Management of hereditary dyslipidaemia; the paradigm of autosomal dominant hypercholesterolaemia.
Inherited, or autosomal dominant, hypercholesterolaemia, with an average global prevalence of one in 500 individuals, is one of the most frequent inherited metabolic disorders. The disorder is associated with a high risk for premature cardiovascular disease (CVD) and death as a consequence of accelerated atherosclerosis. Although the molecular genetic basis is largely elucidated and effective medical treatment, in the form of inhibitors of intracellular cholesterol synthesis, is available, the disorder is severely underdiagnosed and undertreated. On the other hand, with the well-understood aetiology, the accurate diagnosis, the availability of sensitive predictive makers and efficacious therapy, this disorder can serve as a model for disease management: from early presymptomatic diagnosis, accurate prognosis, optimal treatment and large-scale screening to population-based prevention of CVD.


Parity and age at menopause in a Danish sample.
A random sample of 151 Danish women who had undergone natural menopause reported the age at which this occurred and answered a questionnaire. A significant association was found between parity and age at menopause after correction for the effects of age at the first and last births, weight, smoking and occupation. However, there is no evidence that the age at menopause has fallen in recent decades, even though the average parity in developed populations has dropped dramatically over this period. It is therefore possible that potential fertility is a confounding variable in the relationship between parity and age at menopause.


p60(v-src) and serum control cell shape and apoptosis via distinct pathways in quail neuroretina cells.
We made use of QNR cells transformed by a thermosensitive (tsNY68) strain of the Rous sarcoma virus (RSV) to compare the effect of p60(v-src) and serum in cultured nerve cells. In this system, both p60(v-src) heat inactivation and serum removal resulted in growth arrest in G1. In both cases, growth arrest was reversible since cell proliferation was rapidly re-induced following respectively p60v-src renaturation or serum re-addition. However, cells did not fully recover their ability to grow in soft agar, suggesting that, in contrast to the cell cycle machinery, the transforming capacities of these cells have been irreversibly altered. We found that p60(v-src) kinase activity prevented detachment from the substratum and cell death following serum removal. Thermal inactivation of p60(v-src) at restrictive temperature (41.5 degrees C), but not serum removal, resulted in dramatic morphological changes, which occurred 4 h after temperature shift up to 41.5 degrees C. Later on, typical features of apoptotic cells could be observed. Cell death was greatly reduced by the caspase-3 inhibitor ZVAD.FMK, but not by the caspase-1 inhibitor Ac-YVAD.CHO. Together, these results suggested that p60(v-src) and serum factors act on distinct pathways, at least in part. In an attempt to identify the signalling pathways involved in the cell response to p60(v-src) down regulation, we found that Erk and Rac were rapidly inactivated following temperature shift up to 41.5 degrees C. Thus, the combined effects of p60(v-src) and serum factors on the cytoskeleton dynamics and the apoptosis machinery are essential for full neoplastic transformation of neuroretina cells.


The effect of carrier characteristics and female age on preimplantation genetic testing results of blastocysts from Robertsonian translocation carriers.
To analyze factors affecting segregation and ploidy results from Robertsonian carriers, and determine chromosomes involved impact chromosome stability during meiosis and mitosis. This retrospective study include 928 oocyte retrieval cycles from 763 couples with Robertsonian translocations undergoing preimplantation genetic testing for structural rearrangements (PGT-SR) using next-generation sequencing (NGS) between December 2012 and June 2020.The segregation patterns of the trivalent of 3423 blastocysts were analyzed according to the carrier's sex and age. A total of 1492 couples who received preimplantation genetic testing for aneuploidy (PGT-A) were included as the control group and matched according to maternal age and testing time stage. A total of 1728 (50.5%) normal/balanced embryos were identified from 3423 embryos diagnosed. The rate of alternate segregation in male Robertsonian translocation carriers was significantly higher than that in female carriers (82.3% vs. 60.0%, P < 0.001). However, the segregation ratio exhibited no difference between young and older carriers. Further, increasing maternal age decreased the proportion of transferable embryo cycle in both female and male carriers. And the ratio of chromosome mosaic from the Robertsonian translocation carrier group was significantly higher than that in the PGT-A control group (1.2% vs. 0.5%, P < 0.01). The meiotic segregation modes were affected by the carrier sex and were independent of the carrier's age. Advanced maternal age decreased the probability of obtaining a normal/balanced embryo. In additional, the Robertsonian translocation chromosome could increase the possibility of chromosome mosaicism during mitosis in blastocysts.


Wide-Awake Approach for Terrible Triad Injury Fixation: A Report of Two Cases.
The wide-awake local anesthesia no tourniquet (WALANT) technique has been widely used for various upper extremity surgeries, but its use for surgical fixation of terrible triad injuries has yet to be reported in the literature. Two cases of terrible triad injuries surgically treated under WALANT are presented. Coronoid screw fixation and radial head replacement were performed for the first case, and radial head fixation and coronoid suture lasso were performed for the second. Intraoperative stability during the active range of motion of both the elbows was tested after fixation. Difficulties encountered included pain near the coronoid due to its deep location causing difficulty injecting local anesthetic, and shoulder pain during the surgery due to prolonged preoperative immobilization. WALANT for terrible triad fixation is a viable alternative to general and regional anesthesia in a select number of patients with the added benefit of intraoperative elbow stability testing during active range of motion.


Freeze-substitution: the addition of water to polar solvents enhances the retention of structure and acts at temperatures around -60 degrees C.
High-pressure freezing followed by freeze substitution and plastic embedding is becoming a more widely used method for TEM sample preparation. Here, we have investigated the influence of solvents, fixative concentrations and water content in the substitution medium on the sample quality of high-pressure frozen, freeze-substituted and plastic embedded mammalian cell culture monolayers. We found that the visibility of structural details was optimal with acetone and that extraction increased with both increasing and decreasing solvent polarity. Interestingly, the addition of water to polar solvents increased the sample quality, while being destructive when added to apolar solvents. The positive effect of water addition is saturable in acetone and ethanol at 5%(v/v), but even addition of up to 20% water has no negative effect on the sample structure. Therefore, a medium based on acetone containing fixatives and 5% water is most optimal for the substitution of mammalian cell cultures. In addition, our results suggest that the presence of water is critical for the retention of structure at temperatures around -60 degrees C.


Factors affecting components of fitness in a gall-making wasp (Cynips divisa Hartig).
The galls of the agamic generation of the cynipid gall-wasp Cynips divisa were studied; these galls are found only on the main veins of the leaf. Galls are concentrated on the middle veins of leaves, and generally occur closer to the midrib than to the edge of the leaf. Survival of the gall-maker and fecundity of the energing wasp depend on wasp size and position of the gall. There is a striking pattern in gall size according to the number of galls on the vein. The number of galls on a vein appears therefore to have a strong effect on potential fecundity.


Antifungal properties of the anti-hypertensive drug: aliskiren.
Aliskiren, the first in a new class of orally active renin inhibitors, is licensed for the treatment of hypertension. It inhibits plasma renin activity directly, thereby reducing generation of angiotensin II. In this study, we have explored the anti-Candida properties of aliskiren. Candida albicans was cultured in the presence or absence of aliskiren for various time periods. Subsequently, inhibition of growth, germtube formation, adhesion, early/matured biofilm development and secreted aspartic protease (SAP) activity were studied. When cultured in the presence of aliskiren, Candida showed significant reduction in the activity of aspartic proteases. Aliskiren impaired in vitro growth of C. albicans. It also affected two other virulence factors, germtube and adhesion. There is reduction in early and matured biofilm when treated with aliskiren. Aliskiren could be considered as a candidate for antifungal drug development.


Inhalation toxicology: methodological and regulatory challenges.
Highly standardized and controlled inhalation studies are required for hazard identification to make test results reproducible and comparable and also to fulfill general regulatory requirements for the registration of new drugs, pesticides, or notification of chemicals. Inhalation studies have numerous experimental variables; these are related to substance-specific physical factors such as particle size and phase and that a specific "exposure dose" can be achieved by two variables, viz. exposure concentration and duration. Variables related to the exposure or dosing regimen may become important, especially for short-acting substances. In addition, specific use or product patterns, e.g. specialized configurations designed for inhalation drug delivery or end-user products emitting aerosols may challenge traditional approaches. The testing of innocuous, poorly soluble particulates in the fine and ultrafine size range is a demanding exercise because the toxic manifestation of particle-induced effects often requires long postexposure periods. The difference in toxic potency of such particles may emerge from differences related to particle clearance, rate of dissolution within lung tissue, liberation of redox-active, free metal ions or the initiation of a somewhat self-amplifying and self-perpetuating pulmonary inflammation. Due to the heterogeneity of deposition of inhaled materials within the respiratory tract, each specific site of the tract may be exposed differently. Ensuing toxic responses may either be related to the solubility or insolubility of the inhaled material. The many facets of inhalation exposure and consequent occurrence of toxic effects caused by systemic and/or localized direct biochemical or secondary physiological effects appear to be a methodological challenge for alternative test approaches. Accordingly, it is experimentally challenging to articulate a unifying denominator of dose at critical cellular targets in both in vivo and in vitro test systems due to the complex dependence on test material-specific characteristics.


Burden of Cause-Specific Mortality Associated With PM2.5 Air Pollution in the United States.
Ambient fine particulate matter (PM2.5) air pollution is associated with increased risk of several causes of death. However, epidemiologic evidence suggests that current knowledge does not comprehensively capture all causes of death associated with PM2.5 exposure. To systematically identify causes of death associated with PM2.5 pollution and estimate the burden of death for each cause in the United States. In a cohort study of US veterans followed up between 2006 and 2016, ensemble modeling was used to identify and characterize morphology of the association between PM2.5 and causes of death. Burden of death associated with PM2.5 exposure in the contiguous United States and for each state was then estimated by application of estimated risk functions to county-level PM2.5 estimates from the US Environmental Protection Agency and cause-specific death rate data from the Centers for Disease Control and Prevention. Nonlinear exposure-response functions of the association between PM2.5 and causes of death and burden of death associated with PM2.5. Annual mean PM2.5 levels. A cohort of 4 522 160 US veterans (4 243 462 [93.8%] male; median [interquartile range] age, 64.1 [55.7-75.5] years; 3 702 942 [82.0%] white, 667 550 [14.8%] black, and 145 593 [3.2%] other race) was followed up for a median (interquartile range) of 10.0 (6.8-10.2) years. In the contiguous United States, PM2.5 exposure was associated with excess burden of death due to cardiovascular disease (56 070.1 deaths [95% uncertainty interval {UI}, 51 940.2-60 318.3 deaths]), cerebrovascular disease (40 466.1 deaths [95% UI, 21 770.1-46 487.9 deaths]), chronic kidney disease (7175.2 deaths [95% UI, 5910.2-8371.9 deaths]), chronic obstructive pulmonary disease (645.7 deaths [95% UI, 300.2-2490.9 deaths]), dementia (19 851.5 deaths [95% UI, 14 420.6-31 621.4 deaths]), type 2 diabetes (501.3 deaths [95% UI, 447.5-561.1 deaths]), hypertension (30 696.9 deaths [95% UI, 27 518.1-33 881.9 deaths]), lung cancer (17 545.3 deaths [95% UI, 15 055.3-20 464.5 deaths]), and pneumonia (8854.9 deaths [95% UI, 7696.2-10 710.6 deaths]). Burden exhibited substantial geographic variation. Estimated burden of death due to nonaccidental causes was 197 905.1 deaths (95% UI, 183 463.3-213 644.9 deaths); mean age-standardized death rates (per 100 000) due to nonaccidental causes were higher among black individuals (55.2 [95% UI, 50.5-60.6]) than nonblack individuals (51.0 [95% UI, 46.4-56.1]) and higher among those living in counties with high (65.3 [95% UI, 56.2-75.4]) vs low (46.1 [95% UI, 42.3-50.4]) socioeconomic deprivation; 99.0% of the burden of death due to nonaccidental causes was associated with PM2.5 levels below standards set by the US Environmental Protection Agency. In this study, 9 causes of death were associated with PM2.5 exposure. The burden of death associated with PM2.5 was disproportionally borne by black individuals and socioeconomically disadvantaged communities. Effort toward cleaner air might reduce the burden of PM2.5-associated deaths.


The Course of SARS-COV2 Infection Was Not Severe in a Crohn's Patient Who Administered Maintenance Anti-TNF Therapy Overlapping the Early Pre-Symptomatic Period of Infection.
The Inflammatory Bowel Disease (IBD) population, which may require treatment with immunosuppressive medications, may be uniquely vulnerable to COVID-19 infection. In fact, there is some evidence these medications may inhibit the cytokine storm that is theorized to cause a rapid decline seen in COVID-19. In addition, the digestive symptoms of COVID-19 can be difficult to distinguish from the activation of IBD. We present an interesting case of a Crohn's patient inadvertently administering anti-cytokine therapy during the pre-symptomatic period of COVID-19 infection. Immune suppression during early infection with SARS-COV2 risks a poor immune response to the virus and could theoretically result in a more severe course of infection.


Apparatus for EEG recording and electrical stimulation of discrete brain areas in an unrestrained small animal.
An apparatus that permits the observation of behavior, recording of EEG and electrical stimulation of the brain can be built from readily available and inexpensive components. This type of apparatus has a variety of uses in biomedical research.


Corrigendum: Genetic predisposition between COVID-19 and four mental illnesses: A bidirectional, two-sample Mendelian randomization study.
[This corrects the article DOI: 10.3389/fpsyt.2021.746276.].


Outcome of transurethral resection of bladder tumour under spinal anaesthesia combined with obturator nerve block in Sri Lanka.
Transurethral resection of bladder tumour (TURBT) is done under general anaesthesia (GA) with muscle relaxation to prevent obturator jerk and bladder perforation. TURBT under spinal anaesthesia (SA) with obturator nerve block (ONB) may prevent the obturator jerk while eliminating the disadvantages of GA. To assess the outcome of TURBT under SA and ONB. Patients undergoing TURBT for lateral wall tumours from 01.11.2017 to 30.10.2020 were prospectively studied. Anterior branch of obturator nerve with plain Bupivacaine was blocked with the guidance of an ultrasound scan and a nerve stimulator. Significant obturator jerk which necessitated conversion to GA was defined as failed ONB. Out of 72 patients with mean age of 66.7 years underwent ONB, 61 (84.7%) were men. Fifty two (72.2%) had unilateral and 20 (27.8%) had bilateral blocks. Sixty one (84.7%) patients had no obturator jerk whereas 5 (7%) had a mild jerk which did not preclude safe resection. Six patients (8.3%) had a failed ONB requiring conversion to GA. None had a bladder perforation requiring laparotomy, developed neurovascular injury or anaesthetic toxicity and only one patient required intensive care monitoring. SA with anterior branch of ONB is an effective and safe alternative to GA with muscle relaxation for TURBT although a randomized trial is necessary to determine the true efficacy and safety over the other.


A novel animal model of osteonecrosis of the femoral head based on 3D printing technology.
Osteonecrosis of the femoral head (ONFH) is a prevalent orthopedic condition characterized by the disruption of blood supply to the femoral head, leading to ischemia of internal tissues, subchondral bone fractures, necrosis, and eventual collapse of the weight-bearing portion of the femoral head. This condition results in severe functional impairment, pain, and even disability of the hip joint. Existing animal models of ONFH have limitations in replicating the natural disease progression accurately. Thus, there is a critical need to develop a novel animal model capable of better simulating localized pressure on the human femoral head to facilitate ONFH-related research. In this study, we present a novel approach for modeling ONFH, which involves integrating stress factors into the modeling process through the utilization of 3D printing technology and principles of biomechanics. A total of 36 animals were randomly assigned to six groups, where they received either the novel modeling technique or the traditional hormone induction method. Subsequently, an 8-week treatment period was implemented, followed by conducting micro-CT scans and histological evaluations to assess tissue outcomes. The study evaluated the cytotoxicity of the material used in the new model, and it was observed that the material did not exhibit any cytotoxic effects on cells. Additionally, the novel model successfully replicated the pathological features of ONFH, including femoral head collapse, along with a substantial presence of empty bone lacunae, cartilage defects, and subchondral bone fractures in the subchondral bone region. In conclusion, our study provides evidence that the new model shows the ability to simulate the progression of the disease, making it a valuable tool for research in this field and can contribute to the development of better treatment strategies for this debilitating condition. It holds great promise for advancing our understanding of the pathogenesis of ONFH and the potential therapeutic interventions for this challenging clinical problem.


Effect of combination antiviral therapy on hematological profiles in 151 adults hospitalized with severe coronavirus disease 2019.
The current diagnosis and medicines approach in coronavirus disease 2019 (COVID-19) does not reflect the heterogeneous characteristics of this disease. This study aims to find a new antiviral combination regimen by investigating the frequency of clinically relevant and objectively identified comorbidities, and the clustering of these clinical syndromes and varying results of treatment with antiviral drugs in patients hospitalized with severe COVID-19. This study recruited 151 severe COVID-19 infection cases diagnosed in our hospital examination and illustrated the clinical potential during a consecutive 25-day medication period. Potential differences in disease severity and clinical characteristics, hematological profile, and current pharmacologic treatments (single agent, double or triple combinations, and the combined antiviral drugs plus Lianhua Qingwen) among comorbidity clusters were explored. Although disease severity was comparable among three clusters, it was markedly different in terms of laboratory test status. Coagulable abnormality was mainly present in cluster 1 and cluster 2. Other indicators were normal, except for a significant increase of neutrophils presented in cluster 2. Patients showed the most complicated haematological results in cluster 3, including severe coagulation abnormalities, leukocytosis, neutrophilic granulocytosis, and lymphopenia. Our results for the first time suggest that a quadruple combination therapy (Ribavirin, Lopinavir/ritonavir, Umifenovir, and Lianhua Qingwen) can be considered as a preferred treatment approach to severe COVID-19 patients. After treatment, abnormal coagulation and leukocyte had markedly improved with a better prognosis. This study expands the understanding of the co-occurrence of combination therapy in patients with COVID-19, which provides the probability of developing novel combined therapy. Furthermore, explore clinical trials of variable antivirus treatments based on subgroup analyses or on using subgroups in the selection criteria would be the next step.


Molecular, biochemical, and clinical analyses of five patients with carbamoyl phosphate synthetase 1 deficiency.
Carbamoyl phosphate synthetase 1 deficiency (CPS1D) is a rare urea cycle disorder. The aim of this study was to present the clinical findings, management, biochemical data, molecular genetic analysis, and short-term prognosis of five children with CPS1D. The information of five CPS1D patients was retrospectively studied. We used targeted next-generation sequencing to identify carbamoyl phosphate synthetase 1 (CPS1) variants in patients suspected to have CPS1D. Candidate mutations were validated by Sanger sequencing. In silico and structure analyses were processed for the pathogenicity predictions of the identified mutations. The patients had typically clinical manifestations and biochemical data of CPS1D. Genetic analysis revealed nine mutations in the CPS1 gene, including recurrence of c.1145C > T, five of which were firstly reported. Seven mutations were missense changes, while the remaining two were predicted to create premature stop codons. In silico and structure analyses showed that these genetic lesions were predicted to affect the function or stability of the enzyme. We reported five cases of CPS1D. Five novel mutations of CPS1 gene were found. Mutations of CPS1 have private nature, and most of them are missense compound heterozygous. The mutation affecting residue predicted to interfere the catalytic sites, the internal tunnel, or the regulatory domain results in severe phenotype.


Clinical significance of fibrinopeptide A in acute lymphocytic and non-lymphocytic leukaemia.
Fibrinopeptide A (FPA) was systematically investigated in 74 patients with acute leukaemia at different stages of the disease (50 with non-lymphocytic leukaemia, ANLL; 24 with lymphocytic leukaemia, ALL). At diagnosis, 75% of the cases had high FPA levels (86% in ANLL and 54% in ALL) with significantly higher levels in ANLL than in ALL (13.4 vs 4.4 ng/ml; p less than 0.001). Patients with DIC (20 cases in ANLL and 1 case in ALL) had significantly higher levels (p less than 0.001). FPA levels were neither correlated with fibrinogen or FDP levels nor with blast cell count. During chemotherapy, median FPA did not show significant changes whereas, at the end of therapy, a return toward normality was generally observed both in ALL and ANLL apart from the group of patients with acute promyelocytic leukaemia. Among the 24 patients who entered post-remission follow-up (13 ANLL and 11 ALL), 10 cases out of the 11 relapsing (6/6 with ANLL and 4/5 with ALL) had increased FPA 1 to 2 months before the ascertainment of the relapse. However, 16% and 9% of the samples obtained on different occasions, respectively from ANLL and ALL cases in maintained first remission, showed FPA above the normal limit. This study demonstrates that subclinical activation of blood coagulation, as indicated by high FPA level, is common both in lymphocytic and non-lymphocytic leukemia and suggests that this phenomenon is related to disease activity.


Confocal Analysis of Arabidopsis Root Cell Divisions in 3D: A Focus on the Endodermis.
The development of multicellular organisms requires coordinated cell divisions for the production of diverse cell types and body plan elaboration and growth. There are two main types of cell divisions: proliferative or symmetric divisions, which produce more cells of a given type, and formative or asymmetric divisions, which produce cells of different types. Because plant cells are surrounded by cell walls, the orientation of plant cell divisions is particularly important in cell fate specification and tissue or organ morphology. The cellular organization of the Arabidopsis thaliana root makes an excellent tool to study how oriented cell division contributes to tissue patterning during organ development. To understand how division plane orientation in a specific genotype or growth condition may impact organ or tissue development, a detailed characterization of cell division orientation is required. Here we describe a confocal microscopy-based, live imaging method for Arabidopsis root tips to examine the 3D orientations of cell division planes and quantify formative, proliferative, and atypical endodermal cell divisions.


Development and evolution of the neural crest: an overview.
The neural crest is a multipotent and migratory cell type that forms transiently in the developing vertebrate embryo. These cells emerge from the central nervous system, migrate extensively and give rise to diverse cell lineages including melanocytes, craniofacial cartilage and bone, peripheral and enteric neurons and glia, and smooth muscle. A vertebrate innovation, the gene regulatory network underlying neural crest formation appears to be highly conserved, even to the base of vertebrates. Here, we present an overview of important concepts in the neural crest field dating from its discovery 150 years ago to open questions that will motivate future research.


Cerebrovascular lesions in patients with frontotemporal lobar degeneration: a neuropathological study.
Cerebrovascular lesions are frequently observed in Alzheimer brains. Not all of them are due to cerebral amyloid angiopathy. Some of them are related to the severity of the degenerative process itself, implying additional vascular factors in the pathogenesis of Alzheimer's dementia. The aim of the study was to investigate the impact of cerebrovascular pathology on brains with frontotemporal lobar degeneration (FTLD). Twenty-two brains with autopsy-proven FTLD were compared to 15 brains of age-matched patients without evident cognitive decline, who died from an illness not related to a brain disease. The prevalence and the severity of small ischaemic and haemorrhagic lesions were determined. Vascular risk factors and the use of antithrombotic agents were also recorded. The patients with FTLD were heterogeneous concerning age of onset, disease duration, clinical presentation, genetic background and neuropathological typing. Cerebrovascular risk factors and lesions were overall rare in FTLD brains without differences in their prevalence and severity compared to the controls. Only white matter changes were more prevalent in the FTLD group (p = 0.04) and showed a trend to greater severity (p = 0.08). Cerebrovascular pathology is not contributing to the evolution of the disease process of patients with FTLD. The isolated prevalence of white matter changes should not be considered as a vascular indicator.


Health-promoting lifestyle and its predictors among health-related and non-health-related university students in Taiwan: a cross-sectional quantitative study.
University students majoring in different disciplines are believed to have different personality traits, courses exposure, and future roles, which may further affect their health behaviors and health status. The purpose of this study was to investigate the differences in health-promoting lifestyle (HPL) and its predictors among health-related and non-health-related students. The research participants were university students in the main island of Taiwan, and a two-stage sampling approach was adopted to obtain the samples from November 2020 to March 2021. First, 37 universities were randomly selected based on the ratio of public and private universities in each region of Taiwan. Then, based on the ratio of health-related and non-health-related majors of selected university, 25-30 students were randomly drawn from each university according to the student ID number to complete self-administered questionnaires, which included items for personal factors, perceived health status (PHS), health conception (HC), and health-promoting lifestyle profile (HPLP). A total of 1062 valid questionnaires were recovered, including 458 from health-related students and 604 from non-health-related students. Chi-squared test, independent samples t-test, one-way ANOVA, Pearson product-moment correlation analysis, and multiple regression analysis were performed. The results showed that gender (p < 0.001), residential status (p = 0.023), body mass index (p = 0.016), and daily sleep duration (p = 0.034) of the students majoring in different disciplines were different. Health-related students having better HC (p = 0.002) and HPLP (p = 0.040) than non-health-related students. In addition, for both majors, females, low PHS scores, and low scores for functional/role, clinical, and eudaimonistic dimensions of HC were important indicators of a relatively negative HPLP, while health-related students who exercised 75 min or less per week and non-health-related students with a monthly disposable income of 15,000 TWD or less or who dined out 15 times or more per week also required attention in the promotion of HPL (health-related majors: adjusted R2 = 0.481, p < 0.001; non-health-related majors: adjusted R2 = 0.443, p < 0.001). Students majoring in each discipline who had poor HPLP which is mentioned above should be prioritized in the provision of appropriate exercise or nutritional support programs on campus to promote their awareness and ability to pay attention to their health.


Childhood reflux and urinary infection: a follow-up of 10-41 years in 226 adults.
To ascertain the outcome of childhood vesicoureteric reflux (VUR), 226 adults (37 males), mean age 27 years, were studied after 10-35 years, extended to 41 years by postal questionnaire in 161. At presentation (mean age 5 years) all had VUR (grade III-V in 68) and urinary tract infection (UTI); there was renal scarring in 85 (acquired before referral in 11 and during follow-up in 1), hypertension in 6 and impaired renal function in 5. They were managed and followed prospectively by one paediatrician; 63% of these children remained free from UTI; VUR persisted in 63 and had resolved in 69% of 193 children managed medically. At follow-up, 61% of adults had remained free from infection; 17 adults had hypertension and/or raised plasma creatinine, 16 with scarred kidneys. Their deterioration was predictable because of scar type, blood pressure or plasma creatinine levels in childhood. No new scars developed after puberty. Renal growth rates were unaffected by initial severity or persistence of VUR. On the later questionnaire, 9 further adults, mean age 38 years, had moderate hypertension. The adults with complications were those with extensive renal scarring and/or at least borderline hypertension in childhood. Those with VUR, but no scarring, and managed carefully in childhood, did not suffer serious consequences as adults. There is a need for early recognition and treatment of children with VUR and UTI to limit scar development.


Immunotherapy plus chemotherapy showed superior clinical benefit to chemotherapy alone in advanced NSCLC patients after progression on osimertinib.
Osimertinib is the standard first-line treatment for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation. Resistance to osimertinib remains a clinical challenge. However, the optimal therapy for these patients is still controversial. In this study, we aimed to assess the efficacy and safety of immunotherapy plus chemotherapy (IO+C) compared with chemotherapy (C) in NSCLC patients after progression on osimertinib. Advanced NSCLC patients after progression on osimertinib were retrospectively reviewed. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety were evaluated between the patients treated with IO+C and C. A total of 40 patients were included in the study. There were 20 patients each in the IO+C group or C group. The ORR was significantly higher in patients in the IO+C group (45% vs. 25%, p < 0.01). The median PFS was 6.4 months for patients in the IO+C group compared to 2.8 months for patients in C group (HR: 0.41, 95% confidence interval [CI]: 0.20-0.82, p < 0.01). The median OS was significantly longer in the IO+C group than the C group (OS: 12.8 vs. 10.5 months, HR: 0.39, 95% CI: 0.19-0.80, p < 0.01). In subgroup analysis, patients of both sexes, age ≤ 65, bone or adrenal metastasis, exon19 del mutation, and third-line treatment obtained more OS benefits from immunotherapy. The safety profile of both groups was comparable. Our study provides the clinical evidence of favoring immunotherapy plus chemotherapy in NSCLC patients after progression on osimertinib.


Histological changes in the ovaries of Dysdercus cingulatus (F.) caused by the "paper factor".
The histological changes in the ovarioles of the red cotton bug following treatment with "Paper Factor" to the adults are discussed. The changes in the shape of egg, resorption of the yolk and the formation of compound chambers with double nuclei were probably caused through deformation either in the germarium or follicular epithelial cells.


Ocular manifestations of 22q11.2 microduplication.
To report a new ocular manifestation of the dup22q11 syndrome and explore involved genes that may offer insight to mechanisms of pathogenesis. Case series. Two male patients with this syndrome diagnosed with dup22q11.2. Medical records were reviewed. Duplication was detected in the oligo-single nucleotide polymorphism chromosomal microarray and duplicated genes within the segment where determined by literature and database review. Potential associations between the ophthalmologic manifestations and their physiopathology were investigated. Microarray results and identification of candidate genes within the duplicated segment. Our patients demonstrate previously unreported findings of dup22q11.2, including Marcus Gunn jaw winking, Duane's retraction syndrome, and other abnormal eye movements consistent with a congenital cranial dysinnervation disorder (CCDD), retinal vascular tortuosity, and primary infantile glaucoma. The duplicated segment in case 1 includes SNAP29, which could be linked with the development of retinal vascular tortuosity, and MAPK1, which seems to play a role in axonal development through the semaphorin pathway, which may serve as a candidate gene for CCDD. In case 2, the CLDN5 gene is within the duplicated segment. CLDN5 could be involved in the pathophysiology of glaucoma. Our cases expand the ocular phenotype for duplication of 22q11 and serve to identify potential candidate genes for the development of CCDD, retinal vascular tortuosity, and glaucoma.


Affinity labeling of the catalytic and AMP allosteric sites of 3-hydroxy-3-methylglutaryl-coenzyme A reductase kinase by 5'-p-fluorosulfonylbenzoyladenosine.
The nucleotide analogue 5'-p-fluorosulfonylbenzoyladenosine (FSBA) reacts irreversibly with rat liver cytosolic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase kinase, causing a rapid loss of the AMP activation capacity and a slower inactivation of the catalytic activity. The rate constant for loss of AMP activation is about 10 times higher (kappa 1 = 0.112 min-1) than the rate constant of inactivation (kappa 2 = 0.0106 min-1). There is a good correspondence between the time-dependent inactivation of reductase kinase and the time-dependent incorporation of 5'-p-sulfonylbenzoyl[14C]adenosine ([14C]SBA). An average of 1.65 mol of reagent/mol of enzyme subunit is bound when reductase kinase is completely inactivated. The time-dependent incorporation is consistent with the postulate that covalent reaction of 1 mol of SBA/mol of subunit causes complete loss of AMP activation, whereas reaction of another mole of SBA/mol of subunit would lead to total inactivation. Protection against inactivation by the reagent is provided by the addition of Mg2+, AMP, Mg-ATP, or Mg-AMP to the incubation mixtures. In contrast, addition of ATP, 2'-AMP, or 3'-AMP has no effect on the rate constants. Mg-ATP protects preferentially the catalytic site against inactivation, whereas Mg-AMP at low concentration protects preferentially the allosteric site. Mg-ADP affords less protection than Mg-AMP to the allosteric site when both nucleotides are present at a concentration of 50 microM with 7.5 mM Mg2+. Experiments done with [14C]FSBA in the presence of some protectants have shown that a close correlation exists between the pattern of protection observed and the binding of [14C]SBA. The postulate is that there exists a catalytic site and an allosteric site in the reductase kinase subunit and that Mg-AMP is the main allosteric activator of the enzyme.


Interobserver variability in the diagnosis of ulcerative colitis-associated dysplasia by telepathology.
Telepathology (TP) is the practice of remote diagnostic consultation of electronically transmitted, static, digitalized images. The diagnostic efficacy of TP-based consultation services has not been widely tested. Dysplasia that arises in association with chronic ulcerative colitis (CUC) is, at present, the most important marker of an increased risk of malignancy in patients with this disease. Unfortunately, dysplasia is difficult to diagnose histologically and, as a result, suffers from a significant degree of intra- and interobserver variability. Furthermore, it is often necessary to obtain expert consultation of potential CUC-associated dysplasia cases before treatment. Therefore, the aim of this study was to evaluate the utility and interobserver variability of diagnosing dysplasia in CUC with the use of TP. Static, electronically transmitted, digitalized images of 38 CUC cases with areas considered negative, indefinite, or positive for dysplasia (low or high grade) were evaluated independently by four gastrointestinal pathologists. All cases were then graded by each of the pathologists by light-microscopic examination of the hematoxylin and eosin-stained glass slides. The degree of interobserver variability was determined by kappa statistics. Overall, there was a fair degree of agreement (kappa = 0.4) among the four reviewing pathologists after analysis of the digitalized images. The poorest level of agreement was in the indefinite and low-grade dysplasia categories. Grouping together several diagnostic categories (for instance, indefinite and low-grade dysplasia, or low-grade dysplasia and high-grade dysplasia) had no effect on the overall level of agreement. The degree of variability in interpretation of glass slides was slightly better (kappa = 0.43) but still remained fair. After reviewing all cases by glass slide analysis, the diagnosis was changed in 38% of the slides; in the majority of these, the grade of dysplasia was increased. Use of TP for consultation in CUC-associated dysplasia has a moderate level of interobserver agreement. Because of a variety of technical reasons, diagnoses rendered by evaluation of digitalized images tended to be of a lower grade than that observed after a review of the glass slides.


Rotational behavior produced by unilateral ventral noradrenergic bundle lesions: evidence for a noradrenergic-dopaminergic interaction in the brain.
In this study the effect of unilateral electrocoagulation of the ventral noradrenergic bundle (VB) on rotational behavior produced by dopaminergic agonists was investigated. Unilateral lesions to the VB produced a decrease in the concentration of noradrenaline but not dopamine, serotonin or 5-hydroxyindoleacetic acid (5-HIAA) in the ipsilateral part of the forebrain. These lesions produced also strong and dose-dependent preference for ipsilateral rotation after systemic injection of apomorphine or amphetamine. The results are discussed in terms of possible interaction between noradrenergic and dopaminergic systems and it is proposed that the VB plays a regulatory role in the function of brain nigro-striatal dopaminergic system.


The care of older people.
This ongoing study examines the use of a biographical approach to enhance patient-centred care of older people.


Anti-HIV Factors: Targeting Each Step of HIV's Replication Cycle.
Similar to other animal viruses, HIV-1 relies on the contributions of the cellular machinery to ensure efficient virus propagation. However, human cells have evolved refined mechanisms to block key steps of the virus life-cycle, thereby suppressing viral replication. These cellular proteins are generally known as restriction factors, and they provide an early antiviral defense. So far, five potent restriction factors have been shown to effectively block HIV and/or SIV replication. These are TRIM5 proteins, SAMHD-1, members of the APOBEC3 (A3) family, Mx2 and Tetherin/BST-2. Here, we review the antiviral mechanisms of these and other antiviral factors, their interaction with the innate immune responses, and how their functions might be exploited to clear and prevent HIV infection. Since the majority of vaccine approaches against HIV have failed so far, it is imperative to start looking at alternative strategies for vaccine and therapy development. By better understanding how HIV hijacks the cellular machinery for its own benefit in completing its life-cycle, and how the virus adapts to circumvent our intrinsic immunity, we will be better equipped to design compounds that specifically interrupt virus replication and spread.


Five-year outcomes of probable rheumatoid arthritis treated with methotrexate or placebo during the first year (the PROMPT study).
To assess long-term disease outcome of undifferentiated arthritis (UA) after initial treatment with methotrexate (MTX) or placebo. 110 patients with UA were randomised to receive MTX (n=55) or placebo (n=55) for 1 year. After 5 years the outcomes for diagnosis (rheumatoid arthritis, 1987 criteria (RA (1987)), UA or UA in remission) and radiographic progression were compared between treatment arms and anti-citrullinated protein antibody (ACPA)-positive and -negative patients. Outcomes were recalculated for patients who, with hindsight, might have been classified at baseline as having RA according to the 2010 criteria (RA (2010)). 25 patients in the MTX group and 29 in the placebo group progressed to RA (1987) (p=0.45). MTX delayed progression from UA to RA (1987) but only in ACPA-positive patients. Drug-free remission was achieved in 35 patients, 20 of whom were initially treated with MTX, and 32 were ACPA-negative. ACPA-positive patients had more radiographic progression, regardless of treatment. Forty-three patients (39%) could be reclassified as having had RA (2010) at baseline, 6/24 (25%) of whom achieved remission after placebo treatment. After 5 years there is no lasting benefit of a 1 year initial course of MTX for patients with undifferentiated arthritis, compared with initial placebo. Progression to classifiable RA was not suppressed, drug-free remission not induced and the progression of radiological damage was similar in both groups. Reclassification at baseline with the 2010 criteria showed that 25% of patients with RA (2010) achieved spontaneous drug-free remission.


Rapid Initiation of Antiretroviral Therapy Following Diagnosis of Human Immunodeficiency Virus Among Patients with Commercial Insurance Coverage.
New guidelines for the treatment of human immunodeficiency virus (HIV) advocate for rapid initiation of antiretroviral therapy (ART) ≤ 7 days after HIV diagnosis with agents that have a high genetic barrier to resistance, good tolerability, and convenient dosing. To describe characteristics, time to ART initiation, and health care costs in commercially insured patients living with HIV in the United States who are treated ≤ 60 days after HIV diagnosis. IBM MarketScan Research Databases (January 1, 2012-December 31, 2017) were used to identify ART-naive adults with HIV-1, ≥ 6 months of continuous eligibility before first HIV diagnosis, and ART initiation ≤ 60 days of first diagnosis. ART regimen had to include a protease inhibitor (PI), an integrase strand transfer inhibitor (INSTI), or a non-nucleoside reverse transcriptase inhibitor (NNRTI) with ≥ 2 nucleoside reverse transcriptase inhibitors. Cohorts were formed based on time to ART initiation after diagnosis: ≤ 7 days or 8-60 days. Health care costs were evaluated at 6, 12, 24, and 36 months after diagnosis among patients with ≥ 36 months of continuous eligibility. Among 9,351 patients, median time to treatment was 31.0 days. Patients initiating ART > 60 days after HIV diagnosis were excluded (N = 2,608 [27.9%]), while 6,743 (72.1%) initiated ART ≤ 60 days after diagnosis and were analyzed; 18.3% and 81.7% were classified in the ≤ 7 days and 8-60 days cohorts, respectively. For all analyzed patients, mean age was 38.0 (SD = 12.0) years and 13.2% were female; 12.7%, 56.2%, and 31.1% initiated a PI, INSTI, or NNRTI-based regimen, respectively. Elvitegravir (32.9%), efavirenz (20.9%), dolutegravir (18.5%), and darunavir (8.5%) were the most commonly used antiretrovirals; most patients (74.3%) were initiated on single-tablet regimens. PI-based regimens were more common in the ≤ 7 days cohort (PI = 18.1%; darunavir = 11.4%) than in the 8-60 days cohort (PI = 11.5%; darunavir = 7.8%). INSTI-based regimens were more common in the 8-60 days cohort (INSTI = 57.7%; elvitegravir = 33.8%) than in the ≤ 7 days cohort (INSTI = 49.2%; elvitegravir = 29.1%). NNRTI-based regimens were as common in the ≤ 7 days (32.7%) and 8-60 days (30.7%) cohorts. Mean total accumulated costs were lower among patients in the ≤ 7 days cohort than in the 8-60 days cohort at all time points analyzed after diagnosis (e.g., 36 months: ≤ 7 days = $109,456; 8-60 days = $116,870). Total per-patient per-month costs decreased over time in the ≤ 7 days (i.e., 6 months = $4,359; 36 months = $3,040) and 8-60 days cohort (6 months = $4,727; 36 months = $3,246). Although 72.1% of patients initiated ART ≤ 60 days after HIV diagnosis, only 18.3% initiated ART ≤ 7 days. Many patients initiating ART ≤ 7 days used suboptimal agents with low rather than high genetic barriers to resistance (i.e., efavirenz and elvitegravir) or agents (dolutegravir) coformulated with other antiretrovirals that require testing to prevent hypersensitivity reactions. Patients in the ≤ 7 days cohort showed lower total health care costs relative to those in the 8-60 days cohort, highlighting the potential long-term benefits of rapid ART initiation. This study was supported by Janssen Scientific Affairs, which was involved in the study design, interpretation of results, manuscript preparation, and publication decisions. Emond, Lefebvre, Lafeuille, and Côté-Sergent are employees of Analysis Group, a consulting company that was contracted by Janssen Scientific Affairs to conduct this study and develop the manuscript. Benson, Tandon, Chow, and Dunn are employees of Janssen Scientific Affairs and stockholders of Johnson & Johnson. Part of the material in this study has been presented at the AMCP 2019 Annual Meeting; March 25-28, 2019; San Diego, CA.


[Pathological fractures of long medullary bones due to malignant tumours: indications for osteosynthesis (author's transl)].
51 cases of pathological fracture, mostly due to metastatic malignant tumours, are reviewed in respect to the methods and results of operative treatment. These results are compared with those of other authors. It is found that resection of the tumour and osteosynthesis combined with the use of bone cement is the best way of treatment to relieve the patients of pain, mobilize them as soon as possible and improve the quality of their short, remaining lifespan. Despite the positive approach towards operative treatment there are some limiting findings which indicate that an operation should not be undertaken in those patients whose estimated survival time is less than the time of recovery and mobilization.


Concentration of lidocaine hydrochloride in newborn gastric fluid after elective caesarean section and vaginal delivery with epidural analgesia.
Lidocaine concentrations were measured after vaginal delivery or Caesarean section with epidural anaesthesia in samples of maternal and umbilical blood and in newborn gastric contents. The pH of the gastric aspirate was also determined in a number of neonates. Gastric lidocaine concentrations were higher and the pH was lower after vaginal delivery in comparison to Caesarean section. A significant inverse correlation exists between gastric pH and gastric lidocaine concentration, Neonate gastric lidocaine concentration was significantly higher than in maternal or umbilical venous plasma after vaginal delivery, but not after Caesarean section. Due to these differences, gastric lavage for the treatment of neonatal lidocaine intoxication may be more beneficial in reducing foetal systemic local anaesthetic concentration after vaginal than after elective abdominal delivery.


Profiling of different bioactive compounds in functional drinks by high-performance liquid chromatography.
In the present work, an HPLC method is proposed to simultaneously detect and quantify water- and fat-soluble vitamins, phenolic compounds, carotenoids and chlorophylls in a single run, by using an ultradeactivated C18 column and gradient separation using trifluoroacetic acid, water and methanol. It is shown that the HPLC method provides baseline separation of all these compounds with good resolution values in 40 min. Moreover, other figures of merit of the method show a good linear response and low detection limits for all the compounds considered in the present study. Furthermore, the usefulness of this method is demonstrated via its successful application to the analysis of different beverages from different natural origin (orange, strawberry, apple, peach pineapple, plum and blackcurrant juices, soybean milk, beers) without the need of any previous sample preparation. A good correlation is also found by comparing the total phenol content (measured by Folin-Ciocalteu method) with the sum of total phenolic compounds obtained using the proposed HPLC method. By using statistical tools, the main compounds associated with antioxidant activity of the extracts (measured by 1,1-diphenyl-2-picrylhydrazyl radical scavenging) were assessed.


A reduced concentration of brain interstitial amino acids is associated with depression in subarachnoid hemorrhage patients.
The amino-acids tryptophan, phenylalanine and tyrosine seem to play an important role in the pathophysiology of depressive disorders. We measured daily brain extracellular levels of these amino-acids using cerebral microdialysis (CMD) and high performance liquid chromatography in 26 consecutive subarachnoid hemorrhage (SAH) patients and associated them with the presence of depressive disorders. Patients were grouped as follows: medical history of depression (prior to SAH), antidepressant intake 12 months after SAH (but not before), or neither. CMD-tryptophan, CMD-phenylalanine and CMD-tyrosine levels were significantly lower in patients with preexisting depressive disorders compared to those without depression (p < 0.01). Disease severity and SAH-related complications were not associated with amino-acid concentrations. We found a positive correlation between nutritionally administered and brain interstitial levels of tryptophan and phenylalanine in non-depressed patients (R = 0.26 and R = 0.24, p < 0.05), which was not present in patients with preexisting depression (p > 0.1). In conclusion, brain interstitial levels of tryptophan, phenylalanine and tyrosine measured in the context of the clinical management of SAH were significantly decreased in patients with a medical history of depression. This study supports the hypothesis that the availability of these neurotransmitter precursor amino-acids in the human brain may play an important role in the pathophysiology of depressive disorders.


YAP and Wnt3a independently promote AECIIs proliferation and differentiation by increasing nuclear β‑catenin expression in experimental bronchopulmonary dysplasia.
Arrested alveolar development is the main pathological characteristic of neonatal bronchopulmonary dysplasia (BPD); however, a number of studies aiming to improve alveolarization have focused on alveolar epithelial cell damage and impairment. Previously, the authors reported that the Wnt signaling plays a key role in alveolar injury and repair by regulating alveolar epithelial type II cell (AECII) proliferation and differentiation. In the present study, the authors wished to investigate whether Yes‑associated protein (YAP), a transcriptional coactivator in the Hippo signaling pathway, affects AECII proliferation and differentiation via the Wnt/β‑catenin pathway in BPD. It was found that YAP regulated AECII proliferation and differentiation. A decreased expression of YAP, Wnt3a and nuclear β‑catenin was observed in lung tissues affected by BPD. In vitro, YAP and Wnt3a overexpression in BPD promoted AECII proliferation and differentiation into AECIs by increasing the nuclear transfer of β‑catenin and vice versa. The effects of a decreased Wnt3a expression in primary AECIIs in BPD were compensated by YAP overexpression, as were the effects of Wnt3a knockdown in primary AECIIs. On the whole, the findings of the present study demonstrate that YAP and Wnt3a independently promote AECII proliferation and differentiation in experimental BPD by increasing the nuclear β‑catenin levels. Therefore, Wnt3a or YAP may be candidate regulatory targets for improving the outcomes of BPD.


The impact of avocado intake on anthropometric measures among Hispanic/Latino children and adolescents: A cluster randomized controlled trial.
While the association between avocado consumption and low metabolic risk has been shown in some studies conducted in adults, little is known about the potential effects of avocado consumption on health outcomes in children and adolescents. Thus, we investigated the impact of two levels of avocado allotment, plus a standard nutrition education, on measures of adiposity in children and adolescents (<18 years old). Children (aged 5-12, n = 58) and adolescents (aged 13-17, n = 32) in seventy-two families that self-identified as Hispanic, with at least 3 members over the age of 5 that resided in the same home, were free of severe chronic disease, and not on specific diets, were randomized to one of two levels of avocado allotment plus bi-weekly nutrition education sessions. Low allotment families received 3 avocados per week, while high allotment families received 14 avocados per week for 6 months. We performed an intention-to-treat analysis, using unpaired, 2-sided t-tests to test the mean changes in anthropometric measures of adiposity (body mass index (BMI), waist circumference, hip circumference, and weight) between children and adolescents from high and low allotment families after the 6-month intervention. At six months, there were no significant differences in body mass index, waist circumference, hip circumference, or waist circumference to weight ratio by avocado allotment group. In children, there was a significant difference in weight (difference in means: 1.10, 95% CI: 0.09, 2.10, p-value = 0.03) and waist circumference to height ratio (difference in means: 0.27, 95% CI: 0.12, 0.41, p-value <0.01) between the avocado allotment groups at six months, but these did not remain significant after sensitivity analyses including per-protocol analyses. In adolescents only, there was a significant reduction in waist to hip circumference ratio in the high allotment group compared to the low allotment group after 6 months (difference in means: -0.05, 95% CI: -0.08, 0.00, p-value = 0.04) that persisted after multiple sensitivity analyses. Different levels of avocado availability among children and adolescents does not appear to result in significant changes in anthropometric measures. Further study is needed to determine whether avocado consumption promotes metabolic health in this age group.


Humans as inverted bats: A comparative approach to the obstetric conundrum.
The narrow human birth canal evolved in response to multiple opposing selective forces on the pelvis. These factors cannot be sufficiently disentangled in humans because of the limited range of relevant variation. Here, we outline a comparative strategy to study the evolution of human childbirth and to test existing hypotheses in primates and other mammals. We combined a literature review with comparative analyses of neonatal and female body and brain mass, using three existing datasets. We also present images of bony pelves of a diverse sample of taxa. Bats, certain non-human primates, seals, and most ungulates, including whales, have much larger relative neonatal masses than humans, and they all differ in their anatomical adaptations for childbirth. Bats, as a group, are particularly interesting in this context as they give birth to the relatively largest neonates, and their pelvis is highly dimorphic: Whereas males have a fused symphysis, a ligament bridges a large pubic gap in females. The resulting strong demands on the widened and vulnerable pelvic floor likely are relaxed by roosting head-down. Parturition has constituted a strong selective force in many non-human placentals. We illustrated how the demands on pelvic morphology resulting from locomotion, pelvic floor stability, childbirth, and perhaps also erectile function in males have been traded off differently in mammals, depending on their locomotion and environment. Exploiting the power of a comparative approach, we present new hypotheses and research directions for resolving the obstetric conundrum in humans.


State of emergency contraception in the U.S., 2018.
Emergency contraception is indicated in instances of unprotected sexual intercourse, including reproductive coercion, sexual assault, and contraceptive failure. It plays a role in averting unintended pregnancies due to inconsistent use or non-use of contraception. Options for emergency contraception vary by efficacy as well as accessibility within the U.S. This paper provides an overview of levonorgestrel (Plan B One-Step and generic counterparts), ulipristal acetate (sold as ella), and the copper intrauterine device (IUD, sold as ParaGard), including the mechanisms of action, administration, efficacy, drug interactions, safety, side effects, advantages, and drawbacks. It will also review current misconceptions about emergency contraception and access for subpopulations, including adolescents, immigrants, survivors of sexual assault, rural populations, and military/veteran women. This paper will address barriers such as gaps in knowledge, and financial, health systems, and practice barriers. Continuing areas of research, including the impact of body weight on the efficacy of emergency contraceptive pills and potential interactions between ulipristal acetate and ongoing hormonal contraceptives, are also addressed.


Influence of placement sites of the active recording electrode on CMAP configuration in the trapezius muscle.
We investigated how the active electrode placement site influences compound muscle action potential (CMAP) configuration of the upper trapezius muscle (TM). A nerve conduction study of the accessory nerve was performed, and the CMAPs obtained with two different placement sites, i.e., placement of the active recording electrode on the belly of the upper TM (CMAP-A) and placement of the electrode 2 cm behind the belly (CMAP-B), were compared. CMAPs were also obtained with the active recording electrode placed in the supraspinous fossa (CMAP-C). All CMAPs were recorded from 21 healthy volunteers. The mean peak-to-peak amplitude of CMAP-B was 3.4 mV higher than that of CMAP-A (11.0 ± 4.0 mV vs. 14.4 ± 4.9 mV; P < 0.01). The mean peak-to-peak amplitude of CMAP-C was 10.3 ± 5.0 mV. CMAP of the upper TM was always higher when the active recording electrode was placed 2 cm behind the belly of the muscle. When stimulating the accessory nerve, a current spread occurs to the C5 spinal nerve root and another CMAP originating from the supraspinatus muscle occurs in the supraspinous fossa. The volume conduction from the supraspinatus muscle affects the active recording electrode on the TM, resulting in an increase in CMAP amplitude.


Human Stromal Cell Aggregates Concentrate Adipose Tissue Constitutive Cell Population by In Vitro DNA Quantification Analysis.
Regenerative cell strategies rely on stromal cell implants to attain an observable clinical outcome. However, the effective cell dose to ensure a therapeutic response remains unknown. To achieve a higher cell dose, the authors hypothesized that reducing the volume occupied by mature adipocytes in lipoaspirate will concentrate the stromal vascular fraction present in the original tissue. Human standardized lipoaspirate (n = 6) was centrifuged (1200 g for 3 minutes) and the water phase was discarded. Mechanical disaggregation was achieved by shearing tissue through 2.4- and 1.2-mm Luer-to-Luer transfers. After a second centrifugation (800 g for 10 minutes), stromal cell aggregates were separated from the supernatant oil phase. Lipoaspirate percentage composition was determined by its constituent weights. Cell content was measured by total DNA quantification, and partial cell viability was determined by image cytometry. Tissue sections were evaluated histologically (hematoxylin and eosin and Masson trichrome stains). Stromal cell aggregates reduced the standardized lipoaspirate mass to 28.6 ± 4.2 percent. Accordingly, the cell density increased by 222.6 ± 63.3 percent (from 9.9 ± 1.4 million cells/g to 31.3 ± 6.6 million cells/g; p < 0.05). Cell viability was unaffected in stromal cell aggregates (71.3 ± 2.5 percent) compared to standardized lipoaspirate (72.2 ± 2.3 percent), and histologic analysis revealed high-density areas enriched with stromal cells (622.9 ± 145.6 percent) and extracellular matrix (871.2 ± 80.3 percent). Stromal cell aggregates represent a biological agent that triplicates the cell density versus unprocessed lipoaspirate, low on oil and water fluids, and enriched extracellular matrix components.


Refractory enuresis related to alarm therapy.
To clarify refractory enuresis related to alarm therapy, we evaluated the possibility of the prediction of refractory cases, the effectiveness of alarm therapy for cases refractory to pharmacotherapy and the prognosis of non-responders to alarm therapy. First, the effectiveness of alarm therapy in 55 monosymptomatic patients and 29 with daytime symptoms was evaluated. Next, another 37 patients with monosymptomatic nocturnal enuresis were treated by enuresis alarm. Possible predictive factors of therapeutic effect were compared between the 'effective' patients and the 'no-change' patients. The effectiveness of alarm monotherapy for non-responders to pharmacotherapy was evaluated. The prognosis of non-responders to alarm therapy at 6 months was also studied. In the 55 monosymptomatic patients, the total effective rate at 3 months was 59%, while that in the 29 patients with daytime symptoms was only 38%. In the 37 patients with monosymptomatic nocturnal enuresis, there were no significant differences between the effective patients and the no-change patients in possible predictive factors. Even in patients who had previously had pharmacotherapy, the effective rate of alarm therapy was 64%, while it was 57% in patients without previous therapy. The effective rates of DDAVP and imipramine for non-responders to alarm monotherapy were only 25% and 33%, respectively. Daytime symptoms were the only predictive factor of alarm therapy. Alarm therapy was effective for cases refractory to pharmacotherapy. Non-responders to alarm therapy were also refractory to pharmacotherapy.


Long-term survival after single aortic or mitral valve replacement with the present model of Smeloff-Cutter valves.
Two hundred fourteen survivors of single aortic (AVR) or mitral valve replacement (MVR) were evaluated. The present model of the Smeloff-Cutter prosthesis was used in these patients, and the series was started in September, 1966, following the last structural change in the valve. Clinical follow-up ended in September, 1976. Bleeding, thromboembolism, and peristent left ventricular dysfunction were the major complications. Thromboembolism occurred at a rate of 0.13 percent per month of patient follow-up. Late deaths occurred in 19.2 percent of patients, half of these within the first year. Acturarial data indicated a 5 year survival rate of approximately 75 percent after both mitral and aortic replacements. Bleeding and thromboembolism were more frequent causes of death after mitral replacement. Myocardial function was of greatest importance in long-term survival after replacement of either valve. Variations in warfarin dosage significantly affected both bleeding and thromboembolic complications.


Control of oral malodour by dentifrices measured by gas chromatography.
To evaluate the effect of toothpaste treatments on levels of oral volatile sulphur compounds (VSCs) measured by gas chromatography in two clinical studies. These were blinded, randomised, controlled, crossover studies with 16 (study A) or 20 (study B) healthy volunteers between the ages of 19-54. Study A: breath samples were collected at baseline, immediately and lhr after brushing. Four dentifrices (Zinc A, Zinc B, commercially available triclosan dentifrice and zinc free control) were evaluated. Study B: breath samples were collected at baseline, immediately, 1, 2, 3 and 7 hours after treatment. Subjects consumed a light breakfast then provided an additional breath sample between baseline assessment and treatment. Two dentifrices (gel-to-foam and a commercially available triclosan dentrifrice) were evaluated. Breath samples were collected in syringes and analysed for VSCs (hydrogen sulphide, methyl mercaptan and Total VSCs) utilising gas chromatography (GC) with flame photometric detection. Study A: immediately after treatment, a statistically significant reduction in VSCs from baseline was observed for Zinc A product only. A statistically significant reduction in VSCs from baseline was observed after 1 hour for all products. Both zinc products exhibited a significantly greater reduction from baseline VSCs than Colgate Total and Control at all time points. Study B: a statistically significant reduction in VSCs from baseline was observed at all time points for both products. The gel-to-foam product exhibited significantly greater reduction from baseline Total VSC concentration than Colgate Total at all time points from 1 hour post-treatment. Control of oral malodour by toothpaste treatment, evaluated as VSC levels using GC, has been demonstrated. Zinc is effective at reducing VSCs and the efficacy of zinc is formulation dependent. A gel-to-foam dentifrice was more effective at reducing VSCs than Colgate Total up to 7 hours.


The endosomal pH regulator NHE9 is a driver of stemness in glioblastoma.
A small population of self-renewing stem cells initiate tumors and maintain therapeutic resistance in glioblastoma (GBM). Given the limited treatment options and dismal prognosis for this disease, there is urgent need to identify drivers of stem cells that could be druggable targets. Previous work showed that the endosomal pH regulator NHE9 is upregulated in GBM and correlates with worse survival prognosis. Here, we probed for aberrant signaling pathways in patient-derived GBM cells and found that NHE9 increases cell surface expression and phosphorylation of multiple receptor tyrosine kinases (RTKs) by promoting their escape from lysosomal degradation. Downstream of NHE9-mediated receptor activation, oncogenic signaling pathways converged on the JAK2-STAT3 transduction axis to induce pluripotency genes Oct4 and Nanog and suppress markers of glial differentiation. We used both genetic and chemical approaches to query the role of endosomal pH in GBM phenotypes. Loss-of-function mutations in NHE9 that failed to alkalinize endosomal lumen did not increase self-renewal capacity of gliomaspheres in vitro. However, monensin, a chemical mimetic of Na+/H+ exchanger activity, and the H+ pump inhibitor bafilomycin bypassed NHE9 to directly alkalinize the endosomal lumen resulting in stabilization of RTKs and induction of Oct4 and Nanog. Using orthotopic models of primary GBM cells we found that NHE9 increased tumor initiation in vivo. We propose that NHE9 initiates inside-out signaling from the endosomal lumen, distinct from the established effects of cytosolic and extracellular pH on tumorigenesis. Endosomal pH may be an attractive therapeutic target that diminishes stemness in GBM, agnostic of specific receptor subtype.


Architecture of the basal region of the subcommissural organ in the brush-tailed possum (Trichosurus vulpecula).
The architecture of the basal region of the subcommissural organ (SCO) and the subjacent neuropil was studied in the brush-tailed possum, Trichosurus vulpecula (Marsupialia). Several structural features suggest that the basal mode of SCO-secretion may be as prominent as the well-established apical secretion. Some of the features that speak in favour of basal secretion are: (1) the existence of deep processes of secretion-laden SCO cells which reach and surround the capillaries in the hypendyma and the subjacent neuropil; (2) the presence of perivascular spaces, some of which may contain a material that resembles the secretory product of the SCO; (3) positive staining by means of paraldehyde-fuchsin of secretory material in the pericapillary zone of vessels in the hypendyma and its corresponding neuropil; (4) presence of labyrinths of the basal lamina of capillaries and associated nerves. The presence of nerve and other cell processes adjacent to the perivascular space, labyrinths and capillary wall suggests discharge into the capillaries of material such as the basal secretory product of the SCO. However, the absence of fenestrae in capillary endothelium in the context of the foregoing observations is enigmatic and speaks against the possibility of a conventional release of secretion. Nevertheless, it is possible that a secretory product containing particles of low molecular weight combined with some specific features of the local capillary endothelium, which facilitate transport, may be critical factors making possible transfer of such product(s) from the SCO to the capillaries.


Don't save the ball!
To identify, over a period of 12 months, all attendances at an accident and emergency department by children over the age of 5 years with an injury to a wrist, hand, or finger, and to examine those sustained as a result of a blow from a ball. The case notes of all children aged 6-13 years attending the Accident and Emergency Department of the Royal Aberdeen Children's Hospital in the year 2001 as a result of a wrist, hand, or finger injury sustained from a blow by a ball were reviewed, and the cause, type, and severity of the injury noted. A total of 187 children were identified; 69% were boys and football was the main sport involved. Most (93%) were radiographed, and 40% were positive; most fractures were sustained outwith school. Hand dominance was not significant. These injuries are common and may be preventable with modification of rules, equipment, and coaching. A register of youth sporting injuries may show if there are any detrimental long term effects.


Descriptive Epidemiology of Chronic Obstructive Pulmonary Disease in US Nursing Home Residents With Heart Failure.
Chronic obstructive pulmonary disease (COPD) is highly prevalent in older adults with heart failure and heart failure is highly prevalent in older adults with COPD. Information is presently lacking about the extent to which COPD and heart failure co-occur among nursing home residents. The objective of this study was to describe the epidemiology of, and factors associated with, COPD among nursing home residents with heart failure. This cross-sectional study included 97,495 long-term stay nursing home residents with heart failure in 2018. The Minimum Data Set 3.0 (MDS) provided information on sociodemographic characteristics, comorbid conditions, and activities of daily living. Heart failure and COPD were defined based on notes at admission, hospitalizations, progress notes, and through physical examination findings. The majority of the study population were ≥75 years old (74.1%), women (67.3%), and Non-Hispanic Whites (77.4%). Nearly 1 in 5 residents had reduced ejection fraction findings, 23.1% had a preserved ejection fraction, and 53.8% of nursing home residents with heart failure had COPD. This pulmonary condition was less frequently noted in women, residents of advanced age, and racial/ethnic minorities and more frequently diagnosed in residents with comorbid conditions such as pneumonia, anxiety, obesity, diabetes mellitus, and coronary artery disease. We found a high prevalence of COPD, and identified several factors associated with COPD, in nursing home residents with heart failure. Our findings highlight challenges in the clinical management of COPD in nursing home residents with heart failure and how best to meet the care needs of this understudied population.


Occurrence and recurrence of spontaneous chronic subdural haematoma is associated with a factor XIII deficiency.
In some patients, chronic subdural haematoma (cSDH) appears to occur spontaneously with frequent re-bleeding events. The pathophysiology of this phenomenon is still poorly understood. Because coagulation factor XIII (FXIII) is known to be involved in vascular integrity, endothelial barrier function and wound healing, we evaluated the role of FXIII in spontaneous cSDH. We prospectively scrutinised the origin of cSDH in 117 patients and identified a subgroup of patients suffering from spontaneous cSDH who were included in this study. We analysed the plasma activity of FXIII and standard coagulation parameters and compared these data to age- and sex-matched healthy controls. We assessed the occurrence of re-bleeding events using clinical and imaging data and compared FXIII activity in patients with and without re-bleeding events. Out of 117 cSDH patients, 18 individuals suffered from spontaneous cSDH in this study. The patients with spontaneous cSDH showed significantly lower FXIII activity than the control group (65% [52.75, 80.25] (median [IQR]) vs. 93% [81, 111], P=0.001), whereas standard coagulation parameters did not differ significantly between the groups. Six patients developed re-bleeding events after haematoma evacuation, and these patients expressed significantly lower FXIII activity compared to the other 12 patients (47.5% [33.5, 64] vs. 78.5% [58, 87], P=0.005). The patient group with FXIII≤68.5% differed significantly from the group with FXIII>68.5% when categorised by the occurrence of re-bleeding events (n=6/9 vs. n=0/9, P=0.009). This cut-off value predicted the re-bleeding events with a sensitivity of 100% and a specificity of 75% (positive predictive value: 66%, negative predictive value: 100%). FXIII deficiency may play a pathophysiological role in spontaneous cSDH, so we suggest investigating FXIII activity because it may predict re-bleeding events after treatment. In individuals with considerably low FXIII activity, FXIII substitution may mitigate the chronic nature of this disease.


Concentration, source apportionment and potential carcinogenic risks of polycyclic aromatic hydrocarbons (PAHs) in roadside soils.
PAHs are organic pollutants that have carcinogenic and mutagenic impacts on human health and are a subject of great concern. The soil-bound polycyclic aromatic hydrocarbons (PAHs) in the urban areas can be very lethal to human health. The concentrations, sources, and possible cancer risks of 15 PAHs were analysed by collecting roadside soil samples in Lucknow, India. The range of ∑15PAHs was found to be 478.94 ng/g to 8164.07 ng/g with a mean concentration of 3748.23 ng/g. The highest contribution (32.5%) was found to be from four-ring PAHs, followed by six-ring (24.5%) and five-ring (16.7%) PAHs. The source apportionment through diagnostic ratios ANT/(ANT + PHE) against FL-2/(FL-2+PYR) highlighted the dominance of petroleum, wood, coal, and grass combustion as sources of PAHs in the study area. Source apportionment was also done through positive matrix factorization, confirming the dominance of 'vehicular emissions' (49%), followed by 'coal and biomass combustion' (∼39%), and 'leakages, volatilization and petroleum combustion' (∼12%) as potential sources. The results from lifetime cancer risks (ILCR) varied in the range of 7.5 × 10-4 and 1.3 × 10 × -2 illustrating 'high cancer risk'. The total cancer risk susceptibility of children was found to be 31% more than that of adults. The highest risk associated with toxic equivalent concentration (TEQ) was found at site S8 highlighting the impact of the presence of an international airport, and huge traffic load. The present study will prove to be useful for information related to human exposure to PAHs content in soil in the study area and as baseline study for policy makers, stakeholders, and researchers.


Transport and sedimentation of solid particles in Bénard hexagonal cells.
The motion of particles moving under gravity in the velocity field of a liquid in a Bénard hexagonal cell is studied experimentally and numerically for Stokes flow conditions. We then explain the settlement of particles in the centers of cells to form a regular quincunx. It is found that sedimentation also occurs preferentially along the lines connecting the centers of adjacent cells to form a triangle deposition tessellation. Finally, it is explained why particles occupy the central part of each convective cell while the peripheral part of the cell quickly becomes limpid. Numerical results are in agreement with the experimental observations of Bénard and those of the present study.


A novel protein, p19/6.8, specific for cardiac and slow skeletal muscle.
Upon in vitro translation of mRNAs from slow (soleus) muscles of the mouse a hitherto undescribed translation product has been detected that was absent from fast skeletal muscles and was termed p19/6.8 according to its position in 2-dimensional gels. mRNA for p19/6.8 was also found in the ventricle of the heart. p19/6.8 was not detectable by Coomassie blue staining but could be characterised by fractionation of in vivo labelled muscle tissue. It was found to sediment with the particulate fraction at 14,000 x g. The expression of p19/6.8 mRNA appears to be down-regulated in muscles with phasic activity.


Diet and Physical Activity Prevention Research Supported by the U.S. NIH From 2012-2017.
Poor diet and inadequate physical activity are common contributors to preventable death in the U.S. This paper provides a summary of the NIH-sponsored research on disease prevention that underlies public health and clinical recommendations to improve diet and physical activity. A representative sample (n=11,082) of research grants and cooperative agreements (research projects) representing the NIH prevention research portfolio between 2012 and 2017 were hand coded by trained analysts in 2017-2018. This manuscript describes the rationale(s), exposure(s), outcome(s), population(s), and study design(s) in prevention research focused on diet and physical activity and compares this research to identified research gaps in the field. A relatively stable 7.8% (95% CI=7.0%, 8.8%) and 5.0% (95% CI=4.4%, 5.7%) of the NIH prevention research projects were focused on diet and physical activity, respectively, during 2012-2017. These projects often explored diet and physical activity together in the context of obesity, included observational studies, and focused on a general adult population. Few of these projects focused on development of improved assessment methods. Approximately 50% of these studies were related to research gaps identified by the 2015 Dietary or 2018 Physical Activity Guidelines Advisory Committee Scientific Reports. Opportunities exist for more engagement by NIH and scientific investigators in diet- and physical activity-focused prevention research, particularly around assessment and known research gaps.


Giant Panda Maternal Care: A Test of the Experience Constraint Hypothesis.
The body condition constraint and the experience condition constraint hypotheses have both been proposed to account for differences in reproductive success between multiparous (experienced) and primiparous (first-time) mothers. However, because primiparous mothers are typically characterized by both inferior body condition and lack of experience when compared to multiparous mothers, interpreting experience related differences in maternal care as support for either the body condition constraint hypothesis or the experience constraint hypothesis is extremely difficult. Here, we examined maternal behaviour in captive giant pandas, allowing us to simultaneously control for body condition and provide a rigorous test of the experience constraint hypothesis in this endangered animal. We found that multiparous mothers spent more time engaged in key maternal behaviours (nursing, grooming, and holding cubs) and had significantly less vocal cubs than primiparous mothers. This study provides the first evidence supporting the experience constraint hypothesis in the order Carnivora, and may have utility for captive breeding programs in which it is important to monitor the welfare of this species' highly altricial cubs, whose survival is almost entirely dependent on receiving adequate maternal care during the first few weeks of life.


Injectable antimicrobial hydrogels with antimicrobial peptide and sanguinarine controlled release ability for preventing bacterial infections.
The emergence of antibiotic resistant bacteria represents a significant and common clinical problem worldwide as infections are becoming increasingly common. It is urgent to broaden the sources of biomaterials that can prevent both bacterial infection and antibiotic resistance. In this work, oxidized sodium alginate/aminated hyaluronic acid (OSA/AHA) hydrogel with various proportions was developed based on Schiff base reaction. Herein, polydopamine (PDA)-Bmkn2 nanoparticle and sanguinarine were incorporated into hydrogels to enhance antibacterial properties. The prepared PDA-Bmkn2 nanoparticles, with uniform particle size and good dispersion, could serve as a delivery system for Bmkn2. The prepared hydrogels showed appropriate swelling ratio, extremely good mechanical strengths and improved biodegradability. Meanwhile, the Bmkn2 and sanguinarine were released from the hydrogels in a sustainable manner. Furthermore, OSA/AHA/sanguinarine/PDA-Bmkn2 hydrogel (less than 10 μg/mL BmKn2 and 0.2 μg/mL sanguinarine) had excellent biocompatibility. Antibacterial experiments confirmed that OSA/AHA/sanguinarine/PDA-Bmkn2 hydrogel had effective antimicrobial activity on Escherichia coli and Staphylococcus aureus. Therefore, the prepared injectable hydrogels with good biocompatibility and excellent synergistic antibacterial activity promise great potential for preventing localized bacterial infections.


Attenuated T cell responses to a high-potency ligand in vivo.
αβ T cell receptor (TCR) recognition of foreign peptides bound to major histocompatibility complex (pMHC) molecules on the surface of antigen presenting cells is a key event in the initiation of adaptive cellular immunity. In vitro, high-affinity binding and/or long-lived interactions between TCRs and pMHC correlate with high-potency T cell activation. However, less is known about the influence of TCR/pMHC interaction parameters on T cell responses in vivo. We studied the influence of TCR/pMHC binding characteristics on in vivo T cell immunity by tracking CD4(+) T cell activation, effector, and memory responses to immunization with peptides exhibiting a range of TCR/pMHC half-lives and in vitro T cell activation potencies. Contrary to predictions from in vitro studies, we found that optimal in vivo T cell responses occur to ligands with intermediate TCR/pMHC half-lives. The diminished in vivo responses we observed to the ligand exhibiting the longest TCR/pMHC half-life were associated with attenuation of intracellular signaling, expansion, and function over a broad range of time points. Our results reveal a level of control over T cell activation in vivo not recapitulated in in vitro assays and highlight the importance of considering in vivo efficacy of TCR ligands as part of vaccine design.


Discovery of (phenoxy-2-hydroxypropyl)piperidines as a novel class of voltage-gated sodium channel 1.7 inhibitors.
A novel class of NaV1.7 inhibitors has been identified by high-throughput screening followed by structure activity relationship studies. Among this series of compounds, piperidine 9o showed potent human and mouse NaV1.7 inhibitory activities with fair subtype selectivity over NaV1.5. Compound 9o successfully demonstrated analgesic efficacy in mice comparable to that of the currently used drug, mexiletine, but with an expanded central nervous system safety margin.


Factors associated with immunosenescence during early adulthood in HIV-infected patients after durable efficient combination antiretroviral therapy.
Perinatally HIV-infected patients face the consequences of both chronic infection effects per se and long-term combination antiretroviral therapy (cART) on immunosenescence. Aims of our study were to evaluate which factors independently contribute to immunosenescence in HIV-infected young adults with a very different HIV infection duration (perinatally HIV-infected young individuals -pHIVy- and age-matched non perinatally HIV-infected youths -npHIVy), after durable efficient cART. We considered low thymic and bone marrow output, respectively evaluated by quantifying T-cell receptor excision circles (TRECs), K-deleting recombination excision circles (KRECs), and shorter telomeres lenght (TL) as surrogate biomarkers of immunosenescence. Twenty-one pHIVy and 19 npHIVy (with a mean HIV duration of 3-8 years) were included; mean age was 27 years for both groups. Immunosenescence biomarkers were comparable between pHIVy and npHIVy (despite longer HIV-infection, higher frequency of AIDS events, past cART-free periods and concomitant chronic viral infections in pHIVy). At the multivariate analysis, CD4+ was the only variable independently associated with TRECs and TL. Our data suggest that a good level of thymic activity can compensate the deleterious effects of past periods without cART, if HIV replication is suppressed for a sufficient time.


Hydrophobicity and dielectric properties across an isostructural family of MOFs: a duet or a duel?
An isoreticular family of metal-organic frameworks is post-synthetically subjected to polymer grafting. Surface hydrophobicity analysis, adsorption experiments, and impedance spectroscopy characterise the water molecules adsorbed, both on the surface and in the pores, while resolving how molecular mobility is impacted.


Electrodeposition of Ni-Mo alloy coatings from choline chloride and propylene glycol deep eutectic solvent plating bath.
Ni-Mo alloy coatings were deposited on a copper base material from a non-aqueous plating bath based on a deep eutectic solvent (DES) of choline chloride and propylene glycol in a 1:2 molar ratio containing 0.2 mol dm-3 NiCl2 · 6H2O and 0.01 mol dm-3 (NH4)6Mo7O24·4H2O. Uniform and adherent Ni-Mo deposits with a nodular morphology were obtained at all the deposition potentials investigated (from - 0.5 to - 0.9 V vs. Ag). By shifting the potential from - 0.5 to - 0.9 V, the deposition current density increased from - 0.4 to - 1.5 mA cm-2 and the overall surface roughness increased. It was also accompanied by an increase in the Mo content from ~ 7 to ~ 13 wt% in the potential range from - 0.5 to - 0.7 V. A further change in the potential from - 0.8 to - 0.9 V caused a decrease in the Mo content to ~ 10 wt% and a deterioration in the quality of the coating. For the most uniform coating, deposited at - 0.6 V and having a thickness of ca. 660 nm, the crystallite size did not exceed 10 nm. With the content of Ni (89 at.%) and Mo (11 at.%), the selected area electron diffraction (SAED) analysis allowed us to identify the cubic phase Ni3.64Mo0.36. The corrosion resistance of Ni-Mo coatings in 0.05 mol dm-3 NaCl solution generally increased during exposure of 18 h, as evidenced by ever higher polarization resistance. Finally, regardless of the applied deposition potential, low corrosion currents (in the range of 0.1-0.3 μA cm-2) have been measured for the coatings. EIS revealed that charge transfer resistances were the highest (57-67 kΩ cm2) for coatings deposited at - 0.5 V, - 0.6 V and - 0.7 V. Further increase in the deposition potential in the negative direction was unfavorable.


The Flexor Pollicis Longus Tendon Does Not Lie Parallel to the Thumb Metacarpal.
Repair of the flexor pollicis longus (FPL) tendon by tendon retriever can be challenging because of uncertainty of the optimal direction. This study aims to describe the FPL tendon path in the thenar eminence. In 18 hands of 9 cadavers, the angle of the FPL tendon was, after dissection, measured in relation to the axis formed between the metacarpophalangeal (MCP) joint of the thumb and the dorsal carpometacarpal joint (MC1-axis) and the axis formed between the second MCP joint and the distal edge of the trapezium (MC2-axis). The FPL does not follow the angle of the thumb metacarpal. The FPL runs ulnarly from the MC1-axis at a median of 32.5° in abduction and 30.6° in adduction. In relation to the MC2-axis, it runs at a median of 47.5° in abduction and 25° in adduction. The FPL tendon path can be preoperatively marked using: (1) the MC1-axis from which it runs ulnarly approximately at an angle of 30° in both abduction and adduction; or (2) the MC2-axis from which it runs radially at an angle of 47.5° in abduction and at an angle of 25° in adduction. We conclude that the FPL tendon path can be preoperatively marked using these axes and does not parallel the metacarpal axes of the thumb.


The health behaviour of northern Finnish men in adolescence and adulthood.
The aim of the study was to produce data about health behaviour among men born in Northern Finland in 1966. A particular concern was to find out how well health behaviour in adolescence predicts health behaviour in adulthood. The family questionnaire on health and development was submitted in 1980 when the subjects were 14 years of age. The response rate was 97%. The second questionnaire survey was carried out 10 years later with 2500 respondents. The final response rate was 60%. The results indicated that health behaviour in adolescence predicted health behaviour in adulthood as far as smoking and physical exercise were concerned. Over half (65%) of those who were non-smokers in their youth did not smoke as adults. Similarly the majority (71%) of those who had taken physical exercise at least once a week in their youth continued to do so in adulthood. Most of the subjects (85%) used alcohol in adulthood. A good family situation was connected with healthy habits. In the case of drinking, however, the subjects whose fathers belonged to social classes I-II used alcohol to a somewhat greater extent than others. It is important to conceive of health behaviour as an element connected with a person's life situation. Health research should be incorporated into cultural research and should have closer co-operation with other disciplines.


Drag of a Cottrell atmosphere by an edge dislocation in a smectic-A liquid crystal.
In a recent letter (P. Oswald et al., EPL 103, 46004 (2013)), we have shown that a smectic-A phase hardens in compression normal to the layers when the liquid crystal is doped with gold nanoparticles. This is due to the formation of Cottrell clouds nearby the core of the edge dislocations and the appearance of an additional drag force that reduces their mobility. We theoretically calculate the shape of the Cottrell cloud and the associated drag force as a function of the climb velocity of the dislocations. The main result is that the drag force depends on velocity and vanishes when the temperature tends to the smectic-A-to-nematic transition temperature. The role of the diffusion anisotropy is also evaluated.


Deoxyribonucleic acid content as an indicator of progression of squamous cell carcinogenesis in the esophagus: comparative analysis on imprint-cytospin and tissue section preparation.
The purpose of this study was to explore the potential use of image analysis on tissue sections preparation as a predictive marker of early malignant changes during squamous cell (SC) carcinogenesis in the esophagus. Results of DNA ploidy quantification on formalin-fixed, paraffin-embedded tissue using two different techniques were compared: imprint-cytospin and 6 microm thick tissue sections preparation. This retrospective study included 26 surgical specimens of squamous cell carcinoma (SCC) from patients who underwent surgery alone at the Department of Surgery in CHUV Hospital in Lausanne between January 1993 and December 2000. We analyzed 53 samples of healthy tissue, 43 tumors and 7 lymph node metastases. Diploid DNA histogram patterns were observed in all histologically healthy tissues, either distant or proximal to the lesion. Aneuploidy was observed in 34 (79%) of 43 carcinomas, namely 24 (75%) of 32 early squamous cell carcinomas and 10 (91%) of 11 advanced carcinomas. DNA content was similar in the different tumor stages, whether patients presented with single or multiple synchronous tumors. All lymph node metastases had similar DNA content as their primary tumor. Early malignant changes in the esophagus are associated with alteration in DNA content, and aneuploidy tends to correlate with progression of invasive SCC. A very good correlation between imprint-cytospin and tissue section analysis was observed. Although each method used here showed advantages and disadvantages; tissue sections preparation provided useful information on aberrant cell-cycle regulation and helped select the optimal treatment for the individual patient along with consideration of other clinical parameters.


Radiotherapy for hypopharynx cancers.
We present the update of the recommendations of the French society of oncological radiotherapy on radiotherapy for hypopharynx. Intensity-modulated radiotherapy is the gold standard treatment for hypopharynx cancers. Early T1 and T2 tumors could be treated by exclusive radiotherapy or surgery followed by postoperative radiotherapy in case of high recurrence risk. For locally advanced tumours requiring total pharyngolaryngectomy (T2 or T3) or with significant lymph nodes involvement, induction chemotherapy followed by exclusive radiotherapy or concurrent chemoradiotherapy were possible. For T4 tumour, surgery must be proposed. The treatment of lymph nodes is based on initial primary tumour treatment. In non-surgical procedure, for 35 fractions, curative dose is 70Gy (2Gy per fraction) and prophylactic dose are 50 to 56Gy (2Gy per fraction in case of sequential radiotherapy or 1.6Gy in case of integrated simultaneous boost) radiotherapy; for 33 fractions, curative dose is 69.96Gy (2.12Gy per fraction) and prophylactic dose is 52.8Gy (1.6Gy per fraction in integrated simultaneous boost radiotherapy or 54Gy in 1.64Gy per fraction); for 30 fractions, curative dose is 66Gy (2.2Gy per fraction) and prophylactic dose is 54Gy (1.8Gy per fraction in integrated simultaneous boost radiotherapy). Doses over 2Gy per fraction could be done when chemotherapy is not used regarding potential larynx toxicity. Postoperatively, radiotherapy is used in locally advanced cancer with dose levels based on pathologic criteria, 60 to 66Gy for R1 resection and 54 to 60Gy for complete resection in bed tumour; 50 to 66Gy in lymph nodes areas regarding extracapsular spread. Volume delineation were based on guidelines cited in this article.


Topiramate in patients with learning disability and refractory epilepsy.
Management of seizures in learning disabled people is challenging. This prospective study explored the efficacy and tolerability of adjunctive topiramate (TPM) in patients with learning disability and refractory epilepsy attending a single centre. Sixty-four patients (36 men, 28 women, aged 16-65 years) were begun on adjunctive TPM after a 3-month prospective baseline on unchanged medication. Efficacy end points were reached when a consistent response was achieved over a 6-month period at optimal TPM dosing. These were seizure freedom or > or =50% seizure reduction (responder). Appetite, behaviour, alertness, and sleep were assessed by caregivers throughout the study. Sixteen (25%) patients became seizure free with adjunctive TPM. There were 29 (45%) responders. A further 10 (16%) patients experiencing a more modest improvement in seizure control continued on treatment at the behest of their family and/or caregivers. TPM was discontinued in the remaining nine (14%) patients, mainly because of side effects. Final TPM doses and plasma concentrations varied widely among the efficacy outcome groups. Many patients responding well to adjunctive TPM did so on < or =200 mg daily. Mean carer scores did not worsen with TPM therapy. TPM was effective as add-on therapy in learning-disabled people with difficult-to-control epilepsy. Seizure freedom is a realistic goal in this population.