Reproductive Biology of Leptocybe invasa Fisher & La Salle (Hymenoptera: Eulophidae).
Leptocybe invasa Fisher & La Salle (Hymenoptera: Eulophidae) is an invasive pest in Eucalyptus plantations around the world. The successful colonization of L. invasa is possibly related to its reproductive biology. The objective of this study was to examine the reproductive biology of L. invasa. In Guangxi Province, the sex ratio (proportion of female, 0.99) of L. invasa was female-dominant throughout the year based on natural and artificial infestation. This result was similar to the ratios observed for other geographic populations in China, including those in Fujian (0.99), Guangdong (0.98), Hainan (0.95), Jiangxi (0.96), and Sichuan (0.99). The offspring sex ratio favored females. A large number of females emerged from the galls produced by females, with few males found. Galls on the petioles and midribs of Eucalyptus plants could be caused by newly emerged females with mature eggs. The lengths of the ovariole, spermatheca, common oviduct, and reproductive glands did not differ among L. invasa females, but their lateral oviducts showed differences from 0 to 42 h after emergence, indicating that this insect is proovigenic. These results could explain why L. invasa populations can rapidly increase in invaded areas.


The upper limit of human smooth pursuit velocity.
The maximum smooth pursuit eye velocity was determined in five human subjects. Eye movements were recorded with the d.c.-coupled EOG. On each trial the target moved in a ramp, at a constant velocity between 10 and 200 deg/sec. In four subjects eye velocity was approximately 90% of target velocity up to a target velocity of 100 deg/sec. Eye velocity then saturated with a large variability from trial to trial (standard deviation 16 deg/sec). The fifth subject had eye velocities only 60% of these values.


Incidence of endophthalmitis after intravitreal injection of an anti-VEGF agent with or without topical antibiotics.
Intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) is the standard treatment modality in various types of retinal diseases. However, endophthalmitis remains the most serious complication. Despite the lack of evidence that antibiotics prevent endophthalmitis, topical antibiotics are still used routinely in Japan. We conducted a retrospective multicenter study by analyzing records from patients who underwent IVI of anti-VEGF agents with or without antibiotic treatment. In the analysis of a total of 147,440 eyes, the incidence of endophthalmitis was 0.007%: 0.005% with no use of antibiotics, 0.009% with antibiotic pretreatment, 0.012% with posttreatment, and 0.005% with pre- and posttreatment. There was no statistically significant difference among the four groups (chi-square test, p = 0.57). Most facilities used masks, sterilized gloves, and drapes. Nine of the 10 eyes that developed endophthalmitis received topical antibiotics, and all infected eyes underwent IVI with aflibercept, not the prefilled syringe delivery system. In four patients who received multiple IVI, the detection of causative bacteria revealed resistance to used antibiotics. Data from this large population, treated with or without antibiotics, suggests that antibiotic prophylaxis does not reduce the rate of endophthalmitis after IVI.


Synaptosomal uptake and levels of serotonin in rat brain areas after p-chloroamphetamine or B-9 lesions.
In contrast to the pronounced fall in 5HT levels and synaptosomal uptake caused by p-chloroamphetamine, bilateral lesions of the B-9 cell group caused minimal regional changes, except for 35% decreases in the metathalamus-thalamus. We conclude therefore that the prolonged biochemical effects of p-chloroamphetamine are not due to a selective cytotoxic action on B-9 cells; and that a lateral 5HT pathway, possibly from the B-9 cell group, projects to the metathalamus-thalamus.


Vitamin D, bones and muscle: myth versus reality.
Evidence regarding the efficacy and dosing of vitamin D on fall and fracture prevention, with or without calcium, is characterised by uncertainty. A panel of experts was organised at the First Australasian Conference on Sarcopenia and Frailty in Melbourne, Australia, in November 2016 to provide an interpretation of the current evidence and to give their opinions regarding the supplementation of vitamin D in three hypothetical cases. The authors conclude that (i) target serum 25(OH)D concentration should be 50 to 60 nmol/L year round, with a conservative upper limit <100 nmol/L; (ii) change in serum concentrations at any given dose is highly variable among individuals; (iii) dosing interval may need to be <2 months to have a continuous benefit; (iv) a loading dose can raise levels to target quickly, but there is no evidence yet that this has any positive effect on falls or fracture outcomes; and (v) a maintenance dose of 1000 IU/day, or given as an equivalent dose weekly or monthly, is sufficient for most individuals.


Acute phase proteins in ruminants.
The physiological response to infections and injuries involves local inflammation and the initiation of events leading to a systemic response, also called acute phase reaction (APR). This multiplicity of changes is distant from the site of injury, and includes fever, leukocytosis and quantitative and qualitative modification of a group of non-structurally related proteins present in blood and other biological fluids, collectively named Acute Phase Proteins (APP). Proteomic investigations of serum or plasma following natural or experimental infection frequently reveal substantial alterations in the APP, several of which are high abundance proteins in these fluids. The present review will focus on the results of recent research on ruminant APP. Highlight points will include: - The structure and the functions of the main APPs in ruminants, as well as the regulatory mechanisms that trigger their systemic and local expression in both physiological and pathological conditions.- The clinical aspects of APPs in ruminants, including the current and future application to veterinary diagnosis and animal production.- The APP in small and wildlife ruminants.- Alteration in APP detected by proteomic investigations.


"Have a little less, feel a lot better": Mixed-method evaluation of an alcohol intervention.
The aim of the mixed-methods study reported here was to evaluate the impact of a "gain-framed", multimedia campaign to encourage heavier drinking men aged 45-64 years to drink less. Quantitative analyses were based on pre-intervention panel surveys of 3057 men in intervention regions and 500 in the control region, and post-intervention panel surveys of 1508 men in intervention regions and 219 in the control region. Qualitative analyses entailed thematic analysis of interviews with 14 men: five who had reduced their drinking after seeing the campaign, four who had considered reducing but did not, and five who did not consider changing. Interviews focused on men's responses to the campaign, and their ideas for how to improve it. In quantitative analyses, the campaign was associated with significant changes in alcohol consumption, and significant increases in readiness to change and likelihood of using moderate drinking strategies. In qualitative analyses, men appreciated the friendly, non-threatening tone and that the message was straightforward, meaningful, achievable, and was gain-framed - i.e., emphasised the benefits of drinking less rather than the harms of drinking too much. However, the men who did not change their behaviour also identified several barriers to responding in ways encouraged by the message. It would be important to address their views of their drinking as not problematic, as pleasurable, and as socially expected, and also their sense of not feeling empowered to initiate or maintain behaviour change.


Explaining the Black-white depression paradox: Interrogating the Environmental Affordances Model.
The Environmental Affordances (EA) model posits that Black Americans' engagement with unhealthy behaviors (i.e. smoking, alcohol use, eating calorie-dense foods) to cope with stressor exposure may simultaneously account for their observed greater risk of chronic physical illness, and their observed equal or lesser prevalence of depression, relative to white Americans - the so-called "Black-white depression paradox." However, the specific mechanisms through which such effects might arise have been theorized and analyzed inconsistently across studies, raising concerns regarding the appropriateness of existing empirical tests of the model as well as the validity of the conclusions. We specify the two mechanisms most consistent with the EA model - 'Mediation-only' and 'Mediation and Modification' - and derive a priori predictions based on each. We systematically test these pathways using a subset of 559 participants of the Child Health and Development Study who were included in an adult follow-up study between 2010 and 2012 and self-identified as Black or white. Results failed to support either of the two mechanisms derived from the EA model, challenging the validity and utility of the model for explaining racial differences in depression; efforts to develop alternative hypotheses to explain the paradox are needed.


Biomarkers for hazard identification in humans.
Oxidative stress enhances lipid peroxidation (LPO), which both are implicated in the promotion and progression stages of carcinogenesis, in particular under conditions of chronic inflammation and infections. Exocyclic etheno-DNA adducts, which are formed by LPO-products such as 4-hydroxy -2-nonenal, are strongly pro-mutagenic DNA lesions. The development of ultra-sensitive detection methods for etheno-adducts in human tissues, white blood cells( WBC) and urine has provided evidence that these adducts are elevated in affected organs of cancer-prone patients, probably acting as a driving force to malignancy. Two recent studies that yielded some new insights into disease causation are briefly reviewed: DNA-damage in WBC of mother-newborn child pairs, and lipid peroxidation derived DNA damage in patients with cancer-prone liver diseases. Our results indicate that biomonitoring of etheno-DNA adducts in humans are promising tools (i) to better understand disease aetiopathogenesis, allowing hazard identification(ii) to monitor disease progression and (iii) to verify the efficacy of chemopreventive and therapeutic interventions. Such clinical trials are warranted.


Underlying mechanisms of epithelial splicing regulatory proteins in cancer progression.
Cancer is the second-leading disease-related cause of global mortality after cardiovascular disease. Despite significant advances in cancer therapeutic strategies, cancer remains one of the major obstacles to human life extension. Cancer pathogenesis is extremely complicated and not fully understood. Epithelial splicing regulatory proteins (ESRPs), including ESRP1 and ESRP2, belong to the heterogeneous nuclear ribonucleoprotein family of RNA-binding proteins and are crucial regulators of the alternative splicing of messenger RNAs (mRNAs). The expression and activity of ESRPs are modulated by various mechanisms, including post-translational modifications and non-coding RNAs. Although a growing body of evidence suggests that ESRP dysregulation is closely associated with cancer progression, the detailed mechanisms remain inconclusive. In this review, we summarize recent findings on the structures, functions, and regulatory mechanisms of ESRPs and focus on their underlying mechanisms in cancer progression. We also highlight the clinical implications of ESRPs as prognostic biomarkers and therapeutic targets in cancer treatment. The information reviewed herein could be extremely beneficial to the development of individualized therapeutic strategies for cancer patients.


Gastric emptying of liquid meals and pancreatic and biliary secretion after subtotal gastrectomy or truncal vagotomy and pyloroplasty in man.
Pancreatic and biliary secretion and gastric emptying rates of a liquid test meal (LTM) were determined in normal persons, in patients with subtotal gastrectomy with gastroduodenostomy (STG-BI) or with gastrojejunostomy (STG-BII), and in patients with truncal vagotomy and pyloroplasty (V&P). In all operated persons, rapid gastric emptying diluted intraluminal contents, with consequent abnormally low concentrations of trypsin and bile salts initially, a pattern that was not corrected by addition of intravenous hormones to the meal stimulus. Trypsin output in V&P's after the LTM was significantly depressed to 40% of normal, but was normal in the STG groups. The delay in reaching normal values for trypsin and bile salt concentrations, was more marked in STG-BII owing to sequestration of secretions in the afferent loop. The low luminal concentrations of digestive secretions for the first 60 to 80 min after a LTM are therefore attributable to rapid gastric emptying in all operated groups, and in V&P to a depressed pancreatic enzyme response also. In STG-BII, afferent loop sequestration exaggerates the delay in attainment of normal intraluminal concentrations. The combined disturbance in STG-BII produces greater abnormalities than seen in STG-BI.


Management of radiation-induced moist skin desquamation using hydrocolloid dressing.
Moist skin desquamation has been of concern to radiation oncologists, nurses and patients since the inception of this mode of therapy. As radiation treatment machines became more sophisticated, severe reactions became less of a problem. However, with the increasing use of chemotherapy and radiation as combined modalities, moist skin reaction is occurring with greater frequency. A noncomparative study of 20 patients using a hydrocolloid occlusive dressing (Duoderm) was initiated. The purpose of the study was to determine whether moist occlusive healing would be beneficial. The dressing was evaluated on the basis of healing time, safety, wound temperature, bacterial growth, and comfort. Data were collected using photographs, bacterial cultures, temperature probes, and patient evaluations. Eighteen patients completed the study. All patients' skin reactions healed. There were no wound infections evident. Mean healing time was 12 days, with mean wound temperature relative to body core -0.8 degree C on day 1 and -1.2 degrees C on the healed site. Patient results on comfort were: 8 of 18 excellent, 7 of 18 good, 3 of 18 fair, and 0 of 18 poor. The results of this study indicate that a hydrocolloid occlusive dressing can be effective in the healing process of moist skin reaction that is due to radiation therapy.


The influence of parity on multinodular goiter prevalence in areas with moderate iodine deficiency.
Despite the observation that parity may increase the risk of thyroid carcinoma, very few studies have investigated the possible repercussion of parity on thyroid benign pathology. Recently, parity has been identified as one of the factors contributing to a larger thyroid size in healthy females. The aim of this work was to investigate a possible role for parity on the prevalence of multinodular goiter in iodine deficient areas. For this purpose, the reproductive histories of 2 cohorts of women, normal (Group I, 235 cases) and non-toxic multinodular goiter (NTMNG) affected (Group II, 274 cases) were compared. All subjects were euthyroid and had no previous history of thyroid function abnormalities. The number of full-term previous pregnancies (2.55+/-0.11 vs 1.77+/-0.10) and age (47.7+/-0.76 vs 42.3+/-0.83 yr) were found significantly higher (p<0.001) in multinodular goiter (MNG) patients than controls. Parity and age were found to be directly correlated (p<0.001), nevertheless the partial correlation coefficients demonstrated an independent and statistically significant difference for both variables between normal and NTMNG. Therefore, the independent effects of parity and age were further investigated. The effect of age on NTMNG prevalence seems to be weaker, in fact significant differences (p<0.001) for age between patients and controls were detected only when the effect of parity was absent (nulliparous), while with increasing gestations the effect of age disappeared. Our results indicate that age plays a minor role compared to parity which can therefore be considered as a stronger risk factor. In conclusion, the present study shows that, at least in iodine deficient regions, non-toxic multinodular goiter women show a statistically significant higher parity rate than healthy controls. Age may play a certain role but only when additional stronger risk factors are absent.


Improvement of Catalytic Efficiency, Thermo-stability and Dye Decolorization Capability of Pleurotus ostreatus IBL-02 laccase by Hydrophobic Sol Gel Entrapment.
In serious consideration of the worldwide environmental issues associated with the extensive use of the textile dyes and effluents generated thereof, the scientists across the world are in search for potential treatment technologies for their treatment. In such scenario the ligninolytic enzymes provide a potential alternative because they are cost effective, eco-friendly and can be applied to wide range of dye containing industrial effluents. Laccase produced from Pleurotus ostreatus IBL-02 during decolorization of the reactive textile dye Drimarene brilliant red K-4BL (DBR K-4BL) was purified and immobilized by hydrophobic gel entrapment. The crude laccase was 4.2-fold purified with specific activity of 573.52 U/mg after passing through the DEAE-Sepharose ion exchange and Sephadex-G-100 chromatography columns. P. ostreatus IBL-02 laccase was found to be a homogenous monomeric protein as evident by single band corresponding to 67 kDa on native and sodium dodesylsulfate polyacrylamide gel electrophoresis (PAGE). The laccase was immobilized by entrapment in Sol-gel matrix of trimethoxysilane (T) and proplytetramethoxysilane (P) prepared using different T:P molar ratios. The free and immobilized laccases were compared to investigate the effect of immobilization on catalytic efficiency and thermo-stability features. Laccase immobilized in the Sol-gel of 1:5 T:P ratio was optimally active and thermo-stable fraction at pH 5, 60°C with half-life of 3 h and 50 min. Laccases immobilized in 1:2 and 1:5 T:P ratio gels had significantly higher Km (83 and100mM) and Vmax (1000 and 1111 mM/mg) values as compared to free laccase. After 5 h reaction time varying decolorization percentages with a maximum of 100% were achieved for different dyes and effluents. In summary, P. ostreatus IBL-02 laccase was immobilized by entrapping in a Sol-gel matrix with an objective to enhance its catalytic and stability properties. Sol-gel entrapped laccase presented potential efficiency as a biocatalyst when applied for decolorization of different dyes and effluents. The main benefits of the Sol-gel matrix immobilization processes are the eco-friendly approach, chemical free and energy saving reaction conditions.


The binding of plasminogen fragments to cultured human umbilical vein endothelial cells.
Glu-plasminogen, kringle 1-5, kringle 1-3, and miniplasminogen exhibited strong binding to human umbilical vein endothelial cells (HUVEC). On the other hand, no significant binding was obtained with microplasminogen and kringle 4. Kringle 1-5 and miniplasminogen, which both contained kringle 5, specifically inhibited the binding of plasminogen to HUVEC while kringle 1-3 did not. The results implied plasminogen molecule contained at least two binding sites, with which it interacted HUVEC. The stronger binding site was located in kringle 5 and the weaker one was in kringle 1-3. Kringle 4 and the active site domain exhibited no significant binding to HUVEC. The interaction of plasminogen with HUVEC is mainly through binding site on kringle 5.


The mechanical characteristics and performance evaluation of a newly developed silicone airway stent (GINA stent).
Central airway obstruction (CAO) can be attributed to several benign or malignant conditions. Although surgery is the preferred therapeutic option for the management of CAO, bronchoscopic treatment can be performed in scenarios where the surgical procedure is not possible. Recent years have witnessed several improvements in the field of bronchoscopic treatment, especially with regard to airway stents. Current research involves new attempts to overcome the existing shortcomings pertaining to the stents (migration, mucostasis, and granulation tissue formation). The authors have recently developed a new silicone airway stent (GINA stent) with an anti-migration design, dynamic structure that enables the reduction of stent cross-sectional area, and radio-opacity. The present study aimed to evaluate the mechanical characteristics and performance of the novel GINA stent using a porcine tracheal stenosis model. In the current study, all the tests involved the comparison of the GINA stent [outer diameter (OD, mm): 14; length (L, mm): 55] with the Dumon stent (OD: 14; L: 50). The mechanical tests were performed using a digital force gauge, in order to determine the anti-migration force, expansion force, and flexibility. The present study evaluated the short-term (3 weeks) performance of the two stents after implantation [GINA (n = 4) vs. Dumon (n = 3)] in the porcine tracheal stenosis model. The results pertaining to the comparison of the mechanical properties of the GINA and Dumon stents are stated as follows: anti-migration force (18.4 vs. 12.8 N, P = 0.008); expansion force (11.9 vs. 14.5 N, P = 0.008); and flexibility (3.1 vs. 4.5 N, P = 0.008). The results pertaining to the comparison of the short-term performance of the GINA and Dumon stents are stated as follows: mucus retention (0/4 vs. 0/3); granulation tissue formation (0/4 vs. 0/3); and migration (1/4 vs. 2/3). The GINA stent displayed better mechanical properties and comparable short-term performance, compared to the Dumon stent.


Influences of psychosocial factors and home food availability on healthy meal preparation.
The involvement of children in healthy meal preparation activities has emerged as a potential strategy to promote healthy eating behaviour among children. However, there is a lack of understanding of children's internal (psychosocial factors) and external factors (home food availability) that may support the practice of preparing healthy meals. This study aimed to determine children's psychosocial factors of healthy meal preparation within themselves and their external environment of home food availability as predictors for the practice of healthy meal preparation. Public schools (n = 8) from all three zones (Bangsar-Pudu, Keramat and Sentul) in Kuala Lumpur, Malaysia, were selected through stratified random sampling. Two hundred children aged 9-11 and their parents participated. Children's psychosocial factors towards healthy meal preparation and their home food availability were assessed through children and parents, respectively, using validated questionnaires. Majority of the schoolchildren (86.5%) had poor practice of healthy meal preparation. Increased attitude (r = 0.344, P < 0.001) and self-efficacy (r = 0.501, P < 0.001) of healthy meal preparation and the availability of fruits (r = 0.304, P < 0.001), vegetables (r = 0.243, P < 0.001) and healthful ready-to-eat foods (r = 0.227, P = 0.001) at home were positively correlated with the practice of preparing healthy meals. After adjusting for age, sex and monthly household income, increased self-efficacy (P < 0.001), availability of fruits (P = 0.01) and lower availability of less healthful ready-to-eat food (P = 0.01) were associated with better healthy meal preparation practices. Outcomes revealed that positive self-efficacy of healthy meal preparation, home food availability of fruits and less healthful alternatives were associated with the practice of healthy meal preparation and thus should be targeted in future health-promotion strategy.


Thrombotic thrombocytopenic purpura presenting as a sudden headache with focal neurologic findings.
We report a case of thrombotic thrombocytopenic purpura presenting as a sudden headache with associated neurologic deficits. The diagnosis of this rare disorder is discussed, with special attention given to a potential pitfall in evaluation and treatment--platelet transfusion.


Mental Health Disparities Between Lesbian Mothers and Heterosexual Parents: the Mediating Role of Positivity.
Previous evidence has shown better mental health outcomes for lesbian mothers, in comparison with heterosexual parents. The present study explored the mediating role of positivity (i.e., the tendency to view life with a positive outlook) in determining these mental health differences. Seventy-two Israeli lesbian mothers by donor insemination (from 36 families) were compared with 72 Israeli heterosexual parents by assisted reproduction (without donated gametes; from 36 families) on positivity, life satisfaction, and depressive symptomatology. All parents were cisgender and had at least one child born through assisted reproduction, aged 3-10 years. Data were collected between December 2019 and February 2021. Mediational analyses indicated that lesbian mothers reported greater positivity, which was, in turn, associated with greater life satisfaction and less depressive symptomatology. The results pinpoint the possible protective and strengthening role of positivity for lesbian mothers in the pronatalist and familistic environment of Israel. The research contributes to the literature on the mental health of parents with diverse sexual orientations living outside of the USA and Europe. Policy Implications Policymakers and mental health professional should be knowledgeable about the importance of improving positivity as a strategy for reducing depressive symptomatology and promoting life satisfaction among lesbian mothers. Moreover, policy makers and legislators are called to ease the access of sexual minority individuals to parenthood, as in this population parenthood associates with heightened mental health outcomes.


Spontaneous pneumorrhachis, pneumomediastinum, pneumopericardium, and subcutaneous emphysema. Rare features of Hamman Syndrome.
Pneumorrhachis (air within the spinal canal), Pneumomediastinum (abnormal air in the mediastinum), Pneumopericardium (air in the pericardial space), and Subcutaneous emphysema (air trapped under the skin) are rare conditions which are rare features of Hamman Syndrome. Some of pulmonary diseases that relate to pneumorrhachis have been reported in the literature; but Hamman Syndrome with Pneumorrhachis and Pneumopericardium due to violent coughs that triggered by tongue scraping are very rare. A 20-year-old male with no previous lung disease or trauma was brought to the emergency department due to acute chest pain, dyspnea, choking, syncope, and neck swelling which started after several self-induced coughs when he was brushing his tongue. Chest CT scan revealed Pneumorrhachis, pneumomediastinum, Pneumopericardium and extensive subcutaneous emphysema associated with lung contusions. Barotrauma due to violent coughs that triggered by tongue scraping may lead to lung injury resulting in Hamman Syndrome with rare features of pneumorrhachis and Pneumopericardium. To our knowledge this is the first case report of Hamman syndrome with pneumorrhachis and Pneumopericardium secondary to tongue brushing-induced lung injury in Somalia. Violent coughs from tongue scarping can lead to Hamman Syndrome with Pneumorrhachis and Pneumopericardium.


Neurocysticercosis: the effectiveness of the cysticidal treatment could be influenced by the host immunity.
Neurocysticercosis, a clinically and radiologically pleomorphic parasitic disease, is still endemic to most non-developed countries of Latin America, Africa, and Asia. Anti-helminthic drugs (AHD) are generally effective and rapidly destroy parenchymal cysticerci. In contrast, several cycles of AHD are frequently necessary to damage extraparenchymally located parasites. The present study was designed to evaluate whether differences in the immunological profile of the patients is involved in the diversity of the response to AHD. To this end, a global gene expression microarray and a cytokine analysis were made. Responder patients were those showing a radiological reduction greater than 50 % in the parasite burden following AHD treatment. Microarray pre- and post-treatment comparisons showed that a total of eighteen immune-related genes were up-regulated in the five responder patients with respect the expression profile seen in the four non-responder subjects. The function of up-regulated genes exerted pro-inflammatory (RORγC, Sema4A, SLAMF3, SLAMF6), anti-inflammatory (TGFβ, TNFRSF25, TNFRS18, SLAMF1, ILF2), or immunomodulatory effects (CXCL2, RUNX3, SLAMF9, TGFBR3). To further explore the causes of the heterogeneity in the response to treatment, a wide ELISA cytokine analysis was performed in serum, PBMC supernatants, and CSF samples from 39 responder and 26 non-responder patients. Responder patients showed higher CSF IL-17A levels (P = 0.04) and higher supernatant IL-6 levels (P = 0.03) 60 days after treatment. These results suggest a possible influence of pro-inflammatory cytokines on the response to AHD as observed by radiological methods, and thus the possible participation of the host immunity in the effectiveness of AHD treatment.


A Developmental Model of the Sexual Minority Closet: Structural Sensitization, Psychological Adaptations, and Post-closet Growth.
Across the lifespan, most sexual minority individuals experience the closet-a typically prolonged period in which no significant others know their sexual identity. This paper positions the closet as distinct from stigma concealment given its typical duration in years and absolute removal from sources of support for an often-central identity typically during a developmentally sensitive period. The Developmental Model of the Closet proposed here delineates the vicarious learning that takes place before sexual orientation awareness to shape one's eventual experience of the closet; the stressors that take place after one has become aware of their sexual orientation but has not yet disclosed it, which often takes place during adolescence; and potential lifespan-persistent mental health effects of the closet, as moderated by the structural, interpersonal, cultural, and temporal context of disclosure. The paper outlines the ways in which the model both draws upon and is distinct from earlier models of sexual minority identity formation and proposes several testable hypotheses and future research directions, including tests of multilevel interventions.


Immunohistologic studies on subpopulations of lymphocytes in cattle with enzootic bovine leukosis.
The distribution of subpopulations of lymphocytes in lymph nodes and tumors from cattle with enzootic bovine leukosis (EBL) was examined by immunohistochemistry using a panel of monclonal antibodies against leukocyte differentiation molecules of EBL. The lesions in lymph nodes could be divided into three types based on the extent of infiltration and proliferation of neoplastic cells with provirus and differential expression of leukocyte differentiation molecules. The number of B-B2+, sIgM+ cells was reduced in frequency in follicles during the neoplastic cell proliferation. CD4- and CD8-positive alpha/beta T cells and gamma/delta T cells positive for WC1 (workshop cluster designation) were also reduced in frequency in areas infiltrated with neoplastic cells. Almost all neoplastic cells were B-B2- and IgM-positive. However, there were a few B-B2- and/or IgM-negative cells or cells stained faintly in all cases. WC1+ cells were not observed in tumor tissues. However, CD4+ and CD8+ cells were observed throughout tumor tissues, suggesting a role for these cells in tumor immunity.


CD8 T cell response and its released cytokine IFN-γ are necessary for lung alveolar epithelial repair during bacterial pneumonia.
Alveolar epithelial regeneration depends on the activity of resident quiescent progenitor cells. Alveolar epithelial type II (AT2) cells are known as the alveolar epithelial progenitor cells. They exit quiescent state, proliferate rapidly in response to injury and differentiate into alveolar epithelial type I (AT1) cells to regenerate the damaged alveolar epithelium. Although AT2 cell plasticity has been a very intense field of research, the role of CD8 T cell response and their released cytokine IFN-γ, in regulating AT2 cell plasticity and alveolar epithelial repair and regeneration after injury remains largely unknown. We used flow cytometry to quantify the amount of CD8 T cells in mouse lungs after bacterial pneumonia caused by Streptococcus pneumoniae. To determine whether CD8 T cells and their released cytokine IFN-γ are necessary for AT2 cell activity during alveolar epithelial regeneration, we performed loss of function studies using anti-CD8 or anti-IFN-γ monoclonal antibody (mAb) treatment in vivo. We assessed the effects of CD8 T cells and cytokine IFN-γ on AT2 cell differentiation capacity using the AT2- CD8 T cell co-culture system in vitro. We detected a transient wave of accumulation of CD8 T cells in mouse lungs, which coincided with the burst of AT2 cell proliferation during alveolar epithelial repair and regeneration in mice following bacterial pneumonia caused by Streptococcus pneumoniae. Depletion of CD8 T cells or neutralization of cytokine IFN-γ using anti-CD8 or anti-IFN-γ monoclonal antibody significantly reduced AT2 cell proliferation and differentiation into AT1 cells in mice after bacterial pneumonia. Furthermore, co-culture of CD8 T cells or cytokine IFN-γ with AT2 cells promoted AT2-to-AT1 cell differentiation in both murine and human systems. Conversely, blockade of IFN-γ signaling abrogated the increase in AT2-to-AT1 cell differentiation in the AT2- CD8 T cell co-culture system. Our data demonstrate that CD8 T-cell response and cytokine IFN-γ are necessary for promoting AT2 cell activity during alveolar epithelial repair and regeneration after acute lung injury caused by bacterial pneumonia.


Does maintenance/consolidation chemotherapy have a role in the management of small cell lung cancer (SCLC)? A metaanalysis of the published controlled trials.
The role of maintenance/consolidation chemotherapy was assessed in the management of small cell lung cancer (SCLC) via a metaanalytic approach. The Medline and Cochrane databases were searched for relevant randomized clinical trials that compared maintenance chemotherapy with follow-up. Quality of trials was assessed by European Lung Cancer Working Party (ELCWP) score. Odds ratios and rate differences were used as the effect size. Mantel-Haenszel tests with fixed and random effect models were conducted for 1- and 2-year overall survival (OAS) and progression-free survival (PFS). Fourteen relevant randomized clinical trials to date, encompassing 2550 patients, with trial sizes ranging from 36 to 610, were identified. Both 1- and 2-year mortality were reduced with maintenance/consolidation chemotherapy. With the fixed model, odds ratios for 1- and 2-year OAS were 0.67 (95% confidence interval [CI] = 0.56-0.79), P < 0.001, and also 0.67 (95% CI = 0.53-0.86), P < 0.001. Likewise, 1- and 2-year PFS were better with maintenance/consolidation chemotherapy, with odds ratios of 0.49 (95% CI = 0.37-0.63), P < 0.001, and 0.64 (95% CI = 0.45-0.92), P < 0.015. The random model gave similar results. In accordance, maintenance chemotherapy improved 1- and 2-year OAS by 9% (from 30-39%) and 4% (from 10-14%), respectively. Similarly, 1- and 2-year PFS were also improved. Maintenance/consolidation chemotherapy improves survival in SCLC. New randomized clinical trials are needed to further refine the place of this approach in the management of SCLC.


Left-right differences in the Hoffmann reflex recovery curve associated with handedness in normal subjects.
The relation between handedness and the Hoffmann (H) reflex recovery curve was studied in normal subjects. In right handers, the H response recovery curve from the right leg was significantly lower than that from the left leg. The opposite finding was obtained from the left handers. In mixed handers (ambidexters), there was no significant difference between the recovery curves from the right and left legs. It was concluded that there is a close relationship between handedness and the height of the H response recovery curves from the right and left sides.


Echocardiographic evaluation of paravalvular aortic regurgitation of a patient with recurrent aortic valve replacements.
Paravalvular regurgitation (PVR) is a serious complication after surgical valve replacement. Echocardiography is the gold standard technique to assess the severity of PVR with an integrated approach. A 48-year-old male underwent aortic valve replacement due to infective endocarditis (IE). During in-hospital cardiac rehabilitation after a redo surgery for a new IE three years later, an echo-free anterior space around the valve with several PVRs through transthoracic echocardiography (TTE) was identified. On transesophageal echocardiography (TOE) a double PVR (anterior and posterior) with abscessual cavity was detected. The patient's conditions worsened within six months with hemodynamic instability: a massive PVR due to a large abscess cavity next to the right cusp was confirmed by TTE and TOE and a third surgery was carried out. On the third admission at our Rehabilitation Unit the echo features were normal. Patient did not report any cardiovascular symptoms at 1 year follow-up.


Archaeomonad (Chrysophyta) cysts: ecological and paleoecological significance.
Archaeomonads are chrysophyte cysts abundant in Weddell Sea sea ice, but they form in the water column in response to conditions that occur in areas where no sea ice is present. The association between archaeomonads and sea ice depends on a particular sequence of oceanographic conditions, beginning with lateral advection followed by vertical harvesting on rising ice crystals. Comparing fossil and modern distributions suggests archaeomonads underwent an ecological transition or expansion in the Early Tertiary Period, from sediment underlying anoxic waters to sediments underlying sea ice.


Axial Pain and Arthritis in Diagnosed Inflammatory Bowel Disease: US National Health and Nutrition Examination Survey Data.
To estimate the nationally representative prevalence of chronic axial pain, inflammatory back pain (IBP), axial spondyloarthritis (axSpA), and peripheral arthritis in persons diagnosed with inflammatory bowel disease (IBD). US National Health and Nutrition Examination Survey (NHANES) data from the 1976-1980 and 2009-2010 survey cycles. In NHANES 1976-1980, the chronic axial pain prevalence in participants with diagnosed ulcerative colitis (UC) was 19.5% vs 7.2% in the general population (P<.01). Neck or upper back, lower back, and Amor criteria-based axial pain were also significantly increased (11.2%, 14.5%, and 13.0%, respectively, vs 3%-5% in the general population (P<.01). In those with diagnosed UC, 40% had axial pain onset at an age older than 45 years; 30.2% reported peripheral arthralgias, and 12.2% reported peripheral arthritis. Arthritis findings on examination were uncommon. In NHANES 2009-2010, axial pain in those diagnosed with IBD had similar patterns. Despite high rates of chronic axial pain in those with IBD, few cases met the IBP and axSpA classification criteria. This apparent discrepancy is unexplained. However, in IBD, axial pain onset at an age older than 45 years is common; and these may not meet IBP and axSpA age criteria. Also, neck pain was increased in those with IBD but is not included in most IBP and axSpA criteria. Peripheral arthralgias and chronic arthritis symptoms were common, but examination findings were not, suggesting that tenosynovitis or enthesitis is more likely than frank arthritis to occur in patients with UC.


The Molecular Genetic Expression as a Novel Biomarker in the Evaluation and Monitoring of Patients With Osteosarcoma-Subtype Bone Cancer Disease.
One of the leading causes of death among patients with malignancies is represented by bone cancer. According to current studies, the leading cause of death among these patients is represented by late diagnosis, poor response to therapy, and the lack of accuracy in terms of clinical evaluation. In this regard, there have been developed a series of methods of diagnosis and evaluation, the most investigated being represented by miRNA expression. In this updated work, we want to present a series of changes in the expression of miRNAs in bone cancer. Moreover, we want to present the implications of miRNAs in targeted therapy in such patients. Studies available in scientific databases such as PubMed and Scopus were examined. The studies were searched using the keywords "miRNAs expression", "bone cancer", "genetic therapy" and "genetic biomarkers." For the evaluation and monitoring of bone cancer, the expression of miRNAs can be successfully used due to increased specificity. Using miRNAs as gene therapy can be also considered a therapeutic method of the future, mainly due to selective and targeted response of the body.


Simple assessment of homogeneity in pharmaceutical mixing processes using a near-infrared reflectance probe and control charts.
Determination of homogeneous mixing of the active pharmaceutical ingredient (API) is an important in-process control within the manufacturing of solid dosage forms. In this paper two new near-infrared (NIR) based methods were presented; a qualitative and a quantitative method. Both methods are based on the calculation of net analyte signal (NAS) models which were very easy to develop, specific with respect to the API and required no additional reference analysis. Using a well-mixed batch as a 'golden standard' batch, control charts were developed and used for monitoring the homogeneity of other batches with NIR. The methods were fast, easy to use, non-destructive and provided statistical tests of homogeneity. A mixing study was characterized with the two methods and the methods were validated by comparison with traditional HPLC analysis.


Cell viability assays: introduction.
The measurement of cell viability plays a fundamental role in all forms of cell culture. Sometimes it is the main purpose of the experiment, such as in toxicity assays. Alternatively, cell viability can be used to -correlate cell behaviour to cell number, providing a more accurate picture of, for example, anabolic -activity. There are wide arrays of cell viability methods which range from the most routine trypan blue dye exclusion assay to highly complex analysis of individual cells, such as using RAMAN microscopy. The cost, speed, and complexity of equipment required will all play a role in determining the assay used. This chapter aims to provide an overview of many of the assays available today.


Structural studies of the final enzyme in the alpha-aminoadipate pathway-saccharopine dehydrogenase from Saccharomyces cerevisiae.
The 1.64 A structure of the apoenzyme form of saccharopine dehydrogenase (SDH) from Saccharomyces cerevisiae shows the enzyme to be composed of two domains with similar dinucleotide binding folds with a deep cleft at the interface. The structure reveals homology to alanine dehydrogenase, despite low primary sequence similarity. A model of the ternary complex of SDH, NAD, and saccharopine identifies residues Lys77 and Glu122 as potentially important for substrate binding and/or catalysis, consistent with a proton shuttle mechanism. Furthermore, the model suggests that a conformational change is required for catalysis and that residues Lys99 and Asp281 may be instrumental in mediating this change. Analysis of the crystal structure in the context of other homologous enzymes from pathogenic fungi and human sources sheds light into the suitability of SDH as a target for antimicrobial drug development.


Detection and characterization of hepatitis A virus circulating in Egypt.
Hepatitis A virus (HAV) still poses a considerable problem worldwide. In the current study, hepatitis A virus was recovered from wastewater samples collected from three wastewater treatment plants over one year. Using RT-PCR, HAV was detected in 43 out of 68 samples (63.2%) representing both inlet and outlet. Eleven positive samples were subjected to sequencing targeting the VP1-2A junction region. Phylogenetic analysis revealed that all samples belonged to subgenotype IB with few substitutions at the amino acid level. The complete sequence of one isolate (HAV/Egy/BI-11/2015) showed that the similarity at the amino acid level was not reflected at the nucleotide level. However, the deduced amino acid sequence derived from the complete nucleotide sequence showed distinct substitutions in the 2B, 2C, and 3A regions. Recombination analysis revealed a recombination event between X75215 (subgenotype IA) and AF268396 (subgenotype IB) involving a portion of the 2B nonstructural protein coding region (nucleotides 3757-3868) assuming the herein characterized sequence an actual recombinant. Despite the role of recombination in picornaviruses evolution, its involvement in HAV evolution has rarely been reported, and this may be due to the limited available complete HAV sequences. To our knowledge, this represents the first characterized complete sequence of an Egyptian isolate and the described recombination event provides an important update on the circulating HAV strains in Egypt.


Acetylcholinesterases of blood-feeding flies and ticks.
Acetylcholinesterase (AChE) is the biochemical target of organophosphate (OP) and carbamate pesticides for invertebrates, vertebrate nerve agents, and AChE inhibitors used to reduce effects of Alzheimer's disease. Organophosphate pesticides (OPs) are widely used to control blood-feeding arthropods, including biting flies and ticks. However, resistance to OPs in pests affecting animal and human health has compromised control efficacy. OP resistance often results from mutations producing an OP-insensitive AChE. Our studies have demonstrated production of OP-insensitive AChEs in biting flies and ticks. Complementary DNA (cDNA) sequences encoding AChEs were obtained for the horn fly, stable fly, sand fly, and the southern cattle tick. The availability of cDNA sequences enables the identification of mutations, expression and characterization of recombinant proteins, gene silencing for functional studies, as well as in vitro screening of novel inhibitors. The southern cattle tick expresses at least three different genes encoding AChE in their synganglion, i.e. brain. Gene amplification for each of the three known cattle tick AChE genes and expression of multiple alleles for each gene may reduce fitness cost associated with OP-resistance. AChE hydrolyzes the neurotransmitter, acetylcholine, but may have additional roles in physiology and development. The three cattle tick AChEs possess significantly different biochemical properties, and are expressed in neural and non-neural tissues, which suggest separation of structure and function. The remarkable complexity of AChEs in ticks suggested by combining genomic data from Ixodes scapularis with our genetic and biochemical data from Rhipicephalus microplus is suggestive of previously unknown gene duplication and diversification. Comparative studies between invertebrate and vertebrate AChEs could enhance our understanding of structure-activity relationships. Research with ticks as a model system offers the opportunity to elucidate structure-activity relationships for AChE that are important for advances in targeted pest control, as well as potential applications for medicine and biosecurity.


Measurement of right ventricular ejection fraction by contrast echocardiography.
We evaluated 20 healthy subjects with no cardiac disease (8 males, 12 females, age 49+/-12) to determine the accuracy of right ventricular ejection fraction measurement with contrast echocardiography performed with D-galactose (Echovist 300). All patients underwent two dimensional echocardiography where the right ventricular ejection fraction was calculated by the Simpson's rule first without contrast, then after the injection of 5 ml D-galactose in the same position and compared to the right ventricular ejection fraction measured by the first pass radionuclide angiography on the same day. Subjects had a normal left ventricular ejection fraction of 66+/-5 and a body mass index of 28.9+/-1.2. The correlation between echocardiographic and radionuclide derived right ventricular ejection fraction significantly increased when contrast was used (r=0.81 vs. r=0.6). The r value for interobserver variability also increased significantly with contrast use (r=0.98 vs. r=0.7). We conclude that D-galactose contrast injection significantly enhances border detection and improves the accuracy of right ventricular ejection fraction calculations with echocardiography making it a simple and reliable method.


Bronchoscopy in suspected pulmonary TB with negative induced-sputum smear and MTD(®) Gen-probe testing.
In our institution, patients with suspected pulmonary TB undergo multiple induced-sputum sampling for microscopy, culture and nucleic acid amplification (NAA) with the MTD(®) Gen-probe assay. Those with negative induced-sputum results still suspected with TB are then referred for bronchoscopy. We sought to determine the diagnostic yield of bronchoscopy in these patients with negative initial induced-sputum results both via smear and NAA testing. We identified 30 consecutive cases of suspected pulmonary TB between 2001 and 2007, who had undergone a diagnostic bronchoscopy after negative results on induced-sputum smears and the MTD(®) Gen-probe on at least 2 samples. The cohort (M = 20 & F = 10) had a median age of 37 (range 16-85 yrs); were predominantly foreign born (27/30); HIV-negative (29/30) individuals with strongly positive TST's (mean 18 + 5 mm). Induced-sputum cultures were negative for M-TB in all patients after a full 60-day incubation period. BAL was culture positive for M-TB in 3/30 cases (10%) with 2 strains being pan-sensitive and the third being INH resistant. BAL microscopy with acid-fast smear (n = 30) and BAL Gen-probe (n = 23) were negative in all cases. A third of the patients (9/27, 33%) with negative bronchoscopy results were treated for culture negative TB. Treatment for latent TB was initiated in 5/27 (18%) individuals whereas 13/27 (48%) received no further treatment. Bronchoscopy provided diagnostic confirmation of pulmonary TB in 10% of subjects at least 2 negative induced-sputum samples by smear microscopy and NAA testing.


Medicine in Extreme Environments: A New Medical Student Elective Class for Wilderness, Aerospace, Hyperbaric, Exercise, and Combat Medicine.
We developed an elective course titled Medicine in Extreme Environments (MEE) at the University of Texas Southwestern Medical Center for first- and second-year medical students. This course covered physiology, research, clinical practice, and career guidance regarding the fields of wilderness, space, hyperbaric, combat, and exercise medicine. The primary aim was to generate interest in and awareness of these seldom covered fields of medicine by exposing medical students to these disciplines during their preclinical years. A postcourse questionnaire was implemented to investigate whether the MEE course increased awareness of, interest in, and knowledge in the fields of medicine included in the curriculum. Through 2 iterations of the class, a total of 67 students enrolled in the course, and 38 students completed the questionnaire. After course completion, 95% felt they better understood the work and lifestyle of the fields covered, 100% learned more about concepts of each field, and 74% agreed that the elective influenced the direction of their future careers to include some part of the fields emphasized. Although only a limited number of students enrolled in this course, these initial findings suggest that the MEE curriculum may have some utility in promoting awareness of and interest in these medical disciplines among students who attend the course. With continued student and faculty support, this course will likely be continued annually at our institution. We believe that certain aspects of this course may be useful in helping develop similar courses at other medical schools.


Which method to measure dentomaxillary discrepancy?
Tooth-size assessment is a useful indicator of dental crowding which constitutes one of the main parameters in tooth-size arch-length discrepancy (TSALD). Systematic TSALD evaluation is imperative in all patients consulting for dentofacial orthopedic treatment. The present study aims to compare four measurement techniques for calibrating tooth size. It was performed on casts taken from 30 Moroccan patients consulting at the Dentofacial Orthopedics Department of the Rabat School of Dentistry. Four measurement methods were used to calculate the largest mesiodistal diameter of mandibular teeth mesial to the first molars. Statistical analysis showed that the methods using a digital caliper, the analog vernier caliper and the computerized technique are reliable, accurate, and interchangeable. In contrast, the analog caliper with no vernier is less accurate.


Atypical chest pain: a computer-assisted study.
We have recently developed a Data Bank for Digestive Disorders, with primary data derived from the performance of upper gastrointestinal endoscopy. By using this system to analyze the clinical characteristics of patients with atypical chest pain, we found information from the patient's history (reflux, dysphagia, abdominal pain) useful in determining final diagnosis. Further development of the system may allow more selective use of diagnostic procedures for patients with digestive disorders.


Expression and regulation of nuclear receptor coactivators in glucocorticoid action.
Nuclear receptor coactivators are involved in receptor-mediated transcriptional activation of target genes in a hormone-sensitive manner, and the mechanism of their transactivation has been studied in recent years. The glucocorticoid receptor (GR) interacts with several coactivators, including steroid receptor coactivator-1 (SRC-1) family and CREB-binding protein (CBP). Since coactivators function as transcription amplifiers, subtle changes in expression levels of coactivators in certain cells would markedly intensify receptor-mediated transcriptional activity. The regulation of coactivators by glucocorticoid action, however, has not yet been clarified. In this study, we have shown that one of the coactivators interacting with GR, SRC-1, is downregulated by dexamethasone (DEX) both in vivo and in vitro. In experiments on Sprague-Dawley rats in vivo, the downregulation of SRC-1 was observed in heart, stomach, kidney, liver, and cerebrum, and in experiments on two types of kidney-derived cells in vitro, similar downregulation of SRC-1 was demonstrated in both types of cells. DEX-mediated downregulation of SRC-1 mRNA recovered in 4-8 h, while the downregulation of SRC-1 protein lasted for 12 h and its levels returned to the basal level, 24 h after DEX treatment. Other coactivators examined in this study showed no remarkable changes in expression by DEX treatment, implying that ligand-mediated downregulation of SRC-1 has a pivotal role in the physiology of glucocorticoid action.


Transfer of metal element in soil plant chicken food chain: health risk assessment.
This investigation was done for the assurance of potassium amassing in four assortments of maize (grains, shoot and root), soil, and water and in seven tissues of chickens (kidney, liver, heart, bone, gizzard, breast meat). The analysis of variance showed significant differences for potassium concentration in water in all sources of water; however, the season and variety significantly influenced the quantity of potassium in cereals. The corn varieties MMRI, Sadaf, and Pearl behaved differently when treated with water from various sources. Water taken from sewage had a higher concentration of potassium compared to canal and groundwater that is why the maize plants irrigated with this water had a higher grouping. Data regarding potassium concentration in different body parts of chicken showed that season and treatment have a significant effect on the potassium concentration in chicken organs. The variety was non-significant for the potassium concentration only in the bone. Season × Variety interaction was only significant in blood, meat heart, and gizzard. Season × Treatment and Variety × Treatment interactions were significant in the heart, kidney, and gizzard. The potassium contents were higher in the chicken body parts that were reared on grains irrigated with sewage water as compared to other groups. The potassium contents were higher in the chicken meat (96.23 ± 0.00) reared on grains of the Pearl variety raised with the sewage water. In a nutshell, the irrigation of grains with sewage water led to accumulation of nutrients greater than those irrigated with ground or canal water.


Immunosuppressive Total Nodal Irradiation-Based Reconditioning Regimens After Graft Rejection or Graft Failure in Pediatric Patients Treated With Myeloablative Allogeneic Hematopoietic Cell Transplantation.
This retrospective analysis aimed to address the efficacy of total nodal irradiation (TNI)-based reconditioning regimens in pediatric patients with graft failure/rejection after allogeneic hematopoietic cell transplantation. Thirty-three pediatric patients with malignant (n = 25) and nonmalignant diseases (n = 8) were treated with a TNI-based reconditioning regimen. All patients received a 7-Gy single dose combined with anti-T lymphocyte antibody OKT3 (n = 16), anti-thymocyte globulin (n = 24), fludarabine (n = 31), and/or thiotepa (n = 28), followed by an infusion of peripheral blood stem cells (n = 31) or bone marrow transplant (n = 2). Twenty-eight of 33 patients had haploidentical family donors. After a median of 11 days, engraftment was seen in 32 of 33 children. Two children died 34 days after retransplantation because of either disease relapse or treatment-related multiple organ failure. Severe acute toxicity was reported in only 1 child (systemic inflammatory response syndrome-like reaction; recovery after cortisone treatment). The average follow-up was 60.2 months (range, 1.1-162.5 months). Event-free and overall survival rates at 2/5 years follow-up were 62.0%/58.6% and 65.1%/61.7%, respectively. Despite sustained engraftment, 12 patients died from disease relapse (n = 3), Moschkowitz syndrome (n = 1), or multiple organ failure (n = 8). Follow-up data were available for 18 of 21 survivors, with a median follow-up of 92.8 months (range, 3.6-162.5 months). Hypothyroidism was present in 78.6% of patients, and sex/growth hormonal insufficiencies were reported for 37.5%. Mean forced expiratory volume in 1 second after TNI was 84%; mean vital capacity was 79%. Severe growth failure (<3rd percentile) occurred in 28.6% (height) and 35.7% (weight) of patients. No secondary malignancies were reported. In the high-risk group of patients with graft failure/rejection after allogeneic hematopoietic cell transplantation, the TNI-based reconditioning regimen seems to allow sustained engraftment combined with a favorable toxicity profile, leading to long-term event-free and overall survival. Late toxicity after a median follow-up of over 7.5 years includes growth failure, manageable hormonal deficiencies, and a low risk of decrease of lung function.


Mechanistic Insights into Factor VIII Immune Tolerance Induction via Prenatal Cell Therapy in Hemophilia A.
Prenatal stem cell and gene therapy approaches are amongst the few therapies that can promise the birth of a healthy infant with specific known genetic diseases. This review describes fetal immune cell signaling and its potential influence on donor cell engraftment, and summarizes mechanisms of central T cell tolerance to peripherally-acquired antigen in the context of prenatal therapies for Hemophilia A. During early gestation, different subsets of antigen presenting cells take up peripherally-acquired, non-inherited antigens and induce the deletion of antigen-reactive T-cell precursors in the thymus, demonstrating the potential for using prenatal cell and gene therapies to induce central tolerance to FVIII in the context of prenatal diagnosis/therapy of Hemophilia A. Prenatal cell and gene therapies are promising approaches to treat several genetic disorders including Hemophilia A and B. Understanding the mechanisms of how FVIII-specific tolerance is achieved during ontogeny could help develop novel therapies for HA and better approaches to overcome FVIII inhibitors.


Evidence for glycosyltransferases in trout liver microsomes (Salmo gairdneri).
1. Trout (Salmo gairdneri) serum is rich in glycoproteins which are synthetized in liver. 2. An attempt to localize glycosyltransferases in hepatocytes is described, using cellular fractionation and marker enzyme determination. 3. Galactosyltransferase, mannosyltransferase, N-acetyl-glucosaminyl transferase, glucosyltransferase, sialyltransferase (on exogenous acceptor) are found in a microsomal fraction obtained by centrifugation at 117 X 10(5) g min of the post-mitochondrial supernatant. 4. Mannose is transferred to endogenous lipids and proteins.


Surgically Treated Brain Metastases from Uterine Origin: A Case Series and Systematic Review.
We aimed to describe our institutional case series of 9 surgically treated uterine brain metastases and perform a survival analysis through a systematic review and a pooled individual patient data study. This study was divided into 2 sections: 1) a retrospective, single center patient series assessing outcomes of neurosurgical treatment modalities in patients with malignancy arising in the uterus with brain metastases and 2) a systematic review of the literature between 1980 and 2021 regarding treatment outcomes of individual patients with intracranial metastasis of uterine origin. Pooled cohort survival analysis was done via univariate and Cox regression multivariable analysis and Kaplan-Meier curves. Final statistical analysis included a total of 124 pooled cohort patients: one hundred fifteen patients from literature review studies plus 9 patients from our institution. Median age at the time of diagnosis was 54 years. Median time from diagnosis of the primary cancer to brain metastasis was 19 months (0-166 months). Surgery and radiotherapy resulted in the highest median OS of 11 months (P < 0.001). Multivariable analyses indicated that the presence of more than one central nervous systemlesion had an increased risk on OS (P = 0.003). Microsurgery, stereotactic radiosurgery, and whole brain radiotherapy remain the evidence-based mainstay applicable to the treatment of multiple brain metastases. Brain metastases of cancer arising in the uterus appear to result most often in multiple lesions with dismal prognosis. The seemingly most efficacious treatment modality is surgery and radiotherapy. However, this treatment is often not an option when more than 1 or 2 brain lesions are present.


Primary leiomyosarcoma of the thyroid gland.
A primary leiomyosarcoma of the thyroid gland in a 72 year old Japanese woman is described. This is the second case reported in the English literature. The patient presented with a 7 month history of a gradually expanding tumor in the right neck. The surgical specimen taken by thyroid lobectomy revealed a relatively well demarcated tumor, 2 x 2 x 3 cm in size, confined to the right lobe. Histologically, the tumor showed a classical leiomyosarcomatous appearance of interlacing fascicles of spindle-shaped cells with occasional blunt-ended nuclei and a high frequency of mitotic figures. Immunohistochemistry of the tumor cells clearly showed smooth muscle differentiation; the cells were positive for desmin, muscle-specific actin and vimentin and negative for cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, thyroglobulin and calcitonin. The patient was free of disease for 3 years and 11 months without further treatment when evidence of multiple bone metastases appeared on bone scintigraphy. She died of pneumonia 4 years and 3 months after the lobectomy.


FGF-2 enhances fibrogenetic changes in TGF-β2 treated human conjunctival fibroblasts.
The objective of the current study was to examine the effects of fibroblast growth factor-2 (FGF-2) on conjunctival fibrogenesis that was induced by the presence of transforming growth factor-β2 (TGF-β2). Two-dimension (2D) and three-dimension (3D) cultured human conjunctival fibroblasts (HconF) were used for this purpose. The 2D and 3D cultured HconF were characterized by transendothelial electrical resistance (TEER) and FITC dextran permeability measurements (2D), real-time metabolic analyses (2D), size and stiffness measurements (3D), and the mRNA expression of extracellular matrix molecules, their modulators, Tissue inhibitor of metalloproteinases and matrix metalloproteinases and ER-stress related genes (2D and 3D). FGF-2 significantly increased planar proliferation, as evidenced by TEER values and FITC dextran permeability, and shifted glucose metabolism to the energetic phenotype of 2D HconF cells, and the stiffness of the 3D spheroids, and these effects were further enhanced in the presence of TGF-β2. Analyses of the expression of possible candidate molecules involved in cell architecture and stress indicated that some additive effects caused by both factors were also recognized in some of these molecules. The findings reported herein indicate that the FGF-2, either along or additively with TGF- β2 increased the fibrogenetic changes on the plane as well as in the spatial space of HconF cells.


Method for calculating dose when lung tissue lies in the treatment field.
The absorbed dose in lung and beyond lung as a result of increased lung transmission of x and gamma irradiation is described. The correction factor used to calculate the absorbed dose is a function of beam energy, field area, lung density, and lung and soft tissue depth. Agreement between measurements and calculations in the Alderson phantom is within 3%. An example of how this technique can be used is described.


The role of morphine in regulation of cancer cell growth.
Morphine is considered the "gold standard" for relieving pain and is currently one of the most effective drugs available clinically for the management of severe pain associated with cancer. In addition to its use in the treatment of pain, morphine appears to be important in the regulation of neoplastic tissue. Although morphine acts directly on the central nervous system to relieve pain, its activities on peripheral tissues are responsible for many of the secondary complications. Therefore, understanding the impact, other than pain control, of morphine on cancer treatment is extremely important. The effect of morphine on tumor growth is still contradictory, as both growth-promoting and growth-inhibiting effects have been observed. Accumulating evidence suggests that morphine can affect proliferation and migration of tumor cells as well as angiogenesis. Various signaling pathways have been suggested to be involved in these extra-analgesic effects of morphine. Suppression of immune system by morphine is an additional complication. This review provides an update on the influence of morphine on the growth and migration potential of tumor cells.


mTOR pathway is involved in ADP-evoked astrocyte activation and ATP release in the spinal dorsal horn in a rat neuropathic pain model.
ATP/ADP-evoked spinal astrocyte activation plays a vital role in the development of neuropathic pain. We aim to investigate the role of mammalian target of rapamycin (mTOR) pathway on the spinal astrocyte activation in the neuropathic pain development in rats. Sprague Dawley (SD) rats were subjected to chronic constriction of the sciatic nerve (CCI). Rapamycin or ADP was intrathecally injected daily to explore their effects on spinal astrocyte activation and pain development. Expression of glial fibrillary acidic protein (GFAP) and mTOR in the spinal dorsal horn was assessed by immunohistochemistry. Von Frey hairs and Hargreaves paw withdrawal test were conducted to evaluate mechanical allodynia and thermal sensitivity, respectively. Firefly luciferase ATP assay was used to assess the change of ATP level in cerebrospinal fluid (CSF) and medium of cultured astrocytes. GFAP expression was enhanced in the ipsilateral spinal dorsal horn from day 3 after surgery. GFAP and mTOR expression in the rat spinal dorsal horn on post-surgical day 14 was enhanced by daily intrathecal injection of ADP, which was inhibited by rapamycin. Rapamycin decreased lower mechanical pain threshold and the thermal withdrawal latency. Intrathecal injection of ADP enhanced the ATP release, which was partially inhibited by rapamycin. Study of cultured astrocytes indicated that ATP could be released from astrocytes. Our data demonstrated that ADP enhanced neuropathic pain in CCI rats, which was inhibited by rapamycin. This study indicates that targeting mTOR pathway could serve as a novel therapeutic strategy in neuropathic pain management.


Three's Company: Neuroimmune activation, sex, and memory at the tripartite synapse.
The neuroimmune system is required for normal cognitive functions such as learning and memory in addition to its critical role in detecting and responding to invading pathogens and injury. Understanding the functional convergence of neurons, astrocytes, and microglia at the synapse, particularly in the hippocampus, is key to understanding the nuances of such diverse roles. In the healthy brain, communication between all three cells is important for regulating neuronal activation and synaptic plasticity mechanisms, and during neuroinflammation, the activity and functions of all three cells can produce and be modulated by inflammatory cytokines. An important remaining component to this system is the conclusive evidence of sex differences in hippocampal plasticity mechanisms, hormone modulation of synaptic plasticity, functional properties of hippocampal neurons, and in neuroimmune activation. Sex as a biological variable here is necessary to consider given sex differences in the prevalence of memory-related disorders such as Alzheimer's disease and Post-Traumatic Stress disorder, both of which present with neuroimmune dysregulation. To make meaningful progress towards a deeper understanding of sex biases in memory-related disease prevalence, I propose that the next chapter of psychoneuroimmune research must focus on the signal integration and transduction at the synapse between experience-dependent plasticity mechanisms, neuroimmune activation, and the influence of biological sex.


Effect of hypertonic medium on protein synthesis of Mahoney and LSc poliovirus.
The initiation of synthesis of Mahoney virus protein is more sensitive to high osmolarity than initiation of synthesis of LSc virus protein. Production of Mahoney virus protein appears to be only slightly more resistant to high osmolarity than synthesis of HeLa-Rhino cell protein.


[Study of macrophages infiltrating rat cardiac allografts. II.--Cytoenzymatic analysis of cells infiltrating the grafts and of peritoneal macrophages in isograft and allograft recipients (author's transl)].
Cytoenzymatic analysis of cells infiltrating heart transplants in the rat confirms the high participation of monocytes and macrophages. However, when comparing iso and allografts, only slight differences are observed in the lysosomal enzyme specific colorations, whereas a striking difference in these colorations is found between heart infiltrates and peritoneal exsudates from these recipients. This could favour the hypothesis of a local macrophage activating process within the graft but seems more probably due to differences in cell maturation stages.


[Multimodality imaging in the cardiac catheterization laboratory].
Cardiac catheterization has greatly contributed to the progress made in the management of congenital heart diseases (CHD). Initially used in diagnosis, it allowed the understanding of heart diseases, their anatomy and hemodynamics. Gradually, the development of interventional cardiology has played a major role in the management of these malformations (Patent ductus arteriosus [PDA] and atrial septal defect [ASD] closure, pulmonary dilatation, percutaneous pulmonary valve implantation…). The development of such technology was made possible through the concomitant development of imaging techniques: fluoroscopy, ultrasound, MRI and CT. Imaging should provide an accurate view of the lesions, the surrounding cardiac structures, as well as medical devices and catheters used. Here we address the field of fusion images. The principle of image fusion is based on the association by superposition of several imaging techniques: real-time fluoroscopy and slice imaging performed offline, or ultrasound imaging performed simultaneously. The goal is to improve the overall view of the organ, its surrounding structures and as the consequence to help the interventional cardiologist.


Orally administrated aluminum-maltolate complex enhances oxidative stress in the organs of mice.
Recently, aluminum (Al) in drinking water has been proposed to be a risk factor for development of Alzheimer's disease (AD). Because the physiological role of Al in humans is not yet known, we previously examined this role using an experimental animal model. Our results revealed a greater accumulation of Al in the brain, liver, kidney and spleen of mice who received long-term (90 days) administration of an Al complex, aluminum-maltolate (ALM), than in untreated controls. This observation prompted us to examine the degree of injury in the organs of mice in terms of lipid peroxidation evaluated by thiobarbituric acid reactive substances (TBARS) and NOx levels in order to determine the effects of Al accumulation. Six-week-old mice were given drinking water containing AlCl3 or ALM for 120 days. TBARS and NOx levels were found to change depending on the organs and chemical forms of Al. In particular, TBARS and NOx levels in the brain of mice given ALM for 30, 60 and 120 days were significantly increased compared with those of the control group. In addition, nervous degeneration was detected in the brain of the ALM-treated group. These results indicate that the chemical form of Al alters the distribution and oxidative stress in the brain. In addition, we propose a more precise method of determining Al levels in biological systems using neutron activation analysis. When the biological samples are irradiated with a neutron flux, both 27Al and 31P can be counted to 28Al by the reactions, 27Al(n,gamma)28Al and 31P(n,alpha)28Al, respectively. The level of Al in the organs can then be determined by subtraction of the radioactivity due to 28Al originated in 31P from the total radioactivity of the samples.


Effects of dipentylnitrosamine (DPNA) on the respiratory tract of rats.
Wistar rats (40 males and 40 females), treated over a period of 25 weeks with subcutaneous injections of dipentylnitrosamine (DPNA) at doses of 0, 62.5, 125 and 250 mg/kg body weight showed dose-dependent, sex-related, proliferative and metaplastic alterations in the upper and lower respiratory tract within one year. The biologic behavior of the induced lung tumors is very similar to that of human lung adenocarcinomas.


Liver simulated allocation model does not effectively predict organ offer decisions for pediatric liver transplant candidates.
The SRTR maintains the liver-simulated allocation model (LSAM), a tool for estimating the impact of changes to liver allocation policy. Integral to LSAM is a model that predicts the decision to accept or decline a liver for transplant. LSAM implicitly assumes these decisions are made identically for adult and pediatric liver transplant (LT) candidates, which has not been previously validated. We applied LSAM's decision-making models to SRTR offer data from 2013 to 2016 to determine its efficacy for adult (≥18) and pediatric (<18) LT candidates, and pediatric subpopulations-teenagers (≥12 to <18), children (≥2 to <12), and infants (<2)-using the area under the receiver operating characteristic (ROC) curve (AUC). For nonstatus 1A candidates, all pediatric subgroups had higher rates of offer acceptance than adults. For non-1A candidates, LSAM's model performed substantially worse for pediatric candidates than adults (AUC 0.815 vs. 0.922); model performance decreased with age (AUC 0.898, 0.806, 0.783 for teenagers, children, and infants, respectively). For status 1A candidates, LSAM also performed worse for pediatric than adult candidates (AUC 0.711 vs. 0.779), especially for infants (AUC 0.618). To ensure pediatric candidates are not unpredictably or negatively impacted by allocation policy changes, we must explicitly account for pediatric-specific decision making in LSAM.


Calcium-lowering action of glucocorticoids in adrenalectomized-parathyroidectomized rats. Specificity and relative potency of natural and synthetic glucocorticoids.
The specificity and potency of glucocorticoids to lower serum calcium (Ca) in rats after parathyroidectomy (PTX) and adrenalectomy (ADX) were examined. Rats fasted overnight were given sc injections of various steroids immediately after the operations. The fall in serum calcium 5 h after PTX-ADX in rats given hypocalcemic doses of corticosterone was compared to that after injection of a test steroid. At high doses, progesterone, estradiol, testosterone, and aldosterone were inactive, whereas glucocorticoids were consistently hypocalcemic. These results indicate that the Ca-lowering effect is specific for steroids with glucocorticoid activity. Potency estimates were made by comparing the dose-response of natural and synthetic glucocorticoids to that of corticosterone, the major glucocorticoid in rats. The mean potency of hydrocortisone was 8.2 times that of corticosterone. Prednisolone was about 9.6, triamcinolone 33, betamethasone 109, and dexamethasone 301 times as potent as corticosterone. Thus, the use of the calcium-lowering action as a bioassay has provides a specific and rapid in vivo method to compare potencies of glucocorticoids consistent with those obtained by anti-inflammatory and glycogen deposition assays. The importance of this interesting calcitonin-like action of glucocorticoids in normal physiology of calcium metabolism is not yet established.


[Pathological findings after radical prostatectomy in men eligible for active surveillance (French trial SURACAP): is the misclassification rate acceptable?].
To analyze pathological data of the radical prostatectomy specimen in patients operated for clinically-localized prostate cancer and who meet strict criteria for active surveillance necessary to be included in the French trial SURACAP. The data of patients who underwent a radical prostatectomy at our institution between 1998 and 2010 were reviewed. We only included the patients that met the usual criteria for active surveillance: clinical stage T1-2a tumor, PSA ≤ 10 ng/mL, biopsy Gleason sum inferior or equal to 6 with no pattern of grade 4 or 5, cancer involvement inferior or equal to two biopsy cores, inferior to 3 mm of malignant tissue in each positive biopsy core. From them, only those who were diagnosed from a second line biopsies cores were included for further analysis. Overall, 48 patient who met the "SURACAP" criteria had a laparoscopic radical prostatectomy at out institution. Mean age was 65.4 years. The mean preoperative PSA was 6.1 ng/mL. Clinical stage of the tumor was T1c in 95% of patients and T2a in 5%. Biopsy Gleason score was 6 (3+3) in 100%. Pathological analysis of the surgical specimen showed that 19% of patients had a seminal vesicle invasion or an extracapsular extension. The Gleason score of the pathological specimen was 6 (3+3) in 57% of patients, 7 (3+4) in 38% and 8 (4+4) in 5% of patients. The Gleason score upgrading was 43% of patients. In our experience, 19% of patients who meet the criteria for active surveillance show an extracapsular extension or a seminal vesicle invasion on pathological analysis. Active surveillance is still under evaluation.


The Calcilytic Drug Calhex-231 Ameliorates Vascular Hyporesponsiveness in Traumatic Hemorrhagic Shock by Inhibiting Oxidative Stress and miR-208a-Mediated Mitochondrial Fission.
The calcium-sensing receptor (CaSR) plays a fundamental role in extracellular calcium homeostasis in humans. Surprisingly, CaSR is also expressed in nonhomeostatic tissues and is involved in regulating diverse cellular functions. The objective of this study was to determine if Calhex-231 (Cal), a negative modulator of CaSR, may be beneficial in the treatment of traumatic hemorrhagic shock (THS) by improving cardiovascular function and investigated the mechanisms. Rats that had been subjected to THS and hypoxia-treated vascular smooth muscle cells (VSMCs) were used in this study. The effects of Cal on cardiovascular function, animal survival, hemodynamics, and vital organ function in THS rats and the relationship to oxidative stress, mitochondrial fusion-fission, and microRNA (miR-208a) were investigated. Cal significantly improved hemodynamics, elevated blood pressure, increased vital organ blood perfusion and local oxygen supply, and markedly improved the survival outcomes of THS rats. Furthermore, Cal significantly improved vascular reactivity after THS in vivo and in vitro. Cal also restored the THS-induced decrease in myosin light chain (MLC) phosphorylation (the key element for VSMC contraction). Inhibition of MLC phosphorylation antagonized the Cal-induced restoration of vascular reactivity following THS. Cal suppressed oxidative stress in THS rats and hypoxic-VSMCs. Meanwhile, THS induced expression of mitochondrial fission proteins Drp1 and Fis1 and decreased expression of mitochondrial fusion protein Mfn1 in vascular tissues. Cal reduced expression of Drp1 and Fis1. In hypoxic-VSMCs, Cal inhibited mitochondrial fragmentation and preserved mitochondrial morphology. In addition, miR-208a mimic decreased Fis1 expression, and miR-208a inhibitor prevented Cal-induced Fis1 downregulation in hypoxic-VSMCs. Calhex-231 exhibits outstanding potential for effective therapy of traumatic hemorrhagic shock, and the beneficial effects result from its protection of vascular function via inhibition of oxidative stress and miR-208a-mediated mitochondrial fission.


Orthotic devices in running injuries.
The most significant problems that we found in our running population were hamstring contractures, which affected 80 per cent, and Achilles tendon contractures, which affected 40 per cent. On first seeing a running patient who has a connective tissue stress type of injury in his or her lower extremity, we first place the patient through a 6-week trial of stretching our contractures, as this will usually correct the problem. We can correct up to 50 per cent of the problems we see just by pursuing a good stretching program. In general, the running injuries most helped by orthotic devices are the posterior tibial syndrome and pes planovalgum. It is easy to understand how the orthotic device works in these situations because it actually controls the subtalar joints and prevents increased stress on the arch of the foot and the posterior tibial tendon. Orthotic devices are also very helpful for metatarsalgia and calcaneal spurs. By directly relieving the stress area in these two conditions, one can usually expect a good result.


A novel method for the measurement of elemental selenium produced by bacterial reduction of selenite.
The measurement of elemental selenium (Se(0)) is needed to assess the rate and magnitude of bacteria reduction of selenite or selenate. We have developed a spectrophotometric method for the measurement Se(0) that is rapid and can be employed to measure the quantity of Se(0) produced by bacterial cultures. This method employs the use of 1M Na(2)S to convert the insoluble elemental selenium to a red-brown solution and with this method there is a direct correlation between concentration of elemental selenium and the absorption at 500nm. To demonstrate the utility of this assay, we have followed the reduction of selenite to Se(0) by Moraxella bovis, and by bacterial consortia in soil and water samples.


Transcriptome-based identification of the Sinorhizobium meliloti NodD1 regulon.
The NodD1 regulon of Sinorhizobium meliloti was determined through the analysis of the S. meliloti transcriptome in response to the plant flavone luteolin and the overexpression of nodD1. Nine new genes regulated by both NodD1 and luteolin were identified, demonstrating that NodD1 controls few functions behind nodulation in S. meliloti.


Correlation Between Different Stages of Diabetic Nephropathy and Neuropathy in Patients with T2DM: A Cross-Sectional Controlled Study.
Early detection of diabetic peripheral neuropathy (DPN) is critical in patients with type 2 diabetes mellitus (T2DM) due to the lack of targeted therapy for DPN. We have investigated the relationship between different stages of diabetic nephropathy and DPN in an attempt to elucidate whether albuminuria can be used as an early warning signal of DPN progression. A total of 217 T2DM patients who met the inclusion criteria were recruited from the Department of Endocrinology, Nanfang Hospital between January 2016 and June 2016. These patients were placed in groups based on urinary albumin excretion rate (UAER) and estimated glomerular filtration rate. Nerve conduction studies, the Semmes-Weinstein monofilament test (SWMT) and the vibration perception threshold (VPT) test were conducted. Multiple linear regression analysis, multivariate logistic regression and receiver-operating characteristic (ROC) analysis were performed to investigate the relationship between different stages of diabetic nephropathy and DPN in these patients. Significant differences were observed in the conduction velocity (CV) and amplitude of sensory/motor nerve potential among the T2DM patients at different stages of diabetic nephropathy (all p < 0.05). The UAER and duration of diabetes were found to be independent factors associated with the mean CV and amplitude of sensory/motor nerve potential (all p < 0.05). A disease duration of > 10 years (p = 0.025) and a higher total cholesterol value (p = 0.024) were found to be significantly associated with abnormal SWMT results. A UAER of > 300 mg/24 h (p = 0.007) and a diastolic blood pressure of > 100 mmHg (p = 0.042) were associated with a higher risk for abnormal VPT. A UAER of > 300 mg/24 h (p < 0.001) and a disease duration of > 10 years (p = 0.02) were observed to be significantly correlated with DPN. The ROC analysis showed that the optimal cutoff values of UAER and duration as indicators of DPN were 90.5 mg/24 h and 9.5 years, respectively (both p < 0.001). The results suggest that diabetic nephropathy is closely associated with the development of DPN in T2DM patients and that UAER and disease duration can be used as warning indicators of DPN progression. ChiCTR-ROC-16007701.


A new immune-competent animal model of mucosally derived squamous cell carcinoma.
To develop an immune-competent animal model for mucosally derived squamous cell carcinoma (SCCA). Fifteen Fischer 344 rats were inoculated with 1, 2, 5, 10, or 20 x 10(6) FAT7 cells in their flanks. The animals were observed for tumor growth and metastasis. All animals developed tumors that grew exponentially. Pulmonary metastases developed in all animals and 13% developed lymph node metastases. The FAT7 flank tumor in Fischer 344 rats is a new animal model that closely resembles the behavior of human mucosal head and neck cancer. The existence of an immune-competent, mucosally derived, and reliable animal model of SCCA that somewhat resembles human head and neck SCCA gives the opportunity to perform immune-modulating experiments on head and neck cancer in these animals. B-3.


Microsurgical lumbosacral ganglionectomy, anatomic rationale, and surgical results.
Recent anatomic and physiologic work suggests that there may be substantial numbers of unmyelinated sensory axons in the ventral roots. The cell bodies of origin for these unmyelinated axons would presumably be located in the dorsal ganglion. We have performed 18 microsurgical lumbosacral ganglionectomies over the past two years for chronic lumbosacral pain syndromes. In spite of preoperative nerve block trials, good results were obtained in only 10 of 18 patients. Four patients obtained some pain relief, and four patients no pain relief whatsoever. Microganglionectomy in the lumbosacral area is probably easier technically than the more traditional intradural rhizotomy, but may not yield any better results.


Bean yellow mosaic virus subgroup; search for the group specific sequences in the 3' terminal region of the genome.
In order to examine relationships among viruses of the bean yellow mosaic subgroup of the Potyvirus genus, several isolates of bean yellow mosaic virus (BYMV) and clover yellow vein virus (C1YVV) were compared by amino acid sequence of the coat protein and nucleotide sequence of the 3' terminal non-coding region. The sequence comparisons showed that BYMV and C1YVV were distinct viruses but had close affinity to each other (85-95% homology among isolates of a virus but 70-77% homology between viruses), justifying establishment of the BYMV subgroup. There was an oligonucleotide consensus sequence present in the 3' terminal non-coding region of all potyviruses examined. This consensus sequence divided the potyviruses into three groups whose significance is not clear.


Formation of de novo centromeres and construction of first-generation human artificial microchromosomes.
We have combined long synthetic arrays of alpha satellite DNA with telomeric DNA and genomic DNA to generate artificial chromosomes in human HT1080 cells. The resulting linear microchromosomes contain exogenous alpha satellite DNA, are mitotically and cytogenetically stable in the absence of selection for up to six months in culture, bind centromere proteins specific for active centromeres, and are estimated to be 6-10 megabases in size, approximately one-fifth to one-tenth the size of endogenous human chromosomes. We conclude that this strategy results in the formation of de novo centromere activity and that the microchromosomes so generated contain all of the sequence elements required for stable mitotic chromosome segregation and maintenance. This first-generation system for the construction of human artificial chromosomes should be suitable for dissecting the sequence requirements of human centromeres, as well as developing constructs useful for therapeutic applications.


A Scoping Review of 4 Decades of Outcomes in Nonsurgical Root Canal Treatment, Nonsurgical Retreatment, and Apexification Studies-Part 2: Outcome Measures.
Inconsistencies in the definitions of endodontic outcome terminology jeopardize evaluations of proposed interventions and patient care quality. This scoping review aimed to provide groundwork to develop a set of basic outcomes in endodontics. We performed a comprehensive literature search for randomized controlled trials, cohort studies, case-control studies, and case series (≥10 patients) published after 1980 with patients ≥10 years of age with any preoperative pulpal and periapical diagnosis in permanent teeth requiring nonsurgical root canal treatment, retreatment, or apexification. Abstracted data on outcome assessment methods, assessors, and domains were reported after univariate and bivariate analyses. Treatment outcomes were evaluated radiographically (88%) or clinically (73%). Although 2-dimensional radiography exceeded 3-dimensional radiography, the use of the latter has increased since 2010, mostly for nonsurgical retreatments. Of 19 identified outcomes, 5 were most frequent: success (168 studies, 40%), radiographic healing (128 studies, 30%), survival (of an asymptomatic tooth [48 studies, 12%] or of a procedure code in administrative databases [31 studies, 7%]), pain assessment (14 studies, 3%), and quality of life (11 studies, 3%). Clinician-centered outcomes have been most frequently studied since the 1980s (71%), in academic settings (76%), and using a prospective design (45%). Patient-centered outcomes were reported in 19% of studies before 2010 and 30% since 2010. They were more common among retrospective studies (49%). Patient-centered outcome measures are lacking in endodontic studies. The state of available research can provide a baseline for the development of a core outcome set in endodontics, which should represent the important patient-centered outcomes in conjunction with well-validated clinician-centered outcomes.


The feasibility of home self-assessment of vital signs and symptoms: A new key to telehealth for individuals?
During the COVID-19 pandemic, social distancing and self-isolation called for innovative, readily implementable, and effective short-term health solutions. The objective of this study was to assess the feasibility of self-assessment of vital signs and symptoms with electronic transmission of results, by self-isolating individuals with positive SARS-CoV-2 polymerase chain reaction (PCR) test. The secondary objective was to describe the association between the presence of abnormal vital signs and severe symptoms as well as their evolution over time. Participants with positive SARS-CoV-2 PCR test were asked to perform twice daily standardized vital signs measurements and self-assessment of symptoms for 14 consecutive days. All data were transmitted electronically through a mobile application and a web-based platform. Participants were provided with decision support tools based on the severity of their condition and a weekly nurse practitioner telephone follow-up. Abnormal values for vital signs and severe symptoms were determined. Per participant and per days, proportions of abnormal vital signs and severe symptoms were calculated. Data from 46 participants (mean age 54.1 ± 6.9 years, 54% male) were available for analysis. On average, participants performed the standardized self-assessment for 12.3 ± 3.4 days (89% performed at least 7 measurement days and 61% completed all 14 days). The highest proportions abnormal values for vital signs were for oximetry (20.1%) and respiratory rate (12.1%). The highest proportions of severe symptoms were for fatigue (16.9%) and myalgia. (10.2%). The combined proportion of abnormal vital signs and severe symptoms was maximal on day 1 with 20.3% of total measurements, with a linear decrease to 3.5% on day 14. Remote initiation of home measurements of vital signs and symptoms, self-management of these measures, accompanied by a decision support tool and supported by preplanned nurse follow-up are feasible. This could allow to opening up new insight for the care of sick individuals.


Usefulness of 64-detector computed tomography in the diagnosis and management of patients with congenital heart disease.
Although congenital heart defects are the most common major congenital abnormalities, the associated mortality has been decreasing due to improvements in their diagnosis and treatment. We assessed the usefulness of 64-multidetector computed tomography in the diagnosis and management of these patients. This 5-year observational, analytical, retrospective, cohort study included a total of 222 tomographic studies of patients with congenital heart disease. Computed tomography scans were read twice and medical records were reviewed. We assessed the complexity of the disease, patient, and radiological technique, and evaluated the contribution of new data in relation to clinical suspicion and diagnostic change. A confidence interval was set at 95% and a P value of<.05 was used as the cutoff for statistical significance. In 35.1% of patients, the treatment procedure was performed after computed tomography without other tests. Additional diagnostic catheterization was performed in 12.5% of patients. There were new findings in 77% of patients (82.9% with complex disease), which prompted a change in patient management in 35.6%. All unexpected reports described new findings. No significant differences were found by age, sex, study period, urgency of the test order, patient complexity, or difficulty of the technique. Use of 64-detector computed tomography yields good diagnostic performance in congenital heart disease, prompts changes in management in more than one-third of patients, and reveals new findings in relation to the presumed diagnosis in 77% of patients.


Objective features of subjective cognitive decline in a United States national database.
Functional and cognitive features of subjective cognitive decline (SCD) were identified in a longitudinal database from the National Alzheimer's Coordinating Center. Cognitively normal older adults with (SCD+) and without (SCD-) self-reported memory complaints (N = 3915) were compared on (1) baseline Functional Assessment Questionnaire ratings, (2) baseline scores and longitudinal rate of change estimates from nine neuropsychological tests, and (3) final clinical diagnoses. SCD+ had higher baseline ratings of functional impairment, reduced episodic memory practice effects and poorer performance on neuropsychological tests of psychomotor speed and language, and higher frequencies of mild cognitive impairment and dementia diagnoses at the end of follow-up compared with the SCD-group. Subtle clinical features of SCD identified in this large cohort are difficult to detect at the individual level. More sensitive tests are needed to identify those with SCD who are vulnerable to cognitive decline and dementia.