspecific DNA sites. One Mr 94,000 entity was bound per specific DNA site. A modified GR purification procedure resulted in increased amounts of Mr 72,000 polypeptide (1.6:1, 94,000:72,000 molar ratio), compared to previous GR preparations. Glycerol gradient centrifugation followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the specific GR X DNA complex contained similar amounts of Mr 94,000 and Mr 72,000 polypeptide. It is as yet uncertain if the Mr 72,000 polypeptide is a functional subunit of GR or a co-purifying contaminant only.


[The founding and the first years of the first Dutch Dental Association: Nederlandsch Tandheelkundig Genootschap].
During the last half of the 19th century dentistry in the Netherlands met little social appreciation. The charismatic leader of Dutch dentistry, Dr. Theodore Dentz, dentist and physician, took the initiative to found the first Dutch dental organisation in 1880. His goals were to improve the image of his profession, to strive for better education and to strengthen the bond between the best dentists in the country. After about 1910 changes in society and dentistry forced 'het Genootschap' to delegate their work in the field of social and professional representation to the newly founded Dutch Dental Association. After that time 'het Genootschap' converted itself into a scientific invitation society.


Gene frequency distribution of the BoLA-DRB3 locus in Saavedreño Creole dairy cattle.
The objective of this study is to describe the gene frequency distribution of the bovine lymphocyte antigen (BoLA)-DRB3 locus in Saavedreño Creole dairy cattle and to compare it with previously reported patterns in other cattle breeds. One hundred and twenty-five Saavedreño Creole dairy cattle were genotyped for the BoLA-DRB3.2 allele by polymerase chain reaction and restriction fragment length polymorphism. Twenty-two out of 53 previously identified BoLA-DRB3.2 alleles were detected, with gene frequencies ranging from 0.4 to 16.8%. Seventy percent of the variation corresponded to the seven most frequent alleles (BoLA-DRB3.2*7, *8, *11, *16, *27, *36, and *37). The studied population exhibits a high degree of expected heterozygosity (he = 0.919). The FIS index did not show significant deviation from Hardy-Weinberg equilibrium. However, the neutrality test showed an even gene frequency distribution. This result could be better explained assuming balancing selection instead of neutral or positive selection for one or a few alleles. In conclusion, the results of this study demonstrated that BoLA-DRB3.2 is a highly polymorphic locus in Saavedreño Creole dairy cattle, with significant variation in allele frequency among cattle breeds.


A systematic approach to estimating the effectiveness of multi-scale IAQ strategies for reducing the risk of airborne infection of SARS-CoV-2.
The unprecedented coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made more than 125 million people infected and more than 2.7 million people dead globally. Airborne transmission has been recognized as one of the major transmission routes for SARS-CoV-2. This paper presents a systematic approach for evaluating the effectiveness of multi-scale IAQ control strategies in mitigating the infection risk in different scenarios. The IAQ control strategies across multiple scales from a whole building to rooms, and to cubical and personal microenvironments and breathing zone, are introduced, including elevated outdoor airflow rates, high-efficiency filters, advanced air distribution strategies, standalone air cleaning technologies, personal ventilation and face masks. The effectiveness of these strategies for reducing the risk of COVID-19 infection are evaluated for specific indoor spaces, including long-term care facility, school and college, meat plant, retail stores, hospital, office, correctional facility, hotel, restaurant, casino and transportation spaces like airplane, cruise ship, subway, bus and taxi, where airborne transmission are more likely to occur due to high occupancy densities. The baseline cases of these spaces are established according to the existing standards, guidelines or practices. Several integrated mitigation strategies are recommended and classified based on their relative cost and effort of implementation for each indoor space. They can be applied to help meet the current challenge of ongoing COVID-19, and provide better preparation for other possible epidemics and pandemics of airborne infectious diseases in the future.


Aldehyde Dehydrogenase, Liver Disease and Cancer.
Acetaldehyde dehydrogenase 2 (ALDH2) is the key enzyme responsible for metabolism of the alcohol metabolite acetaldehyde in the liver. In addition to conversion of the acetaldehyde molecule, ALDH is also involved in other cellular functions. Recently, many studies have investigated the involvement of ALDH expression in viral hepatitis, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), liver fibrosis, and liver cancer. Notably, ALDH2 expression has been linked with liver cancer risk, as well as pathogenesis and prognosis, and has emerged as a promising therapeutic target. Of note, approximately 8% of the world's population, and approximately 30-40% of the population in East Asia carry an inactive ALDH2 gene. This review summarizes new progress in understanding tissue-specific acetaldehyde metabolism by ALDH2 as well as the association of ALDH2 gene polymorphisms with liver disease and cancer. New research directions emerging in the field are also briefly discussed.


The effects of temperature and busulfan (Myleran) on the yellowtail tetra Astyanax altiparanae (Pisces, Characiformes) spermatogenesis.
We aimed to standardize a protocol to suppress spermatogenesis in the characiform fish, Astyanax altiparanae, for future use as a host in germ cell transplant research, opening opportunities for a range of studies, such as spermatogenesis analyses and transgenesis because this species presents livestock characteristics to be used as a biological model. The effects of the chemotherapeutic busulfan (formulated as Myleran), which is used as medicine, therefore not as toxic to humans manipulation as analytical grade busulfan (Fluka) used in previous studies, were evaluated at physiological temperature of 28 °C, ideal for growth and reproduction of A altiparanae, and also at increased temperature 35 °C. The temperature groups were divided into three treatment groups: busulfan, DMSO only, and an untreated control. Macroscopic, histologic, stereological, and ultrastructure analysis showed that, at 28 °C, busulfan did not cause depletion of germ cells in A altiparanae. However, at 35 °C, sterilization was observed 3 weeks after the initial application. Similar results were obtained with maintenance of fish at 35 °C for a longer period with no accompanying Myleran treatment. This procedure allows reduction in stress and lower mortality resulting from manipulation during busulfan injection and is also suitable for mass treatment because large numbers of fish can be incubated in warm water.


Impact of Radiotherapy Dose on Dentition Breakdown in Head and Neck Cancer Patients.
PURPOSE: To evaluate the severity of post-radiation dental lesions and possible correlation with radiation dose to the teeth in patients treated for head and neck cancers. METHODS AND MATERIALS: Data from 93 head and neck radiotherapy patients treated between 1997 and 2008 were analyzed retrospectively. The main effect, radiation dose to the individual teeth, was evaluated with covariates of elapsed time after radiation, xerostomia, topical fluoride use, and oral hygiene status included. Patients' radiotherapy plans were used to calculate cumulative exposure for each tooth. Patients' teeth were evaluated using a validated index and then categorized as having none/slight or moderate/severe post-radiation damage. RESULTS: Patients (31 females, 62 males) ranged in age from 18-82 yrs (mean=57). The number of teeth/patient ranged from 3-30 (mean=20) with a total of 1873 teeth evaluated. Overall, 51% of teeth had moderate/severe damage, with the remaining having little or none. Using odds ratios and 95% confidence intervals, the odds for moderate/severe damage were 2-3x greater for teeth exposed to between 30-60 Gy as compared to no radiation. However, for teeth exposed to ≥60 Gy as compared to no radiation the odds of moderate/severe tooth damage was greater by a magnitude of 10 times. CONCLUSIONS: The results indicate that there is minimal tooth damage below 30 Gy (salivary gland threshold), a greater than 1:1 increased dose-response between 30-60y likely related to salivary gland damage, and a critical threshold of ≥60Gy which may be linked to direct effects of radiation on tooth structure. These findings suggest that care should be taken during the treatment planning process to limit tooth dose, and when clinically possible to limit tooth dose to less than 60 Gy.


A new DNA polymorphism in the beta-globin gene cluster can be used for antenatal diagnosis of beta-thalassaemia.
Restriction endonuclease analysis of the human beta-globin gene cluster has revealed a new DNA polymorphism at a Pvu II recognition site approximately 3.5 kilobases from the 3' end of the Agamma-globin gene. In patients from the Mediterranean area, the Pvu II polymorphism was associated equally with both normal and beta-thalassaemia chromosomes. In patients of Indian and Pakistani origin the polymorphism was almost exclusively associated with only the normal chromosome. Therefore this site may prove very useful for the antenatal diagnosis of beta-thalassaemia by acting as a genetic marker for the normal chromosome in linkage analysis of family members.


A preclinical overview of emerging therapeutic targets for glomerular diseases.
Introduction: Animal models have provided significant insights into the mechanisms responsible for the development of glomerular lesions and proteinuria; they have also helped to identify molecules that control the podocyte function as suitable target-specific therapeutics. Areas covered: We discuss putative therapeutic targets for proteinuric glomerular diseases. An exhaustive search for eligible studies was performed in PubMed/MEDLINE. Most of the selected reports were published in the last decade, but we did not exclude older relevant milestone publications. We consider the molecules that regulate podocyte cytoskeletal dynamics and the transcription factors that regulate the expression of slit-diaphragm proteins. There is a focus on SGLT2 and sirtuins which have recently emerged as mediators of podocyte injury and repair. We also examine paracrine signallings involved in the cross-talk of injured podocytes with the neighbouring glomerular endothelial cells and parietal epithelial cells. Expert opinion: There is a need to discover novel therapeutic moleecules with renoprotective effects for those patients with glomerular diseases who do not respond completely to standard therapy. Emerging strategies targeting components of the podocyte cytoskeleton or signallings that regulate cellular communication within the glomerulus are promising avenues for treating glomerular diseases.


Lost in Translation: Simple Steps in Experimental Design of Neurorehabilitation-Based Research Interventions to Promote Motor Recovery Post-Stroke.
Stroke continues to be a leading cause of disability. Basic neurorehabilitation research is necessary to inform the neuropathophysiology of impaired motor control, and to develop targeted interventions with potential to remediate disability post-stroke. Despite knowledge gained from basic research studies, the effectiveness of research-based interventions for reducing motor impairment has been no greater than standard of practice interventions. In this perspective, we offer suggestions for overcoming translational barriers integral to experimental design, to augment traditional protocols, and re-route the rehabilitation trajectory toward recovery and away from compensation. First, we suggest that researchers consider modifying task practice schedules to focus on key aspects of movement quality, while minimizing the appearance of compensatory behaviors. Second, we suggest that researchers supplement primary outcome measures with secondary measures that capture emerging maladaptive compensations at other segments or joints. Third, we offer suggestions about how to maximize participant engagement, self-direction, and motivation, by embedding the task into a meaningful context, a strategy more likely to enable goal-action coupling, associated with improved neuro-motor control and learning. Finally, we remind the reader that motor impairment post-stroke is a multidimensional problem that involves central and peripheral sensorimotor systems, likely influenced by chronicity of stroke. Thus, stroke chronicity should be given special consideration for both participant recruitment and subsequent data analyses. We hope that future research endeavors will consider these suggestions in the design of the next generation of intervention studies in neurorehabilitation, to improve translation of research advances to improved participation and quality of life for stroke survivors.


Scanned intensity modulations for 50 MV photons.
Optimization of the dose distributions by individual beam compensation is a useful tool in conformal radiation therapy. Intensity modulation by electromagnetic scanning of a narrow elementary beam allows fast dose delivery and causes little change in beam quality compared with other methods, especially for high energies such as 50 MV. Intensity modulated beams from the MM50 accelerator were measured and compared with calculations based on Monte Carlo simulations. Good agreement between measurements and calculations were found, typically within 1% for central dose profiles. The steepest wedge angle that was produced with the scanning beam technique was of 45 degrees or 3.5% cm(-1) for a 20 cm x 20 cm field, slightly varying with depth. The elementary 50 MV photon 'pencil beam' for a full range, high-z bremsstrahlung target, is a wide dose distribution at 10 cm depth in water which limits the modulation gradient and hence the complexity of the modulation by the scanning of a photon pencil beam only. Scanned wedge beam distributions were modelled in the treatment planning system and a pelvic treatment with three fields was used to illustrate a clinical application. The resulting dose volume data were compared for different radiation qualities but with similar beam portals. 'Energy modulation' by field matching with lower photon energies was performed to sharpen the penumbra towards organs at risk.


Migraine headache in affectively ill latino adults of mexican american origin is associated with bipolarity.
The objective of this cross-sectional study was to determine the prevalence of migraine headache among depressed Latino adults of Mexican American origin meeting the criteria for bipolar disorder (BPD) or major depressive disorder (MDD) relative to patients in a psychiatric comparison group. In a mental health clinic for the indigent, consecutively and systematically evaluated acutely depressed Latino adults received structured diagnostic psychiatric interviews based on modules extracted from the Structured Clinical Interview for DSM-IV. All were asked as part of routine assessment whether they had headaches "in the last week." Patients with unilateral, pounding, pulsating headache were classified as having migraine headache. The prevalence of migraine headache among the patients with BPD and MDD was contrasted with that of patients in a psychiatric comparison group composed of patients with disorders other than schizophrenia or schizoaffective disorder. Logistic regression was used to test for associations and control for confounding effects. The data were collected between August 2001 and November 2004. Eighty-seven patients had BPD and 123 had MDD. Bipolar patients were 2.9 times more likely to have migraine headaches than patients with MDD (P < .0001). There was a trend for patients with MDD to have a higher prevalence of migraine than patients in the psychiatric comparison group. Bipolar patients had a high prevalence of migraine headache relative to patients with MDD. This study suggests that migraine is linked to bipolarity.


Antimicrobial and antibiofilm effects of abietic acid on cariogenic Streptococcus mutans.
Dental caries is a type of oral microbiome dysbiosis and biofilm infection that affects oral and systemic conditions. For healthy life expectancy, natural bacteriostatic products are ideal for daily and lifetime use as anti-oral infection agents. This study aimed to evaluate the inhibitory effects of abietic acid, a diterpene derived from pine rosin, on the in vitro growth of cariogenic bacterial species, Streptococcus mutans. The effective minimum inhibitory concentration of abietic acid was determined through observation of S. mutans growth, acidification, and biofilm formation. The inhibitory effects of abietic acid on the bacterial membrane were investigated through the use of in situ viability analysis and scanning electron microscopic analysis. Cytotoxicity of abietic acid was also examined in the context of several human cell lines using tetrazolium reduction assay. Abietic acid was found to inhibit key bacterial growth hallmarks such as colony forming ability, adenosine triphosphate activity (both planktonic and biofilm), acid production, and biofilm formation. Abietic acid was identified as bacteriostatic, and this compound caused minimal damage to the bacterial membrane. This action was different from that of povidone-iodine or cetylpyridinium chloride. Additionally, abietic acid was significantly less cytotoxic compared to povidone-iodine, and it exerted lower toxicity towards epithelial cells and fibroblasts compared to that against monocytic cells. These data suggest that abietic acid may prove useful as an antibacterial and antibiofilm agent for controlling S. mutans infection.


Optical Nanobiosensor-Based Point-of-Care Testing for Cardiovascular Disease Biomarkers.
Cardiovascular disease is a global health threat, and detecting cardiac biomarkers is essential for early-stage diagnosis and personalized treatment. Traditional approaches have limitations, but optical nanobiosensors offer rapid, highly selective, and sensitive detection. Optical nanobiosensors generate biosignals that transfer light signals while analytes bind with the bioreceptors. Optical nanobiosensors have advantages such as ease of monitoring, low cost, a wide detection range, and high sensitivity without any interference. An optical nanobiosensor platform is a promising approach for point-of-care cardiac biomarker detection with a low detection limit. This review mainly focuses on the detection of cardiovascular disease biomarkers based on various optical nanobiosensor approaches that have been reported during the last five years, and we have categorized them based on optical signal readouts. A detailed discussion of the classification of cardiovascular disease biomarkers, design strategies of optical biosensors, types of optically active nanomaterials, types of bioreceptors, functionalization techniques, various assay types, and sensing mechanisms is presented. Then, we summarize the optical signaling readout-based various nanobiosensors systems for the detection of cardiovascular disease biomarkers. Finally, we summarize and conclude with the recent development of point-of-care testing (PoCT) for cardiovascular disease biomarkers used in various optical readout techniques.


Altered sensitivity of posttranslationally modified microtubules to methylmercury in differentiating embryonal carcinoma-derived neurons.
The effects of methylmercury (MeHg) on microtubules (MTs) in differentiating neurons derived from retinoic acid-induced embryonal carcinoma (EC) cells in culture were examined by immunofluorescence microscopy. Undifferentiated EC cells contained mostly kinetically labile tyrosinated (TYR) MTs which extended from the centrosome and a small population of stable acetylated (ACT) MTs usually (but not exclusively) associated with the centrosome. TYR MTs of undifferentiated cells underwent concentration- and time-dependent disassembly upon exposure to low concentrations of MeHg (1-2 microM), whereas ACT MTs were resistant to MeHg at low concentrations, with many remaining intact even in 5 microM MeHg. After 2 days in retinoic acid the appearance of short neuritic processes was indicative of early differentiation. TYR MTs predominated both in the short neurites and cell soma and remained susceptible to low concentrations of MeHg. ACT MTs also extended into the short neurites but were most often found in small bundles within the perikarya. ACT MTs remained more resistant to MeHg than TYR MTs. The neuron-specific tubulin isotype betaIII was first detected during the second day of differentiation. MTs labeled with antibodies to betaIII showed similar sensitivity to MeHg as TYR MTs, suggesting that MTs containing betaIII were largely tyrosinated. After 4 and 6 days of differentiation a greater number of betaIII-positive neurons were present with progressively longer and often branching neurites. TYR MTs were present in cell soma and neurites while ACT MTs were found almost exclusively in neurites. TYR MTs remained highly susceptible to MeHg (most notably in perikarya) in comparison to ACT MTs at all stages of differentiation; however, with increasing time in culture, even TYR MTs gained appreciable stability to MeHg. These data indicate that microtubules in developing neurons become progressively more resistant to disassembly by MeHg, suggesting that the most critical period of MT susceptibility occurs very early in development in vivo.


Epidemiology of osteoarthritis.
To summarize the current state of the evidence regarding osteoarthritis (OA) prevalence, incidence and risk factors at the person-level and joint-level. This was a narrative review that took a comprehensive approach regarding inclusion of potential risk factors. The review complements prior reviews of OA epidemiology, with a focus on new research and emerging topics since 2017, as well as seminal studies. Studies continue to illustrate the high prevalence of OA worldwide, with a greater burden among older individuals, women, some racial and ethnic groups, and individuals with lower socioeconomic status. Modifiable risk factors for OA with the strongest evidence are obesity and joint injury. Topics of high interest or emerging evidence for a potential association with OA risk or progression include specific vitamins and diets, high blood pressure, genetic factors, metformin use, bone mineral density, abnormal joint shape and malalignment, and lower muscle strength/quality. Studies also continue to highlight the heterogenous nature of OA, with strong interest in understanding and defining OA phenotypes. OA is an increasingly prevalent condition with worldwide impacts on many health outcomes. The strong evidence for obesity and joint injury as OA risk factors calls for heightened efforts to mitigate these risks at clinical and public health levels. There is also a need for continued research regarding how potential person- and joint-level risk factors may interact to influence the development and progression of OA.


Test effort in persons with Chronic Fatigue Syndrome when assessed using the Validity Indicator Profile.
The current study examined the potential contribution of suboptimal effort to the cognitive deficits that are associated with Chronic Fatigue Syndrome (CFS) using the Validity Indicator Profile (VIP). Unlike most tests of effort, the VIP distinguishes between intentional and unintentional poor performance and does not assess cognitive functions that are affected by CFS, thereby reducing the risk of mistakenly attributing genuinely poor performance to reduced effort. The VIP was administered to 54 persons with CFS and 54 matched healthy community controls, and performance categorized into 1 of 4 response styles (valid: compliant; invalid: suppressed, irrelevant, inconsistent), based on the level of effort expended (high or low) and the intention to perform well or not. VIP performance was classified as valid for the majority of participants (CFS and controls), indicating high levels of effort and an intention to perform well. Three participants in the CFS group and four in the control group showed low levels of effort but an intention to do well (invalid: inconsistent). No participant performed in a manner indicative of an intent to perform poorly (invalid: suppressed, inconsistent). These findings suggest that poor effort is unlikely to contribute to cognitive test performance of persons with CFS.


Toll-like receptor-2 deficiency induces schizophrenia-like behaviors in mice.
Dysregulation of the immune system contributes to the pathogenesis of neuropsychiatric disorders including schizophrenia. Here, we demonstrated that toll-like receptor (TLR)-2, a family of pattern-recognition receptors, is involved in the pathogenesis of schizophrenia-like symptoms. Psychotic symptoms such as hyperlocomotion, anxiolytic-like behaviors, prepulse inhibition deficits, social withdrawal, and cognitive impairments were observed in TLR-2 knock-out (KO) mice. Ventricle enlargement, a hallmark of schizophrenia, was also observed in TLR-2 KO mouse brains. Levels of p-Akt and p-GSK-3α/β were markedly higher in the brain of TLR-2 KO than wild-type (WT) mice. Antipsychotic drugs such as haloperidol or clozapine reversed behavioral and biochemical alterations in TLR-2 KO mice. Furthermore, p-Akt and p-GSK-3α/β were decreased by treatment with a TLR-2 ligand, lipoteichoic acid, in WT mice. Thus, our data suggest that the dysregulation of the innate immune system by a TLR-2 deficiency may contribute to the development and/or pathophysiology of schizophrenia-like behaviors via Akt-GSK-3α/β signaling.


Differentiation of burn wounds in an in vivo porcine model using terahertz spectroscopy.
The accuracy of current burn triage techniques has remained between 50-70%. Accordingly, there is a significant clinical need for the quantitative and accurate assessment of partial-thickness burn injuries. Porcine skin represents the closest animal model to human skin, and is often used in surgical skin grafting procedures. In this study, we used a standardized in vivo porcine burn model to obtain terahertz (THz) point-spectroscopy measurements from burns with various severities. We then extracted two reflection hyperspectral parameters, namely spectral area under the curve between approximately 0.1 and 0.9 THz (-10 dB bandwidth in each spectrum), and spectral slope, to characterize each burn. Using a linear combination of these two parameters, we accurately classified deep partial- and superficial partial-thickness burns (p = 0.0159), compared to vimentin immunohistochemistry as the gold standard for burn depth determination.


Yersinia pestis Ail recruitment of C4b-binding protein leads to factor I-mediated inactivation of covalently and noncovalently bound C4b.
The outer membrane protein Ail of Yersinia pestis mediates several virulence functions, including serum resistance. Here, we demonstrate that Ail binds C4b-binding protein (C4BP), the primary fluid-phase regulator of the classical and lectin pathways. Noncovalent binding of C4 and C4b to Ail was also observed. C4BP bound to Ail can act as a cofactor to the serine protease factor I (fI) in the cleavage of fluid-phase C4b. Employing a panel of C4BP alpha-chain mutants, we observed that the absence of complement control protein domain 6 and 8 reduced binding to Ail. Immunoblot analysis of normal human serum (NHS)-treated bacteria revealed minimal C4b alpha'-chain complexes with bacterial outer membrane targets. Addition of the anti-C4BP monoclonal antibody MK104 to NHS restored C4b-alpha' chain target complexes, suggesting that C4b binds covalently to targets on the Y. pestis surface. C4b bound to Ail noncovalently was also cleaved in a C4BP and fI-dependent manner, leaving the C4c fragment bound to Ail. MK104 also prevented the cleavage of noncovalently bound C4b. Collectively, these data suggest that when C4BP is bound to Ail, fI can cleave and inactivate C4b that has bound covalently to bacterial surface structures as well as C4b bound noncovalently to Ail.


Subunit principles in midface fractures: the importance of sagittal buttresses, soft-tissue reductions, and sequencing treatment of segmental fractures.
The patterns of midface fractures were related to postoperative computed tomography scans and clinical results to assess the value of ordering fracture assembly in success of treatment methods. A total of 550 midface fractures were studied for their midface components and the presence of fractures in the adjacent frontal bone or mandible. Preoperative and postoperative computed tomography scans were analyzed to generate recommendations regarding exposure and postoperative stability related to fracture pattern and treatment sequence, both within the midface alone and when combined with frontal bone and mandibular fractures. Large segment (Le Fort I, II, and III) fractures were seen in 68 patients (12 percent); more comminuted midface fracture combinations were seen in 93 patients (17 percent). Midface and mandibular fractures were seen in 166 patients (30 percent). Midface, mandible, and nasoethmoid fractures were seen in 38 patients (7 percent). Frontal bone and midface fractures were seen in 131 patients (24 percent). Split-palate fractures accompanied 8 percent of midface fractures. Frontal bone, midface, and mandibular fractures were seen in 54 patients (10 percent). The midface, because of weak bone structure and comminuted fracture pattern, must therefore be considered a dependent, less stable structure. Its injuries more commonly occur with fractures of the frontal bone or mandible (two-thirds of cases) and, more often than not (>60 percent), are comminuted. Comminuted and pan-facial (multiple area) fractures deserve individualized consideration regarding the length of intermaxillary immobilization. Examples of common errors are described from this patient experience.


An effect of alcohol on the distribution of spatial attention.
Previous research on the effects of alcohol on visual performance led us to the prediction that alcohol should interfere with the distribution of visual spatial attention. This prediction was examined in two experiments that measured the effect of alcohol on reaction time (RT) for tasks that differed in visual spatial attention requirements. In the first experiment, 48 adult volunteers (33 female) responded to either the onset or offset of one of five potential targets without alcohol to determine the relative demands on attention of stimulus onset and offset. The spatial extent of the five-target display was also varied. In the second experiment, the effect of alcohol was determined for both the onset and the offset tasks in 12 adult volunteers (nine female). The offset task was found to place greater demands on spatial attention as the increase in display area result in relatively greater increases in RT. Alcohol increased RT in the offset task for the larger, but not the smaller, display, and there were no significant effects of alcohol for the onset task. The results indicate that alcohol impairs performance on tasks that place greater demands on visual spatial attention and likely disrupts the ability to shift attention from one spatial locus to another during serial search.


Relative versus absolute risk of dying reduction after using insecticide-treated nets for malaria control in Africa.
Four recently completed large-scale randomized controlled trials have assessed the impact of insecticide-treated bednets and curtains on overall child mortality in Africa. These results have sparked numerous discussions among implementing agency representatives and researchers about the public health significance of the results. For the interpretation of impact, most of the arguments have been based on the observed decrease in protective efficacy (a relative measure of impact) with increasing malaria transmission (range: 14-29%, regression for trend: F = 245 on 1,2 DF, P < 0.003). However, an analysis of the absolute measure of impact (the risk difference) showed a different pattern. The impact ranges from 3.8 to 6.9 lives saved per 1000 children protected per year, without a significant trend (F = 2.8 on 1,2 DF, P = 0.2) and with equally high values in both low and high transmission sites. When assessing the public health importance of an intervention, both relative and absolute decrease in risk should be considered.


Metagenomics analysis reveals features unique to Indian distal gut microbiota.
Various factors including diet, age, geography, culture and socio-economic status have a role in determining the composition of the human gut microbiota. The human gut microbial composition is known to be altered in disease conditions. Considering the important role of the gut microbiome in maintaining homeostasis and overall health, it is important to understand the microbial diversity and the functional metagenome of the healthy gut. Here, we characterized the microbiota of 31 fecal samples from healthy individuals of Indian ethnic tribes from Ladakh, Jaisalmer and Khargone by shotgun metagenomic sequencing. Sequence analysis revealed that Bifidobacterium and Prevotella were the key microbes contributing to the differences among Jaisalmer, Khargone and Ladakh samples at the genus level. Our correlation network study identified carbohydrate-active enzymes and carbohydrate binding proteins that are associated with specific genera in the different Indian geographical regions studied. Network analysis of carbohydrate-active enzymes and genus abundance revealed that the presence of different carbohydrate-active enzymes is driven by differential abundance of genera. The correlation networks were different in the different geographical regions, and these interactions suggest the role of less abundant genera in shaping the gut environment. We compared our data with samples from different countries and found significant differences in taxonomic composition and abundance of carbohydrate-active enzymes in the gut microbiota as compared to the other countries.


Corticotropin-releasing factor 2 receptor localization in skeletal muscle.
Our objective in this study was to localize the corticotropin-releasing factor 2 receptor (CRF2R) in rodent and human skeletal muscle. We found CRF2R protein to be abundant in neural tissues in skeletal muscle, including large nerve fibers and bundles, neural tissue associated with mechanoreceptors, muscle spindles, and the Golgi tendon organ. CRF2R protein was also abundant in blood vessels in skeletal muscle. CRF2R protein was also observed, although with less abundance, in the endo/perimysial regions in skeletal muscle. The localization of the CRF2R to blood vessels is consistent with the CRF2R-mediated vascular phenomena observed previously, but the observation of CRF2R in neural tissue in skeletal muscle is a novel finding with an unknown function.


Surface expression of the beta T cell receptor (TCR) chain in the absence of other TCR or CD3 proteins on immature T cells.
T cell receptor (TCR) beta genes are rearranged prior to TCR alpha genes. A productively rearranged TCR beta gene suppresses further V beta gene rearrangement. Here we show that in beta TCR transgenic mice the TCR beta-chain can be expressed on the surface of immature CD4-8- thymocytes, but not on mature T cells, in the absence of any other known TCR chain and proteins of the CD3 complex. Analysis by NEPHGE and SDS-PAGE showed that at least some beta TCR exists on the surface as a large disulfide-linked complex with unknown acidic molecules. The introduction of the beta TCR gene into scid mice resulted in the expression of the beta TCR on the cell surface of thymocytes and induced the expression of CD4 and CD8 co-receptors as well as transcription of the alpha TCR locus.


Development of a nomogram to predict survival in advanced biliary tract cancer.
The prognosis of advanced biliary tract cancer (BTC) patients remains poor due to limited efficacy of chemotherapy and difficulties in management. Thus, prediction of survival is crucial for the clinical management of advanced BTC. The aim was to develop and validate a nomogram to predict 6-month and 12-month survival in advanced BTC patients treated with chemotherapy. A multivariable Cox regression model was used to construct a nomogram in a training set (JCOG1113, a phase III trial comparing gemcitabine plus S-1 [GS] and gemcitabine plus cisplatin, n = 351). External validity of the nomogram was assessed using a test set (JCOG0805, a randomized, phase II trial comparing GS and S-1 alone, n = 100). Predictive performance was assessed in terms of discrimination and calibration. The constructed nomogram included lymph node metastasis, liver metastasis, carbohydrate antigen 19-9, carcinoembryonic antigen, albumin, and C-reactive protein. Uno's concordance index was 0.661 (95% confidence interval [CI] 0.629-0.696) in the training set and 0.640 (95% CI 0.566-0.715) in the test set. The calibration plots for 6-month and 12-month survival showed good agreement in the two analysis sets. The present nomogram can facilitate prediction of the prognosis of advanced BTC patients treated with chemotherapy and help clinicians' prognosis-based decision-making.


Duodenal prostaglandin synthesis and acid load in health and in duodenal ulcer disease.
We sought to test the hypothesis that duodenal ulcer disease results from an imbalance between duodenal acid load, an injurious force, and mucosal prostaglandin generation, a protective factor. Ten patients with duodenal ulcer and 8 healthy controls were studied. The duodenal acid load after an amino acid soup was quantified by a double-marker technique. Mucosal biopsy specimens were taken endoscopically from the duodenal bulb before and after the test meal. Prostaglandin synthesis activity was measured by incubating biopsy homogenates in excess [14C]arachidonic acid. Although mean duodenal acid load was higher in duodenal ulcer, ranges overlapped. Neither the qualitative nor quantitative profile of mucosal prostaglandin synthesis activities differed significantly between test groups. Prostaglandin synthesis activities, however, tended to increase post cibum in controls, but change little or decrease in duodenal ulcer. Only by comparing the responses with a meal of both parameters together (duodenal acid load and the change in prostaglandin synthesis activities) was there complete or nearly complete separation of duodenal ulcer from controls. Greatest discrimination was observed with prostacyclin (6-keto-PGF1 alpha). We conclude that in health, mucosal prostaglandin generation in the duodenum is induced post cibum in relation to duodenal acid load; this may be a physiologic example of adaptive cytoprotection. In duodenal ulcer there may be a defect in such a mechanism.


Anaemia and blood transfusion in African children presenting to hospital with severe febrile illness.
Severe anaemia in children is a leading cause of hospital admission and a major cause of mortality in sub-Saharan Africa, yet there are limited published data on blood transfusion in this vulnerable group. We present data from a large controlled trial of fluid resuscitation (Fluid Expansion As Supportive Therapy (FEAST) trial) on the prevalence, clinical features, and transfusion management of anaemia in children presenting to hospitals in three East African countries with serious febrile illness (predominantly malaria and/or sepsis) and impaired peripheral perfusion. Of 3,170 children in the FEAST trial, 3,082 (97%) had baseline haemoglobin (Hb) measurement, 2,346/3,082 (76%) were anaemic (Hb <10 g/dL), and 33% severely anaemic (Hb <5 g/dL). Prevalence of severe anaemia varied from 12% in Kenya to 41% in eastern Uganda. 1,387/3,082 (45%) children were transfused (81% within 8 hours). Adherence to WHO transfusion guidelines was poor. Among severely anaemic children who were not transfused, 52% (54/103) died within 8 hours, and 90% of these deaths occurred within 2.5 hours of randomisation. By 24 hours, 128/1,002 (13%) severely anaemic children had died, compared to 36/501 (7%) and 71/843 (8%) of those with moderate and mild anaemia, respectively. Among children without severe hypotension who were randomised to receive fluid boluses of 0.9% saline or albumin, mortality was increased (10.6% and 10.5%, respectively) compared to controls (7.2%), regardless of admission Hb level. Repeat transfusion varied from ≤2% in Kenya/Tanzania to 6 to 13% at the four Ugandan centres. Adverse reactions to blood were rare (0.4%). Severe anaemia complicates one third of childhood admissions with serious febrile illness to hospitals in East Africa, and is associated with increased mortality. A high proportion of deaths occurred within 2.5 hours of admission, emphasizing the need for rapid recognition and prompt blood transfusion. Adherence to current WHO transfusion guidelines was poor. The high rates of re-transfusion suggest that 20 mL/kg whole blood or 10 mL/kg packed cells may undertreat a significant proportion of anaemic children. Future evaluation of the impact of a larger volume of transfused blood and optimum transfusion management of children with Hb of <6 g/dL is warranted.


Restraint of tool path ripple based on surface error distribution and process parameters in deterministic finishing.
The influence from the regular tool path to micro fabrication errors in deterministic finishing is studied through the simulations and experiments. The random pitch tool path based on the surface error distribution and the process parameters is designed to reduce this residual error when adopting the regular path to achieve the corrective polish. A nucleated glass flat mirror is polished with this method on the experimental installation UPF700-7 developed by ourselves. The surface accuracy is improved from the initial λ/30(RMS, 90%aperture, λ = 632.8 nm) to the final λ/200 in 5 minutes and the medium-high spatial frequency errors induced by the regular path is restricted well at the same time. The accuracy of the simulation and the validity of the random pitch tool path are both proved through the experiments.


Choroidal ganglion cell plexus and retinal vasculature in monkeys with laser-induced glaucoma.
The choroid of primates possesses an elaborate nitrergic nerve fiber plexus containing a great number of ganglion cells. Postganglionic nerve fibers innervate mainly the choroidal vasculature. In addition, the choroid contains an elastic muscular system closely associated to the vasculature. The goal of the present investigation was to analyze how sustained IOP elevation would affect the choroidal vasculature with its specialized innervation and the adjacent retina. For this purpose the posterior eye segment of 15 rhesus monkeys which after laser coagulation of the trabecular meshwork developed elevated IOP up to 4 years were studied using immunohistochemical and histochemical methods, and scanning electron microscopy of corrosion casts. The most striking finding was a significant reduction of choroidal thickness and loss of choroidal ganglion cells and nerve fibers, especially in the central portion of the choroid. Corrosion casts of the choroidal vasculature showed a slight decrease in capillary density and a decrease in length of the arterioles in glaucomatous eyes. Whole mount preparations of the retina stained for NADPH diaphorase revealed a significant reduction in positively stained amacrine cells, reduction in diameter of arterioles and changes in the staining pattern of the retinal vasculature, particularly in the perimacular region.


Sexual Risk Behavior and Lifetime HIV Testing: The Role of Adverse Childhood Experiences.
Despite the success of HIV prevention drugs such as PrEP, HIV incident transmission rates remain a significant problem in the United States. A life-course perspective, including experiences of childhood adversity, may be useful in addressing the HIV epidemic. This paper used 2019 BRFSS data to elucidate the role that childhood adversity plays in the relationship between HIV risk and HIV testing. Participants (n = 58,258) completed self-report measures of HIV risk behaviors, HIV testing, and adverse childhood experiences (ACEs). The median number ACEs in the sample was 1, with verbal abuse (33.9%), and parental separation (31.3%) being the most common ACEs reported. Bivariate findings showed that all ACEs were associated with increased HIV risk and testing. However, increased risk was not correlated with increased HIV testing, with the highest incongruence related to mental health problems of household member (53.48%). While both self-reported HIV risk and ACEs were positively associated with HIV testing, their interaction had a negative association with testing (aPR = 0.51, 95%CI 0.42, 0.62). The results highlight the need for targeted HIV prevention strategies for at-risk individuals with a history of childhood adversity.


[The oxygen effect in E. coli cells. Role of the photoreactivated component in modifying the oxygen effect in E. coli WP2 uvrA6 cells].
A study was made of a contribution of photoreactivated lesions to the oxygen effect (OE) manifestation in cells of UV-sensitive E. coli WP2 uvrA6. It was shown that the contribution of the photoreactivated lesions depends upon radiation energy and gas conditions in which radiation is delivered. The OE value in the uvrA6-mutant may be modified in the irradiation conditions preventing induction of the photoreactivated lesions (gamma-irradiation in the presence of nigrosine, and X-irradiation).


Proliferation and colony-forming ability of peritoneal exudate cells in liquid culture.
Peritoneal exudate cells, obtained from mice injected with thioglycollate medium and cultured in medium containing L-cell-conditioned medium, will proliferate in an exponential fashion for 18 days with a doubling time of 68 h. After a 2 h pulse of tritiated thymidine, labeled adherent cells increased to a maximum of 22-34% during the 1st and 2nd wk of culture. Increasing the cell concentration from 2 times 10-3 to 2 times 10-5 cells/culture reduced exponential growth to 10 days and the doubling time was increased to 81.6 h. Under these culture conditions, peritoneal exudate cells were shown to form colonies on the surface of culture dishes when plated at low density. The cells within the colony were shown to be macrophages using yeast and antibody-coated sheep erythrocytes as a test for phagocytic function. The plating efficiolonies arose from a single precursor cell. The adherent cell population contains the colony-forming precursors. These precursors can be stimulated to form colonies for at least 2 wk by the addition of conditioned medium to cultures at various times after plating. While very few colony-forming cells could be demonstrated in the unstimulated peritoneal lavage, their numbers begin to increase in the exudate 4 h after injection of thioglycollate medium and reach a maximum by day 3 and then decrease. Isolated colonies may be useful in studying the function of macrophages.


Elevated levels of plasma beta-endorphin and gamma 3-melanocyte stimulating hormone in the polycystic ovary syndrome.
The authors have suggested that dysfunction of a central structure (above the pituitary level) is the primary etiologic factor responsible for the production of the polycystic ovary syndrome. To investigate further the functional integrity of the hypothalamic pituitary axis, plasma levels of beta-endorphin, gamma 3-melanocyte stimulating hormone, and gamma 1-melanocyte stimulating hormone-like immunoreactivity were measured in six patients with polycystic ovary syndrome, and in ten women with normal ovarian function. The limit of sensitivity for the radioimmunoassays was 20 pg/mL. Plasma beta-endorphin was significantly higher in polycystic ovary syndrome than in control subjects: (mean +/- SE) 60 +/- 10 versus 30 +/- 4 pg/mL, respectively (P less than .05). gamma 3-Melanocyte stimulating hormone was detectable in four of six patients with polycystic ovary syndrome (mean for the whole group: 45 +/- 15 pg/mL); it was undetectable in all the control subjects. Control of plasma beta-endorphin and gamma 3-melanocyte stimulating hormone secretion in PCO was evaluated with metyrapone and dexamethasone. Overnight administration of metyrapone to polycystic ovary syndrome patients resulted in rises of beta-endorphin and gamma 3-melanocyte stimulating hormone. Dexamethasone suppressed only partially (to basal concentrations) beta-endorphin and gamma 3-melanocyte stimulating hormone levels. Plasma adrenocorticotropic hormone concentrations were within the normal range and displayed the expected changes in response to metyrapone and dexamethasone. The present report presents an additional central (hypothalamic-pituitary) abnormality in patients with the polycystic ovary syndrome.


Elevated precipitation alters the community structure of spring ephemerals by changing dominant species density in Central Asia.
Global climate change is one of the most pressing conservation challenges; in particular, changes in precipitation regimes have already substantially influenced terrestrial ecosystems. However, the mechanisms influencing precipitation changes on individual plants and the plant communities in desert grasslands have yet to be fully elucidated. We therefore examine the influence of increased precipitation on plant community compositions in the Gurbantunggut Desert, Xinjiang, northwestern China, from 2005 to 2009. We found that growth of all plant species and the community productivities increased markedly with enhanced water input. Cover of ephemeral synusia also significantly increased due to increased precipitation, implying that the role of the ephemeral community for stabilization of sand dunes was strengthened by increased precipitation. The response of plant community compositions to increased precipitation was primarily reflected as changes in plant density, while increased precipitation did not affect plant species richness and the diversity index. Dominant species drove the response of plant density to increasing precipitation during the five-year study period. However, the relative responses of rare species were stronger than those of the dominant species, thereby potentially driving species turnover with long-term increased precipitation. This finding improved our understanding of how increased precipitation drives the changes in plant community composition in desert grasslands and will help to better predict changes in the community composition of ephemerals under future global climate change scenarios.


Acute transverse myelitis and acute motor axonal neuropathy developed after vaccinations against seasonal and 2009 A/H1N1 influenza.
Acute transverse myelitis (ATM) has been described as an uncommon complication of vaccinations and is rarely accompanied by inflammatory peripheral neuropathy. We report a case of a 77-year-old woman who developed ATM and acute motor axonal neuropathy (AMAN) following vaccinations against seasonal and 2009 A/H1N1 influenza. She manifested ophthalmoplegia, quadriparesis and sensory impairment. MR imaging showed a longitudinally-extensive spinal cord lesion, and nerve conduction study revealed motor axonal polyneuropathy. Despite prompt treatment, her symptoms poorly recovered. While concurrent ATM and AMAN may suggest the presence of a common antigen, their scarcity indicates the importance of other factors causing immunologic disruptions.


Fears and other suspected risk factors for carrying lethal weapons among urban youths of middle-school age.
To estimate the strength of a suspected causal association between fearfulness and carrying a lethal weapon among urban middle-school students, while holding constant other suspected risk factors. A prospective study of an epidemiological sample assessed at baseline in 1992 and 1 year later, with relative risk estimates derived from the conditional form of the multiple logistic regression model used to hold constant alternative explanatory variables. An urban environment in the mid-Atlantic region of the United States. An epidemiological sample of 1131 youths enrolled in public middle schools. Carrying a lethal weapon for protection or defense during a 1-year observation interval after the baseline assessment of fears and other suspected risk factors. Of the 1131 youths, 194 (17%) reported carrying a lethal weapon for protection or defense during the 1-year interval of follow-up observation after baseline; 937 youths (83%) reported that they had not carried a lethal weapon for any reason. Self-reported fears, deviant peer affiliation, and worrying were associated with risk of starting to carry a weapon. For youths with the lowest worrying scores, the lowest neighborhood danger scores, and the least affiliation with deviant peers, self-reported fears were associated with risk of starting to carry a lethal weapon (relative risk estimate, 1.68; 95% confidence interval, 1.11-2.52; P = .01), even after holding constant age, sex, and conduct problems. However, the fear of crowded or closed-in places and the fear of leaving home alone were more salient risk factors than the fear of using public transportation or the fear of open spaces. In this study, youths with fears were at greater risk of carrying a lethal weapon for protection or defense, even when alternative explanatory variables were taken into account. Pending confirmation by other investigators, this new finding could point out a useful target for public health interventions to reduce the carrying of weapons and associated violence in urban America.


Recent advances in stem cell research for the treatment of diabetes.
The success achieved over the last decade with islet transplantation has intensified interest in treating diabetes, not only by cell transplantation, but also by stem cells. The formation of insulin-producing cells from pancreatic duct, acinar, and liver cells is an active area of investigation. Protocols for the in vitro differentiation of embryonic stem (ES) cells based on normal developmental processes, have generated insulin-producing cells, though at low efficiency and without full responsiveness to extracellular levels of glucose. Induced pluripotent stem cells, which have been generated from somatic cells by introducing Oct3/4, Sox2, Klf4, and c-Myc, and which are similar to ES cells in morphology, gene expression, epigenetic status and differentiation, can also differentiate into insulin-producing cells. Overexpression of embryonic transcription factors in stem cells could efficiently induce their differentiation into insulin-expressing cells. The purpose of this review is to demonstrate recent progress in the research for new sources of β-cells, and to discuss strategies for the treatment of diabetes.


Longevity expectations in the pension fund, insurance, and employee benefits industries.
Considerable progress has been made in many areas of biomedical science since the 1960s, suggesting likely increases in life expectancy and decreases in morbidity and mortality in the adult population. These changes may pose substantial risks to the pensions and benefits industries. While there is no significant statistical evidence demonstrating rapid decreases in mortality rates, there are conflicting opinions among demographers and biogerontologists on the biological limits of the human lifespan and trends in life expectancy. We administered a survey of the International Employee Benefits Association (IEBA), a large, international industry group. Industry professionals employed by consulting (35%), insurance (24%), pension (14%), and other (27%) companies responded to 32 questions. Respondents showed reasonably conservative views on the future of longevity and retirement, including that for women. The respondents formed their personal longevity expectations based on their family history and, to a lesser degree, on the actuarial life tables. Most of the sample expressed no desire to life past age 100 years, even if the enabling technologies required to maintain a healthy youthful state were available, and only a few respondents in the sample expressed a desire to live for the maximum period (at least) offered by the survey question. The majority of the respondents would not undergo any invasive procedures, and only 56% of the respondents would opt for noninvasive therapies to extend their healthy lifespans to 150 years of age if these were available.


A clinical study of the LiVac laparoscopic liver retractor system.
All retractors for laparoscopic operations on the gallbladder or stomach apply an upward force to the under-surface of the liver or gallbladder, most requiring an additional skin incision. The LiVac laparoscopic liver retractor system (LiVac retractor) comprises a soft silicone ring attached to suction tubing and connected to a regulated source of suction. The suction tubing extends alongside existing ports. When placed between the liver and diaphragm, and suction applied, a vacuum is created within the ring, keeping these in apposition. Following successful proof-of-concept animal testing, a clinical study was conducted to evaluate the performance and safety of the retractor in patients. The study was a dual-centre, single-surgeon, open-label study and recruited ten patients scheduled to undergo routine upper abdominal laparoscopic surgery including cholecystectomy, primary gastric banding surgery or fundoplication. The study was conducted at two sites and was approved by the institutions' ethics committees. The primary objective of the study was to evaluate the performance of the LiVac retractor in patients undergoing upper abdominal single- or multi-port laparoscopic surgery. Performance was measured by the attainment of milestones for the retractor and accessory bevel, where used, and safety outcomes through the recording of adverse events, physical parameters, pain scales, blood tests and a post-operative liver ultrasound. The LiVac retractor achieved both primary and secondary performance and safety objectives in all patients. No serious adverse events and no device-related adverse events or device deficiencies were reported. The LiVac retractor achieved effective liver retraction without clinically significant trauma and has potential application in multi- or single-port laparoscopic upper abdominal surgery. As a separate incision is not required, the use of the LiVac retractor in multi-port surgery therefore reduces the number of incisions.