A Modified Hughes Flap for Correction of Refractory Cicatricial Lower Lid Retraction With Concomitant Ectropion.
Correction of lower eyelid retraction commonly involves one or more techniques, including recession of the eyelid retractors, spacer grafts, horizontal lid tightening, and midface lifting. However, patients presenting with cicatricial lower lid retraction following prior eyelid surgery often have scarring and concomitant ectropion or entropion that cause unpredictable wound healing, recicatrization, and suboptimal outcomes. The modified Hughes tarsoconjunctival flap is typically used to repair full-thickness eyelid defects. Prior reports describe treating refractory lower lid retraction with a modified Hughes flap placed beneath the tarsus after full-thickness blepharotomy. We present our experience with a novel surgical technique for treating refractory cicatricial lower lid retraction using a modified Hughes flap above the tarsus after excision of the scarred lid margin. Three patients were treated using this technique. The upper edge of the lower eyelid and associated scar tissue are excised. A modified Hughes flap is mobilized and secured above the posterior lamellar remnant. A full-thickness skin graft is placed over the flap. The flap is divided 4-5 weeks later. This surgical technique was employed in all 3 cases. All cases were revisional, with 2 having extensive multioperative histories with multiple unsuccessful reconstructions and lid retraction repairs. All patients had improvement in cicatricial eyelid retraction, lagophthalmos, exposure keratopathy, and resolution of concomitant cicatricial ectropion. The technique of using a modified Hughes flap to reconstruct above the tarsus with excision of the scarred lid margin was effective in correcting refractory cicatricial lower lid retraction. This procedure can be considered in multioperative cases in which traditional techniques for lower lid retraction repair have failed. Reconstructing a new lid margin reduces the risk of recicatrization and suboptimal results.


Crystal structure of the α-ketoglutarate-dependent non-heme iron oxygenase CmnC in capreomycin biosynthesis and its engineering to catalyze hydroxylation of the substrate enantiomer.
CmnC is an α-ketoglutarate (α-KG)-dependent non-heme iron oxygenase involved in the formation of the l-capreomycidine (l-Cap) moiety in capreomycin (CMN) biosynthesis. CmnC and its homologues, VioC in viomycin (VIO) biosynthesis and OrfP in streptothricin (STT) biosynthesis, catalyze hydroxylation of l-Arg to form β-hydroxy l-Arg (CmnC and VioC) or β,γ-dihydroxy l-Arg (OrfP). In this study, a combination of biochemical characterization and structural determination was performed to understand the substrate binding environment and substrate specificity of CmnC. Interestingly, despite having a high conservation of the substrate binding environment among CmnC, VioC, and OrfP, only OrfP can hydroxylate the substrate enantiomer d-Arg. Superposition of the structures of CmnC, VioC, and OrfP revealed a similar folds and overall structures. The active site residues of CmnC, VioC, and OrfP are almost conserved; however Leu136, Ser138, and Asp249 around the substrate binding pocket in CmnC are replaced by Gln, Gly, and Tyr in OrfP, respectively. These residues may play important roles for the substrate binding. The mutagenesis analysis revealed that the triple mutant CmnCL136Q,S138G,D249Y switches the substrate stereoselectivity from l-Arg to d-Arg with ∼6% relative activity. The crystal structure of CmnCL136Q,S138G,D249Y in complex with d-Arg revealed that the substrate loses partial interactions and adopts a different orientation in the binding site. This study provides insights into the enzyme engineering to α-KG non-heme iron oxygenases for adjustment to the substrate stereoselectivity and development of biocatalysts.


Comparison of pain perception in normotensives and borderline hypertensives by means of a tooth pulp-stimulation test.
Recent studies indicate a reduced sensitivity to pain in genetically and experimentally hypertensive rats. A similar finding is also reported for human established hypertension. However, to our knowledge, no data have been reported in borderline hypertension. The aim of this study was to assess in subjects with borderline hypertension the sensory and pain thresholds by a noninvasive pulp-stimulation test performed with a commercial pulp tester that delivered stepwise increased electrical stimuli to four healthy teeth. The data reported are the means of measurements. In order to assess the possible importance of differences in the selection of the controls, two distinct groups of normotensives were chosen, one of volunteers and the other of outpatients. Significantly higher values for the pain and sensory thresholds were observed in borderline hypertensives compared with pooled normotensives. No significant effect on pain perception could be observed for sex, whereas a significant tendency toward higher threshold levels was found for younger subjects. In two normotensive groups, the sensory and pain thresholds were significantly higher in volunteers than in patients. These results suggest that changes in pain perception are present not only in established hypertension but also in borderline hypertension and, moreover, that differences in the selection of normotensive controls can have important influences on the results.


[Role of vacuum therapy in the management of the septic abdomen].
Progress in intensive care medicine contributed substantially in lowering the mortality rate of patients suffering from diffuse secondary peritonitis. In the medical care of patients presenting a septic abdomen the persisting septic focus is one of the greatest problems. This is associated with other problems like temporary closure of the abdomen, complications due to re-laparotomies, healing of the abdominal wall after soft tissue infection, loss of abdominal wall musculature, or persisting enteral fistulas. The vacuum therapy is used with increasing frequency for the treatment of septic complications in different areas of the body. The excellent drainage characteristics of the vacuum therapy appear to be a therapeutic option for the control of surgically untreatable septic processes in the abdominal cavity. More and more experience is gathered with the successful treatment of enterocutaneous fistulas, small intestine and pancreatic fistulas as well as anastomotic leakage after rectal surgery. There exist hardly any evidence-based recommendations for the application of vacuum therapy for treatment of the septic abdomen. But the good results of temporary closure of open abdomen of trauma patients by the vacuum therapy arises hope that the results can be transferred to the treatment modalities of persisting peritonitis. Additionally, these patients could profit from the drainage characteristics of the vacuum therapy.


Inherited Thrombophilia in the Era of Direct Oral Anticoagulants.
Severe inherited thrombophilia includes rare deficiencies of natural anticoagulants (antithrombin and proteins C and S) and homozygous or combined factor V Leiden and FII G20210A variants. They are associated with a high thrombosis risk and can impact the duration of anticoagulation therapy for patients with a venous thromboembolism (VTE) event. Therefore, it is important to diagnose thrombophilia and to use adapted anticoagulant therapy. The widespread use of direct anticoagulants (DOACs) for VTE has raised new issues concerning inherited thrombophilia. Concerning inherited thrombophilia diagnosis, DOACs are directed toward either FIIa or FXa and can therefore interfere with coagulation assays. This paper reports DOAC interference in several thrombophilia tests, including the assessment of antithrombin, protein S, and protein C activities. Antithrombin activity and clot-based assays used for proteins C and S can be overestimated, with a risk of missing a deficiency. The use of a device to remove DOACs should be considered to minimize the risk of false-negative results. The place of DOACs in the treatment of VTE in thrombophilia patients is also discussed. Available data are encouraging, but given the variability in thrombosis risk within natural anticoagulant deficiencies, evidence in patients with well-characterized thrombophilia would be useful.


Impact of intensity of conditioning therapy in patients aged 40-60 years with AML/myelodysplastic syndrome undergoing allogeneic transplantation.
The optimum intensity of conditioning therapy in patients aged 40-60 years with AML and myelodysplastic syndrome (MDS) undergoing allogeneic haematopoietic cell transplantation (alloHCT) remains uncertain. We compared outcomes of reduced intensity conditioning (RIC) and conventional intensity conditioning (CIC) in 101 consecutive patients (CIC, 62; RIC, 39) with AML and MDS aged 40-60 years undergoing alloHCT from 2002 to 2008 at our centre. The median age, unrelated transplants and co-morbidity index were higher in the RIC group. Median OS and EFS were 31.0 months (95% confidence interval (CI): 12.8-59.3) and 20.7 months (95% CI: 11.0-30.4), respectively, with no significant difference between the two cohorts. The 3-year treatment-related mortality (TRM) and relapse were 28% (95% CI: 21-39) and 25% (95% CI: 17-36), respectively, with no significant difference between the two cohorts. No difference in OS, EFS, TRM or relapse was observed between the two cohorts in the multivariate model. Only disease risk was significantly associated with OS (Hazard ratio (HR): 1.85, CI: 1.01-3.45), EFS (HR: 1.73, 95% CI: 1.00-3.10) and cumulative relapse (HR: 3.24, 95% CI: 1.08-10.12). Disease biology rather than intensity of conditioning regimen seems to determine outcomes of alloHCT in patients aged 40-60 years with AML/MDS.


Risks Related to the Use of Non-Steroidal Anti-Inflammatory Drugs in Community-Acquired Pneumonia in Adult and Pediatric Patients.
Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to alleviate symptoms during community-acquired pneumonia (CAP), while neither clinical data nor guidelines encourage this use. Experimental data suggest that NSAIDs impair neutrophil intrinsic functions, their recruitment to the inflammatory site, and the resolution of inflammatory processes after acute pulmonary bacterial challenge. During CAP, numerous observational data collected in hospitalized children, hospitalized adults, and adults admitted to intensive care units (ICUs) support a strong association between pre-hospital NSAID exposure and a delayed hospital referral, a delayed administration of antibiotic therapy, and the occurrence of pleuropulmonary complications, even in the only study that has accounted for a protopathic bias. Other endpoints have been described including a longer duration of antibiotic therapy and a greater hospital length of stay. In all adult series, patients exposed to NSAIDs were younger and had fewer comorbidities. The mechanisms by which NSAID use would entail a complicated course in pneumonia still remain uncertain. The temporal hypothesis and the immunological hypothesis are the two main emerging hypotheses. Current data strongly support an association between NSAID intake during the outpatient treatment of CAP and a complicated course. This should encourage experts and scientific societies to strongly advise against the use of NSAIDs in the management of lower respiratory tract infections.


Advances in stem cell therapy for the lower urinary tract.
Lower urinary tract diseases are emotionally and financially burdensome to the individual and society. Current treatments are ineffective or symptomatic. Conversely, stem cells (SCs) are regenerative and may offer long-term solutions. Among the different types of SCs, bone marrow SCs (BMSCs) and skeletal muscle-derived SCs (SkMSCs) have received the most attention in pre-clinical and clinical trial studies concerning the lower urinary tract. In particular, clinical trials with SkMSCs for stress urinary incontinence have demonstrated impressive efficacy. However, both SkMSCs and BMSCs are difficult to obtain in quantity and therefore neither is optimal for the eventual implementation of SC therapy. On the other hand, adipose tissue-derived SCs (ADSCs) can be easily and abundantly obtained from "discarded" adipose tissue. Moreover, in several head-on comparison studies, ADSCs have demonstrated equal or superior therapeutic potential compared to BMSCs. Therefore, across several different medical disciplines, including urology, ADSC research is gaining wide attention. For the regeneration of bladder tissues, possible differentiation of ADSCs into bladder smooth muscle and epithelial cells has been demonstrated. For the treatment of bladder diseases, specifically hyperlipidemia and associated overactive bladder, ADSCs have also demonstrated efficacy. For the treatment of urethral sphincter dysfunction associated with birth trauma and hormonal deficiency, ADSC therapy was also beneficial. Finally, ADSCs were able to restore erectile function in various types of erectile dysfunction (ED), including those associated with diabetes, hyperlipidemia, and nerve injuries. Thus, ADSCs have demonstrated remarkable therapeutic potentials for the lower urinary tract.


[Guillain-Barre syndrome in children. Analysis of 23 cases].
A group of 23 children aged 5 months to 6 years a diagnosis of Guillain Barré syndrome has been analysed. In 2/3 of our patients the illness appeared in autumn-winter period. We considered muscle weaknesses, pain and impairments of cranial nerves to be the main characteristics of the disease. The presence of denervation activity was an indication of worse evolutive prognosis. Hormone treatment was started in 21 cases and plasma exchange in one more, with rapid reduction of the vegetative and the motor symptoms. The progress was considered to be highly favourable in all of them. One child had a recidivant form of this disease.


Adversity before conception will affect adult progeny in rats.
The authors investigated whether adversity in a female, before she conceives, will influence the affective and social behavior of her progeny. Virgin female rats were either undisturbed (controls) or exposed to varied, unpredictable, stressors for 7 days (preconceptual stress [PCS]) and then either mated immediately after the end of the stress (PCS0) or 2 weeks after the stress ended (PCS2). Their offspring were raised undisturbed until tested in adulthood. PCS offspring showed reduced social interaction; in the acoustic startle test, PCS males were less fearful, whereas PCS females were more fearful; in the shuttle task, PCS0 males avoided shock better; and in the elevated maze, PCS0 females were more active and anxious. The 2-week interval between stress and mating assuaged the effects on offspring activity and shock avoidance but not the changes in social behavior and fear in male and female offspring. Hence, PCS to the dam, even well before pregnancy, influences affective and social behavior in her adult offspring, depending on how long before conception it occurred, the behavior tested, and sex. (PsycINFO Database Record (c) 2009 APA, all rights reserved).


Septal Aperture of the Humerus: Etiology and Frequency Rates in Two European Populations.
Analysis of the septal aperture was conducted on two documented European populations. Collections from the National Museum of Natural History Lisbon, Portugal, and University of Athens, Greece, were used for the study. Both collections are modern and documented for sex and age. The Portuguese sample comprises 297 individuals (149 males and 148 females) between the ages of 18 and 88. A septal aperture was observed in 50 individuals resulting in a frequency of 16.83%. The Greek sample comprises 117 individuals (68 males and 49 females) between the ages of 20 and 65. Twenty-five septal apertures were observed, giving a frequency of 21.37%. Both populations had high frequencies which exceeded those observed in European countries in previous studies. Sex analysis shows that both samples confirm that septal apertures are more common in females. The Portuguese sample also supports that septal apertures are more common in the left humerus; however, the Greek sample had a higher frequency of bilateral cases. Measurements of the Portuguese sample were taken to determine whether robusticity correlates with presence of septal apertures. These measurements concluded that there was no difference in robusticity with presence or absence of a septal aperture, challenging previous studies. Anat Rec, 2019. © 2019 American Association for Anatomy Anat Rec, 303:1821-1830, 2020. © 2019 American Association for Anatomy.


Exon-skipping antisense oligonucleotides for cystic fibrosis therapy.
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), and the CFTR-W1282X nonsense mutation causes a severe form of CF. Although Trikafta and other CFTR-modulation therapies benefit most CF patients, targeted therapy for patients with the W1282X mutation is lacking. The CFTR-W1282X protein has residual activity but is expressed at a very low level due to nonsense-mediated messenger RNA (mRNA) decay (NMD). NMD-suppression therapy and read-through therapy are actively being researched for CFTR nonsense mutants. NMD suppression could increase the mutant CFTR mRNA, and read-through therapies may increase the levels of full-length CFTR protein. However, these approaches have limitations and potential side effects: because the NMD machinery also regulates the expression of many normal mRNAs, broad inhibition of the pathway is not desirable, and read-through drugs are inefficient partly because the mutant mRNA template is subject to NMD. To bypass these issues, we pursued an exon-skipping antisense oligonucleotide (ASO) strategy to achieve gene-specific NMD evasion. A cocktail of two splice-site-targeting ASOs induced the expression of CFTR mRNA without the premature-termination-codon-containing exon 23 (CFTR-Δex23), which is an in-frame exon. Treatment of human bronchial epithelial cells with this cocktail of ASOs that target the splice sites flanking exon 23 results in efficient skipping of exon 23 and an increase in CFTR-Δex23 protein. The splice-switching ASO cocktail increases the CFTR-mediated chloride current in human bronchial epithelial cells. Our results set the stage for developing an allele-specific therapy for CF caused by the W1282X mutation.


Development of a health care utilisation data-based index for rheumatoid arthritis severity: a preliminary study.
Health care utilisation ('claims') databases contain information about millions of patients and are an important source of information for a variety of study types. However, they typically do not contain information about disease severity. The goal of the present study was to develop a health care claims index for rheumatoid arthritis (RA) severity using a previously developed medical records-based index for RA severity (RA medical records-based index of severity [RARBIS]). The study population consisted of 120 patients from the Veteran's Administration (VA) Health System. We previously demonstrated the construct validity of the RARBIS and established its convergent validity with the Disease Activity Score (DAS28). Potential claims-based indicators were entered into a linear regression model as independent variables and the RARBIS as the dependent variable. The claims-based index for RA severity (CIRAS) was created using the coefficients from models with the highest coefficient of determination (R2) values selected by automated modelling procedures. To compare our claims-based index with our medical records-based index, we examined the correlation between the CIRAS and the RARBIS using Spearman non-parametric tests. The forward selection models yielded the highest model R2 for both the RARBIS with medications (R2 = 0.31) and the RARBIS without medications (R2 = 0.26). Components of the CIRAS included tests for inflammatory markers, number of chemistry panels and platelet counts ordered, rheumatoid factor, the number of rehabilitation and rheumatology visits, and Felty's syndrome diagnosis. The CIRAS demonstrated moderate correlations with the RARBIS with medication and the RARBIS without medication sub-scales. We developed the CIRAS that showed moderate correlations with a previously validated records-based index of severity. The CIRAS may serve as a potentially important tool in adjusting for RA severity in pharmacoepidemiology studies of RA treatment and complications using health care utilisation data.


[Contribution to studies on the modern health care system in the Republic of Congo: geographical approach].
We carried out a geographic analysis of the modern health care system in the rural areas of Kouilou and Niari (Republic of Congo). Spatial differences in physical (e.g. vegetation, relief) and human (social and demographic profiles) factors must be characterized because they have an effect on the organization and spatial distribution of the health care system. The location of health care structures depended on the structure of the local environment. The health care system seemed primarily to be a component of the economic development determining population distribution in the forest area. In the savannah, it was part of the local administrative framework, the key factor determining the structure of the local space. Health care services were most used in areas with average to large population densities, in which there were the largest number of health care structures. Areas with "marginal" population densities and health care center distributions had the lowest rates of health care use. Health care zones can be defined by considering geographical characteristics and the characteristics of the health care system. This makes health planning (e.g. opening of health centers, improvement of health centers) much easier to undertake.


What are the informational pathways that shape people's use of cannabidiol for medical purposes?
Cannabidiol (CBD) is commonly used to manage symptoms in conditions and diseases for which there is limited clinical research for its application. How consumers arrive and decide to use CBD for medical treatment, despite lacking clinical evidence, is largely unknown. In this paper, we seek to identify the informational pathways through which consumers arrive at CBD for medical purposes. GoFundMe.com campaigns fundraising to purchase CBD between June 2017 and May 2019 were collected using the Crowdfunding for Health Research Portal (CHRP). Product descriptions were thematically analyzed to determine pathways leading to incorporation of CBD into medical treatment. Campaign characteristics such as fundraising ask, funding received, location, campaign title, description, Facebook shares, and number of donors were recorded. Specific medical uses of CBD proposed in campaigns were tabulated. The study identified 164 crowdfunding campaigns primarily from the USA (n=159), with several from Canada (n=5). The campaigns requested $2,219,284.24 (median, $7000) and raised $610,612.87 (median, $1805) from 6825 donors (median, 26). Many campaigns asked for other treatments or illness-related costs not specific to CBD. The campaigns were shared 42,299 times on Facebook (median, 156 shares). Three informational pathways were identified leading to incorporation of CBD into medical treatment, which were self-directed research (n=149), recommendations from a trusted care provider (n=36), and/or experiential insights shared by someone associated with or influencing the crowdfunders personal network (n=30). The proposed uses of CBD were for cancer (n=96), seizure-inducing diseases/conditions (n=48), other/unspecified (n=6), joint/inflammatory diseases (n=6), mental health disorders (n=3), nervous system diseases (n=3), and autoimmune diseases (n=2). Our results suggest that consumers crowdfunding come to CBD through internally motivated reasons versus exposure to advertisements or other forms of marketing. Campaign beneficiaries generally had an unmet medical need that other forms of treatment were not satisfying. Then, through one or more of the informational pathways identified, CBD is considered a potential solution.


Neurogenic hyperalgesia: psychophysical studies of underlying mechanisms.
1. Psychophysical studies were made, in humans, of the sensory characteristics and underlying mechanisms of the hyperalgesia (often termed "secondary hyperalgesia") that occurs in uninjured skin surrounding a local cutaneous injury. The hyperalgesia was characterized by lowered pain thresholds and enhanced magnitude of pain to normally painful stimuli. The "injury" was produced by a single intradermal injection of 10 microliters of 100 micrograms of capsaicin, the algesic substance in hot chili peppers. 2. On injection of capsaicin into the volar forearm, the subjects experienced intense burning pain, accompanied immediately by the formation of three areas of hyperalgesia surrounding the injection site. The largest mean area (55 cm2) was hyperalgesic to a normally painful punctate stimulation of the skin. Nested within this was an area of tenderness to gentle stroking (38 cm2) and a much smaller area of hyperalgesia to heat (2 cm2). An area of analgesia to pinprick, approximately 4 mm in diameter and centered on the injection site, developed within minutes and typically disappeared within 24 h. The hyperalgesia to heat and to stroking disappeared within 1-2 h, whereas the hyperalgesia to punctate stimuli, although gradually decreasing in area, lasted from 13 to 24 h. 3. The radial spread of the mechanical hyperalgesia (to punctate and stroking stimuli) away from the injury was dependent on neural activity and not produced, for example, by algesic substances transported away from the injury. The injection of capsaicin into a small area of anesthetized skin did not produce hyperalgesia in the surrounding, unanesthetized skin. Also, the hyperalgesia in normal skin readily crossed a tight arm band that blocked the circulation of blood and lymph. 4. The spread of mechanical hyperalgesia away from the injury was peripherally mediated via cutaneous nerve fibers because it was blocked by a thin mediolateral strip of cutaneous anesthesia placed 1 cm away from the capsaicin injection site. Hyperalgesia developed normally on the capsaicin side of the strip but not on the other side. 5. Heat stimulation of the skin that produced pain that was equivalent in magnitude and time course to that produced by an injection of capsaicin (10 micrograms) resulted in much smaller areas of mechanical hyperalgesia. It was postulated that there exist special chemosensitive primary afferent nerve fibers that are more effective in producing mechanical hyperalgesia than are the known thermo- and mechanosensitive nociceptive nerve fibers. 6. Once developed, the mechanical hyperalgesia became only partially dependent on peripheral neural activity originating at the site of injury.(ABSTRACT TRUNCATED AT 400 WORDS)


Associations Between Historical Redlining and Present-Day Heat Vulnerability Housing and Land Cover Characteristics in Philadelphia, PA.
Historical, institutional racism within the housing market may have impacted present-day disparities in heat vulnerability. We quantified associations between historically redlined areas with present-day property and housing characteristics that may enhance heat vulnerability in Philadelphia, PA. We used color-coded Home Owners Loan Corporation (HOLC) maps and tax assessment data to randomly select 100 present-day (2018-2019) residential properties in each HOLC grade area (A = Best; B, C, and D = Most hazardous; N = 400 total). We conducted virtual inventories of the properties using aerial and streetview imagery for land cover and housing characteristics (dark roof color, flat roof shape, low or no mature tree canopy, no recently planted street trees) that may enhance heat vulnerability. We used modified Poisson regression models to estimate associations of HOLC grades with the property characteristics, unadjusted and adjusted for historical and contemporary measures of the neighborhood sociodemographic environment. Compared to grade A areas, higher proportions of properties in grade B, C, and D areas had dark roofs, low/no mature tree canopy, and no street trees. Adjusting for historical sociodemographics attenuated associations, with only associations with low or no tree canopy remaining elevated. Adjusting for present-day concentrated racial and socioeconomic deprivation did not substantially impact overall findings. In Philadelphia, PA, HOLC maps serve as spatial representations of present-day housing and land cover heat vulnerability characteristics. Further analyses incorporating longitudinal data on urban redevelopment, reinvestment, and neighborhood change are needed to more fully represent complex relationships among historical racism, residential segregation, and heat vulnerability.


Metabolic reprogramming during hyperammonemia targets mitochondrial function and postmitotic senescence.
Ammonia is a cytotoxic metabolite with pleiotropic molecular and metabolic effects, including senescence induction. During dysregulated ammonia metabolism, which occurs in chronic diseases, skeletal muscle becomes a major organ for nonhepatocyte ammonia uptake. Muscle ammonia disposal occurs in mitochondria via cataplerosis of critical intermediary metabolite α-ketoglutarate, a senescence-ameliorating molecule. Untargeted and mitochondrially targeted data were analyzed by multiomics approaches. These analyses were validated experimentally to dissect the specific mitochondrial oxidative defects and functional consequences, including senescence. Responses to ammonia lowering in myotubes and in hyperammonemic portacaval anastomosis rat muscle were studied. Whole-cell transcriptomics integrated with whole-cell, mitochondrial, and tissue proteomics showed distinct temporal clusters of responses with enrichment of oxidative dysfunction and senescence-related pathways/proteins during hyperammonemia and after ammonia withdrawal. Functional and metabolic studies showed defects in electron transport chain complexes I, III, and IV; loss of supercomplex assembly; decreased ATP synthesis; increased free radical generation with oxidative modification of proteins/lipids; and senescence-associated molecular phenotype-increased β-galactosidase activity and expression of p16INK, p21, and p53. These perturbations were partially reversed by ammonia lowering. Dysregulated ammonia metabolism caused reversible mitochondrial dysfunction by transcriptional and translational perturbations in multiple pathways with a distinct skeletal muscle senescence-associated molecular phenotype.


The season of birth of siblings of psychiatric patients.
The season of birth of the siblings of psychiatric patients was studied to test the hypothesis that an unusual seasonal pattern of maternal conception is the cause of the excess of births in the early months of the year which has been found in national studies of psychotic patients. Information on the month of birth of the siblings was obtained from interviews with psychiatric in-patients born in Britain. The quarterly distribution of births of 670 mentally well siblings of psychotic patients (schizophrenia and manic-depression) was significantly different from that of 1,513 siblings of other psychiatric patients and also from that of all births in England and Wales. The results lend qualified support to the hypothesis, but they were not clear-cut and there was some evidence that the information on birth dates was biased.


Extensively drug-resistant tuberculosis: a case report and literature review.
Extensively drug-resistant tuberculosis (XDR-TB) is an emerging health problem that threatens tuberculosis (TB) control worldwide, since suitable treatment for this disease has not yet been found. We report a case of secondary pulmonary XDR-TB in a 54-year-old, HIV-negative male from Goiânia, Brazil. The patient had long-standing pulmonary tuberculosis (nine years) with extensive bilateral lung damage and had been treated with multiple antituberculosis drugs (self-administered) before XDR-TB diagnosis. The strain of Mycobacterium tuberculosis was resistant to R- rifampicin, H-isoniazid, E-ethambutol, Eto-ethionamide, Ofx-ofloxacin, and Am-amikacin. This patient died with multiple organ failure due to sepsis secondary to bacterial pneumonia.


The release of model macromolecules may be controlled by the hydrophobicity of palmitoyl glycol chitosan hydrogels.
A non-covalently cross-linked palmitoyl glycol chitosan (GCP) hydrogel has been evaluated as an erodible controlled release system for the delivery of hydrophilic macromolecules. Samples of GCP with hydrophobicity decreasing in the order GCP12>GCP11>GCP21 were synthesised and characterised by 1H NMR. Hydrogels were prepared by freeze-drying an aqueous dispersion of the polymer in the presence or absence of either a model macromolecule fluorescein isothiocyanate-dextran (FITC-dextran, MW 4400), and/or amphiphilic derivatives Gelucire 50/13 or vitamin E d-alpha-tocopherol polyethylene glycol succinate. Gels were analysed for aqueous hydration, FITC-dextran release, and bioadhesion, and imaged by scanning electron microscopy. The gels were highly porous and could be hydrated to up to 95x their original weight without an appreciable volume change and most gels eventually eroded. Hydration and erosion were governed by the hydrophobicity of the gel and the presence of the amphiphilic additives. GCP gels could be loaded with up to 27.5% (w/w) of FITC-dextran by freeze-drying a dispersion of GCP in a solution of FITC-dextran. The controlled release of FITC-dextran was governed by the hydrophobicity of the gel following the trend GCP21>GCP11>GCP12. GCP gels were bioadhesive but less so than hydroxypropylmethylcellulose, Carbopol 974NF (7:3) tablets.


Differences in coronary mortality can be explained by differences in cholesterol and saturated fat intakes in 40 countries but not in France and Finland. A paradox.
For decades, the coronary heart disease (CHD) mortality rate has been four or more times higher in Finland than in France despite comparable intakes of dietary cholesterol and saturated fat. A potential answer to this paradox is provided by this study of 40 countries and the analyses of other nutrients in the diets besides cholesterol and saturated fat. CHD death rates for men aged 55 to 64 years were derived from the World Health Organization annual vital statistics. Dietary intakes were gathered from the Food and Agriculture Organization of the United Nations database. Forty countries at various levels of economic development and 40 dietary variables were investigated, including a lipid score that combined the intakes of cholesterol and saturated fat (Cholesterol-Saturated Fat Index [CSI]). The CSI was significantly and positively related to CHD mortality in the 40 countries. The countries with low CSIs had low CHD death rates. Countries with high CSIs had a wide range of CHD death rates. France, Finland, and other Western industrialized countries had similar CSIs. After adjusting for cholesterol and saturated fat, milk and many components of milk (butterfat, milk protein, calcium from milk, and riboflavin) and total calcium remained positively related to CHD mortality for all 40 countries. There were differences in the consumption of these foods and nutrients in France and Finland. Milk and butterfat (fat from milk, cream, cheese, and butter) consumption was higher in Finland than in France. The consumption of plant foods, recently shown to be protective against CHD (vegetables and vegetable oils containing monounsaturated and polyunsaturated fatty acids), was greater in France than in Finland. Over the years, France and Finland, with similar intakes of cholesterol and saturated fat, consistently have had very different CHD mortality rates. This paradox may be explained as follows. Given a high intake of cholesterol and saturated fat, the country in which people also consume more plant foods, including small amounts of liquid vegetable oils, and more vegetables (more antioxidants) had lower rates of CHD mortality. On the other hand, milk and butterfat were associated with increased CHD mortality, possibly through their effects on thrombosis as well as on atherosclerosis.


Reagentless detection of Mycobacteria tuberculosis H37Ra in respiratory effluents in minutes.
Two similar mycobacteria, Mycobacteria tuberculosis H37Ra and Mycobacteria smegmatis are rapidly detected and identified within samples containing a complex background of respiratory effluents using single-particle aerosol mass spectrometry (SPAMS). M. tuberculosis H37Ra (TBa), an avirulent strain, is used as a surrogate for virulent tuberculosis; M. smegmatis (MSm) is utilized as a near-neighbor confounder for TBa. Bovine lung surfactant and human exhaled breath condensate are used as first-order surrogates for infected human lung expirations from patients with pulmonary tuberculosis. This simulated background sputum is mixed with TBa or MSm and nebulized to produce conglomerate aerosol particles, single particles that contain a bacterium embedded within a background respiratory matrix. Mass spectra of single conglomerate particles exhibit ions associated with both respiratory effluents and mycobacteria. Spectral features distinguishing TBa from MSm in pure and conglomerate particles are shown. SPAMS pattern matching alarm algorithms are able to distinguish TBa-containing particles from background matrix and MSm for >50% of the test particles, which is sufficient to enable a high probability of detection and a low false alarm rate if an adequate number of such particles are present. These results indicate the potential usefulness of SPAMS for rapid, reagentless tuberculosis screening.


Small GTPases and the evolution of the eukaryotic cell.
The origin of eukaryotes is one of the major challenges of evolutionary cell biology. Other than the endosymbiotic origin of mitochondria and chloroplasts, the steps leading to eukaryotic endomembranes and endoskeleton are poorly understood. Ras-family small GTPases are key regulators of cytoskeleton dynamics, vesicular trafficking and nuclear function. They are specific for eukaryotes and their expansion probably traces the evolution of core eukaryote features. The phylogeny of small GTPases suggests that the first endomembranes to evolve during eukaryote evolution had secretory, and not phagocytic, function. Based on the reconstruction of putative roles for ancestral small GTPases, a hypothetical scenario on the origins of the first endomembranes, the nucleus, and phagocytosis is presented.


Isoproterenol dose-outflow facility response relationships in the vervet monkey.
Total outflow facility was measured by two-level constant pressure anterior chamber perfusion in surgically untouched vervet monkeys receiving intracameral infusions of mock aqueous humor without or with isoproterenol. Bolus dl-isoproterenol sulfate doses of 1 to 10 micrograms, corresponding respectively to initial intracameral base concentrations of 2 X 10(-5) M and 2 X 10(-4) M, increased facility 30-50%; higher and lower bolus doses were ineffective, as were 0.1 and 1 g doses of 1-isoproterenol hydrochloride (4 X 10(-6) M and 4 X 10(-5) M base). Relatively maintained intracameral dl-isoproterenol concentrations of 2 X 10(-7) M and 2 X 10(-6) M or l-isoproterenol concentrations of 4 X 10(-7) M to 4 X 10(-5) M did not significantly increase facility, although there was great variability with the latter agent. Possible reasons for species, investigator, technique, and dosage-associated differences in results are discussed.


In vivo study of head impacts in football: a comparison of National Collegiate Athletic Association Division I versus high school impacts.
To compare the frequency and magnitude of head impacts between National Collegiate Athletic Association Division I and American high school football players. The long-term goal is to correlate impact forces with injury patterns, leading to improvements in protective headgear. The helmets of football players at the University of Oklahoma (n = 40) and Casady High School (n = 16) were instrumented with the Head Impact Telemetry System (Simbex, Lebanon, NH). Data were collected for practices and games for the 2005 football season and were analyzed by player position and school. Player positions were separated into two groups (skill and line) for analysis. Two case studies of athletes who sustained a concussion are also presented. A total of 54,154 impacts were recorded at the University of Oklahoma and 8326 at Casady High School. College players sustained high-level impacts greater than 98 g more frequently than high school players. The mean linear accelerations for the top 1, 2, and 5% of all impacts were also higher for college players (P < 0.02). Skill position players received 24.6% of all impacts and sustained an impact greater than 98 g once every 70 impacts. In contrast, linemen sustained the highest number of impacts, but most were relatively low-magnitude (20-30 g). Linemen sustained an impact greater than 98 g once every 125 impacts. Differences in the frequency and magnitude of head acceleration after impact exist between a Division I college team and a high school team. Compared with linemen, skill position players typically sustain the highest-level impacts. Additional data collection and analysis are required to correlate concussion diagnosis with acceleration magnitude and impact location.


Microbiological characterization of post-eruption "snowblower" vents at Axial Seamount, Juan de Fuca Ridge.
Microbial processes within the subseafloor can be examined during the ephemeral and uncommonly observed phenomena known as snowblower venting. Snowblowers are characterized by the large quantity of white floc that is expelled from the seafloor following mid-ocean ridge eruptions. During these eruptions, rapidly cooling lava entrains seawater and hydrothermal fluids enriched in geochemical reactants, creating a natural bioreactor that supports a subseafloor microbial "bloom." Previous studies hypothesized that the eruption-associated floc was made by sulfide-oxidizing bacteria; however, the microbes involved were never identified. Here we present the first molecular analysis combined with microscopy of microbial communities in snowblower vents from samples collected shortly after the 2011 eruption at Axial Seamount, an active volcano on the Juan de Fuca Ridge. We obtained fluid samples and white flocculent material from active snowblower vents as well as orange flocculent material found on top of newly formed lava flows. Both flocculent types revealed diverse cell types and particulates when examined by phase contrast and scanning electron microscopy (SEM). Distinct archaeal and bacterial communities were detected in each sample type through Illumina tag sequencing of 16S rRNA genes and through sequencing of the sulfide oxidation gene, soxB. In fluids and white floc, the dominant bacteria were sulfur-oxidizing Epsilonproteobacteria and the dominant archaea were thermophilic Methanococcales. In contrast, the dominant organisms in the orange floc were Gammaproteobacteria and Thaumarchaeota Marine Group I. In all samples, bacteria greatly outnumbered archaea. The presence of anaerobic methanogens and microaerobic Epsilonproteobacteria in snowblower communities provides evidence that these blooms are seeded by subseafloor microbes, rather than from microbes in bottom seawater. These eruptive events thus provide a unique opportunity to observe subseafloor microbial communities.


Beyond fine-tuning: Classifying high resolution mammograms using function-preserving transformations.
The task of classifying mammograms is very challenging because the lesion is usually small in the high resolution image. The current state-of-the-art approaches for medical image classification rely on using the de-facto method for convolutional neural networks-fine-tuning. However, there are fundamental differences between natural images and medical images, which based on existing evidence from the literature, limits the overall performance gain when designed with algorithmic approaches. In this paper, we propose to go beyond fine-tuning by introducing a novel framework called MorphHR, in which we highlight a new transfer learning scheme. The idea behind the proposed framework is to integrate function-preserving transformations, for any continuous non-linear activation neurons, to internally regularise the network for improving mammograms classification. The proposed solution offers two major advantages over the existing techniques. Firstly and unlike fine-tuning, the proposed approach allows for modifying not only the last few layers but also several of the first ones on a deep ConvNet. By doing this, we can design the network front to be suitable for learning domain specific features. Secondly, the proposed scheme is scalable to hardware. Therefore, one can fit high resolution images on standard GPU memory. We show that by using high resolution images, one prevents losing relevant information. We demonstrate, through numerical and visual experiments, that the proposed approach yields to a significant improvement in the classification performance over state-of-the-art techniques, and is indeed on a par with radiology experts. Moreover and for generalisation purposes, we show the effectiveness of the proposed learning scheme on another large dataset, the ChestX-ray14, surpassing current state-of-the-art techniques.


Characteristics and preparation of the last-minute traveler: analysis of vaccine usage in the Global TravEpiNet Consortium.
Last-minute travellers (LMTs) present challenges for health care providers because they may have insufficient time for recommended vaccinations or pre-travel preparation. Our objective was to obtain a better understanding of LMTs in order to help travel medicine providers develop improved strategies to decrease the number of LMTs and potentially reduce travel-related morbidity. We defined LMTs as travellers with a departure date of 7 days or fewer from the medical encounter. We analysed the characteristics and health preparation of 12 494 LMTs who presented to a network of US clinical practices for pre-travel health advice between January 2009 and December 2015. LMTs comprised 16% of all travellers. More LMTs than non-LMTs travelled for business or to visit friends and relatives (VFR) (26% vs 16% and 15% vs 8%, respectively; P < 0.0001). More LMTs also travelled for longer than 1 month (27% vs 21%; P < 0.0001) and visited only urban areas (40% vs 29%; P < 0.0001). At least one travel vaccine was deferred by 18% of LMTs because of insufficient time before departure. Vaccines that required multiple vaccinations, such as Japanese encephalitis and rabies, were the most likely to be deferred because of time constraints. Interventions to improve the timing of pre-travel health consultations should be developed, particularly for business and VFR travellers. Recently endorsed accelerated vaccine schedules for Japanese encephalitis and rabies may help some LMTs receive protection against these infections despite late presentation for pre-travel health care.


[Liability risks of MRSA-management].
Errors in treatment due to insufficient management of hygiene processes, for example handling of MRSA, can cause liability for consequences. The legal principles to handle MRSA result particularly from the so called Infection Protection Act (IfSG). Terms of reference, guidelines and recommendations can provide important support to avoid liability suits. The German health care policy was as well engaged in the problem of MRSA expansion. The judicature confirms that care providers are obliged to contain the risks of avoidable infections by taking organisational und technical precautions.


TRPC1 contributes to light-touch sensation and mechanical responses in low-threshold cutaneous sensory neurons.
The cellular proteins that underlie mechanosensation remain largely enigmatic in mammalian systems. Mechanically sensitive ion channels are thought to distinguish pressure, stretch, and other types of tactile signals in skin. Transient receptor potential canonical 1 (TRPC1) is a candidate mechanically sensitive channel that is expressed in primary afferent sensory neurons. However, its role in the mechanical sensitivity of these neurons is unclear. Here, we investigated TRPC1-dependent responses to both innocuous and noxious mechanical force. Mechanically evoked action potentials in cutaneous myelinated A-fiber and unmyelinated C-fiber neurons were quantified using the ex vivo skin-nerve preparation to record from the saphenous nerve, which terminates in the dorsal hairy skin of the hindpaw. Our data reveal that in TRPC1-deficient mice, mechanically evoked action potentials were decreased by nearly 50% in slowly adapting Aβ-fibers, which largely innervate Merkel cells, and in rapidly adapting Aδ-Down-hair afferent fibers compared with wild-type controls. In contrast, differences were not found in slowly adapting Aδ-mechanoreceptors or unmyelinated C-fibers, which primarily respond to nociceptive stimuli. These results suggest that TRPC1 may be important in the detection of innocuous mechanical force. We concurrently investigated the role of TRPC1 in behavioral responses to mechanical force to the plantar hindpaw skin. For innocuous stimuli, we developed a novel light stroke assay using a "puffed out" cotton swab. Additionally, we used repeated light, presumably innocuous punctate stimuli with a low threshold von Frey filament (0.68 mN). In agreement with our electrophysiological data in light-touch afferents, TRPC1-deficient mice exhibited nearly a 50% decrease in behavioral responses to both the light-stroke and light punctate mechanical assays when compared with wild-type controls. In contrast, TRPC1-deficient mice exhibited normal paw withdrawal response to more intense mechanical stimuli that are typically considered measures of nociceptive behavior.


Effects of the motor cortical quadripulse transcranial magnetic stimulation (QPS) on the contralateral motor cortex and interhemispheric interactions.
Corpus callosum connects the bilateral primary motor cortices (M1s) and plays an important role in motor control. Using the paired-pulse transcranial magnetic stimulation (TMS) paradigm, we can measure interhemispheric inhibition (IHI) and interhemispheric facilitation (IHF) as indexes of the interhemispheric interactions in humans. We investigated how quadripulse transcranial magnetic stimulation (QPS), one form of repetitive TMS (rTMS), on M1 affects the contralateral M1 and the interhemispheric interactions. QPS is able to induce bidirectional plastic changes in M1 depending on the interstimulus intervals (ISIs) of TMS pulses: long-term potentiation (LTP)-like effect by QPS-5 protocol, and long-term depression-like effect by QPS-50, whose numbers indicate the ISI (ms). Twelve healthy subjects were enrolled. We applied QPS over the left M1 and recorded several parameters before and 30 min after QPS. QPS-5, which increased motor-evoked potentials (MEPs) induced by left M1 activation, also increased MEPs induced by right M1 activation. Meanwhile, QPS-50, which decreased MEPs elicited by left M1 activation, did not induce any significant changes in MEPs elicited by right M1 activation. None of the resting motor threshold, active motor threshold, short-interval intracortical inhibition, long-interval intracortical inhibition, intracortical facilitation, and short-interval intracortical inhibition in right M1 were affected by QPS. IHI and IHF from left to right M1 significantly increased after left M1 QPS-5. The degree of left first dorsal interosseous MEP amplitude change by QPS-5 significantly correlated with the degree of IHF change. We suppose that the LTP-like effect on the contralateral M1 may be produced by some interhemispheric interactions through the corpus callosum.


Three dimensional range geometry and texture data compression with space-filling curves.
This paper presents a novel method to effectively store three-dimensional (3D) data and 2D texture data into a regular 24-bit image. The proposed method uses the Hilbert space-filling curve to map the normalized unwrapped phase map to two 8-bit color channels, and saves the third color channel for 2D texture storage. By further leveraging existing 2D image and video compression techniques, the proposed method can achieve high compression ratios while effectively preserving data quality. Since the encoding and decoding processes can be applied to most of the current 2D media platforms, this proposed compression method can make 3D data storage and transmission available for many electrical devices without requiring special hardware changes. Experiments demonstrate that if a lossless 2D image/video format is used, both original 3D geometry and 2D color texture can be accurately recovered; if lossy image/video compression is used, only black-and-white or grayscale texture can be properly recovered, but much higher compression ratios (e.g., 1543:1 against the ASCII OBJ format) are achieved with slight loss of 3D geometry quality.


Combined methylation mapping of 5mC and 5hmC during early embryonic stages in bovine.
It was recently established that changes in methylation during development are dynamic and involve both methylation and demethylation processes. Yet, which genomic sites are changing and what are the contributions of methylation (5mC) and hydroxymethylation (5hmC) to this epigenetic remodeling is still unknown. When studying early development, options for methylation profiling are limited by the unavailability of sufficient DNA material from these scarce samples and limitations are aggravated in non-model species due to the lack of technological platforms. We therefore sought to obtain a representation of differentially 5mC or 5hmC loci during bovine early embryo stages through the use of three complementary methods, based on selective methyl-sensitive restriction and enrichment by ligation-mediated PCR or on subtractive hybridization. Using these strategies, libraries of putative methylation and hydroxymethylated sites were generated from Day-7 and Day-12 bovine embryos. Over 1.2 million sequencing reads were analyzed, resulting in 151,501 contigs, of which 69,136 were uniquely positioned on the genome. A total of 101,461 putative methylated sites were identified. The output of the three methods differed in genomic coverage as well as in the nature of the identified sites. The classical MspI/HpaII combination of restriction enzymes targeted CpG islands whereas the other methods covered 5mC and 5hmC sites outside of these regions. Data analysis suggests a transition of these methylation marks between Day-7 and Day-12 embryos in specific classes of repeat-containing elements. Our combined strategy offers a genomic map of the distribution of cytosine methylation/hydroxymethylation during early bovine embryo development. These results support the hypothesis of a regulatory phase of hypomethylation in repeat sequences during early embryogenesis.


Self-enhanced Electrochemiluminescence Luminophore Based on Pd Nanocluster-Anchored Metal Organic Frameworks via Ion Annihilation for Sensitive Cell Assay of Human Lung Cancer.
Electrochemiluminescence (ECL) has attracted significant interest in the analysis of cancer cells, where the ruthenium(II)-based emitter demonstrates urgency and feasibility to improve the ECL efficiency. In this work, the self-enhanced ECL luminophore was prepared by covalent anchoring of Pd nanoclusters on aminated metal organic frameworks (Pd NCs@MOFs), followed by linkage with bis(2,2'-bipyridine)-5-amino-1,10-phenanthroline ruthenium(II) (RuP). The resultant luminophore showed 214-fold self-magnification in the ECL efficiency over RuP alone, combined by promoting the interfacial photoelectron transfer. The enhanced mechanism through ion annihilation was critically proved by controlled experiments and density functional theory (DFT) calculations. Based on the above, a "signal off" ECL biosensor was built by assembly of tyrosine kinase 7 (PTK-7) aptamer (Apt) on the established sensing platform for analysis of human lung cancer cells (A549). The built sensor showed a lower detection limit of 8 cells mL-1, achieving the single-cell detection. This work reported a self-enhanced strategy for synthesis of advanced ECL emitters, combined by exploring the ECL biosensing devices in the single-cell analysis of cancers.


Force-Field-Based Computational Study of the Thermodynamics of a Large Set of Aqueous Alkanolamine Solvents for Post-Combustion CO2 Capture.
The ability to predict the thermodynamic properties of amine species in CO2-loaded aqueous solutions, including their deprotonation (pKa) and carbamate to bicarbonate reversion (pKc) equilibrium constants and their corresponding standard reaction enthalpies, is of critical importance for the design of improved carbon capture solvents. In this study, we used isocoulombic forms of both reactions to determine these quantities for a large set of aqueous alkanolamine solvent systems. Our hybrid approach involves using classical molecular dynamics simulations with the general amber force field (GAFF) and semi-empirical AM1-BCC charges (GAFF/AM1-BCC) in the solution phase, combined with high-level composite quantum chemical ideal-gas calculations. We first determined a new force field (FF) for the hydronium ion (H3O+) by matching to the single experimental pKa data point for the well-known monoethanolamine system at 298.15 K. We then used this FF to predict the pKa values for 76 other amines at 298.15 K and for all 77 amines at elevated temperatures. Additionally, we indirectly relate the H3O+ hydration free energy to that of H+ and provide expressions for intrinsic hydration free energy and enthalpy of the proton. Using the derived H3O+ FF, we predicted the pKa values of a diverse set of alkanolamines with an overall average absolute deviation of less than 0.72 pKa units. Furthermore, the derived H3O+ FF is able to predict the protonation enthalpy of these amines when used with the GAFF. We also predicted the carbamate reversion constants of the primary and secondary amine species in the data set and their corresponding standard heats of reaction, which we compared with the scarcely available experimental data, which are often subject to significant uncertainty. Finally, we also described the influence of electronic and steric effects of different molecular fragments/groups on the stabilities of the carbamates.


Differentiating autism spectrum disorder from other developmental delays in the first two years of life.
Advances in the identification of the early signs of autism spectrum disorder (ASD) have occurred despite the heterogeneity of the disorder and its variable onset and presentation. Using various methodologies including retrospective studies, community samples, and sibling cohorts, researchers have identified behavioral markers of the disorder that emerge over the first 2 years of life. However, there are characteristics of ASD that overlap with other types of developmental delay (DD), which may complicate differential diagnosis in young children. A review of the literature was conducted to identify the most promising behavioral markers that distinguish ASD from other types of DD in the first 2 years of life. The review identified profiles of behavioral markers in the social realm by 12 months and in the communication realm by 18 months, which along with additional atypical motor behaviors could distinguish ASD from DD. This constellation of features coupled with a flat or declining trajectory in specific aspects of social and communication development, may assist clinicians in targeting early interventions to at-risk infants.


Bent Singlet Cyclobutylcarbene: Computed Geometry, Properties, and Product Selectivity of a Nonclassical Carbene.
Ab initio computations of cyclobutylcarbene (c-C4H7CH) were performed using the UMP4(fc)/6-311++G(2df,2p)//UMP2(full)/6-311++G(d,p) theoretical model. The carbene's most striking feature is its :CH-group. It is markedly bent toward the elongated C1'-C2' bond in the singlet ground-state but not in the triplet state, which is at least 1.1 kcal/mol higher in energy. Nonclassical 3C2E bonding among the C1, C1', and C2' atoms is prominent in the HOMO{-1}. The electron-donating ability of the nonbonding HOMO is thereby enhanced. The intensified nucleophilicity of the singlet carbene is manifested in quantifiable ways. For example, its hard and soft acid and base (HSAB) hardness, HSAB absolute electronegativity, and gas-phase proton affinity rival those of ylide-stabilized N-heterocyclic carbenes. It is computed to act as a nucleophile toward alkenes with higher HSAB hardness values. Transition states from singlet cyclobutylcarbene to bicyclo[2.1.0]pentane, cyclopentene, and methylenecyclobutane were computed and confirmed by intrinsic reaction coordinate calculations. Activation energies depend on the singlet's conformation with regard to c-C4H7 ring-puckering, :CH-group rotation, and :CH-group bending. The singlet's bent :CH-group favors bicyclo[2.1.0]pentane and cyclopentene formation.


Lack of Shiga-like cytotoxin production by enteroinvasive Escherichia coli.
Enteroinvasive Escherichia coli has not been extensively studied for cytotoxin production. We evaluated 30 well-characterized enteroinvasive E. coli strains of all the known invasive serogroups from several geographic regions for their ability to produce Shiga-like cytotoxic activity assayed in a HeLa cell system. None of these strains produced cytotoxic activity that was neutralizable with antibody to Shiga-like toxin I or II.


The Role of Ethnic and National Identifications in Perceived Discrimination for Asian Americans: Toward a Better Understanding of the Buffering Effect of Group Identifications on Psychological Distress.
A robust relationship between perceived racial discrimination and psychological distress has been established. Yet, mixed evidence exists regarding the extent to which ethnic identification moderates this relationship, and scarce attention has been paid to the moderating role of national identification. We propose that the role of group identifications in the perceived discrimination-psychological distress relationship is best understood by simultaneously and interactively considering ethnic and national identifications. A sample of 259 Asian American students completed measures of perceived discrimination, group identifications (specific ethnic identification stated by respondents and national or "mainstream American" identification), and psychological distress (anxiety and depression symptoms). Regression analyses revealed a significant three-way interaction of perceived discrimination, ethnic identification, and national identification on psychological distress. Simple-slope analyses indicated that dual identification (strong ethnic and national identifications) was linked to a weaker relationship between perceived discrimination and psychological distress compared with other group identification configurations. These findings underscore the need to consider the interconnections between ethnic and national identifications to better understand the circumstances under which group identifications are likely to buffer individuals against the adverse effects of racial discrimination.


Differing effects of cGMP and cAMP on ion transport across flounder intestine.
The intestinal epithelium of the winter flounder is highly cation selective and actively absorbs NaCl via a bumetanide-sensitive (Na + K + 2Cl) cotransport system; it also actively secretes K+. Combined addition of adenosine 3',5'-cyclic monophosphate (cAMP) and theophylline was previously shown to partially inhibit NaCl absorption and to increase passive Cl- permeability. Because theophylline increases cyclic GMP (cGMP) and cAMP concentrations, we compared the effects of the 8-Bromo analogues of these two nucleotides on ion transport. cGMP inhibits Cl- absorption, K+ secretion, and Cl- and K+ influx across the brush border as effectively as do furosemide and bumetanide. Even at maximal doses, cAMP is less effective than cGMP in inhibiting ion transport; however, unlike cGMP, it abolishes the cation selectivity of the epithelium by greatly increasing Cl- permeability. The effects of the two nucleotides are not additive with each other or with those of bumetanide, although cGMP or bumetanide can further inhibit transport in cAMP-treated tissues.


Concentrations of Selected Cytokines and Vascular Endothelial Growth Factor in Aqueous Humor and Serum of Diabetic Patients.
Purpose: To investigate the aqueous humor and serum levels of selected cytokines and vascular endothelial growth factor (VEGF) in diabetic patients, implicating their role in the pathogenesis of diabetic eye complications.Materials and methods: Atotal of 65 patients (27 males and 38 females) who underwent cataract surgery were recruited into the study. The study group consisted of 30 cataract patients with type 2 diabetes mellitus, and this group was divided into two subgroups: 14 patients with diabetic retinopathy (DR group) and 16 patients without DR (NDR group). The control group consisted of 35 non-diabetic cataract subjects.Results: Patients in the DR group had significantly higher aqueous humor concentrations of interleukin (IL)-1β, IL-6, IL-8, IL-10, monocyte chemotactic protein (MCP-1) and VEGF. Likewise, serum concentrations of IL-1β, IL-6, IL-8, IL-12, TNF-α and IFN-γ were significantly higher in the DR group as compared to the controls. Aqueous humor concentrations of IL-1β, IL-8, MCP-1 and VEGF were significantly higher in the DR group as compared with the NDR group.Conclusion: Our findings support the hypothesis that chronic inflammation and a disturbance of the immune system play important roles in the pathogenesis of diabetic cataract and DR.


Characterization of aminopeptidases responsible for inactivating endogenous (Met5)enkephalin in brain slices using peptidase inhibitors and anti-aminopeptidase M antibodies.
In addition to "enkephalinase" (EC 18.104.22.168), two enkephalin-hydrolyzing aminopeptidases recently identified in cerebral membranes--aminopeptidase M (EC 18.104.22.168) and a "puromycin-sensitive" aminopeptidase (also designated "MII" or "aminoenkephalinase")--are potentially involved in endogenous enkephalin inactivation. Their participation in the hydrolysis of the endogenous (Met5)enkephalin released by depolarization of slices from rat globus pallidus was assessed, using three inhibitory agents: bestatin, puromycin, and anti-aminopeptidase M antibodies. The selectivity and potency of these agents were first determined by evaluating their IC50 values for inhibition of [3H](Met5)enkephalin hydrolysis by increasingly complex preparations comprising semipurified aminopeptidases, pallidal membranes, and pallidal slices. Bestatin was a fairly potent inhibitor but lacked selectivity, as there was only a 3-fold difference between its IC50 values for the two aminopeptidases, and it displayed restricted diffusion and degradation in the slice preparation. Puromycin discriminated well between the two aminopeptidases (30-fold difference in IC50 values) and did not show any apparent restricted diffusion in the slice preparation. Antiaminopeptidase M antibodies were highly discriminant (greater than 300-fold difference in IC50 values for the two aminopeptidases) but displayed restricted diffusion. Analysis of the concentration-protection curves of the three agents for recovery of the (Met5)enkephalin released from pallidal slices in the presence of the "enkephalinase" inhibitor, thiorphan, indicated that both aminopeptidases participated in enkephalin degradation but that the role of aminopeptidase M was largely predominant, in contrast with its low relative activity in the preparation.


The Molecular and Pharmacological Mechanisms of HIV-Related Neuropathic Pain.
Infection of the nervous system with the human immunodeficiency virus (HIV-1) can lead to cognitive, motor and sensory disorders. HIV-related sensory neuropathy (HIV-SN) mainly contains the HIV infection-related distal sensory polyneuropathy (DSP) and antiretroviral toxic neuropathies (ATN). The main pathological features that characterize DSP and ATN include retrograde ("dying back") axonal degeneration of long axons in distal regions of legs or arms, loss of unmyelinated fibers, and variable degree of macrophage infiltration in peripheral nerves and dorsal root ganglia (DRG). One of the most common complaints of HIV-DSP is pain. Unfortunately, many conventional agents utilized as pharmacologic therapy for neuropathic pain are not effective for providing satisfactory analgesia in painful HIV-related distal sensory polyneuropathy, because the molecular mechanisms of the painful HIV-SDP are not clear in detail. The HIV envelope glycoprotein, gp120, appears to contribute to this painful neuropathy. Recently, preclinical studies have shown that glia activation in the spinal cord and DRG has become an attractive target for attenuating chronic pain. Cytokines/chemokines have been implicated in a variety of painful neurological diseases and in animal models of HIV-related neuropathic pain. Mitochondria injured by ATN and/or gp120 may be also involved in the development of HIV-neuropathic pain. This review discusses the neurochemical and pharmacological mechanisms of HIV-related neuropathic pain based on the recent advance in the preclinical studies, providing insights into novel pharmacological targets for future therapy.


Expression of angiotensin-converting enzyme (CD143) identifies and regulates primitive hemangioblasts derived from human pluripotent stem cells.
We report that angiotensin-converting enzyme (ACE), a critical physiologic regulator of blood pressure, angiogenesis, and inflammation, is a novel marker for identifying hemangioblasts differentiating from human embryonic stem cells (hESC). We demonstrate that ACE+CD45-CD34+/- hemangioblasts are common yolk sac (YS)-like progenitors for not only endothelium but also both primitive and definitive human lymphohematopoietic cells. Thrombopoietin and basic fibroblast growth factor are identified as critical factors for the proliferation of human hemangioblasts. The developmental sequence of human embryoid body hematopoiesis is remarkably congruent to the timeline of normal human YS development, which occurs during weeks 2 to 6 of human gestation. Furthermore, ACE and the renin-angiotensin system (RAS) directly regulate hemangioblast expansion and differentiation via signaling through the angiotensin II receptors AGTR1 and AGTR2. ACE enzymatic activity is required for hemangioblast expansion, and differentiation toward either endothelium or multipotent hematopoietic progenitors is dramatically augmented after manipulation of angiotensin II signaling with either AGTR1- or AGTR2-specific inhibitors. The RAS can therefore be exploited to direct the hematopoietic or endothelial fate of hESC-derived hemangioblasts, thus providing novel opportunities for human tissue engineering. Moreover, the initial events of human hematoendotheliogenesis can be delineated in a manner previously impossible because of inaccessibility to early human embryonic tissues.


Scenario processes for socio-environmental systems analysis of futures: A review of recent efforts and a salient research agenda for supporting decision making.
This paper reviews the latest research on scenarios including the processes and products for socio-environmental systems (SES) analysis, modeling and decision making. A group of scenario researchers and practitioners participated in a workshop to discuss consolidation of existing research on the development and use of scenario analysis in exploring and understanding the interplay between human and environmental systems. This paper presents an extended overview of the workshop discussions and follow-up review work. It is structured around the essential challenges that are crucial to progress support of decision making and learning with respect to our highly uncertain socio-environmental futures. It identifies a practical research agenda where challenges are grouped according to the process stage at which they are most significant: before, during, and after the creation of the scenarios as products. These challenges for SES include: enhancing the role of stakeholder and public engagement in the co-development of scenarios, linking scenarios across multiple geographical, sectoral and temporal scales, improving the links between the qualitative and quantitative aspects of scenario analysis, addressing uncertainties especially surprise, addressing scenario diversity and their consistency together, communicating scenarios including visualization methods, and linking scenarios to decision making.


A Comfortable Solution To Tracheal Anastomosis Protection: Tracheal Retention Sutures.
Fixation of the chin to the anterior chest wall is the most commonly used method of reducing anastomotic tension following a segmental resection of the trachea and reconstruction with primary anastomosis. However, the sutures required for this method may lead to various organic and psychological problems. In five patients who underwent tracheal resection and primary anastomosis, retention sutures were placed on the proximal and distal-lateral edges of the anastomotic line rather than placing a Guardian chin stitch. All patients were mobilised in the early postoperative period and were able to perform their routine daily activities without restrictions. During their average 14.4 months of follow-up, no complications were found in their anastomotic lines during their clinical, radiological, and bronchoscopic assessments. The placement of tracheal retention sutures proved an inexpensive and reliable method to reduce anastomotic tension without additional surgical burden, and was effective in terms of patient comfort.


Studies on meperidine-induced catalepsy in mice.
Anticataleptic effect of different pharmacological agents was studied against meperidine-induced (50 mg/kg i.p.) catalepsy in mice. MAO (A and B) inhibitors, alpha 2-agonists in addition to dopaminergic, GABAergic and serotoninergic agents, were found to be effective in attenuating the cataleptic symptoms. However, naloxone, an opiate antagonist, failed to reverse meperidine-induced akinesia and rigidity. Clorgyline, a specific MAO-A inhibitor, was found to be more potent than the MAO-B inhibitor selegiline.


Human Lupus Plasma Pro-Atherogenic Effects on Cultured Macrophages Are Not Mitigated by Statin Therapy: A Mechanistic LAPS Substudy.
Background and Objectives: Atherosclerotic cardiovascular disease (CVD) remains a major cause of morbidity and mortality in persons with systemic lupus erythematosus (SLE, lupus). Atherosclerosis, which involves interplay between cholesterol metabolism and cellular inflammatory pathways, is primarily treated with statins since statins have lipid-lowering and anti-inflammatory properties. The Lupus Atherosclerosis Prevention Study (LAPS) was designed to investigate the efficacy of statins against CVD in SLE patients. LAPS demonstrated that 2 years of atorvastatin administration did not reduce atherosclerosis progression in lupus patients. In this LAPs substudy, we use cultured macrophages to explore the atherogenic properties of plasma from LAPS subjects to explain the mechanistic rationale for the inability of statins to reduce CVD in lupus. Materials and Methods: THP-1 differentiated macrophages were treated for 18 h with 10% SLE patient plasma obtained pre- and post-atorvastatin therapy or placebo. Gene expression of the following cholesterol transport genes was measured by qRT-PCR. For efflux-ATP binding cassette transporter (ABC)A1 and ABCG1, 27-hydroxylase, peroxisome proliferator-activated receptor (PPAR)γ, and liver X receptor (LXR)α; and for influx-cluster of differentiation 36 (CD36) and scavenger receptor (ScR)A1. Results: Macrophages exposed to plasma from both statin-treated and placebo-treated groups showed a significant decrease in cholesterol efflux proteins ATP binding cassette (ABC) transporters A1 and ABCG1, an increase in 27-hydroxylase, an increase in the LDL receptor and a decrease in intracellular free cholesterol. No change in influx receptors ScRA1 and CD36, nor nuclear proteins LXRα and PPARγ was observed. Conclusions: Statins do not normalize pro-atherogenic changes induced by lupus and these changes continue to worsen over time. This study provides mechanistic insight into LAPS findings by demonstrating that statins are overall ineffective in altering the balance of cholesterol transport gene expression in human macrophages. Furthermore, our study suggests that statins as a CVD treatment may not be useful in attenuating lipid overload in the SLE environment.


Extinction of over-selected stimuli causes emergence of under-selected cues in higher-functioning children with autistic spectrum disorders.
Two experiments examined whether over-selectivity is the product of a post-acquisition performance deficit, rather than an attention problem. In both experiments, children with Autistic Spectrum Disorder were presented with a trial-and-error discrimination task using two, two-element stimuli and over-selected in both studies. After behavioral control by the previously over-selected stimulus was extinguished, behavioral control by the previously under-selected cue emerged without direct training. However, this effect was only found in higher-functioning children, and not with more severely impaired children. These findings suggest that over-selectivity is not simply due to a failure to attend to all of the stimuli presented. They also suggest that extinction of over-selected stimuli may be a fruitful line of intervention for clinical intervention for some individuals.


Determining factors for the prevalence of depressive symptoms among postpartum mothers in lowland region in southern Nepal.
Postpartum depression is the most common mental health problem among women of childbearing age in resource-poor countries. Poor maternal mental health is linked with both acute and chronic negative effects on the growth and development of the child. This study aimed to assess the prevalence and factors associated with depressive symptoms among postpartum mothers in the lowland region in southern Nepal. A hospital-based analytical cross-sectional study was conducted from 1st July to 25th August 2019 among 415 randomly selected postpartum mothers attending the child immunization clinic at Narayani hospital. The postpartum depressive symptoms were measured using the validated Nepalese version of the Edinburg Postnatal Depression Scale (EPDS). The data were entered into EpiData software 3.1v and transferred into Stata version 14.1 (StataCorp LP, College Station, Texas) for statistical analyses. To identify the correlates, backward stepwise binary logistic regression models were performed separately for the dichotomized outcomes: the presence of postpartum depressive symptoms. The statistical significance was considered at p-value <0.05 with 95% confidence intervals (CIs). Among the total 415 study participants, 33.7% (95% CI: 29.2-38.5%) of postpartum mothers had depressive symptoms. Study participant's whose family monthly income <150 USD compared to ≥150 USD (aOR = 13.76, 95% CI: 6.54-28.95), the husband had migrated for employment compared to not migrated (aOR = 8.19, 95% CI:4.11-15.87), nearest health facility located at more than 60 minutes of walking distance (aOR = 4.52, 95% CI: 2.26-9.03), delivered their last child by cesarean section compared to normal (vaginal) delivery (aOR = 2.02, 95% CI: 1.12-3.59) and received less than four recommended antenatal care (ANC) visits (aOR = 2.28, 95% CI:1.25-4.15) had higher odds of depressive symptoms. Participants who had planned pregnancy (aOR = 0.44, 95% CI: 0.25-0.77) were associated with 56% lower odds of depressive symptoms. One-third of the mothers suffered from postpartum depressive symptoms. The participant's husband migrated for employment, family income, distance to reach a health facility, delivery by cesarean section, not receiving recommended ANC visits, and plan of pregnancy were independent predictors for postpartum depressive symptoms. The study results warranted the urgency for clinical diagnosis of PPD and implementation of preventive package in study settings. Mental health education to pregnant women during ANC visits and proper counseling during the antepartum and postpartum period can also play a positive role in preventing postpartum depression.


Factors affecting outcome of acute cervical spine injury: A prospective study.
Injury to the spine and spinal cord is one of the common cause of disability and death. Several factors affect the outcome; but which are these factors (alone and in combination), are determining the outcomes are still unknown. The aim of the study was to evaluate the factors influencing the outcome following acute cervical spine injury. A prospective observational study at single-center with all patients with cervical spinal cord injury (SCI), attending our hospital within a week of injury during a period of October 2011 to July 2013 was included for analysis. Demographic factors such as age, gender, etiology of injury, preoperative American Spinal Injury Association (ASIA) grade, upper (C2-C4) versus lower (C5-C7) cervical level of injury, imageological factors on magnetic resonance imaging (MRI), and timing of intervention were studied. Change in neurological status by one or more ASIA grade from the date of admission to 6 months follow-up was taken as an improvement. Functional grading was assessed using the functional independence measure (FIM) scale at 6 months follow-up. A total of 39 patients with an acute cervical spine injury, managed surgically were included in this study. Follow-up was available for 38 patients at 6 months. No improvement was noted in patients with ASIA Grade A. Maximum improvement was noted in ASIA Grade D group (83.3%). The improvement was more significant in lower cervical region injuries. Patient with cord contusion showed no improvement as opposed to those with just edema wherein; the improvement was seen in 62.5% patients. Percentage of improvement in cord edema ≤3 segments (75%) was significantly higher than edema with >3 segments (42.9%). Maximum improvement in FIM score was noted in ASIA Grade C and patients who had edema (especially ≤3 segments) in MRI cervical spine. Complete cervical SCI, upper-level cervical cord injury, patients showing MRI contusion, edema >3 segments group have worst improvement in neurological status at 6 months follow-up.


Pediatric Cardiovascular Computed Tomography: Clinical Indications, Technique, and Standardized Reporting. Recommendations From the Cardiothoracic Taskforce of the European Society of Pediatric Radiology.
Congenital heart diseases affect 1% of all live births in the general population. The prognosis of these children is increasingly improving due to advances in medical care and surgical treatment. Imaging is also evolving rapidly to assess accurately complex cardiac anomalies prenatally and postnatally. Transthoracic echocardiography is the gold-standard imaging technique to diagnose and follow-up children with congenital heart disease. Cardiac computed tomography imaging plays a key role in the diagnosis of children with congenital heart defects that require intervention, due to its high temporal and spatial resolution, with low radiation doses. It is challenging for radiologists, not primarily specialized in this field, to perform and interpret these studies due to the difficult anatomy, physiology, and postsurgical changes. Technical challenges consist of necessary electrocardiogram gating and contrast bolus timing to obtain an optimal examination. This article aims to define indications for pediatric cardiac computed tomography, to explain how to perform and report these studies, and to discuss future applications of this technique.


Exercise as a behavioral approach to improve mood in persons with traumatic brain injury.
Mood disturbance is a common, long-term, negative consequence of traumatic brain injury (TBI) that is insufficiently addressed by most traditional treatment modalities. A large body of evidence supports the efficacy of exercise training (ET) to broadly improve mood, as measured most often by the Profile of Mood States (POMS). However, this behavioral approach is not used nearly enough in the TBI population, and when it is, mood is rarely measured. This scoping review will evaluate the use of POMS as a mood measure in TBI research and to establish a rationale for using ET as a behavioral approach to broadly improve mood in persons with TBI. This article is protected by copyright. All rights reserved.


Comparison of the Effectiveness of Universal and Targeted Iodine Supplementation in Pregnant Women: A Randomized Controlled Trial.
To compare the effectiveness of universal and targeted iodine supplementation strategies. A randomized controlled trial involving low-risk Thai pregnant women was carried out. The participants were categorized into either the study group, in which iodine supplementation was varied based on median urine iodine concentration, or the control group, which received universal supplementation. Urine samples were collected before the start of treatment and at delivery. The primary outcome was iodine status after each supplementation regime. Two hundred and eight women were randomly categorized into 2 groups, 104 control-group participants and 104 study-group participants. Baseline iodine status in both groups was not significantly different. More than half of the pregnant women were classified as having iodine insufficiency. After supplementation, the proportions of iodine insufficiency in the control and study groups (27.9 and 33.3%, respectively; p value = 0.508) and those of excessive level (19.1 and 11.7%, respectively; p value = 0.247) were not significantly different between the 2 groups. However, iodine level above the requirement was statistically significantly higher in the control group (47.1%) compared with the study group (30.0%; p value = 0.048). The 2 strategies, universal and targeted supplementation, have comparable effectiveness in prevention of iodine deficiency, but the evidence suggests that targeted supplementation is better in avoiding over-supplementation.


Hospitalizations for varicella in children and adolescents in a referral hospital in Hong Kong, 2004 to 2008: a time series study.
Varicella accounts for significant morbidities and remains a public health issue worldwide. Climatic factors have been shown to associate with the incidence and transmission of various infectious diseases. We describe the epidemiology of varicella in paediatric patients hospitalized at a tertiary referral hospital in Hong Kong from 2004 to 2008, and to explore the possible association between the occurrence of varicella infection and various climatic factors. The hospital discharge database of Princess Margaret Hospital was retrospectively analyzed for admissions associated with varicella from 2004 to 2008. Meteorological data were obtained from the monthly meteorological reports from the Hong Kong Observatory website. Time series analysis was performed with Poisson regression using a Generalized Estimating Equation (GEE) approach. During the study period, 598 children were hospitalized for varicella. The mean age on admission was 57.6 months, and the mean duration of hospitalization was 3.7 days. The overall complication rate was 47%. The mean monthly relative humidity, especially in cool seasons, was inversely correlated with the monthly varicella cases of the same month. Varicella can lead to serious complications and prolonged hospitalization, even in previously healthy children. Lower relative humidity in cool seasons is associated with higher number of paediatric varicella hospital admissions. These findings are useful for a better understanding of the pattern of paediatric varicella hospitalization in Hong Kong.


Iterative Group Analysis (iGA): a simple tool to enhance sensitivity and facilitate interpretation of microarray experiments.
The biological interpretation of even a simple microarray experiment can be a challenging and highly complex task. Here we present a new method (Iterative Group Analysis) to facilitate, improve, and accelerate this process. Our Iterative Group Analysis approach (iGA) uses elementary statistics to identify those functional classes of genes that are significantly changed in an experiment and at the same time determines which of the class members are most likely to be differentially expressed. iGA does not require that all members of a class change and is therefore robust against imperfect class assignments, which can be derived from public sources (e.g. GeneOntologies) or automated processes (e.g. key word extraction from gene names). In contrast to previous non-iterative approaches, iGA does not depend on the availability of fixed lists of differentially expressed genes, and thus can be used to increase the sensitivity of gene detection especially in very noisy or small data sets. In the extreme, iGA can even produce statistically meaningful results without any experimental replication. The automated functional annotation provided by iGA greatly reduces the complexity of microarray results and facilitates the interpretation process. In addition, iGA can be used as a fast and efficient tool for the platform-independent comparison of a microarray experiment to the vast number of published results, automatically highlighting shared genes of potential interest. By applying iGA to a wide variety of data from diverse organisms and platforms we show that this approach enhances and accelerates the interpretation of microarray experiments.


Effect of supported employment on vocational rehabilitation outcomes of transition-age youth with intellectual and developmental disabilities: a case control study.
The purpose of this study was to examine the effect of supported employment intervention on the employment outcomes of transition-age youth with intellectual and developmental disabilities served by the public vocational rehabilitation system using a case-control study design. Data for this study were extracted from the Rehabilitation Services Administration Case Service Report (RSA-911) database for fiscal year 2009. The sample included 23,298 youth with intellectual and developmental disabilities aged between 16 and 25 years old at the time of application. The classification and regression tree (CART) method was used to estimate propensity scores and to adjust for selection bias on the basis of all prominent covariates relevant to the dependent variable (i.e., competitive employment). Results yielded six homogeneous subgroups, and receipt of supported employment was found to increase the employment rates across all of the groups. The effect of supported employment was especially strong for youth who were Social Security beneficiaries, special education students, and individuals with intellectual disabilities or autism who were high school graduates. These findings suggest that supported employment is an effective service for enhancing the vocational rehabilitation outcomes of young adults and provides valuable information for policy makers, health care providers, rehabilitation counselors, and educators.


Androgen deprivation therapy improves pneumoperitoneum time during laparoscopic radical prostatectomy in Japanese patients with enlarged prostates.
The aim of this study was to investigate if neoadjuvant hormone therapy (NHT) is associated with surgical outcomes of laparoscopic radical prostatectomy. A total of 286 patients with organ-confined prostate cancer and a preoperative prostate volume that could be estimated by transrectal ultrasound underwent laparoscopic radical prostatectomy between 2006 and 2011 at our institution. We examined whether NHT was associated with pneumoperitoneum time (PT) or estimated blood loss during laparoscopic radical prostatectomy. NHT was performed in 80 patients; the mean duration of NHT was 5.2 ± 0.2 months. Multivariate analysis demonstrated that history of NHT and no NHT were not independent predictors of prolonged PT or higher estimated blood loss. Next, we evaluated 57 patients whose estimated preoperative baseline prostate volume was over 50 mL. Multivariate analysis demonstrated that no history of NHT (P = 0.011) was an independent predictor of prolonged PT. PT was significantly shorter in the NHT group (164.5 ± 39.0 min, n = 26) than in the non-NHT group (184.0 ± 36.7 min, n = 31) (P = 0.048). In the NHT group, mean prostate volume was reduced from 63.7 ± 16.0 mL to 42.1 ± 18.6 mL (33.9% reduction) by NHT. NHT shortened the PT of the patients whose preoperative baseline prostate volume was over 50 mL. This suggests NHT downsized prostate volume, resulting in greater working space and shorter PT.


Viral susceptibility range of the fathead minnow (Pimephales promelas) poikilothermic cell line.
The viral susceptibility range of a poikilothermic cell line derived from the fathead minnow (Pimephales promelas) (FHM) to infection by a number of homoiothermic viruses representing most of the presently recognized viral groups and a member of the psittacosis-lymphogranuloma-trachoma group of agents was studied. All infectious agents, except poliovirus types 1 and 3, infectious bursal agent, and an avian infectious bronchitis virus (IBV) strain, readily multiplied in the FHM cell culture system, producing a detectable cytopathic effect. Although inconclusive evidence was obtained with two other avian IBV strains, these results indicated the ability of the FHM cell culture system to readily support the propagation of a variety of cytopathogenic homoiothermic viral agents.


Intraoperative Ultrasound an Economical Tool for Neurosurgeons: A Single-Center Experience.
Over the past decade, the use of intraoperative image guidance in neurosurgery has gradually gained in importance. Apart from some sophisticated and very expensive techniques, intraoperative ultrasound (IOUS) is a simple and economical technique that allows the surgeon to localize deep-seated lesions under a real-time ultrasonic image display without dissection. The purpose of this study was to present our own preliminary experiences in various (n=1250) neurosurgical procedures carried out at our tertiary care centre in a developing country. A Prospective study was carried out in our department of neurosurgery at Grant Medical College and Sir J J Group of hospitals from January 2010 to May 2019. IOUS was used during various elective neurosurgical procedures done during this period as given in table no below. A total of 1250 patients, 850 supratentorial lesion, 290 infratentorial lesion and 110 spinal lesion, were included in this study. All studies were performed using an ultrasound machine with variable 3.5~7.5 MHz sector transducers. The echogenicity and pathomorphology between IOUS and computed tomography/magnetic resonance imaging (CT/MRI) of various disease entities were compared. Intracranial structures could be well demonstrated by ultrasound once the skull was opened. Most of the intracranial lesions were hyperechoic, except those with a cystic component. IOUS was more sensitive in demonstrating non-enhanced solid lesions and lesions with a cystic component than was preoperative CT/MRI. The border between the tumor and healthy brain was better delineated on IOUS in all cases aiding in tumor resection. High-resolution real-time IOUS is a convenient and user-friendly method for identifying, localizing, and characterizing the pathological focus during an operation. Such information is very important and can enhance surgical results.


Horizontal gene transfer in silkworm, Bombyx mori.
The domesticated silkworm, Bombyx mori, is the model insect for the order Lepidoptera, has economically important values, and has gained some representative behavioral characteristics compared to its wild ancestor. The genome of B. mori has been fully sequenced while function analysis of BmChi-h and BmSuc1 genes revealed that horizontal gene transfer (HGT) maybe bestow a clear selective advantage to B. mori. However, the role of HGT in the evolutionary history of B. mori is largely unexplored. In this study, we compare the whole genome of B. mori with those of 382 prokaryotic and eukaryotic species to investigate the potential HGTs. Ten candidate HGT events were defined in B. mori by comprehensive sequence analysis using Maximum Likelihood and Bayesian method combining with EST checking. Phylogenetic analysis of the candidate HGT genes suggested that one HGT was plant-to- B. mori transfer while nine were bacteria-to- B. mori transfer. Furthermore, functional analysis based on expression, coexpression and related literature searching revealed that several HGT candidate genes have added important characters, such as resistance to pathogen, to B. mori. Results from this study clearly demonstrated that HGTs play an important role in the evolution of B. mori although the number of HGT events in B. mori is in general smaller than those of microbes and other insects. In particular, interdomain HGTs in B. mori may give rise to functional, persistent, and possibly evolutionarily significant new genes.