Comparison of Gating Properties and Use-Dependent Block of Nav1.5 and Nav1.7 Channels by Anti-Arrhythmics Mexiletine and Lidocaine.
Mexiletine and lidocaine are widely used class IB anti-arrhythmic drugs that are considered to act by blocking voltage-gated open sodium currents for treatment of ventricular arrhythmias and relief of pain. To gain mechanistic insights into action of anti-arrhythmics, we characterized biophysical properties of Nav1.5 and Nav1.7 channels stably expressed in HEK293 cells and compared their use-dependent block in response to mexiletine and lidocaine using whole-cell patch clamp recordings. While the voltage-dependent activation of Nav1.5 or Nav1.7 was not affected by mexiletine and lidocaine, the steady-state fast and slow inactivation of Nav1.5 and Nav1.7 were significantly shifted to hyperpolarized direction by either mexiletine or lidocaine in dose-dependent manner. Both mexiletine and lidocaine enhanced the slow component of closed-state inactivation, with mexiletine exerting stronger inhibition on either Nav1.5 or Nav1.7. The recovery from inactivation of Nav1.5 or Nav1.7 was significantly prolonged by mexiletine compared to lidocaine. Furthermore, mexiletine displayed a pronounced and prominent use-dependent inhibition of Nav1.5 than lidocaine, but not Nav1.7 channels. Taken together, our findings demonstrate differential responses to blockade by mexiletine and lidocaine that preferentially affect the gating of Nav1.5, as compared to Nav1.7; and mexiletine exhibits stronger use-dependent block of Nav1.5. The differential gating properties of Nav1.5 and Nav1.7 in response to mexiletine and lidocaine may help explain the drug effectiveness and advance in new designs of safe and specific sodium channel blockers for treatment of cardiac arrhythmia or pain.


Experimental and theoretical studies on the hydrogen-bond-promoted enantioselective hetero-Diels-Alder reaction of Danishefsky's diene with benzaldehyde.
The enantioselective hetero-Diels-Alder (HDA) reaction of Danishefsky's diene with benzaldehyde has been achieved catalytically by a series of alpha,alpha,alpha',alpha'-tetraaryl-1,3-dioxolane-4,5-dimethanol (TADDOL) derivatives through hydrogen-bonding activation, affording 2-phenyl-2,3-dihydro-4H-pyran-4-one after trifluoroacetic acid workup in moderate yield and good enantioselectivity. The alpha,alpha'-aryl substituents in the TADDOL molecules are found to exert a significant impact on both the activity and the enantioselectivity of the catalysis. In combination with the experimental investigations, the mechanism of the present reaction has also been studied theoretically using the ONIOM (B3LYP/6-31G:PM3) method with trans-1,3-dimethoxy-1,3-butadiene as the model for Danishefsky's diene. In agreement with the experimental findings, the calculation results indicate that this TADDOL-catalyzed HDA reaction proceeds via a concerted mechanism through an asynchronous and zwitterionic transition structure (TS). The carbonyl group of benzaldehyde is activated by forming an intermolecular hydrogen bond with one of the hydroxy groups of TADDOL. Meanwhile, the intramolecular hydrogen bond between the two hydroxy groups in TADDOL is found to facilitate the intermolecular hydrogen bonding with benzaldehyde. The sense of asymmetric induction is well-rationalized by the analysis of the relative energies of TADDOL-complexed TSs, while the different stereocontrol capabilities exhibited by TADDOLs in the reaction can be qualitatively established on the basis of the structural features of their corresponding TSs.


Dog kidney: anatomical relationships between intrarenal arteries and kidney collecting system.
The detailed findings of canine intrarenal anatomy (collecting system and arteries) are presented. Ninety-five three-dimensional endocasts of the kidney collecting system together with the intrarenal arteries were prepared using standard injection-corrosion techniques and were studied. A single renal artery was observed in 88.4% of the casts. The renal artery divided into a dorsal and a ventral branch. Using the branching pattern of the ventral and dorsal divisions of the renal artery, the vessels were classified in type I or type II. Type I presented a cranial and a caudal artery, whereas type II presented a mesorenal and a caudal artery. Cranial branches of dorsal and ventral arteries supplied the cranial pole in 90.5% of the specimens. Caudal branches of the dorsal and the ventral divisions of the renal artery irrigated both the caudal pole and the mid-zone of the kidney in 95.8% and 98.9% of the cases, respectively. In all casts, caudal branches of both dorsal and ventral arteries supplied the caudal pole. Therefore, the caudal branches of the ventral and dorsal divisions of the renal artery are of utmost importance in the kidney arterial supply. Although many results of renal and intrarenal anatomy in dogs may not be completely transposed to humans, the anatomical relationship between arteries and the collecting system in the cranial pole of the dog kidney is similar to those in man. This fact supports the use of the dog as an animal model for urologic procedures at the cranial pole.


Clinical Cancer Advances 2013: Annual Report on Progress Against Cancer from the American Society of Clinical Oncology.
Since its founding in 1964, the American Society of Clinical Oncology (ASCO) has been committed to improving cancer outcomes through research and the delivery of quality care. Research is the bedrock of discovering better treatments--providing hope to the millions of individuals who face a cancer diagnosis each year. The studies featured in "Clinical Cancer Advances 2013: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology" represent the invaluable contributions of thousands of patients who participate in clinical trials and the scientists who conduct basic and clinical research. The insights described in this report, such as how cancers hide from the immune system and why cancers may become resistant to targeted drugs, enable us to envision a future in which cancer will be even more controllable and preventable. The scientific process is thoughtful, deliberate, and sometimes slow, but each advance, while helping patients, now also points toward new research questions and unexplored opportunities. Both dramatic and subtle breakthroughs occur so that progress against cancer typically builds over many years. Success requires vision, persistence, and a long-term commitment to supporting cancer research and training. Our nation's longstanding investment in federally funded cancer research has contributed significantly to a growing array of effective new treatments and a much deeper understanding of the drivers of cancer. But despite this progress, our position as a world leader in advancing medical knowledge and our ability to attract the most promising and talented investigators are now threatened by an acute problem: Federal funding for cancer research has steadily eroded over the past decade, and only 15% of the ever-shrinking budget is actually spent on clinical trials. This dismal reality threatens the pace of progress against cancer and undermines our ability to address the continuing needs of our patients. Despite this extremely challenging economic environment, we continue to make progress. Maintaining and accelerating that progress require that we keep our eyes on the future and pursue a path that builds on the stunning successes of the past. We must continue to show our policymakers the successes in cancer survival and quality of life (QOL) they have enabled, emphasizing the need to sustain our national investment in the remarkably productive US cancer research enterprise. We must also look to innovative methods for transforming how we care for-and learn from-patients with cancer. Consider, for example, that fewer than 5% of adult patients with cancer currently participate in clinical trials. What if we were able to draw lessons from the other 95%? This possibility led ASCO this year to launch CancerLinQ, a groundbreaking health information technology initiative that will provide physicians with access to vast quantities of clinical data about real-world patients and help achieve higher quality, higher value cancer care. As you read the following pages, I hope our collective progress against cancer over the past year inspires you. More importantly, I hope the pride you feel motivates you to help us accelerate the pace of scientific advancement. Clifford A. Hudis, MD, FACP President American Society of Clinical Oncology.


Timing and dynamics of single cell gene expression in the arabinose utilization system.
The arabinose utilization system of Escherichia coli displays a stochastic all-or-nothing response at intermediate levels of arabinose, where the population divides into a fraction catabolizing the sugar at a high rate (on-state) and a fraction not utilizing arabinose (off-state). Here we study this decision process in individual cells, focusing on the dynamics of the transition from the off- to the on-state. Using quantitative time-lapse microscopy, we determine the time delay between inducer addition and fluorescence onset of a GFP reporter. Through independent characterization of the GFP maturation process, we can separate the lag time caused by the reporter from the intrinsic activation time of the arabinose system. The resulting distribution of intrinsic time delays scales inversely with the external arabinose concentration, and is compatible with a simple stochastic model for arabinose uptake. Our findings support the idea that the heterogeneous timing of gene induction is causally related to a broad distribution of uptake proteins at the time of sugar addition.


Elevated levels of homocysteine increase IL-6 production in monocytic Mono Mac 6 cells.
Hyperhomocysteinemia is a risk factor for atherosclerosis and thrombosis. The aim of this study was to analyze if exposure of monocytic cells to increased levels of homocysteine (HCY) induces the accumulation of inflammatory mediators. Interleukin (IL)-6 production by monocytic cell line Mono Mac 6 (MM6) was 1.7-fold increased in the presence of 50 micromol/l HCY and 3.5-fold with 200 micromol/l HCY. Incubation with homocystine resulted in a comparable dose-dependent increase, but neither cysteine nor methionine stimulated IL-6 accumulation. Elevated homocysteine concentrations did not affect the production of IL-8 and monocytic chemotactic protein-1 (MCP-1) in MM6. Furthermore, lipopolysaccharide (LPS) stimulation of MM6, cultured with elevated HCY (200 micromol/l) levels, resulted in a 3.5-fold increased response after 18 h, whereas no effect on LPS-induced IL-8 and MCP-1 response was observed. In conclusion, increased concentrations of homocysteine induce IL-6 accumulation in monocytic cells. After treatment with homocysteine, monocytic cells become more susceptible to endotoxin. This study is in favor of an association between homocysteine and monocytic IL-6 production.


[The indices of cellular-vascular, coagulatory haemostasis and fibrinolysis in arterial hypertension of patients of different age groups].
The contrastive analysis of the indices of cellular and vascular, coagulatory haemostasis and fibrinolysis in arterial hypertension (AH) was held among the patients of different age groups. 69 patients with AH were researched. The average age of afflicted people in the first blockette is 50,9+/-0,7 years, in the second blockette - 70,7+/-1,5. In order to evaluate the condition of haemostasis the afflicted people were researched in the following indices: amount of thrombocytes, hemolysate-aggregative test (HAT), leukocytic-thrombocytic aggregation (LTA), activity of Villebrand factor (FV), inactivation index of thrombin (IIT), activated partial thromboplastin time (APTT), prothrombin index (PTI), fibrinogen, antithrombin III (AIII), Hageman-dependent fibrinolysis (HDF), lupous anticoagulants (LA), autocoagulatory test (ACT). All the examined patients with AH showed considerable abnormalities in cellular and vascular and coagulatory links of haemostasis and the system of fibrinolysis. It is observed, that aged afflected people with AH have progressive hyperaggregation of thrombocytes, the activity of Villebrand factor increases, the rise of coagulatory link activity of haemostasis and the exhaustion of anticoagulants' products is more considerable, the subsequent fibrinolysis depression is observed, but hyperfibrinogenemia accrues. The received results show the heterogeneity of AH in different age groups.


SARS-CoV-2, which induces COVID-19, causes kawasaki-like disease in children: role of pro-inflammatory and anti-inflammatory cytokines.
Acute severe respiratory syndrome coronavirus-2 (SARS-CoV-2) caused a global pandemic coronavirus disease 2019 (COVID-19). In humans, SARS-CoV-2 infection leads to acute respiratory distress syndrome which presents edema, hemorrhage, intra-alveolar fibrin deposition, and vascular changes characterized by thrombus formation, micro-angiopathy and thrombosis. These clinical signs are mediated by pro-inflammatory cytokines. In recent studies it has been noted that COVID-19 pandemic can affect patients of all ages, including children (even if less severely) who were initially thought to be immune. Kawasaki disease is an autoimmune acute febrile inflammatory condition, which primarily affects young children. The disease can present immunodeficiency with the inability of the immune system to fight inflammatory pathogens and leads to fever, rash, alterations of the mucous membranes, conjunctiva infection, pharyngeal erythema, adenopathy, and inflammation. In the COVID-19 period, virus infection aggravates the condition of Kawasaki disease, but it has also been noted that children affected by SARS-V-2 may develop a disease similar to Kawasaki's illness. However, it is uncertain whether the virus alone can give Kawasaki disease-like forms. As in COVID-19, Kawasaki disease and its similar forms are mediated by pro-inflammatory cytokines produced by innate immunity cells such as macrophages and mast cells (MCs). In light of the above, it is therefore pertinent to think that by blocking pro-inflammatory cytokines with new anti-inflammatory cytokines, such as IL-37 and IL-38, it is possible to alleviate the symptoms of the disease and have a new available therapeutic tool. However, since Kawasaki and Kawasaki-like diseases present immunodeficiency, treatment with anti-inflammatory/immunosuppressant molecules must be applied very carefully.


Wound healing potential of flowers extracts of Woodfordia fruticosa Kurz.
Wound healing or repair is the body's natural process of regenerating dermal and epidermal tissue. Woodfordia fruticosa Kurz (Family: Lythraceae) is used traditionally in wound healing by the tribals of Chhattisgarh district. However, there is a paucity of scientific data in support. In this study, we evaluated antimicrobial activity of petroleum ether, chloroform, ethanolic and aqueous extracts against a diverse range of gram +ve and gram -ve bacteria along with pathogenic fungi. The wound healing activity of ethanolic extract was also evaluated at dose levels of 250 and 500 mg/kg body wt in rats by excision, incision and dead space wound healing models along with histopathology of wound area of skin. The ethanolic extract showed potent wound healing activity, as evident from the increase in the wound contraction and breaking strength in dose-dependent manner. Treatment with ethanolic extract (250 and 500 mg/kg body wt) showed significant dose-dependently decrease in epithelization period and scar area. Hydroxyproline, hexuronic acid and hexosamine contents, the important constituents of extracellular matrix of healing were also correlated with the observed healing pattern. During early wound healing phase, pro-inflammatory cytokines TNF-alpha, IL-6 and anti-inflammatory cytokine IL-10 levels were found to be upregulated by the ethanolic extract treatment. The ethanolic extract exhibited a strong and broad spectrum antimicrobial activity, as compared to other extracts. It showed very low Minimum inhibitory concentration (MIC) values and inhibited the growth of E. coli, Staphylococcus aureus and Candida albicans in concentration of 2.5 microg/disc. Thus, the results of the present study demonstrated the strong wound healing potential and antimicrobial activities of W. fruticosa, flowers, supporting the folklore use of the plant by the tribal people of Chhattisgarh district.


[Mechanism of vascular calcification].
Vascular calcification in dialysis patients is associated with morbidity and mortality risks. Recent evidence suggests that vascular calcification is an active process resembling osteogenesis and chondrogenesis process. In this process, hyperphosphatemia is one of the important regulators. Inorganic phosphates directly regulate vascular calcification in vitro through a sodium-dependent phosphate cotransporter and promote expression of the osteoblastic differentiation markers.


Biodegradable fiducial markers for X-ray imaging - soft tissue integration and biocompatibility.
This study aims at the development of materials for biodegradable fiducial markers for X-ray based medical imaging and their anchorage in soft tissue. Towards this goal a degradable polymer matrix of poly(l-lactide-co-ε-caprolactone) (P[LAcoCL]) was combined with barium sulfate (BaSO4) and hydroxyapatite (HAp) as radio-opaque fillers. Low pressure plasma treatment was applied to the composite materials to improve cell adhesion and subsequent tissue integration. In particular, the effects of oxygen and ammonia plasmas were evaluated and compared using X-ray photoelectron spectroscopy, atomic force microscopy and dynamic water contact angle measurements as well as in vitro studies using the murine fibroblast cell line L929. To exclude the cytotoxic effects of degradation products of P[LAcoCL] and released BaSO4 or HAp cytotoxicity assays with the degradation products of the composite materials were conducted. The results obtained by this broad range of analytical techniques suggest the application of composites of P[LAcoCL] with BaSO4 and HAp as promising material systems for innovative fiducial markers for soft tissue in X-ray based medical imaging.


Gender and Racial Disparities in Survival After Surgery Among Papillary and Patients With Follicular Thyroid Cancer: A 45-Year Experience.
Demographic disparities have been described for survival after thyroid cancer surgery using national registries and databases. At the institution level, we hypothesized that assessing survival after thyroid cancer surgery in a long-term cohort with diverse gender and racial groups would reveal disparities in survival. We examined medical records of patients with papillary or follicular thyroid cancer undergoing thyroidectomy, lobectomy, and other surgical procedures from 1971 to 2016 at a tertiary referral center. We obtained information on demographics, cancer stage, procedure, and radioactive iodine (RAI). We measured survival using Kaplan-Meier estimates and Cox proportional hazards models. A total of 1440 (91%) patients with papillary cancer and 144 (9%) patients with follicular thyroid cancer underwent total thyroidectomy (1297, 82%), lobectomy (261, 16.5%), and other surgical procedures (26, 1.5%). Most patients (1131, 71%) were woman, and 909 (57%) were older than 45 years. Race/ethnicity included 805 (51%) white, 161 (10%) African Americans, and 618 (39%) other race/ethnicities. Both 10- and 20-year survival rates in nonwhite males were worse compared with nonwhite females (P < .0001). After controlling for age, cancer type, stage, surgical procedure, RAI, and year of surgery, nonwhite males had a higher mortality risk compared with nonwhite females (P = .0376, confidence interval (CI): 1.03-2.43), white males (P < .0001, CI: 1.88-6.54), and white females (P < .0001, CI: 3.31-9.90). Our diverse cohort demonstrates significant gender and racial disparities in survival after thyroid cancer surgery. To improve health outcomes and reduce health disparities among nonwhite males, interventions and long-term care management should target potentially modifiable causes of worse outcomes in this group.


Home enteral nutrition with formula diets.
Home enteral nutrition can be successfully used on a long-term basis to maintain nutrition and a reasonably normal lifestyle in patients with chronic intestinal dysfunction. Patients can be easily taught the methods involved, a nocturnal regime allowing a more normal lifestyle. The use of a pump-controlled system is recommended. Side-effects are few, generally transient and not severe. Home enteral nutrition has advantages over home intravenous feeding with respect to ease of administration and organisation, fewer and less severe complications, and cost.


Cognitive behaviour therapy for anxiety in adolescent with early prodromal of psychosis at boarding school.
Early prodromal of psychosis starts in adolescent indicated by non specific symptoms which may result in the changes of behaviour, role, function, and social interaction. Cognitive behaviour therapy is a strategic intervention in reducing anxiety symptom. The purpose of this research is to find out the effects of cognitive behaviour therapy for anxiety in adolescent with early prodromal of psychosis. The design of this research was Quasi experimental design: pre-post test with control group. Samples were selected after the screening on adolescents in boarding school with the Prodromal Questionnaire (PQ16). Subjects were 78 respondents consisting of 39 each groups, obtained by random sampling technique. Nursing intervention was provided to intervention group 1, while cognitive behaviour therapy was provided to intervention group 2. The measurement of anxiety in adolescents is by using the Hamilton Anxiety Rating Scale for Anxiety (HARS). The analysis was performed by Repeated Anova and Independent t-test. The result of the research shows that anxiety level decrease significantly on those two groups, whilst the decrease of anxiety and early prodromal of psychosis in the intervention group 2 indicates more decrease than intervention group 1. Cognitive behaviour therapy is recommended to reduce anxiety in adolescent with early prodromal of psychosis.


Giardia lamblia allergenic extract as diagnosis procedures for determining sensitization to this protozoa.
We studied 200 patients assisting at the Allergy Department and the Gastroenterology Department in "Hermanos Ameijeiras" Clinical-Surgical Hospital. They were clinically and immunologically tested for giardiasis through duodenal fortis or gall bladder drainage and total IgE serum levels. All patients underwent intradermal and skin prick tests with Giardine allergenic extract. These skin tests showed high sensitivity and increased specificity. Thus, our procedure in diagnosis is accurate, accessible and economical.


Effects of NO synthase inhibitors on the synovial microcirculation in the mouse knee joint.
Production of nitric oxide by the inducible NO synthase (iNOS) is known to be enhanced in chronic joint inflammation and osteoarthritis as well as aseptic loosening of joint prostheses. Initial studies yielded promising results after inhibition of the nitric oxide synthase (NOS). However, the effect of NOS inhibition has not been studied at the site of the primary function of NO, the microcirculation of the synovium in vivo. Using our recently developed model for the in vivo study of synovial microcirculation in the mouse knee joint, the effects of selective versus nonselective inhibition of iNOS were investigated by means of intravital fluorescence microscopy. After resection of the patella tendon, the synovial fatty tissue was exposed for intravital microscopy. Diameter of arterioles, functional capillary density (FCD), diameter of venules, venular red blood cell velocity and leukocyte-endothelial cell interaction were quantitatively analyzed before, and 10 and 60 min after intravenous injection of NOS inhibitors [selective iNOS inhibitor N-iminoethyl-L-lysine (L-NIL), and nonselective NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME)]. Our results demonstrate that L-NAME causes a significant decrease in the arteriolar diameter and FCD associated with an increase in the leukocyte accumulation in the synovium in vivo. In contrast, L-NIL neither altered the microhemodynamics nor the leukocyte-endothelial cell interaction in the synovium, indicating its potential use for selective inhibition of iNOS in joint inflammation. Using our method, further studies will provide new insights into the unknown effect of NOS inhibition on the synovial microvasculature in inflammatory joint disease in vivo.


The effect of catastrophizing and depression on chronic pain--a prospective cohort study of temporomandibular muscle and joint pain disorders.
Although most cases of temporomandibular muscle and joint disorders (TMJD) are mild and self-limiting, about 10% of TMJD patients develop severe disorders associated with chronic pain and disability. It has been suggested that depression and catastrophizing contributes to TMJD chronicity. This article assesses the effects of catastrophizing and depression on clinically significant TMJD pain (Graded Chronic Pain Scale [GCPS] II-IV). Four hundred eighty participants, recruited from the Minneapolis/St. Paul area through media advertisements and local dentists, received examinations and completed the GCPS at baseline and at 18-month follow-up. In a multivariable analysis including gender, age, and worst pain intensity, baseline catastrophizing (β 3.79, P<0.0001) and pain intensity at baseline (β 0.39, P<0.0001) were positively associated with characteristic of pain intensity at the 18th month. Disability at the 18-month follow-up was positively related to catastrophizing (β 0.38, P<0.0001) and depression (β 0.17, P=0.02). In addition, in the multivariable analysis adjusted by the same covariates previously described, the onset of clinically significant pain (GCPS II-IV) at the 18-month follow-up was associated with catastrophizing (odds ratio [OR] 1.72, P=0.02). Progression of clinically significant pain was related to catastrophizing (OR 2.16, P<0.0001) and widespread pain at baseline (OR 1.78, P=0.048). Results indicate that catastrophizing and depression contribute to the progression of chronic TMJD pain and disability, and therefore should be considered as important factors when evaluating and developing treatment plans for patients with TMJD.


Water use for shale gas extraction in the Sichuan Basin, China.
This study investigates the use of water for extracting shale gas in the Sichuan Basin of China. Both net water use and water intensity (i.e., water use per unit of gas produced) of shale wells are estimated by applying a process-based life cycle inventory (LCI) model. The results show that the net water use and water intensity are around 24500 m3/well and 1.9 m3 water/104 m3 gas respectively, and that the fracturing and completion stage of shale gas extraction accounts for the largest share in net water use. A comparison shows that China's water use for shale gas extraction is generally higher than that of other countries. By considering the predicted annual drilling activities in the Sichuan Basin, we find that the annual water demand for shale gas development is likely to be negligible compared to total regional water supply. However, considering the water demand for shale gas extraction and the water demand from other sectors may make water availability a significant concern for China's shale gas development in the future.


Intraocular lens implantation in unilateral congenital cataract with minimal levels of persistent fetal vasculature in the first 18 months of life.
To describe the incidence of unilateral congenital cataract associated with minimal (ultrasonically undetectable) levels of persistent fetal vasculature in the first 18 months of the life and to report surgical methods for intraocular lens implantation, using 25-gauge vitrectomy system. Retrospective review was made on 16 consecutive patients with bilateral or unilateral congenital cataract in the first 18 months of the life who underwent surgery at Okayama University Hospital after the introduction of the 25-gauge vitrectomy system from October 2005 to March 2013. As the standard of care at this hospital in the study period, intraocular lenses were not implanted in children with bilateral cataract while intraocular lenses were implanted in those with unilateral cataract. Ten children with bilateral cataract underwent lensectomy in both eyes with a 25-gauge vitreous cutter under irrigation with a 25-gauge infusion cannula, inserted from two side ports at the corneal limbus. Six children with unilateral cataract underwent intraocular lens implantation and posterior capsulotomy after lens aspiration from limbal side ports. No patient showed vitreous abnormalities on ultrasound examinations before the surgery. At the surgery, all 10 children with bilateral cataract showed no additional abnormalities. In contrast, 3 children with unilateral cataract at the age younger than 12 months showed white fibrous tissue in the anterior vitreous integrated with the posterior lens capsule while the other 3 children with unilateral cataract at the age from 12 to 18 months did not have vitreous abnormalities. The fibrous tissue was cut together in the process of posterior capsulotomy from a 25-gauge trocar inserted at 1.5 mm posterior from the corneal limbus. Unilateral congenital cataract in the first 12 months of the life has a high incidence for the association with anterior type of persistent fetal vasculature which could not be detected by preoperative ultrasound examinations. Intraocular lens implantation was technically feasible in unilateral cataract with or without minimal levels of persistent fetal vasculature in the first 18 months of the life.


[Spontaneous pneumomediastinum and subcutaneous emphysema associated with bronchospasm in a woman with no history of asthma].
Spontaneous pneumomediastinum most relevant triggering events are cough, vomiting, nutritional problems, physical activity and use of inhaled drugs. Association of spontaneous pneumomediastinum with non-asthma-related bronchospasm is an infrequent event. This is the case of a 21-year-old woman without personal or family history of asthma, allergic rhinitis or atopy who during late puerperium had 39 °C fever, paroxysmal cough and chest oppression of sudden onset, as well as wheezing and subcutaneous emphysema of the neck; she had no previous nasal symptoms. Chest X-ray revealed free air in the mediastinum and left lateral side of the neck. Possible cause of the condition was attributed to bronchospasm related to airway infection. Treatment was based on bronchodilators, systemic steroids and supplementary oxygen administration. The symptoms subsided after 48 hours. In the clinical case herein presented, spontaneous pneumomediastinum precipitating factor appeared to be paroxysmal cough associated with bronchospasm and, hence, we suggest for this entity to be suspected in patients even if there is no previous history of asthma.


Ventilator Settings Can Substantially Impact Patients' Comfort.
With increasing realization that sedatives may complicate care of mechanically ventilated patients, greater emphasis might turn to promoting comfort by titration of ventilator settings. Patients with acute on chronic respiratory failure (ACRF) with underlying chronic obstructive pulmonary disease (COPD) demonstrate different levels of comfort in response to varying ventilator settings compared to those with underlying obesity hypoventilation syndrome (OHS). Patients recovering from ACRF with underlying COPD or OHS were randomized to varying combinations of ventilator modes (assist control and pressure support), tidal volumes, and inspiratory flows for 3 minutes/setting. For each ventilator setting, physiologic variables were recorded and patients indicated their level of comfort using a 10-point Borg scale. In all, 20 patients, aged 68 ± 13 years (standard deviation) and ventilated for 4.9 days, were enrolled. Of 20 patients, 13 had COPD and 7 had OHS. No ventilator mode, flow, or tidal volume provided consistently greater comfort between the groups, but patients reported substantial ranges of comfort (up to 8 Borg points) across the ventilator settings studied. There were no significant differences in heart rate, blood pressure, or airway pressures within patients across ventilator settings or between the groups, but patients with OHS were more tachypneic compared to patients with COPD while breathing on assist control of 6 mL/kg (constant flow 60 L/min) and 8 mL/kg (decelerating flow 40 L/min). There was no correlation between comfort and systolic blood pressure, heart rate, or respiratory rate. Ventilator parameters may impact patients' comfort substantially. Future studies may help identify evidence-based methodology for gauging comfort following changes in ventilator settings and the settings that are most likely to positively impact various groups of patients.


Detection and measurement of oral malodour in periodontitis patients.
Malodour has been correlated with the concentration of volatile sulphur compounds produced in the oral cavity by metabolic activity of bacteria colonizing the periodontal sites and the dorsum of the tongue. The aim of this study was to detect malodour in mouth air organoleptically and using a portable sulphide monitor and to correlate it with the clinical parameters, halitosis linked toxins and BANA, using tongue and subgingival plaque samples. The halitosis grading is also correlated with the microbial colonies of the subgingival plaque sample. 20 patients with chronic periodontitis with 5-7 mm pocket depth, radiographic evidence of bone loss and presence of oral malodour participated in this study. Assessment of mouth air was done organoleptically and by using a portable sulphide monitor. The clinical parameter, plaque index (PI), gingival index (GI), gingival bleeding index (BI), were obtained from all the areas. Samples for BANA and to detect halitosis linked toxins were taken from the dorsal surface of the tongue and periodontal pockets ranging 5-7 mm. Halitosis related microbial colonies were identified using anaerobic culturing from the subgingival plaque. The scores of PI, GI, BI and sample that tested positive for halitosis linked toxins and with the halitosis grading were not significant. The presence of tongue coating and the halitosis grading and toxin levels were significant. BANA has shown to be non contributory due to technical problems. Anaerobic culture has shown to identify Streptococcus, Bacteroides, Fusobacterium, Porphyromonas and Prevotella colonies. The results confirmed that there was no correlation between the clinical parameters, halitosis linked toxins and halitosis grading. The microbial colonies have shown to correlate with the presence of oral malodour.


A tightly bound protein-porphyrin complex isolated from the plasma of a patient with variegate porphyria.
Free acid porphyrins were isolated from plasma of a patient with variegate porphyria. Part of the total porphyrin content--which included protoporphyrin IX, harderoporphyrin and uroporphyrin in a molar ratio of 1.2:1:0.5 and traces of pentacarboxylic porphyrin--was extractable with ethyl acetate/acetic acid as described previously [1]. Unextractable porphyrins remained in the precipitate formed after mixing the lower liquid layer and precipitate from the extraction procedure (Fig. 1, [1]) with excess ethyl acetate/acetic acid. A portion of this precipitate was hydrolyzed in 8 mol/l HCl; its porphyrins were extracted with N-butanol and analyzed by high pressure liquid chromatography; another portion was chromatographed on Sephadex G-150 with 1 mol/l MgCl2, and the major porphyrin-protein pool was hydrolyzed in 8 mol/l HCl, reacted separately with AgNO3 and Ag2SO4, and subjected to cellulose acetate and polyacrylamide-gel electrophoresis. The results support the hypothesis that a dicarboxylic porphyrin, a major portion of which was unextractable by standard procedures [1] and which appeared to be covalently bound to a protein of approximately 68 000 mol. wt. that moved with human serum albumin during cellulose acetate electrophoresis, is the preponderant porphyrin in this plasma.


Employers' perception of the costs and the benefits of hiring individuals with autism spectrum disorder in open employment in Australia.
Research has examined the benefits and costs of employing adults with autism spectrum disorder (ASD) from the perspective of the employee, taxpayer and society, but few studies have considered the employer perspective. This study examines the benefits and costs of employing adults with ASD, from the perspective of employers. Fifty-nine employers employing adults with ASD in open employment were asked to complete an online survey comparing employees with and without ASD on the basis of job similarity. The findings suggest that employing an adult with ASD provides benefits to employers and their organisations without incurring additional costs.


LESCs: Lateralizing Eyelid Sleep Compression Study.
To study the hypothesis that in normal patients, changes in eyelid elasticity may occur asymmetrically and in relation to the side on which the individual sleeps. Prospective, consecutive, single-center study within a large, tertiary-referral ophthalmology department within a university hospital. This prospective study was carried out consecutively on 262 normal patients. The 3 inclusion criteria were 1) age≥55 years, 2) absence of facial nerve palsy, and 3) absence of eyelid trauma or surgery. Immediately before the ocular plastic surgeon assessed the patient, each patient was questioned in a separate consulting room by the attending orthoptist as to his or her customary side of sleeping. After detailed explanation, the "history-masked" ocular plastic surgeon then assessed the patient's upper eyelid laxity, the main outcome measurement. This was performed by asking the seated patient to look down and then gently grasping the upper eyelids close to the eyelid margin, just medial to the lateral commissure. The ocular plastic surgeon, with thumbs pronated, simultaneously distracted both upper eyelids superiorly, laterally, and anteriorly. The measured separation of the upper eyelid from the globe conjunctiva was obtained using calipers. Eyelid laxity grading was designated as grade 1: 0 to 1.9 mm; grade 2: 2.0 to 3.9 mm; grade 3: 4 to 9 mm; and grade 4: floppy. Two hundred sixty-two patients (58% females) who consecutively satisfied the selection criteria were evaluated, of which 70.22% (183/262) patients had significantly greater laxity of the upper eyelid that corresponded to the side on which they customarily slept. An unpaired t test used to compare the eyelid laxity between the sleeping side and nonsleeping side was statistically significant (p<0.001). Normal patients demonstrate a correlation between the side on which they historically or customarily sleep and the laxity of their ipsilateral upper eyelid.


Incident stroke and mortality associated with new-onset atrial fibrillation in patients hospitalized with severe sepsis.
New-onset atrial fibrillation (AF) has been reported in 6% to 20% of patients with severe sepsis. Chronic AF is a known risk factor for stroke and death, but the clinical significance of new-onset AF in the setting of severe sepsis is uncertain. To determine the in-hospital stroke and in-hospital mortality risks associated with new-onset AF in patients with severe sepsis. Retrospective population-based cohort of California State Inpatient Database administrative claims data from nonfederal acute care hospitals for January 1 through December 31, 2007. Data were available for 3,144,787 hospitalized adults. Severe sepsis (n = 49,082 [1.56%]) was defined by validated International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 995.92. New-onset AF was defined as AF that occurred during the hospital stay, after excluding AF cases present at admission. A priori outcome measures were in-hospital ischemic stroke (ICD-9-CM codes 433, 434, or 436) and mortality. Patients with severe sepsis were a mean age of 69 (SD, 16) years and 48% were women. New-onset AF occurred in 5.9% of patients with severe sepsis vs 0.65% of patients without severe sepsis (multivariable-adjusted odds ratio [OR], 6.82; 95% CI, 6.54-7.11; P < .001). Severe sepsis was present in 14% of all new-onset AF in hospitalized adults. Compared with severe sepsis patients without new-onset AF, patients with new-onset AF during severe sepsis had greater risks of in-hospital stroke (75/2896 [2.6%] vs 306/46,186 [0.6%] strokes; adjusted OR, 2.70; 95% CI, 2.05-3.57; P < .001) and in-hospital mortality (1629 [56%] vs 18,027 [39%] deaths; adjusted relative risk, 1.07; 95% CI, 1.04-1.11; P < .001). Findings were robust across 2 definitions of severe sepsis, multiple methods of addressing confounding, and multiple sensitivity analyses. Among patients with severe sepsis, patients with new-onset AF were at increased risk of in-hospital stroke and death compared with patients with no AF and patients with preexisting AF.


Evaluation of a postgraduate educational programme for occupational physicians on work rehabilitation guidelines for patients with low back pain.
The postgraduate educational programme for occupational physicians on guidelines for work rehabilitation of patients with low back pain was evaluated as to what extent did knowledge of the guidelines increase, and did the workers improve their performance at work. An experimental group (n=25) attended an educational programme and a reference group did so (n=20) 6 months later. Knowledge and performance were assessed for both groups, before and after education of the experimental group. Knowledge was assessed for the reference group after education. Knowledge increased significantly more in the experimental group. The reference group's score increased further after education. The experimental group's adjusted gain score for performance indicators was significantly positive. Analysis of covariance also showed a significant effect for the experimental group for increased performance score. The educational programme improved the quality of care because knowledge and performance of occupational physicians improved and complied better with practice guidelines.


Oral flora meningoencephalitis diagnosis by next-generation DNA sequencing.
Standard culture methods may fail to detect the causative agents of bacterial infection for various reasons including specimen collection after antibiotic administration, or when standard techniques or environmental conditions are not appropriate for growth of the microorganisms. Conventional 16S rRNA gene sequencing is sometimes a useful alternative technique for identification of bacteria, but is confounded by polymicrobial infection. We present a case of a patient who developed a serious neurological infection for which causative oral flora organisms were observed by microscopy, failed to culture but were identified by next-generation DNA sequencing. A male in his forties developed sinus pain and congestion, followed by facial and eye pain, and several weeks later acute-onset confusion and neck stiffness. Cerebrospinal fluid examination revealed pleocytosis and several bacterial morphologies, which were subsequently identified by next-generation sequencing as oral flora constituents Porphyromonas endodontalis , Fusobacterium nucleatum , Streptococcus constellatus , Prevotella species and Parvimonas micra . Oral flora can cause meningoencephalitis and brain abscess formation if translocation occurs by injury or surgical procedures. Next-generation sequencing is often not available at healthcare facilities, or when available may not have been validated for a wide spectrum of specimen sources, but is available at reference laboratories and should be considered when routine methods fail to provide a diagnosis for serious infections.


[Impact of intervention on tobacco related knowledge, attitudes and practice of smokers].
To evaluate the impact of intervention on tobacco related knowledge, attitudes and practice of smokers. An observational study was conducted among the smokers seeking counsel at smoking cessation clinic in our hospital from October 2008 to August 2013. First, a face to face counsel and mental intervention for more than 30 minutes was given to smoker, then 4 interventions through telephone call for 15-20 minutes for each time were conducted 1 week later, 1 month later, 3 months later and 6 months later, respectively. The controls were smokers receiving health examination in our hospital. No interventions were conducted among them. The tobacco related knowledge, attitudes and practice at baseline survey and follow up 1 year later were compared between intervention group and control group. The intervention group included 414 smokers and the control group included 213 smokers. Intentional analysis indicated that the awareness/acceptance rates of 5 items about tobacco related knowledge and attitudes at follow up 1 year later was higher than those at baseline survey in intervention group. The smoking cessation rate was 27.3% in intervention group and 4.7% in control group. Multivariate logistic regression analysis indicated that the smoking cessation rate was positively correlated with intervention, female, highly nicotine dependence and positive change of tobacco related knowledge and attitudes (smoking can cause heart disease, all kinds of tobacco advertisements should be prohibited, smoking waste money and restaurant should be smoking free) with OR (95% CI): 2.85 (2.00-4.07), 3.34 (1.23-9.07), 2.78 (1.64-4.72), 2.30 (1.03-5.15), 5.33 (1.47-19.32), 6.32 (1.56-25.62) and 10.47 (2.25-48.84), respectively. The awareness rate of tobacco related harm was high among the smokers seeking counsel at smoking cessation clinic. Systematic smoking cessation intervention can improve smokers' tobacco related knowledge and attitudes and increase smoking cessation rate.


[Isolated tumor cells in bone marrow predicts reduced survival in lymph node-negative non-small-cell lung cancer].
It became recently evident that isolated tumor cells undetectable by conventional tumor staging are frequently present in bone marrow of patients with apparently localized non-small cell lung cancer (NSCLC). The clinical relevance of this minimal hematogenous tumor cell dissemination is under vigorous debate. For tumor cell detection in the bone marrow we used monoclonal antibody CK2 against the epithelial intermediate filament protein cytokeratin 18. The influence of a positive bone marrow finding on clinical outcome was studied in 139 patients with NSCLC postoperatively staged as pT1-4, pN0-2, M0, R0 after a median follow up of 66 months (48-74). Cytokeratin-18-positive cells in bone marrow were demonstrated in 83 (59.7%) patients at the time of primary surgery and in 6 of 12 representative patients analyzed twice 3-18 months after surgery. In patients without histopathological lymph node metastases (pN0; n = 66) the occurrence of > or = 2 tumor cells in bone marrow at primary surgery was a strong and independent predictor for overall survival (p = 0.007) in univariate analysis. The multivariate analysis showed a 2.8 times increased risk for shorter survival in patients with disseminated tumor cells versus patients without such cells. Four of the six patients with a positive CK status after surgery developed a tumor recurrence 11-44 months after the operation, while in none of the patients with a negative bone marrow at all times intervals showed a tumor relapse. Minimal residual bone marrow involvement is an independent prognostic factor for overall survival in patients with node-negative NSCLC, which may help to identify patients in need of an adjuvant systemic therapy. The postoperative persistence or re-appearance of tumor cells in bone marrow indicates that these are not only shredded cells but rather represent true micrometastasis.


Variants in the zinc transporter TMEM163 cause a hypomyelinating leukodystrophy.
Hypomyelinating leukodystrophies comprise a subclass of genetic disorders with deficient myelination of the CNS white matter. Here we report four unrelated families with a hypomyelinating leukodystrophy phenotype harbouring variants in TMEM163 (NM_030923.5). The initial clinical presentation resembled Pelizaeus-Merzbacher disease with congenital nystagmus, hypotonia, delayed global development and neuroimaging findings suggestive of significant and diffuse hypomyelination. Genomic testing identified three distinct heterozygous missense variants in TMEM163 with two unrelated individuals sharing the same de novo variant. TMEM163 is highly expressed in the CNS particularly in newly myelinating oligodendrocytes and was recently revealed to function as a zinc efflux transporter. All the variants identified lie in highly conserved residues in the cytoplasmic domain of the protein, and functional in vitro analysis of the mutant protein demonstrated significant impairment in the ability to efflux zinc out of the cell. Expression of the mutant proteins in an oligodendroglial cell line resulted in substantially reduced mRNA expression of key myelin genes, reduced branching and increased cell death. Our findings indicate that variants in TMEM163 cause a hypomyelinating leukodystrophy and uncover a novel role for zinc homeostasis in oligodendrocyte development and myelin formation.


Etching of graphene in a Hydrogen-rich Atmosphere towards the Formation of Hydrocarbons in Circumstellar Clouds.
We describe a mechanism that explains the formation of hydrocarbons and hydrocarbyls from hydrogenated graphene/graphite; hard C-C bonds are weakened and broken by the synergistic effect of chemisorbed hydrogen and high temperature vibrations. Total energies, optimized structures, and transition states are obtained from Density Functional Theory simulations. These values have been used to determine the Boltzman probability for a thermal fluctuation to overcome the kinetic barriers, yielding the time scale for an event to occur. This mechanism can be used to rationalize the possible routes for the creation of small hydrocarbons and hydrocarbyls from etched graphene/graphite in stellar regions.


Prediction of changes in bone mineral density in the elderly: contribution of "osteogenomic profile".
The contribution of genetic variants to longitudinal bone loss has not been well documented. We constructed an "osteogenomic profile" based on 62 BMD-associated genetic variants and showed that the profile was significantly associated with bone loss, independently from baseline BMD and age. The osteogenomic profile can help predict bone loss in an individual. The rate of longitudinal bone loss (ΔBMD) is a risk factor for fracture. The variation in ΔBMD is partly determined by genetic factors. This study sought to define the association between an osteogenomic profile and ΔBMD. The osteogenomic profile was created from 62 BMD-associated SNPs from genome-wide association studies (GWAS) that were genotyped in 1384 elderly men and women aged 60+ years. Weighted genetic risk scores (GRS) were constructed for each individual by summing the products of the number of risk alleles and the sex-specific regression coefficients [associated with BMD from GWAS]. ΔBMD, expressed as annual percent change-in-BMD, was determined by linear regression analysis for each individual who had had at least two femoral neck BMD measurements. The mean ΔBMD was - 0.65% (SD 1.64%) for women and - 0.57% (SD 1.40%) for men, and this difference was not statistically significant (P = 0.32). In women, each unit increase in GRS was associated with 0.21% (SE 0.10) higher ΔBMD at the femoral neck (P = 0.036), and this association was independent of baseline BMD and age. In logistic regression analysis, each unit increase of GRS was associated with 41% odds (95%CI: 1.07-1.87) of rapid bone loss (ΔBMD ≤ - 1.2%/year; mean of rapid loss group = - 2.2%/year). There was no statistically significant association between ΔBMD and GRS in men. We conclude that the osteogenomic profile constructed from BMD-associated genetic variants is modestly associated with long-term changes in femoral neck BMD in women, but not in men.


Serotonin, noradrenaline and cognitive function: a preliminary investigation of the acute pharmacodynamic effects of a serotonin versus a serotonin and noradrenaline reuptake inhibitor.
Comparisons of the behavioural side-effect profiles of antidepressants that inhibit either serotonin or both serotonin and noradrenaline reuptake, may reveal differences in cognitive and psychomotor functions, which may be attributed to their relative pharmacological selectivity for potentiating monoamine neurotransmission in the central nervous system. The aim of the present study was to determine the acute pharmacodynamic effects of citalopram and venlafaxine, on cognitive and psychomotor performance. Nine healthy male volunteers received a single clinical dose of citalopram, venlafaxine or amitriptyline (positive control) in a double-blind placebo-controlled design. Cognitive and psychomotor tests and a subjective measure of sedation were examined before and 1, 2 and 4 hours after drug administration. Citalopram improved psychomotor responses to sensory stimuli and sustained attention, with significant decreases in movement times of the choice reaction time test and an increase in critical flicker fusion threshold. Venlafaxine did not affect performances on any of the cognitive or psychomotor tests examined. Differences may be related to relative potencies of the compounds for monoamine reuptake inhibition.


Characterisation of Staphylococcus aureus isolates from bloodstream infections, Democratic Republic of the Congo.
Staphylococcus aureus is known worldwide as an invasive pathogen, but information on S. aureus from bloodstream infections in Central Africa remains scarce. A collection of S. aureus blood culture isolates recovered from hospitals in four provinces in the Democratic Republic of the Congo (2009-2013) was assessed. A total of 27/108 isolates were methicillin-resistant S. aureus (MRSA), of which >70% were co-resistant to aminoglycosides, tetracyclines, macrolides and lincosamides. For MRSA and methicillin-susceptible S. aureus (MSSA) isolates, resistance to chloramphenicol and trimethoprim-sulphamethoxazole (TMP-SMX) was <10%. However, 66.7% (72/108) of all isolates harboured the trimethoprim resistance gene dfrG. More than three-quarters (84/108, 77.8%) of isolates belonged to CC5, CC8, CC121 or CC152. Genetic diversity was higher among MSSA (31 spa types) compared to MRSA (four spa types). Most MRSA (23/27, 85.2%) belonged to CC8-spa t1476-SCCmec V and 17/23 (73.9%) MRSA ST8 were oxacillin susceptible but cefoxitin resistant. Among MRSA and MSSA combined, 49.1% (53/108) and 19.4% (21/108) contained the genes encoding for Panton-Valentine leucocidin (lukS-lukF PV, PVL) and toxic shock syndrome toxin-1 (tst, TSST-1), respectively. PVL was mainly detected among MSSA (51/53 isolates harbouring PVL were MSSA, 96.2%) and associated with CC121, CC152, CC1 and CC5. TSST-1 was associated with CC8-spa t1476-SCCmec V. The immune evasion cluster (IEC) genes scn, sak and chp were detected in 81.5% of isolates (88/108, equally represented among MSSA and MRSA). The present study confirms the occurrence of MRSA with high levels of multidrug co-resistance and PVL-positive MSSA among invasive S. aureus isolates in Central Africa.


Predictors of employment status after cardiac surgery.
Preoperative predictors of postoperative employment status were studied in 228 patients (aged 25 to 64 years) who underwent cardiac surgery. Of the 150 patients working in the year before surgery, 73% returned within six months. Of those not so employed, 18% started working. Patients who expected preoperatively to return to work did so at an 82% rate compared with 39% of the others. This was a strong predictor in the multiple regression analysis. Educational level and family income were stronger predictors than occupation or level of physical exertion required. Rates of return were higher in patients with less severe angina and less fatigue preoperatively, but did not differ significantly by sex, surgical procedure, or duration of illness. Seven variables predicted work status correctly for 86% of persons. These results suggest that determinants of return to work are largely present before surgery and that patients' attitudes and expectations play an important role.


Estimating stature from tibia length: a comparison of methods.
Most forensic and biological anthropological studies use the stature-estimation formulae developed by Trotter and Gleser. In recent decades, studies of morphological differences between populations have indicated that population-specific formulae are necessary to obtain accurate estimates. A number of equations have been devised for the Turkish population. Previously, we introduced a "general formula" and three "stature-group-specific formulae" based on tibial length. The purpose of the present study was to determine whether formulae in the literature are suitable for estimating height in the Turkish population. To make this assessment, we compared the accuracy of formulae designed for Turkish people to the accuracy of formulae devised for other populations. We also evaluated the accuracy in short, medium, and tall height groupings. The formulae were tested on 110 healthy Turkish male adults, with estimated height compared to true height in each case. Analysis showed that the Trotter-Gleser formula for Mongoloids was most accurate for estimating stature in the study group as a whole. The formulae of Sağir for the Turkish population and our previously published "general formula" were the next most accurate methods, respectively. When the 110 subjects were categorized as short (1652 mm and below), medium (1653 to 1840 mm), and tall (1841 and above), the stature-group-specific formulae calculated in the present study were more accurate than all other equations for subjects at the height extremes. The results of this study indicate that stature-group-specific formulae are more reliable for forensic cases.


Attentional modulation of visual responses by flexible input gain.
Although it is clear that sensory responses in the cortex can be strongly modulated by stimuli outside of classical receptive fields as well as by extraretinal signals such as attention and anticipation, the exact rules governing the neuronal integration of sensory and behavioral signals remain unclear. For example, most experiments studying sensory interactions have not explored attention, while most studies of attention have relied on the responses to relatively limited sets of stimuli. However, a recent study of V4 responses, in which location, orientation, and spatial attention were systematically varied, suggests that attention can both facilitate and suppress specific sensory inputs to a neuron according to behavioral relevance. To explore the implications of such input gain, we modeled the effects of a center-surround organization of attentional modulation using existing receptive field models of sensory integration. The model is consistent with behavioral measurements of a suppressive effect that surrounds the facilitatory locus of spatial attention. When this center-surround modulation is incorporated into realistic models of sensory integration, it is able to explain seemingly disparate observations of attentional effects in the neurophysiological literature, including spatial shifts in receptive field position and the preferential modulation of low contrast stimuli. The model is also consistent with recent formulations of attention to features in which gain is variably applied among cells with different receptive field properties. Consistent with functional imaging results, the model predicts that spatial attention effects will vary between different visual areas and suggests that attention may act through a common mechanism of selective and flexible gain throughout the visual system.


The quality and comparability of child care data in U.S. surveys.
This paper examines the quality and comparability of child care data obtained from eight waves of data from four nationally representative data sources: the National Longitudinal Survey of Youth (1986 and 1988), the Survey of Income and Program Participation (1986, 1987, 1988, and 1990), the National Child Care Survey, and the National Survey of Families and Households. We examine whether different study designs and survey techniques for asking questions about child care produce similar results on both the levels and determinants of child care. We identified four main sources of difference in the data sets that could impact the quality and comparability of child care research: when the interview is conducted; screening questions used to determine who is asked about child care; the population of parents and children represented in the survey; and the way child care questions are asked. Our findings indicate that summer interviews and screening on mother's work status produce the largest differences in the levels and effects of child care across these studies. Even after removing the effects of summer interviews and screening questions, however, substantial differences exist across the studies.


Silicon-Induced UV Transparency in Phosphate Glasses and Its Application to the Enhancement of the UV Type B Emission of Gd3.
The silicon route to improve the ultraviolet (UV) transparency in phosphate glasses is investigated and further exploited to enhance the UV type B (280-320 nm) emission of gadolinium(III) relevant for biomedical applications. The glasses were synthesized with a barium phosphate composition by melt-quenching in ambient atmosphere and the optical properties investigated by optical absorption and photoluminescence (PL) spectroscopy including emission decay kinetics. An improvement in the UV transparency was gradually developed for the glasses melted merely with increasing amounts of Si powder. A particular PL in the visible was also exhibited for such glasses under excitation at 275 nm, consistent with the presence of Si-induced defects. For Si-Gd codoped glasses, the UV transparency was likewise manifested, while the UV emission from Gd3+ around 312 nm was enhanced with the increase in Si concentration (up to ∼6.7 times). Moreover, along with the Gd3+ PL intensity enhancement, a linear correlation was revealed between the increase in decay times for the Gd3+6P7/2-emitting state and the amount of silicon. It is then suggested that the improved PL properties of gadolinium(III) originate from the increased UV transparency of the host and the consequent precluding of a nonradiative energy transfer from Gd3+ to the matrix. Accordingly, a role of Si as PL quenching inhibitor is supported. The demonstrated efficacy of the Si-Gd codoping concept realized by a facile glass synthesis procedure may appeal to the application of the UV-emitting glasses for phototherapy lamps.


Clinical Presentation and Laboratory Diagnostic Work-Up of a Horse with Tick-Borne Encephalitis in Switzerland.
Tick-borne encephalitis is an important viral tick-borne zoonosis in Europe and Asia. The disease is induced by tick-borne encephalitis virus (TBEV). This report describes a 16-year-old Warmblood gelding presenting with sudden onset of lethargy, ataxia, and muscle fasciculations on the nostrils, the lips, and the eye lids as the most important clinical findings. The horse further had a mild facial nerve paralysis with drooping of the right upper and lower lip. Diagnosis was based on paired serum samples using TBEV-ELISAs revealing high serum IgM in the first sample with normal IgM in the second sample and an increase in serum IgG and neutralizing antibodies, indicating acute and recent infection. TBEV was confirmed by a virus-neutralization test, revealing a fivefold increase in antibodies 32 days after of the onset of clinical signs. Although the specific PCR on cerebrospinal fluid (CSF) was negative, TBEV-specific IgG and IgM were identified in the CSF of the horse. Treatment consisted of anti-inflammatory and anti-oxidative treatment and the horse recovered with a mild drooping of the right nostril as the only remaining clinical sign. TBEV infection is a potential differential diagnosis of neurological disease in horses living in endemic areas and this is the first report to describe the diagnostic criteria in a horse as recommended in humans with suspected TBEV infection.


Postpartum Headache.
Approximately 40% of all women report experiencing headaches during the postpartum period, regardless of a previous headache history. This case narrative describes the clinical case of a 22-year-old woman who presented for the evaluation of an intractable headache for 2½ weeks. It demonstrates the inherent difficulty in diagnosing patients not presenting with "textbook" symptoms and highlights the fact that signs and symptoms of eclampsia/preeclampsia, such as elevated blood pressure, may fall below the threshold for hypertensive emergencies and not be considered in the differential. Emergency department providers must possess a strong knowledge base and skill set to recognize subtle presentations and direct care accordingly to ensure positive patient outcomes.


A mixed-dimensional 1D Se-2D InSe van der Waals heterojunction for high responsivity self-powered photodetectors.
Mixed-dimension van der Waals (vdW) p-n heterojunction photodiodes have inspired worldwide efforts to combine the excellent properties of 2D materials and traditional semiconductors without consideration of lattice mismatch. However, owing to the scarcity of intrinsic p-type semiconductors and insufficient optical absorption of the few layer 2D materials, a high performance photovoltaic device based on a vdW heterojunction is still lacking. Here, a novel mixed-dimension vdW heterojunction consisting of 1D p-type Se nanotubes and a 2D flexible n-type InSe nanosheet is proposed by a facile method, and the device shows excellent photovoltaic characteristics. Due to the superior properties of the hybrid p-n junction, the mix-dimensional van der Waals heterojunction exhibited high on/off ratios (103) at a relatively weak light intensity of 3 mW cm-2. And a broadband self-powered photodetector ranging from the UV to visible region is achieved. The highest responsivity of the device could reach up to 110 mA W-1 without an external energy supply. This value is comparable to that of the pristine Se device at 5 V and InSe device at 0.1 V, respectively. Furthermore, the response speed is enhanced by one order of magnitude over the single Se or InSe device even at a bias voltage. This work paves a new way for the further development of high performance, low cost, and energy-efficient photodetectors by using mixed-dimensional vdW heterostructures.


Helping the helpers. A unique colleague support system for mental health professionals-consumers.
1. There are many professionals in the mental health workforce who have a mental illness themselves (prosumers), but who do not disclose that fact to their employers or colleagues for fear of stigma and discrimination. 2. Prosumers are in a particularly difficult situation; if they disclose, they risk being viewed as their illness, and if they do not disclose, they may not get the kinds of reasonable accommodations and support that would make their job more manageable. 3. Mutual support groups of colleagues are a viable and valuable way for prosumers to assist each other in coping with the stigma and stressors inherent in working in the mental health field.


A randomized trial of peer-delivered self-management support for hypertension.
Peer-led interventions to improve chronic disease self-management can improve health outcomes but are not widely used. Therefore, we tested a peer-led hypertension self-management intervention delivered at regular meetings of community veterans' organizations. We randomized 58 organizational units ("posts") of veterans' organizations in southeast Wisconsin to peer-led vs. professionally delivered self-management education. Volunteer peer leaders at peer-led posts delivered monthly presentations regarding hypertension self-management during regular post meetings. Volunteer post representatives at seminar posts encouraged post members to attend 3 didactic seminars delivered by health professionals at a time separate from the post meeting. Volunteers in both groups encouraged members to self-monitor using blood pressure cuffs, weight scales, and pedometers. Our primary outcome was change in systolic blood pressure (SBP) at 12 months. We measured SBP in 404 participants at baseline and in 379 participants at 12 months. SBP decreased significantly (4.4mm Hg; P < 0.0001) overall; the decrease was similar in peer-led and seminar posts (3.5mm Hg vs. 5.4mm Hg; P = 0.24). Among participants with uncontrolled BP at baseline, SBP decreased by 10.1mm Hg from baseline to 12 months but was again similar in the 2 groups. This pattern was also seen at 6 months and with diastolic blood pressure. Our peer-led educational intervention was not more effective than didactic seminars for SBP control. Although peer-led educational programs have had important impacts in a number of studies, we did not find our intervention superior to a similar intervention delivered by healthcare professionals. ClinicalTrials.gov NCT00571038.


Challenges in cryopreservation of clouded leopard (Neofelis nebulosa) spermatozoa.
The clouded leopard (Neofelis nebulosa) is an endangered species that is difficult to breed in captivity. Species management could benefit from the use of artificial insemination (AI) with frozen-thawed spermatozoa, but there have been no detailed studies of sperm cryosensitivity. The purposes of this study were to: (1) re-characterize seminal characteristics in the clouded leopard 20 years after the first descriptive studies Wildt et al., [Wildt DE, Howard JG, Hall LL, Bush M. Reproductive physiology of the clouded leopard. I. Electroejaculates contain high proportions of pleiomorphic spermatozoa throughout the year. Biol Reprod 1986; 34: 937-947]; and (2) conduct a comparative cryopreservation study on the feasibility of sperm from this species surviving a freeze-thawing stress. Ejaculates were collected from five adult males and subjected to standard analysis, followed by a two-step straw freezing protocol that evaluated the impact of thawing, dilution, centrifugation and in vitro culture (through 4 h) on sperm motility and acrosomal integrity. Additionally, we assessed the impact of both a traditional permeating cryoprotectant (glycerol at a final dilution of 4%) and an unconventional nonpermeating trisaccharide; raffinose (R) at a final dilution of 4% or 8%, with or without 4% glycerol on sperm cryosurvival. The clouded leopard produced an extremely poor quality ejaculate; although approximately 70% of fresh sperm were motile, >80% were malformed. Phase contrast microscopy revealed that 40% of all sperm had abnormal acrosomes, but Coomassie blue staining indicated that acrosomal abnormalities existed in almost 70% of spermatozoa. Upon freeze-thawing, sperm motility declined markedly (P < 0.05) by an average of 40%, regardless of diluent used. Interestingly, raffinose was as effective as glycerol in protecting both sperm motility and acrosomal integrity. Although no acrosomal damage was seen immediately after thawing, < 6% morphologically normal intact acrosomes were present by the last measured time point. In conclusion, the clouded leopard is a rare felid that (at least in North American zoos) is producing extraordinarily poor quality ejaculates. There are so many sperm with unexplained deranged acrosomes that it will be particularly challenging to use traditional AI with thawed sperm as an adjunct management tool.


Anti-inflammatory effect of glucose-lysine Maillard reaction products on intestinal inflammation model in vivo.
Inflammatory bowel diseases (IBDs) are chronic disorders that are characterized by intestinal epithelial inflammation and injury. Currently, the most employed therapies are antibiotics and anti-inflammatory drugs; however, the side effects limit long-term effectiveness. We evaluated the impact of glucose-lysine Maillard reaction products (Glc-Lys MRPs) on colitis, induced in rats by an administration of 5% dextran sulfate sodium (DSS) in drinking water. Glc-Lys MRPs ameliorate DSS-induced colitis, as determined by a decrease in disease index activity, colon weight/length ratio, nitric oxide levels in serum, recovery of body weight loss, colon length and serum lysozyme levels. Furthermore, Glc-Lys MRPs increase the glutathione content and the activity of glutathione peroxidase, superoxide dismutase and catalase, and inhibit lipid peroxidation and myeloperoxidase activity in colon tissues. In particular, Glc-Lys MRPs suppress the mRNA level of the inflammatory cytokines and nuclear factor-κB in colon tissues. This study suggests the potential of Glc-Lys MRPs in preventing or treating IBDs.


Bacterial-induced or passively administered interferon gamma conditions the lung for early control of SARS-CoV-2.
Type-1 and type-3 interferons (IFNs) are important for control of viral replication; however, less is known about the role of Type-2 IFN (IFNγ) in anti-viral immunity. We previously observed that lung infection with Mycobacterium bovis BCG achieved though intravenous (iv) administration provides strong protection against SARS-CoV-2 in mice yet drives low levels of type-1 IFNs but robust IFNγ. Here we examine the role of ongoing IFNγ responses to pre-established bacterial infection on SARS-CoV-2 disease outcomes in two murine models. We report that IFNγ is required for iv BCG induced reduction in pulmonary viral loads, an outcome dependent on IFNγ receptor expression by non-hematopoietic cells. Importantly, we show that BCG infection prompts pulmonary epithelial cells to upregulate IFN-stimulated genes with reported anti-viral activity in an IFNγ-dependent manner, suggesting a possible mechanism for the observed protection. Finally, we confirm the anti-viral properties of IFNγ by demonstrating that the recombinant cytokine itself provides strong protection against SARS-CoV-2 challenge when administered intranasally. Together, our data show that a pre-established IFNγ response within the lung is protective against SARS-CoV-2 infection, suggesting that concurrent or recent infections that drive IFNγ may limit the pathogenesis of SARS-CoV-2 and supporting possible prophylactic uses of IFNγ in COVID-19 management.


Algebraic Structure of Cut Feynman Integrals and the Diagrammatic Coaction.
We study the algebraic and analytic structure of Feynman integrals by proposing an operation that maps an integral into pairs of integrals obtained from a master integrand and a corresponding master contour. This operation is a coaction. It reduces to the known coaction on multiple polylogarithms, but applies more generally, e.g., to hypergeometric functions. The coaction also applies to generic one-loop Feynman integrals with any configuration of internal and external masses, and in dimensional regularization. In this case, we demonstrate that it can be given a diagrammatic representation purely in terms of operations on graphs, namely, contractions and cuts of edges. The coaction gives direct access to (iterated) discontinuities of Feynman integrals and facilitates a straightforward derivation of the differential equations they admit. In particular, the differential equations for any one-loop integral are determined by the diagrammatic coaction using limited information about their maximal, next-to-maximal, and next-to-next-to-maximal cuts.


Viscoelastic Hemostatic Assays: A Primer on Legacy and New Generation Devices.
Viscoelastic hemostatic assay (VHAs) are whole blood point-of-care tests that have become an essential method for assaying hemostatic competence in liver transplantation, cardiac surgery, and most recently, trauma surgery involving hemorrhagic shock. It has taken more than three-quarters of a century of research and clinical application for this technology to become mainstream in these three clinical areas. Within the last decade, the cup and pin legacy devices, such as thromboelastography (TEG® 5000) and rotational thromboelastometry (ROTEM® delta), have been supplanted not only by cartridge systems (TEG® 6S and ROTEM® sigma), but also by more portable point-of-care bedside testing iterations of these legacy devices (e.g., Sonoclot®, Quantra®, and ClotPro®). Here, the legacy and new generation VHAs are compared on the basis of their unique hemostatic parameters that define contributions of coagulation factors, fibrinogen/fibrin, platelets, and clot lysis as related to the lifespan of a clot. In conclusion, we offer a brief discussion on the meteoric adoption of VHAs across the medical and surgical specialties to address COVID-19-associated coagulopathy.


The generation and characterization of antagonist RNA aptamers to human oncostatin M.
Oncostatin M (OSM) is a multifunctional member of the interleukin-6 cytokine family. OSM has been implicated as a powerful proinflammatory mediator and may represent a potentially important, novel therapeutic opportunity for treatment of established rheumatoid arthritis. To further investigate the role of OSM in inflammatory disorders, we have isolated a series of RNA aptamers that bind specifically to human OSM. The highest affinity aptamer, designated ADR58, has been characterized in a series of in vitro and cell based assays. ADR58 has an affinity of 7 nm for human OSM, and it can antagonize OSM binding to the gp130 receptor and specifically antagonize OSM mediated signaling. The aptamer has been truncated in length to 33 bases, all pyrimidine positions are substituted with 2' fluorine, and 14 of 18 purine positions have been substituted with 2' O-methyl to increase stability toward nucleases. This truncated, modified form of ADR58 retains complete affinity and functional activity for OSM. This aptamer may be used as a tool to further investigate the role of OSM in inflammatory disorders and may also have role as a therapeutic agent.


Evaluation of Alcohol-Related Personalized Normative Feedback With and Without an Injunctive Message.
Personalized normative feedback (PNF) has been used extensively to reduce alcohol consumption, particularly among heavy drinkers. However, the majority of PNF studies have used only descriptive norms (real or perceived pervasiveness of a given behavior). The purpose of the current study was to explore the efficacy of PNF both with and without an injunctive message indicating approval or disapproval based on the participants' standing relative to other students' drinking levels. This randomized trial evaluated two brief web-based alcohol intervention conditions (descriptive-norms-feedback-only condition versus a descriptive-plus-injunctive-message condition relative to an assessment-only control condition). Participants included 176 students who had reported at least one heavy drinking episode in the past month. Participants completed baseline and follow-up assessments of perceived norms and drinking. Follow-up assessments were completed at 2 weeks post-intervention by 165 (94%) participants. Analyses were conducted using zero-inflated negative binomial regression models. As expected, the descriptive-norms-only condition was effective in reducing drinking among heavier baseline drinkers at follow-up relative to the control condition. However, contrary to expectations, the descriptive-plus-injunctive-message condition did not predict less drinking at follow-up. This study was unique in using an injunctive message as an adjunct to descriptive-norms feedback within the context of drinking. Findings highlight the need for additional research into the role of defensiveness, which may serve as an impediment to using injunctive norms/messages in interventions for problematic substance use and other potentially stigmatizing behaviors.


[Biochemical mechanisms of impaired neuroimmune interaction in multiple sclerosis].
Neurotransmitters and cytokines that play a key role in the mechanisms of interaction of the nervous and immune systems have been studied in both the blood and cerebrospinal fluid of 195 patients with multiple sclerosis. The findings suggest that neurotransmitters and cytokines play a role in the pathochemical mechanisms of development of the disease and that certain neurotransmitter systems are involved into the development of some neurological symptoms. It was proposed that excitotoxic mechanisms are responsible for the damages to nervous tissue and for death of oligodendroglial cells in multiple sclerosis. Alterations in norepinephrine levels and platelet serotonergic indices may be manifestations of compensatory protective mechanisms that resulted in activation of primarily suppressor T-lymphocytes. The inflammatory cytokines--interferon-gamma and tumor necrosis factor-alpha participate in the mechanisms of pathologic process activation and in the development of the disease. On the contrary, interferon-alpha was supposed to promote remission and involved in the mechanisms of a favorable course of multiple sclerosis that testified the necessity of differential immunocorrection at different stages of the disease.


Integrating testing for sexually transmissible infections into annual health assessments for Aboriginal and Torres Strait Islander young people: a cross-sectional analysis.
In the context of an expanding syphilis epidemic, we assessed the integration of sexually transmissible infection (STI) testing within annual health assessments for Aboriginal and Torres Strait Islander young people aged 16-29years in Aboriginal Community Controlled Health Services between 2018 and 2020. Using routinely collected electronic medical record data from a national sentinel surveillance system (ATLAS), we performed a cross-sectional analysis to calculate the proportion of assessments that integrated any or all of the tests for chlamydia, gonorrhoea, syphilis, and HIV. We used logistic regression to identify correlates of integration of any STI test. Of the 13 892 assessments, 23.8% (95% CI 23.1, 24.6) integrated a test for any STI and 11.5% (95% CI 10.9, 12.0) included all four STIs. Of assessments that included a chlamydia/gonorrhoea test, 66.9% concurrently included a syphilis test. Integration of any STI test was associated with patients aged 20-24years (OR 1.2, 95% CI 1.1-1.4) and 25-29years (OR 1.1, 95% CI 1.0-1.2) compared to 16-19years and patients residing in very remote (OR 4.2, 95% CI 3.7-4.8), remote (OR 2.4, 95% CI 2.1-2.8), and regional areas (OR 2.5, 95% CI 2.2-2.8) compared to metropolitan areas. There was no association with patient sex. Integration of STI testing into annual health assessments for Aboriginal and Torres Strait Islander young people was higher in remote areas where disease burden is greatest. Integration is similar in men and women, which contrasts with most studies that have found higher testing in women.


Spectral properties of the oestrogen-induced rat uterus peroxidase II and some of its derivatives.
1. The visible absorption spectrum of peroxidase II, isolated from the uterine tissue of oestradiol-treated rats, and some of its derivatives were recorded. The spectral properties of this enzyme are very similar to eosinophile peroxidase and lactoperoxidase, suggesting that these enzymes may have a similar form of haem as prosthetic group. 2. The uterine peroxidase is modified upon interaction with H2O2 and the difference spectrum of this modified enzyme is similar to that of complex II of lactoperoxidase. The modified enzyme was found to revert spontaneously to the native enzyme at rates which depended on the concentration of free enzyme and H2O2.


Which primary care specialty? Factors that relate to a choice of family medicine, internal medicine, combined internal medicine-pediatrics, or pediatrics.
This study was conducted to examine factors used by medical students to select a primary care specialty that may differentiate students who choose the primary care specialties of family medicine, internal medicine, pediatrics, and combined internal medicine-pediatrics. A questionnaire was sent to all family physicians and an equal number of other primary care physicians graduating from one of 24 medical schools in 1997-1999. Twelve schools had increasing proportions of graduates choosing family medicine in this study period, and 12 had decreasing proportions. The questionnaire asked about factors related to choice of specialty, which could be grouped into the specialty domains of type of patients, process, content, and setting. For family physicians, the most important factor was patient relationships, and the second most important was wanting an approach to the practice of medicine similar to that of family physicians. Internists indicated as most important wanting to work with adults and as the next most important an "internal medicine approach" to the practice of medicine. Most important for pediatricians was working with children and next most important was having patient relationships like other pediatricians. Those in combined internal medicine-pediatrics most often indicated a desire to work with children and next most important was an approach to medicine like others in their specialty. The most important reasons for choice of specialty were similar for all primary care specialties and related to congruence between the graduate and the physicians in the specialty or the process of providing care within that specialty. The factors that differentiated the four specialties related to the content of the specialty.


Intensive care nurses' experiences during the COVID-19 pandemic: A qualitative study.
Because of the COVID-19 pandemic, health care systems worldwide are working under challenging conditions. Patients, who are seriously ill, require intensive care admission. In fighting COVID-19, nurses are frontline health care workers and, as such, have a great responsibility providing needed specialized patient care in intensive care units (ICU). However, working conditions and emotional factors have an impact on the quality of the care provided. The purpose of the present study was to explore and describe the experiences and perceptions of nurses working in an ICU during the COVID-19 global pandemic. Qualitative research was undertaken, using an empirical approach and inductive content analysis techniques. The selected population consisted of ICU nurses from a tertiary teaching hospital in Spain. Data were obtained via semi-structured videocall interviews from Apr 12th to Apr 30th, 2020. Subsequently, transcribed verbatims were analysed using the template analysis model of Brooks. A total of 17 nurses comprised the final sample after data saturation. Four main themes emerged from the analysis and 13 subthemes: "providing nursing care," "psychosocial aspects and emotional lability," "resources management and safety" and "professional relationships and fellowship." Providing health care by intensive care nursing professionals, during the COVID-19 pandemic, has shown both strong and weak points in the health care system. Nursing care has been influenced by fear and isolation, making it hard to maintain the humanization of the health care. Implications for practice include optimizing resource management (human and material), providing psychological support, and adequate training for ICU nurses, as well as high-quality protocols for future emergency situations.


New developments in optical coherence tomography for glaucoma.
Structural imaging is becoming a powerful adjunct for the diagnosis and progression of glaucoma. There are several competing technologies in this arena. Optical coherence tomography continues to evolve at a fast pace, so it can be challenging to keep up with the latest information. This review covers the recent papers relevant to optical coherence tomography for glaucoma. Retinal nerve fiber layer imaging by optical coherence tomography is reliable. Age, ethnicity, axial length and optic disc size can affect the machine's normative range. Scan quality can be affected by movement, media opacities, myopia and severity of disease. The sensitivity and specificity are variable across multiple studies. Despite this, the technology is beginning to help us understand the structure-function relationship in glaucoma. The next generation optical coherence tomography is around the corner. By understanding the current strengths and limitations of this advancing technology, one can better assess its use in clinical practice.


Clinical and laboratory characteristics of acute leukemia with the 4;11 translocation.
This report describes the clinical and laboratory features of seven cases of acute leukemia associated with the 4;11 chromosomal translocation. All seven children had acute lymphoblastic leukemia by standard morphologic and cytochemical criteria. Leukemic blasts from six of seven patients were terminal deoxynucleotidyl transferase-positive. Immunologic phenotyping suggested the leukemias were of B cell origin; blasts from five patients expressed HLA-DR and p24 (CD-9 antibody), blasts from three patients expressed B4 (CD-19), and blasts from two patients expressed the common acute lymphoblastic leukemia antigen (CD-10). One patient's leukemic blasts contained cytoplasmic immunoglobulin. Analysis of DNA from four of five patients demonstrated additional evidence of B cell differentiation with heavy-chain immunoglobulin gene rearrangement. When DNA from the four patients with heavy-chain immunoglobulin gene rearrangement was analyzed, one patient's DNA demonstrated light-chain immunoglobulin gene rearrangement. However, flow cytometric analysis of blasts from three patients showed the simultaneous expression of the lymphoid-associated antigen B4 (CD-19) and the myeloid-associated antigen My-1 (X-Hapten). Electron microscopic examination of blasts from one patient that expressed both lymphoid- and myeloid-associated antigens demonstrated ultrastructural characteristics of both lineages. These findings suggest that acute leukemia with the t(4;11) abnormality has mixed lineage characteristics as a result of leukemogenesis in a multipotential progenitor cell or aberrant gene expression later in differentiation. Furthermore, serial analysis of karyotype, immunophenotype, and heavy-chain immunoglobulin genes revealed changes in these biologic markers over time, suggesting continued chromosome rearrangement and gene modulation after the leukemogenic event in cells with the t(4;11).


Suppression of collagen-induced arthritis with histone H1.
Besides roles in nucleus mediating the condensation of DNA into chromatin, the involvement of histones in autoimmune diseases, hormone regulation, and killing leukemia cells has been reported. In order to investigate the functions of histones on an autoimmune disease, histone H1 was injected into collagen-induced arthritis (CIA) mice. A dramatic suppression of CIA by histone H1 was observed at a dose of 1 mg/kg bodyweight of mouse. In addition, the increased level of anti-inflammatory cytokine IL-10 was detected in cultured splenocytes from the mouse treated with histone H1. These findings suggest that histone H1 suppresses the collagen-induced arthritis, possibly by increasing the level of IL-10 production.


Expression of CRYM in different rat organs during development and its decreased expression in degenerating pyramidal tracts in amyotrophic lateral sclerosis.
The protein μ-crystallin (CRYM) is a novel component of the marsupial lens that has two functions: it is a key regulator of thyroid hormone transportation and a reductase of sulfur-containing cyclic ketimines. In this study, we examined changes of the expression pattern of CRYM in different rat organs during development using immunohistochemistry and immunoblotting. As CRYM is reportedly expressed in the corticospinal tract, we also investigated CRYM expression in human cases of amyotrophic lateral sclerosis (ALS) using immunohistochemistry. In the rat brain, CRYM was expressed in the cerebral cortex, basal ganglia, hippocampus and corticospinal tract in the early postnatal period. As postnatal development progressed, CRYM expression was restricted to large pyramidal neurons in layers V and VI of the cerebral cortex and pyramidal cells in the deep layer of CA1 in the hippocampus. Even within the same regions, CRYM-positive and negative neurons were distributed in a mosaic pattern. In the kidney, CRYM was expressed in epithelial cells of the proximal tubule and mesenchymal cells of the medulla in the early postnatal period; however, CRYM expression in the medulla was lost as mesenchymal cell numbers decreased with the rapid growth of the medulla. In human ALS brains, we observed marked loss of CRYM in the corticospinal tract, especially distally. Our results suggest that CRYM may play roles in development of cortical and hippocampal pyramidal cells in the early postnatal period, and in the later period, performs cell-specific functions in selected neuronal populations. In the kidney, CRYM may play roles in maturation of renal function. The expression patterns of CRYM may reflect significance of its interactions with T3 or ketimines in these cells and organs. The results also indicate that CRYM may be used as a marker of axonal degeneration in the corticospinal tract.


The relationship between bending stress and the shape of maxillary canines in cercopithecoid monkeys.
Primate canines function in social displays but are also recruited for biting in agonistic encounters. Although the precise nature of the loads such behavior places on the canine crown is unknown, it is thought that bending is a major component of such loads. To date, modeling of canine bending strength has relied on idealized geometric representations. Accounting for the tapering of the crown as well as shape changes along an apical-basal axis provides a more realistic model for assessment of bending stress in canines. We provide such an accounting and evaluate the hypothesis that the morphology of the cercopithecoid canine represents a structural solution for maintaining constant maximum bending stress under apical or distributed loading in a parasagittal plane. This isostress hypothesis is analogous to a design criterion of minimum mass for a given structural requirement. Examining permanent maxillary canines from males and females representing eight West African cercopithecoid species, we reconstructed crown geometry from apex to base using microcomputed tomography. From reconstructed cross-sections, we determined section moduli about a buccolingual centroidal axis. We then determined what the taper should be for a variety of parasagittal loading distributions if the isostress hypothesis were true and compared these theoretical tapers to actual crown geometry. We found that a variety of loading distributions can be accommodated by the canines, particularly among males. These results suggest that our sample of canines are not optimized for resisting particular biting loads, but effectively limit stress gradients associated with a range of behaviors.


The hemolytic-uremic syndrome: prognostic significance of neurological abnormalities.
To define the prognostic significance of neurological symptoms in the hemolytic-uremic syndrome (HUS), the records of 68 patients with this syndrome were reviewed. Major neurological symptoms (convulsions and/or coma) occurred in 22 patients. Nine of them had dysregulation of breathing as well. An analysis of other symptoms and characteristics of the disease in these 9 patients revealed a rapid progression of the disease, a high incidence of colitis, and a high mortality rate (8 of the 9 patients) despite adequate seizures control, replacement of renal function and assisted ventilation. We conclude that the prognosis of HUS patients with severe neurological symptoms including dysregulation of breathing is poor.


Treatment Outcome and Associated Factors of Neonatal Sepsis at Mizan Tepi University Teaching Hospital, South West Ethiopia: A Prospective Observational Study.
Neonatal sepsis is the gravest problem in neonates, ending in significant morbidity and mortality. World wide 6.9 million neonates were spotted with potentially severe bacterial infections needing treatment and 2.6 million of them occurred in sub-Saharan Africa (SSA). Sepsis is the leading cause of neonatal mortality and is perhaps answerable for about 30-50% of the total neonatal deaths per year in emerging countries. This study aims to assess the treatment outcome and associated factors of neonatal sepsis at Mizan Tepi University Teaching Hospital, South West Ethiopia. A hospital-based prospective observational study was done at Mizan Tepi University Teaching Hospital (MTUTH) from May to November 2019 among neonates admitted with sepsis. Data were entered to Epi-data 4.2 and analyzed by SPSS version 21. Bivariate and multivariate Cox regression was used to identify the relationship between dependent and independent variables. All neonates ≤28 days who were admitted to MTUTH at the neonatal intensive care unit (NICU) and neonates diagnosed with sepsis by the attending physician either clinically or laboratory-confirmed included in the study. Of the 211 neonatal sepsis patients, 110 (52.1%) were females, 161 (76.3%) were admitted with late-onset sepsis, 16 (7.6%) were very low birth weight, and 156 (73.9%) were term. About 143 (67.8%) had a good outcome and 68 (32.2%) had a poor outcome. Very low birth weight [P = 0.006, AHR = 1.692, 95% CI: (1.245, 4.36)], age of neonate being less than 4 days at admission [P = 0.001, AHR = 9.67, 95% CI: (2.24, 41.70)], maternal infection [P = 0.032, AHR = 3.186, 95% CI: (1.32, 30.68)], and prolonged length of hospital stay [(P = 0.017, AHR = 12.29, 95% CI: (1.55, 96.31), were significantly associated to mortality. The mortality rate of neonatal sepsis was found to be high. Age of neonate <4 days, birth weight of the neonate <1500 gm, and prolonged length of hospital stay were identified as independently associated factors of increased risk of mortality.


Measuring barbiturates, sedatives, and anticonvulsants in serum by gas-liquid chromatography.
We describe a method for measuring therapeutic and overdose levels of barbiturate, sedative, and anticonvulsant drugs in serum by gas-liquid chromatography (GLC). This method is a unique combination of techniques including a simple extraction, cochromatography of the specimen with authentic carrier drugs, and the use of multiple dissimilar gas chromatographic columns. In this way, a large number of drugs may be identified and quantitated without confusion.