Toxoplasma gondii Seropositivity and Associated Risk Factors in Cats (Felis catus) in Three Provinces in Northeastern China from 2013 to 2019.
Toxoplasma gondii is an important protozoan parasite that can infect a range of animals. Cats are the most important definitive hosts for T. gondii. Therefore, an assessment of the level of T. gondii infection in cats is of public health importance. As limited information about seroprevalence of T. gondii infection in cats in northeastern China was available, 854 serum samples, including 235 cats in Jilin province, 267 cats in Liaoning province, and 352 cats in Heilongjiang province, were examined by an indirect hemagglutination assay (IHA) test, between September 2013 and July 2019. The overall seroprevalence of T. gondii was 19.09% (163/854) at the cutoff 1:64, with 19.60% (69/352), 18.29% (43/235), and 19.10% (51/267) in Heilongjiang, Jilin and Liaoning, respectively. Logistic regression analysis showed that mode of life was highly related to T. gondii infection in cats at the investigation areas. These results could provide foundation data for prevention and control of T. gondii prevalence in these regions. Moreover, the results also suggested that the effective control strategies should continue to be performed.


Genetic characterization of Mycobacterium tuberculosis in the West Bank, Palestinian Territories.
The World Health Organization (WHO) declared human tuberculosis (TB) a global health emergency and launched the "Global Plan to Stop Tuberculosis" which aims to save a million lives by 2015. Global control of TB is increasingly dependent on rapid and accurate genetic typing of species of the Mycobacterium tuberculosis (MTB) complex including M. tuberculosis. The aim of this study was to identify and genetically characterize the MTB isolates circulating in the West Bank, Palestinian Territories. Genotyping of the MTB isolates from patients with pulmonary TB was carried out using two molecular genetic techniques, spoligotyping and mycobacterial interspersed repetitive units-variable number of tandem repeat (MIRU-VNTR) supported by analysis of the MTB specific deletion 1 (TbD1). A total of 17 MTB patterns were obtained from the 31 clinical isolates analyzed by spoligotyping; corresponding to 2 orphans and 15 shared-types (SITs). Fourteen SITs matched a preexisting shared-type in the SITVIT2 database, whereas a single shared-type SIT3348 was newly created. The most common spoligotyping profile was SIT53 (T1 variant), identified in 35.5 % of the TB cases studied. Genetic characterization of 22 clinical isolates via the 15 loci MIRU-VNTR typing distinguished 19 patterns. The 15-loci MIT144 and MIT145 were newly created within this study. Both methods determined the present of M. bovis strains among the isolates. Significant diversity among the MTB isolates circulating in the West Bank was identified with SIT53-T1 genotype being the most frequent strain. Our results are used as reference database of the strains circulating in our region and may facilitate the implementation of an efficient TB control program.


Medical consequences of missed appointments.
"No-show" patients (n = 100) were matched by age and number of appointments scheduled in a six-month period with 100 control patients who kept an appointment. No-show patients were less likely than control patients to have chronic medical problems (78% v 94%, respectively) and to be receiving long-term medications (58% v 73%, respectively) at the time of entry into this study. At follow-up at 29 to 51 weeks, no-show and control patients did not differ significantly in the development of new medical problems or the exacerbation of old medical problems either before or after controlling for differences in baseline health status. No hospitalizations or deaths could be directly attributed to a missed appointment. No-show patients were more likely than control patients to say they felt better at follow-up (42% v 26%, respectively). No-show patients may believe the benefit of keeping an appointment is not worth the inconvenience or expense. We suggest that physicians should carefully justify the need for a follow-up visit and consider negotiating follow-up schedules with their patients.


Those pesky berries ... are they a source of concern?
Plant exposures constitute the 4th most common call to poison information centers. Within the plant category, exposures to unidentified berries are common and often create panic in the public and indecisiveness by health professionals. Are exposures to unidentified berries associated with morbidity and mortality? Can these berry exposures be managed at home or do they necessitate medical evaluation? The AAPCC Toxic Exposure Surveillance System was queried to identify exposures with the "unidentified berry" code for a 10-y period. Data parameters included frequency, age, outcome, patient disposition, referral pattern, symptom progression and therapeutic intervention. The data were analyzed using descriptive statistics. Unidentified berry exposures included 11,237 incidents, making it the 11th most common plant-related exposure. Children < 6 y-of-age accounted for 88.5% of the exposures, and 88.5% occurred during June-October. There were no fatalities, and morbidity included 1 major outcome in an infant and 26 exposures with moderate outcomes. In exposures with a known outcome, no effects (86.0%) and minor effects (13.6%) accounted for 99.6% of exposures. When a patient was initially asymptomatic, 89.7% did not develop symptoms and 10.2% progressed to have minor symptoms, accounting for 99.9% of all exposures. Poison centers referred 7.5% to a health care facility. There was no apparent benefit conferred by decontamination therapy. Exposures to unidentified berries represent common inquiries to poison information centers. They are associated with low morbidity and no mortality. If no initial symptoms are present, it is unlikely that the patient will develop clinically relevant effects.


Amino acid exchange and covalent modification by cysteine and glutathione explain isoforms of fatty acid-binding protein occurring in bovine liver.
A unique property of the liver-type member of the family of fatty acid-binding proteins is the heterogeneic pattern observed upon isolation, which can only partly be ascribed to the state of lipidation. Here we unraveled the structural basis of the heterogeneity of delipidated liver-type fatty acid-binding protein (L-FABP). Charge fractions of L-FABP focusing at pH 6.0 and at pH 7.0/7.1 were first isolated from bovine liver. Upon reduction, however, two distinct isoforms, namely pI 6.0 L-FABP and pI 7.0 L-FABP, were observed. From these isoforms peptides were generated enzymically and chemically by four independent methods. Peptides were separated by reverse phase high performance liquid chromatography and analyzed by Edman degradation and plasma desorption mass spectrometry. The complete amino acid sequences of the isoforms were established; they consist of 127 amino acids and each is N-terminally blocked with an acetyl group. The difference between pI 6.0 L-FABP and pI 7.0 L-FABP was attributed to an asparagine-aspartate exchange at position 105. When tryptic peptides of the pH 7.0/7.1 fraction were analyzed, discrepancies between sequence and mass data of the peptides containing at position 69 the sole cysteine of L-FABP led to the disclosure of a cysteinylation occurring at this position and giving rise to the slightly more basic pH 7.1 species. Moreover, chemical modification studies revealed that a part of the pH 6.0 fraction was pI 7.0 L-FABP that was glutathionylated at Cys69. Neither modification, however, prevented the binding of fatty acids. Together amino acid exchange and covalent modification of cysteine entirely explain the heterogeneity of L-FABP from bovine liver.


Personality correlates of the Fear of Death and Dying Scale.
A total of 88 female and male undergraduates completed the Fear of Death and Dying Scale, the Eysenck Personality Questionnaire, and the State-Trait Anxiety Inventory A-Trait scale. The four subscales on the Fear of Death and Dying Scale correlated significantly with the Neuroticism and Anxiety scales, but were independent of the Lie scale. No sex differences were found on the four subscales. These findings lend support to the validity of the Fear of Death and Dying Scale and its independence of social desirability.


Heavy metal accumulation by Saccharomyces cerevisiae cells armed with metal binding hexapeptides targeted to the inner face of the plasma membrane.
Accumulation of heavy metals without developing toxicity symptoms is a phenotype restricted to a small group of plants called hyperaccumulators, whose metal-related characteristics suggested the high potential in biotechnologies such as bioremediation and bioextraction. In an attempt to extrapolate the heavy metal hyperaccumulating phenotype to yeast, we obtained Saccharomyces cerevisiae cells armed with non-natural metal-binding hexapeptides targeted to the inner face of the plasma membrane, expected to sequester the metal ions once they penetrated the cell. We describe the construction of S. cerevisiae strains overexpressing metal-binding hexapeptides (MeBHxP) fused to the carboxy-terminus of a myristoylated green fluorescent protein (myrGFP). Three non-toxic myrGFP-MeBHxP (myrGFP-H6, myrGFP-C6, and myrGFP-(DE)3) were investigated against an array of heavy metals in terms of their effect on S. cerevisiae growth, heavy metal (hyper) accumulation, and capacity to remove heavy metal from contaminated environments.


A Framework to Guide Economic Analysis of Advance Care Planning.
Advance care planning (ACP) is fundamental to guiding medical care at the end of life. Understanding the economic impact of ACP is critical to implementation, but most economic evaluations of ACP focus on only a few actors, such as hospitals. To develop a framework for understanding and quantifying the economic effects of ACP, particularly its distributional consequences, for use in economic evaluations. Literature review of economic analyses of ACP and related costs to estimate magnitude and direction of costs and benefits for each actor and how data on these costs and benefits could be obtained or estimated. ACP can lead to more efficient allocation of resources by reducing low-value care and reallocating resources to high-value care, and can increase welfare by aligning care to patient preferences. This economic framework considers the costs and benefits of ACP that accrue to or are borne by six actors: the patient, the patient's family and caregivers, healthcare providers, acute care settings, subacute and home care settings, and payers. Program implementation costs and nonhealthcare costs, such as time costs borne by patients and caregivers, are included. Findings suggest that out-of-pocket costs for patients and families will likely change if subacute or home care is substituted for acute care, and subacute care utilization is likely to increase while primary healthcare providers and acute care settings may experience heterogeneous effects. A comprehensive economic evaluation of ACP should consider how costs and benefits accrue to different actors.


Why some women deliver in health institutions and others do not: a cross sectional study of married women in Ghana, 2008.
Existing inequalities in an environment where men wield so much authority can have negative implications for women's reproductive health outcomes. Using a quantitative approach, the study explores the relationship between some selected socioeconomic variables, women's status and choice of place of delivery. All three indicators of status employed by the study were significantly associated with whether a woman had an institutional delivery or not. This association however diminished after controlling for other confounding socio-economic variables. The findings indicate that a woman's status does not act independently to affect her choice of place of delivery but these effects are channelled through some socio-economic variables. Wealth and educational status of the women and their partners emerged predictors of choice of place of delivery. Expansion of economic opportunities for women, as well as female education must be encouraged. In addition, these should not be done in neglect of male education.


The Biology of Eosinophils and Their Role in Asthma.
This review will describe the structure and function of the eosinophil. The roles of several relevant cell surface molecules and receptors will be discussed. We will also explore the systemic and local processes triggering eosinophil differentiation, maturation, and migration to the lungs in asthma, as well as the cytokine-mediated pathways that result in eosinophil activation and degranulation, i.e., the release of multiple pro-inflammatory substances from eosinophil-specific granules, including cationic proteins, cytokines, chemokines growth factors, and enzymes. We will discuss the current understanding of the roles that eosinophils play in key asthma processes such as airway hyperresponsiveness, mucus hypersecretion, and airway remodeling, in addition to the evidence relating to eosinophil-pathogen interactions within the lungs.


Inulin Prebiotic Protects against Lethal Pseudomonas aeruginosa Acute Infection via γδ T Cell Activation.
Pseudomonas aeruginosa (P. aeruginosa) causes harmful lung infections, especially in immunocompromised patients. The immune system and Interleukin (IL)-17-producing γδ T cells (γδ T) are critical in controlling these infections in mice. The gut microbiota modulates host immunity in both cancer and infection contexts. Nutritional intervention is a powerful means of modulating both microbiota composition and functions, and subsequently the host's immune status. We have recently shown that inulin prebiotic supplementation triggers systemic γδ T activation in a cancer context. We hypothesized that prophylactic supplementation with inulin might protect mice from lethal P. aeruginosa acute lung infection in a γδ T-dependent manner. C57Bl/6 mice were supplemented with inulin for 15 days before the lethal P. aeruginosa lung infection, administered intranasally. We demonstrate that prophylactic inulin supplementation triggers a higher proportion of γδ T in the blood, accompanied by a higher infiltration of IL-17-producing γδ T within the lungs, and protects 33% of infected mice from death. This observation relies on γδ T, as in vivo γδ TcR blocking using a monoclonal antibody completely abrogates inulin-mediated protection. Overall, our data indicate that inulin supplementation triggers systemic γδ T activation, and could help resolve lung P. aeruginosa infections. Moreover, our data suggest that nutritional intervention might be a powerful way to prevent/reduce infection-related mortality, by reinforcing the microbiota-dependent immune system.


Low plasma α-tocopherol concentrations and adverse clinical outcomes in diabetic hemodialysis patients.
Trials with the antioxidant vitamin E have failed to show benefit in the general population. Considering the different causes of death in ESRD, this study investigated the association between plasma concentrations of α-tocopherol and specific clinical outcomes in diabetic hemodialysis patients. In 1046 diabetic hemodialysis patients (participants of the German Diabetes and Dialysis Study), α-tocopherol was measured in plasma by reversed-phase HPLC. By Cox regression analyses, hazard ratios were determined for prespecified end points according to baseline plasma α-tocopherol levels: sudden death (n=134), myocardial infarction (n=172), stroke (n=89), combined cardiovascular events (n=398), fatal infection (n=107), and all-cause mortality (n=508). Patients had a mean age of 66±8 years, and mean plasma α-tocopherol level was 22.8±9.6 µmol/L. Levels of α-tocopherol were highly correlated to triglycerides (r=0.63, P<0.001). Patients in the lowest α-tocopherol quartile had (in unadjusted analyses) a 79% higher risk of stroke and a 31% higher risk of all-cause mortality compared with patients in the highest quartile. The associations were attenuated after adjustment for confounders (hazard ratiostroke=1.56, 95% confidence interval=0.75-3.25; hazard ratiomortality=1.22, 95% confidence interval=0.89-1.69, respectively). There was no association between α-tocopherol and myocardial infarction, sudden death, or infectious death. Plasma α-tocopherol concentrations were not independently associated with cardiovascular outcomes, infectious deaths, or all-cause mortality in diabetic hemodialysis patients. The lack of association can partly be explained by a confounding influence of malnutrition, which should be considered in the planning of trials to reduce cardiovascular risk in dialysis patients.


Study on colon-specific 5-Fu pH-enzyme Di-dependent chitosan microspheres.
Colon-specific drug delivery systems (CDDS) can improve the bioavailability of drug through the oral route. A novel formulation for oral administration using pH-enzyme Di-dependent chitosan mcirospheres (MS) and 5-Fu as a model drug has been investigated for colon-specific drug delivery by the emulsification/chemical cross-linking and coating technique, respectively. The influence of polymer concentration, ratio of drug to polymer, the amount of crosslinking agent and the stirring speed on the encapsulation efficiency, particle size in microspheres were evaluated. The best formulation was optimized by an orthogonal design. Drug release studies under conditions mimicking stomach to colon transit have shown that the drug was protected from being released in the physiological environment of the stomach and small intestine. The plasma concentrations of 5-Fu after oral administration of coated chitosan MS to rats were determined and compared with that of 5-Fu solution. The in vivo pharmacokinetics study of 5-Fu loaded pH-enzyme Di-dependent chitosan MS showed sustained plasma 5-Fu concentration-time profile. The in vitro release correlated well with the pharmacokinetics profile. The results clearly demonstrated that the pH-enzyme Di-dependent chitosan MS is potential system for colon-specific drug delivery of 5-Fu.


Biological Activity Evaluation of Novel 1,2,4-Triazine Derivatives Containing Thiazole/Benzothiazole Rings.
Triazine ring is a prominent structural motif found in some azanucleosides whose efficiency improved many times in the research area of antitumor agents. In this study, we have designed and synthesized novel 2-[(5,6-diphenyl-1,2,4-triazin-3-yl)thio]-N-(6- substituted benzo/(thiazol)-2-yl)acetamide (2a-d, 3a-f) derivatives using 1,2,4-triazine core along with two important heterocyles, thiazole and benzothiazole rings. The acquired ten final compounds were screened to investigate their antitumor activity against lung adenocarcinoma cell line, A549 and mouse fibroblast cell line, NIH/3T3. Five compounds with higher antiproliferative activity have been further studied to evaluate whether the cell death due to necrosis or apoptosis using flow cytometry. Compound 3b bearing 6-methylbenzothiazole moiety has been established as the most active antitumor compound with a selective profile and higher apoptotic cell level. All final componds were also screened against acetylcholine/butyrylcholinesterase enzymes to state their anticholinesterase activity.


Factors associated with global longitudinal strain decline in hypertensive patients with normal left ventricular ejection fraction.
Background Early detection of risk factors for left ventricular (LV) dysfunction may be useful in patients with high blood pressure (HBP). Methods Patient from an outpatient HBP clinic underwent a two-dimensional Doppler-coupled echocardiography with determination of LV global longitudinal strain (GLS) by speckle-tracking. Results Among 200 patients (mean age 61.7 ± 9.7 years), 155 were overweight, 93 had diabetes, 83 had dyslipidemia, and 109 had uncontrolled HBP. LV hypertrophy (LVH) was found in 136 patients (68%), including concentric ( n = 106) and eccentric ( n = 30) LVH. Diastolic dysfunction patterns were observed in 178 patients (89%), and increased filling pressures were observed in 37 patients (18.5%). GLS ranged from -25% to -11.6% (mean -16.9 ± 3.2%). Low GLS values (>-17%) were found in 91 patients (45.5%), 68 with and 23 without LVH. In univariate analysis, a reduced GLS was associated with HBP lasting for >10 years (odds ratio (OR) = 3.51, 95% confidence interval (CI) 1.73-7.09; p = 0.002), uncontrolled HBP (OR = 3.55, 95% CI 1.96-6.43; p < 0.0001), overweight (OR = 2.01, 95% CI 0.93-4.31; p = 0.0028), diabetes (OR = 2.21, 95% CI 1.25-3.90; p = 0.006), dyslipidemia (OR = 2.16, 95% CI 1.22-3.84; p = 0.008), renal failure (OR = 4.27, 95% CI 1.80-10.10; p = 0.001), an increased Cornell index (OR = 3.70, 95% CI 1.98-6.90; p < 0.0001), concentric LVH (OR = 9.26, 95% CI 2.62-32.73; p = 0.001), remodeling (OR = 8.51, 95% CI 2.18-33.23; p = 0.002), and filling pressures (OR = 7.1, 95% CI 2.9-17.3; p < 0.0001). In multivariable analysis, duration of HBP ( p = 0.038), uncontrolled BP ( p = 0.006), diabetes ( p = 0.023), LVH ( p = 0.001), and increased filling pressures ( p = 0.003) remained associated with GLS decline. Conclusion Early impairment of LV function, detected by a reduced GLS, is associated with long-lasting, uncontrolled HBP, overweight, related metabolic changes, and is more pronounced in patients with LVH.


Effect of nocturnal sound reduction on the incidence of delirium in intensive care unit patients: An interrupted time series analysis.
Delirium in critically-ill patients is a common multifactorial disorder that is associated with various negative outcomes. It is assumed that sleep disturbances can result in an increased risk of delirium. This study hypothesized that implementing a protocol that reduces overall nocturnal sound levels improves quality of sleep and reduces the incidence of delirium in Intensive Care Unit (ICU) patients. This interrupted time series study was performed in an adult mixed medical and surgical 24-bed ICU. A pre-intervention group of 211 patients was compared with a post-intervention group of 210 patients after implementation of a nocturnal sound-reduction protocol. Primary outcome measures were incidence of delirium, measured by the Intensive Care Delirium Screening Checklist (ICDSC) and quality of sleep, measured by the Richards-Campbell Sleep Questionnaire (RCSQ). Secondary outcome measures were use of sleep-inducing medication, delirium treatment medication, and patient-perceived nocturnal noise. A significant difference in slope in the percentage of delirium was observed between the pre- and post-intervention periods (-3.7% per time period, p=0.02). Quality of sleep was unaffected (0.3 per time period, p=0.85). The post-intervention group used significantly less sleep-inducing medication (p<0.001). Nocturnal noise rating improved after intervention (median: 65, IQR: 50-80 versus 70, IQR: 60-80, p=0.02). The incidence of delirium in ICU patients was significantly reduced after implementation of a nocturnal sound-reduction protocol. However, reported sleep quality did not improve.


Hydrolyzed Collagen Tripeptide Promotes Longitudinal Bone Growth in Childhood Rats via Increases in Insulin-Like Growth Factor-1 and Bone Morphogenetic Proteins.
Previous studies have reported that collagen tripeptide (CTP) derived from collagen hydrolysate has various beneficial effects on health by protecting against skin aging and improving bone formation and cartilage regeneration. Collagen-Tripep20TM (CTP20), which is a low-molecular-weight CTP derived from fish skin, contains a bioactive CTP, Gly-Pro-Hyp >3.2% with a tripeptide content >20%. Herein, we investigated the osteogenic effects and mechanisms of CTP20 (<500 Da) on MG-63 osteoblast-like cells and SW1353 chondrocytes. And we measured promoting ratio of the longitudinal bone growth in childhood rats. First, CTP20 at 100 μg/mL elevated the proliferation (15.0% and 28.2%), alkaline phosphatase activity (29.3% and 32.0%), collagen synthesis (1.25- and 1.14-fold), and calcium deposition (1.18- and 1.15-fold) in MG-63 cells and SW1353, respectively. In addition, we found that CTP20 could promote the longitudinal growth and height of the growth plate of the tibia in childhood rats. CTP20 enhanced the protein expression of insulin-like growth factor-1 (IGF-1) in MG-63 and SW1353 cells, and in the growth plate of childhood rats, along with Janus Kinase 2, and signal transducer and activator of transcription 5 activation in MG-63 and SW1353 cells. CTP20 also elevated the expression levels of bone morphogenetic proteins (BMPs) in MG-63 and SW1353 cells and in the growth plates of childhood rats. These results indicate that CTP20 may promote the endochondral ossification and longitudinal bone growth, through enhancing of IGF-1 and BMPs. (Clinical Trial Registration number: smecae 19-09-01).


Occupational health in Yugoslavia.
Occupational health in Yugoslavia was once well organized in accordance with WHO declarations and ILO conventions and recommendations. Since the 1990s, the system has been disrupted by destruction of the former Yugoslavia, wars, refugees, changes in the economy, and NATO bombardment. Economic trends, main industries, and employment and unemployment conditions in Yugoslavia are presented. The organization of occupational health services, their tasks, and prevailing problems are discussed. Occupational diseases and relevant research and educational opportunities are described. The authors conclude by suggesting approaches to improving worker's health in the future.


Geographic Atrophy Management Consensus (GA-MAC): a Delphi panel study on identification, diagnosis and treatment.
With a paradigm shift in geographic atrophy (GA) treatments now available, establishing consensus on the identification and diagnosis of the disease along with considerations for management of patients with GA will assist eye care professionals (ECP) in their day-to-day practices, leading to improved patient outcomes. A modified Delphi panel process (Geographic Atrophy Management Consensus) consisting of three total surveys and one virtual live meeting held between survey 2 and survey 3. Data were collected from July to October 2022. Participants included expert members of the eye care community that have demonstrated outstanding leadership among peers: a steering committee with three ECPs and a 15-member panel divided between five optometrists, five comprehensive ophthalmologists and five retina specialists. Consensus on statements related to the management of patients with GA was calculated using the RAND/UCLA Appropriateness Method. At the conclusion of the third survey, consensus was reached on 91% of the 77 statements. Critical consensus topics include: (1) optical coherence tomography as the favoured method to diagnose and monitor GA, (2) preferred practice patterns regarding referral of patients to retina specialists and (3) treatment criteria given the advent of emerging therapeutics for GA. Generating awareness of early signs of disease development, progression and identifying the best tools to evaluate GA establishes ideal management and referral strategies. Given the paradigm shift in GA management driven by approved therapies, coupled with the fact that the disease is progressive resulting in devastating vision loss, these strategies are critical to ensure best overall outcomes.


Laparoscopic cryptorchidectomy in a mature llama.
A 5-year-old llama was presented for unilateral cryptorchidism. Clinical findings included an abdominally retained right testicle. Surgical treatment consisted of laparoscopic removal of the abdominally retained testicle and routine closed castration of the descended testicle, which is presented as a therapeutic option for cryptorchidectomy. Key clinical message: Laparoscopic exploration and castration should be considered as a suitable surgical treatment for a llama with abdominally retained testicles.


Lamin B1 levels modulate differentiation into neurons during embryonic corticogenesis.
Lamin B1, a key component of the nuclear lamina, plays an important role in brain development. Ablation of endogenous Lamin B1 (Lmnb1) in the mouse strongly impairs embryonic brain development and corticogenesis. However, the mechanisms underlying these neurodevelopmental effects are unknown. Here, we report that Lamin B1 levels modulate the differentiation of murine neural stem cells (NSCs) into neurons and astroglial-like cells. In vitro, endogenous Lmnb1 depletion favors NSC differentiation into glial fibrillar acidic protein (GFAP)-immunoreactive cells over neurons, while overexpression of human Lamin B1 (LMNB1) increases the proportion of neurons. In Lmnb1-null embryos, neurogenesis is reduced, while in vivo Lmnb1 silencing in mouse embryonic brain by in utero electroporation of a specific Lmnb1 sh-RNA results in aberrant cortical positioning of neurons and increased expression of the astrocytic marker GFAP in the cortex of 7-day old pups. Together, these results indicate that finely tuned levels of Lamin B1 are required for NSC differentiation into neurons, proper expression of the astrocytic marker GFAP and corticogenesis.


Circulating osteoprotegerin and receptor activator of NF-kappaB ligand system in patients with beta-thalassemia major.
Osteoporosis represents an important cause of morbidity in patients with beta-thalassemia major, and its etiology is multifactorial. Thus, the aim of this study was to characterize the possible role of the osteoprotegerin (OPG) and receptor activator of the NF-kappaB ligand (RANKL) system in thalassemia-related bone loss. Serum concentrations of OPG, soluble RANKL (s-RANKL), markers of bone turnover, and lumbar spine bone mineral density (BMD) were measured in random samples of males (n = 29; mean age +/- SEM, 24.26 +/- 1.29 years; range, 13-41 years) and females (n = 31; age, 24.59 +/- 0.95 years; range, 12-34 years) with beta-thalassemia major and in 30 healthy age-, height-, and weight-matched subjects. Thalassemic patients had significantly lower levels of OPG compared with controls (2.54 +/- 0.12 vs. 3.25 +/- 0.122, respectively; P < 0.05) and higher, albeit not statistically significantly, serum levels of s-RANKL (0.350 +/- 0.03 vs. 0.295 +/- 0.046, respectively; P < 0.05). s-RANKL correlated negatively with age (r = -0.3, P < 0.05), and OPG correlated positively with the duration of the interval between the onset of transfusions and chelation therapy (r = 0.52, P < 0.001). Regarding markers of bone metabolism, plasma values of osteocalcin correlated positively with s-RANKL (r = 0.40, P < 0.05) and negatively with OPG/s-RANKL ratio (r = -0.55, P < 0.01). In multiple regression analysis only cross-linked N-teleopeptide of type I collagen (NTX) significantly accounted for BMD. Although the OPG/RANKL system may have some clinical usefulness as a marker of bone turnover in beta-thalassemia, conventional markers of bone turnover more accurately represent changes in the BMD of these patients.


[Progress of researches on carnitines in the clinical therapy of andrology].
Carnitine, an important compound in the beta-oxidative process of mitochondrial fatty acid, plays a significant role in the cardiovascular, nervous, and reproductive system. Recently, carnitine has been used as a therapeutic in the treatment of male infertility, erectile dysfunction, Peyronie's disease, etc. Accordingly, the objective of this review is to summarize the progress in researches on carnitine as a clinical therapy in andrology.


Changes in renal vessels associated with long-term administration of angiotensin converting enzyme inhibitor in Zucker fatty rats.
Background Recently, we showed that long-term angiotensin receptor blocker (ARB) administration induced unusual proliferative changes in smooth muscle cells (SMCs) of afferent arterioles of the kidneys of Zucker fatty rats (ZFRs). In this study, we investigated renal afferent arteriolar changes induced by the long-term administration of an angiotensin converting enzyme inhibitor (ACEI) in ZFRs. Materials and Methods Fourteen 6-week-old male ZFRs were divided into two groups (n=14): the ZFR+ACEI group (n=6) was fed a standard diet containing ACEI (Enalapril, 2 mg/kg/day), and the ZFR control group (n=8) for 12 weeks. Blood pressure and proteinuria were examined and morphological studies on kidneys were performed. Results Remarkable proliferative changes in the afferent arteriolar SMCs were frequently observed in the group given ACEI; (66.1 ± 12.9%) compared with the control group (1.77 ± 1.56%, P<0.001). Conclusions It was indicated that long-term ACEI administration induced unusual proliferative changes in SMCs in afferent arterioles of ZFRs. These changes could reduce intraglomerular pressure by narrowing the lumens of afferent arterioles, but they could cause irreversible damage to the arterioles.


In vitro evaluation of different antimicrobial combinations against carbapenemase-producing Klebsiella pneumoniae: the activity of the double-carbapenem regimen is related to meropenem MIC value.
We evaluated the in vitro activity of different antimicrobial combinations with and without colistin against 39 carbapenem-resistant Klebsiella pneumoniae (CR-Kp) strains (colistin + meropenem/doripenem, colistin + tigecycline, colistin + rifampicin, gentamicin + meropenem, gentamicin + tigecycline and the double-carbapenem regimen meropenem + ertapenem) using the chequerboard method. The triple combination colistin + meropenem + tigecycline was also tested. In addition, killing studies were performed for meropenem + ertapenem. Gentamicin-based combinations showed a high level of synergy. Meropenem + ertapenem was synergic in 12/39 (30.7%) of the strains, whereas based on killing studies 1 × MIC meropenem + 1 × MIC ertapenem and 2 × MIC meropenem + 1 × MIC ertapenem combinations were bactericidal and synergic at 24 h [mean area under the bactericidal curve (AUBC) 54.9 ± 26.1 and 44.2 ± 15.3 compared with 1 × MIC meropenem (134.5 ± 40.1) and 2 × MIC meropenem (126.4 ± 5.4), respectively, P < 0.0001]. When the results were stratified according to meropenem MIC, we found that the degree of synergy significantly increased for isolates with lower meropenem (and not ertapenem) MICs, up to an MIC of 128 mg/L. Among colistin-containing combinations, synergy was observed in 18/39 (46.1%), 33/34 (97%), 24/39 (61.5%) and 17/39 (43.5%) of the strains for colistin + meropenem, colistin + rifampicin, colistin + tigecycline and colistin + doripenem, respectively, including colistin-resistant strains. Colistin + meropenem + tigecycline at subinhibitory concentrations resulted in the absence of growth of 37/39 strains (94.8%). Our in vitro data suggest that colistin might be a valid therapeutic option against CR-Kp, even in the presence of colistin resistance, whereas the double-carbapenem regimen represents a viable option when colistin is not recommended, especially if the meropenem MIC is ≤ 128 mg/L. Since traditional antimicrobial susceptibility reports are not sufficiently informative for clinicians, synergy testing as well as actual meropenem MIC evaluation should always be performed in the case of CR-Kp infections.


[ECMO and cardiopulmonary support].
ECMO (extracorporeal membrane oxygenation) may be viewed as a prolonged cardiopulmonary bypass allowing for a prolonged cardio-respiratory support. Since its introduction in the 60's, its indication has expanded from acute respiratory failure to acute cardiac failure refractory to conventional treatments. The target group involves mainly those patients presenting with a cardiogenic shock following cardiac surgery or acute myocardial infarction. The advantages of this form of circulatory support, when compared with long-term ventricular assist devices, are its less invasive aspect, its ease of implantation and its reduced cost. However, its main limitation lies in its limited duration of 7 to 10 days, in particular because of hemorrhage complications. Currently, ECMO provides a temporary hemodynamical stability in order to perform an invasive cardiac treatment (coronary bypass or percutaneous dilatation), or to assess the eligibility of the patient for a long-term ventricular assist device, which will enable to wait for the availability of an allograft. The latter scenario is crucial nowadays because of the severe lack of organ donors, which is the leading cause of death among patients waiting for a heart transplant.


Experience of rehabilitation specialist nurses in providing bowel care for stroke patients: A qualitative study.
This study aims to explore the experiences of rehabilitation specialist nurses in providing bowel care to stroke patients and to identify the factors that either facilitate or hinder their practice. This was a descriptive qualitative design study. Between May 2022 and October 2022, we conducted in-depth and semi-structured interviews with 12 rehabilitation specialist nurses from two tertiary hospitals in Changsha, China. Thematic analysis was employed to analyse the interview transcripts. Three key themes were revealed from our analysis: (1) acceptance of bowel care as a process, (2) high level of recognition improves the experience and (3) challenges stemming from limited knowledge and rights. Acceptance of bowel care as a dynamic process, coupled with a high level of recognition, enabled nurses to prioritize the health and safety of patients over personal feelings and achieve professional accomplishments. However, they encountered challenges in terms of professional development and restricted prescribing rights for bowel care. The experiences of rehabilitation specialist nurses in providing bowel care are dynamic. These findings have important implications for healthcare improvement, including the need for collaboration with healthcare professionals and nurturing nurses' self-identity, comprehensive training plans, innovative programs and expanding the scope of rehabilitation specialist nurses' rights. This study enhances our understanding of the challenges faced by rehabilitation specialist nurses caring for stroke patients with neurogenic bowel dysfunction. The findings provide insights into how to enhance bowel care experience and develop further in this field. This study adhered to the EQUATOR guideline and utilized the COREQ checklist. This study involved participants who were registered nurses, and there were no contributions from patients or public.


Curvularia microspora sp. nov. associated with leaf diseases of Hippeastrum striatum in China.
An undescribed Curvularia sp. was isolated from the leaf spot disease of Barbados Lily (Hippeastrum striatum (Lam.) Moore). Phylogenetic analyses of combined ITS, 28S, GPD1 and TEF1 sequence data place nine strains of this species in the trifolii-clade, but they clustered together as an independent lineage with strong support. This species was morphologically compared with related species in the trifolii-clade. Based on differences in morphology and phylogeny, it is concluded that this species is a new taxon, introduced as Curvularia microsporasp. nov. Pathogenicity testing determined the new species to be pathogenic on H. striatum.


CSF-1-induced resistance to viral infection in murine macrophages.
Murine peritoneal thioglycollate-elicited macrophages were cultured for 3 days in the presence or absence of highly purified human macrophage colony stimulating factor (CSF-1). The cells were then challenged with vesicular stomatitis virus (VSV) for 24 hr. Ability to resist viral infection was measured in two ways. First, macrophage viability after infection with VSV was measured by washing to remove dead cells, staining the remaining cells with crystal violet, and reading absorbance. Second, a yield reduction assay was used to measure viral replication in the macrophage cultures. Cells treated with CSF-1 (500 to 2000 U/ml) and infected with VSV looked similar microscopically to uninfected cells and had absorbance values twofold to threefold higher than those of infected cultures not treated with CSF-1. The CSF-1-treated cultures also had a virus titer one log lower than that of the untreated cultures. Treatment with partially purified murine CSF-1 induced a similar reduction in virus titer, whereas other murine CSF tested (purified murine GM-CSF, lung-conditioned medium that contains GM-CSF and G-CSF, and WEHI-3B-conditioned medium as a source of IL 3) had little to no effect on virus titer. Antibody to murine IFN-alpha/beta added to the macrophage cultures inhibited the protective effect of CSF-1, indicating that the CSF-1 effect was due to induction of endogenous IFN. Treatment with lipopolysaccharide (1 ng/ml) had some protective effect, which was blocked with polymyxin B. Polymyxin B did not inhibit the effect of CSF-1.


Computational Design of Two-Dimensional Perovskites with Functional Organic Cations.
Two-dimensional (2D) halide perovskites are a class of materials in which 2D layers of perovskite are separated by large organic cations. Conventionally, the 2D perovskites incorporate organic cations as spacers, but these organic cations also offer a route to introduce specific functionality in the material. In this work, we demonstrate, by density functional theory calculations, that the introduction of electron withdrawing and electron donating molecules leads to the formation of localized states, either in the organic or the inorganic part. Furthermore, we show that the energy of the bands located in the organic and inorganic parts can be tuned independently. The organic cation levels can be tuned by changing the electron withdrawing/donating character, whereas the energy levels in the inorganic part can be modified by varying the number of inorganic perovskite layers. This opens a new window for the design of 2D perovskites with properties tuned for specific applications.


[Effectiveness of clonidine and fentanyl addition to bupivacaine in postoperative patient controlled epidural analgesia].
The aim of this prospective randomized double-blinded study was to compare the analgesic and side-effects of bupivacaine in combination with clonidine or fentanyl during patient-controlled-epidural analgesia (PCEA) in the postoperative period after abdominal hysterectomy. 75 patients from 18 to 65 years of age with ASA status I - II were investigated. After preoperative epidural catheterization, the patients were operated in general anesthesia. After surgery, the patients were randomly allocated to 3 PCEA-groups: Group B 0.125 % bupivacaine, Group F 0.125 % bupivacaine plus 1 microg x ml (-1) fentanyl, Group C 0.125 % bupivacaine plus 0.75 microg x ml (-1) clonidine (10 ml loading dose, 5 ml repetitive bolus dose, 10 min lockout time, 30 ml limit within 4 h). During the following 24 hours, hemodynamic parameters, pain score using visual analog scale (VAS), total analgesic consumption, additional analgesic requirements, sedation, satisfaction, nausea scores and probable side-effects were evaluated. Total analgesic consumption was not different between Group F and Group C, but lower than in Group B (p < 0.05). Additional analgesic use was not different between the groups. Group F and Group C had lower VAS-scores in 24 hours than Group B (p < 0.05). Hemodynamic and sedation scores of patients were not different. In Group C, incidence of nausea was lower and satisfaction of patients was higher (p < 0.05). Addition of clonidine or fentanyl to local anesthetics for PCEA can reduce the analgetic demand. Epidural clonidine can reduce postoperative nausea and is connected with higher patients' satisfaction.


Plasma membrane changes in the rat corpus luteum induced by oxygen radical generation.
The luteolytic mechanism was investigated in rat corpora lutea (CL). This study focused on the changes that occur in the plasma membrane. Previous experiments with rat luteal cells indicated that in vitro generation of superoxide radicals by xanthine oxidase disrupted LH-stimulated cAMP production and progesterone secretion similar to the effect of prostaglandin F2 alpha, the luteolytic hormone. In the present study, we observed that xanthine oxidase treatment of plasma membrane samples from CL caused a large decrease in fluidity, which also occurs during prostaglandin F2 alpha-induced luteolysis. This fluidity change was blocked by catalase, bromophenacyl bromide, an inhibitor of phospholipase-A activity, indomethacin, and free radical scavengers, and it was reversed by removal of FFA from the membrane. In addition, xanthine oxidase treatment caused phospholipid breakdown, formation of neutral lipids, a burst of inorganic peroxides, and a sustained rise in the level of lipid peroxides. These results indicate that free radical generation causes several changes that disrupt the plasma membrane of CL cells, and they raise the possibility that phospholipid breakdown could be involved in the mechanism that inhibits LH stimulation of steroidogenesis during luteolysis.


Gender and ethnic differences in social constraints among a sample of New York City police officers.
Gender and ethnic differences in social constraints on and off the job among a sample of 372 police officers was examined. Positive and negative social interactions with supervisors and coworkers, and perceptions of the work environment as well as support and resentment of the job from family and significant others, was included. As hypothesized, women and minority men reported more negative social interactions on the job, such as criticism, bias, and sexual harassment. Few differences were observed for positive social interactions on or off the job, and where differences emerged, women and minority men reported more favorable social interactions. These findings are discussed in terms of implications for intervention, policy, and future research.


Nelson's wound: treatment of spinal cord injury in 19th and early 20th century military conflicts.
During the first half of the 19th century, warfare did not provide a background for a systematic analysis of spinal cord injury (SCI). Medical officers participating in the Peninsular and Crimean Wars emphasized the dismal prognosis of this injury, although authors of sketchy civil reports persuaded a few surgeons to operate on closed fractures. The American Medical and Surgical History of the War of the Rebellion was the first text to provide summary of results in 642 cases of gunshot wounds of the spine. The low incidence of this injury (0.26%) and the high mortality rate (55%) discouraged the use of surgery in these cases. Improvements in diagnoses and the introduction of x-ray studies in the latter half of the century enabled Sir G. H. Makins, during the Boer War, to recommend delayed intervention to remove bone or bullet fragments in incomplete injuries. The civil experiences of Elsberg and Frazier in the early 20th century promoted a meticulous approach to treatments, whereas efficient transport of injured soldiers during World War I increased the numbers of survivors. Open large wounds or cerebrospinal fluid leakage, signs of cord compression in recovering patients, delayed clinical deterioration, or intractable pain required surgical exploration. Wartime recommendations for urological and skin care prevented sepsis, and burgeoning pension systems provided specialized longterm rehabilitation. By the Armistice, the effective surgical treatment and postoperative care that had developed through decades of interaction between civil and military medicine helped reduce incidences of morbidity and dispel the hopelessness surrounding the combatant with an SCI.


What Should We Do about Low Blood Pressure in Preterm Infants.
The management of preterm infants with low blood pressure soon after birth remains unresolved. The definition of what constitutes low blood pressure is uncertain. At birth, mean blood pressure appears to be gestation specific and increases in the first few days of life. Antenatal steroids, delayed cord clamping, and the avoidance of mechanical ventilation are all associated with higher mean blood pressure and less hypotension after birth. Rates of hypotension of 15-50% have been reported in various studies of extremely preterm infants. However, only about 10% of all extremely preterm infants receive inotropes, suggesting that clinicians take into account other factors such as clinical, biochemical, and echocardiographic findings before deciding to intervene. The exact role of functional echocardiography in assessing the need for treatment of low blood pressure in extremely preterm infants remains to be determined. Near- infrared spectroscopy to assess cerebral perfusion may also have a role to play. Volume expansion (usually 10 mL/kg of saline) remains the most commonly used intervention for low blood pressure but evidence of benefit is lacking and there may be safety concerns. Whilst dopamine is the most commonly used inotropic drug, dobutamine, epinephrine, corticosteroids, milrinone, and vasopressin have also been utilised in preterm infants with low blood pressure. Clinical trials with long-term outcomes are needed to determine the most suitable inotrope and when to use it. Early hypotension differs from late hypotension with regard to cause, treatment, and outcome. A number of recent studies aimed at improving the evidence base for the treatment of early hypotension in extremely preterm infants have been terminated early because of poor recruitment. Currently, the answer to the question of what to do about low blood pressure in preterm infants remains unclear.


Influenza virus infection of human alveolar and blood-derived macrophages: differences in accessory cell function and interferon production.
Influenza virus infection in vitro depresses accessory cell function of human peripheral blood-derived macrophages (PBM phi) for lymphocyte proliferative responses, but effects on such functions of alveolar macrophages (AlvM phi) have not been described. AlvM phi were obtained by bronchoalveolar lavage from normal young volunteers, and the effects of influenza virus infection of AlvM phi and autologous PBM phi were compared by measuring the accessory support provided by these cells for phytohemagglutinin-induced proliferation of purified autologous lymphocytes. Accessory cell function of AlvM phi was not altered by viral infection; in contrast, this function was significantly depressed with autologous virus-infected PBM phi. Virus-infected PBM phi produced greater amounts of interferon than did autologous AlvM phi. However, synthesis of interferon or prostaglandins by virus-infected cells could not account, per se, for depression of lymphocyte responses in the presence of PBM phi. These studies detail functional heterogeneity of autologous PBM phi and AlvM phi in response to a common respiratory-tract pathogen, influenza virus.


Daily effects of continuous ICT demands on work-family conflict: Negative spillover and role conflict.
Growing concerns about intensive information and communication technology (ICT) use led to abundant research on its debilitating effects on employees' abilities to meet family demands. Drawing on the stressor-strain model, we conducted a daily diary study to investigate how different types of daily ICT demands experienced during work hours and after work influence work-family conflict (WFC) in the evening. We collected data from 98 full-time employees (793 day-level observations) for 10 consecutive workdays to understand employees' work-nonwork interface experiences, namely, negative spillover and role conflict. First, we examined a multilevel mediation model to test the negative spillover effect of on-the-job ICT demands on WFC in the evening via negative affect (NA) at the end of the workday. Second, we investigated the effects of off-the-job ICT demands on WFC to provide evidence of role conflict in the nonwork domain. Further, we tested the protective role of boundary control in these phenomena. The multilevel analysis results revealed that different types of ICT demands experienced at work have idiosyncratic impacts on WFC. Also, while extended availability after work hours yields greater WFC, this link was weaker for the employees who perceive high boundary control.


Intestinal infections.
Gastrointestinal infections are the significant cause of childhood morbidity and mortality worldwide. Gastrointestinal infections reflects the balance between the intrinsic virulence factors of the enteropathogens and host mechanisms which defend against enteric infections. Host defense factors include gastric acidity, intestinal motility, the normal indigenous intestinal microflora, mucous secretion, and specific mucosal and systemic immune mechanisms. Majority of GI infections are self limited so on one hand antibiotics are not needed and on the other hand the irrational use of antibiotics produces resistant strains. Acute diarrheal diseases which are one of the important intestinal infections, in majority of the cases are viral and have short course. Antibiotics are recommended only in specific cases and in immunocompromised individuals. Gastrointestinal disease is one of the most common manifestations of HIV infection. The gastrointestinal tract contains abundant quantities of lymphoid tissue and is likely to function as a reservoir of HIV infection, a site of profound immune dysregulation, and a target for opportunistic infections. In this situation specific antibiotics are indicated.


[An improved connecting system for artificial hearts].
The certain connection of the artificial ventricles to the vascular system has a decisive importance in the implantation of an artificial heart. Demands concerning tightness, reliability, easy attendance, and anatomic fit are to be considered especially in the construction of a suitable connecting system. A modified bayonet system came in use. The connection between the artificial heart and the vascular system is placed here by distortions of a tightening ring.


Diabetes prevention. A GAMEPLAN for success.
Diabetes prevalence is growing at epidemic proportions, and the greatest increase in number of cases is anticipated to be among older adults. The Diabetes Prevention Program (DPP) showed that diabetes can be prevented or delayed among people with pre-diabetes (impaired glucose tolerance, impaired fasting glucose, or both). The National Diabetes Education Program has developed tools adapted from the DPP that primary care providers can use to counsel middle-age and older patients on diabetes prevention.


Open-shell singlet diradicaloid difluoreno[4,3-b:3',4'-d]furan and its radical cation and dianion.
Difluoreno[4,3-b:3',4'-d]furan (DFFu) was prepared via a short, scalable, multi-step synthesis, and characterized by crystallography, spectroscopic measurements, and theoretical calculations. Even though the results revealed an open-shell singlet diradical character, DFFu is stable under ambient conditions. The radical cationic and dianionic species of DFFu were also synthesized and characterized.


Repetitive Computed Tomography Perfusion for Detection of Cerebral Vasospasm-Related Hypoperfusion in Aneurysmal Subarachnoid Hemorrhage.
Delayed cerebral infarction after aneurysmal subarachnoid hemorrhage (aSAH) still remains the leading cause of disability in patients that survive the initial ictus. It has been shown that computed tomography perfusion (CTP) imaging can detect hypoperfused brain areas. The aim of this study was to evaluate if a single acute CTP examination at time of neurologic deterioration is sufficient or if an additional baseline CTP increases diagnostic accuracy. Retrospective analysis of acute and baseline (within 24 hours after aneurysm treatment) CTP examinations of patients with neurologic deterioration because of vasospasm-related hypoperfusion. Patients without clinical deterioration during the vasospasm period served as control subjects. The following CTP parameters were analyzed for predefined brain regions: time to drain (TTD), mean transit time, time to peak, cerebral blood flow, and volume. Thirty-three patients with and 23 without neurologic deterioration were included. Baseline CTP examination did not ameliorate diagnostic accuracy of the acute CTP examination in symptomatic patients. The same was true for interhemispheric comparison of perfusion parameters of the acute examination. The CTP parameter with the highest diagnostic yield was TTD of the symptomatic brain region (threshold value, 4.7 seconds; sensitivity, 97%; specificity, 96%). Acute CTP examination in case of suspected vasospasm-induced neurologic deterioration after aSAH has the highest diagnostic accuracy to detect misery perfusion. Additional baseline CTP is not needed. The most sensitive parameter to detect critically perfused brain areas is TTD.


Contribution of energy values to the analysis of global searching molecular dynamics simulations of transmembrane helical bundles.
Molecular interactions between transmembrane alpha-helices can be explored using global searching molecular dynamics simulations (GSMDS), a method that produces a group of probable low energy structures. We have shown previously that the correct model in various homooligomers is always located at the bottom of one of various possible energy basins. Unfortunately, the correct model is not necessarily the one with the lowest energy according to the computational protocol, which has resulted in overlooking of this parameter in favor of experimental data. In an attempt to use energetic considerations in the aforementioned analysis, we used global searching molecular dynamics simulations on three homooligomers of different sizes, the structures of which are known. As expected, our results show that even when the conformational space searched includes the correct structure, taking together simulations using both left and right handedness, the correct model does not necessarily have the lowest energy. However, for the models derived from the simulation that uses the correct handedness, the lowest energy model is always at, or very close to, the correct orientation. We hypothesize that this should also be true when simulations are performed using homologous sequences, and consequently lowest energy models with the right handedness should produce a cluster around a certain orientation. In contrast, using the wrong handedness the lowest energy structures for each sequence should appear at many different orientations. The rationale behind this is that, although more than one energy basin may exist, basins that do not contain the correct model will shift or disappear because they will be destabilized by at least one conservative (i.e. silent) mutation, whereas the basin containing the correct model will remain. This not only allows one to point to the possible handedness of the bundle, but can be used to overcome ambiguities arising from the use of homologous sequences in the analysis of global searching molecular dynamics simulations. In addition, because clustering of lowest energy models arising from homologous sequences only happens when the estimation of the helix tilt is correct, it may provide a validation for the helix tilt estimate.


Effect of antidepressant and narcoleptic drugs on N-isopropyl p-iodoamphetamine biodistribution in animals.
N-isopropyl p-iodoamphetamine (IMP) demonstrates a high affinity for lung and brain during the first pass following intravenous injection. Its high brain affinity has been used to advantage for cerebral perfusion imaging, but the effects of drugs on IMP distribution could affect its utility. In this study, we determined the effects of the tricyclic antidepressant imipramine and the MAO inhibitors deprenyl and phenelzine on the biodistribution of IMP. We first determined the effect of loading dose and anesthesia on the biodistribution of IMP. In rats, biodistribution was not dependent on loading dose between 0.1 and 1.1 mg/kg. Anesthesia with thiopental and chloral hydrate depressed lung and brain IMP uptake. In rats, preloading doses of imipramine depressed lung uptake but did not result in increased brain IMP uptake; postloading doses of imipramine did not release IMP from the lung. In rabbits, simultaneous or postloading doses of imipramine resulted in release of IMP from the lung with an increase in brain activity. Both mixed A and B MAO inhibitors (phenelzine) and B selective MAO inhibitors (deprenyl) did not affect IMP distribution in rats. Based on the action of imipramine on IMP uptake and clearance in the lung, we postulate that IMP uptake and metabolism within the lung is related to the mixed function oxidase (MFO) system. As the lung is rich in the MFO system in humans, we would also predict from this study that IMP distribution in patients under antidepressant therapy would not be affected by either tricyclic or MAO inhibitor agents apart from the effect of these drugs on cerebral perfusion.


Changes in the distribution of the 34-kdalton tyrosine kinase substrate during differentiation and maturation of chicken tissues.
We examined the distribution of the 34-kilodalton (34-kD) tyrosine kinase substrate in tissues of adult and embryonic chicken using both a mouse monoclonal antibody and a rabbit polyclonal antibody raised against the affinity purified 34 kD protein. We analyzed the localization by immunoblotting of tissue extracts, by immunofluorescence staining of frozen tissue sections, and by staining sections of paraffin-embedded organs by the peroxidase antiperoxidase method. The 34-kD protein was present in a variety of cells, including epithelial cells of the skin, gastrointestinal, and respiratory tracts, as well as in fibroblasts and chondrocytes of connective tissue and mature cartilage, and endothelial cells of blood vessels. The 34-kD protein was also found in subpopulations of cells in thymus, spleen, bone marrow, and bursa. The protein was not detected in cardiac, skeletal, or smooth muscle cells, nor in epithelial cells of liver, kidney, pancreas, and several other glands. Although most neuronal cells did not contain the 34-kD protein, some localized brain regions did contain detectable amounts of this protein. The 34-kD protein was not detected in actively dividing cells of a number of tissues. Changes in the distribution of the 34-kD protein were observed during the differentiation or maturation of cells in several tissues including epithelial cells of the skin and gastrointestinal tract, fibroblasts of connective tissue, and chondroblasts.


Effects of Gait Self-Efficacy and Lower-Extremity Physical Function on Dual-Task Performance in Older Adults.
Objectives. Despite evidence of self-efficacy and physical function's influences on functional limitations in older adults, few studies have examined relationships in the context of complex, real-world tasks. The present study tested the roles of self-efficacy and physical function in predicting older adults' street-crossing performance in single- and dual-task simulations. Methods. Lower-extremity physical function, gait self-efficacy, and street-crossing success ratio were assessed in 195 older adults (60-79 years old) at baseline of a randomized exercise trial. During the street-crossing task, participants walked on a self-propelled treadmill in a virtual reality environment. Participants crossed the street without distraction (single-task trials) and conversed on a cell phone (dual-task trials). Structural equation modeling was used to test hypothesized associations independent of demographic and clinical covariates. Results. Street-crossing performance was better on single-task trials when compared with dual-task trials. Direct effects of self-efficacy and physical function on success ratio were observed in dual-task trials only. The total effect of self-efficacy was significant in both conditions. The indirect path through physical function was evident in the dual-task condition only. Conclusion. Physical function can predict older adults' performance on high fidelity simulations of complex, real-world tasks. Perceptions of function (i.e., self-efficacy) may play an even greater role. The trial is registered with United States National Institutes of Health ClinicalTrials.gov (ID: NCT01472744; Fit & Active Seniors Trial).


2D-shear wave elastography in the evaluation of suspicious superficial inguinal lymph nodes: Reproducibility and region of interest selection.
To assess the ability of 2D-Shear wave elastography (2D-SWE) to evaluate its reproducibility, to define the optimal orientation and size of the region of interest (ROI), and to differentiate benign from malignant inguinal lymph nodes (LNs). Thirty-two suspicious inguinal LNs from 21 patients were evaluated with 2D-SWE. SWE measurements were obtained in two orthogonal planes. To investigate reproducibility, sensitivity and specificity, circular ROIs with a diameter of 1 mm, 2 mm, 3 mm and 5 mm were placed on the cortex of the LNs. Additionally, one freehand ROI was drawn covering majority of the LN. Two observers performed five sets of SWE measurements for each ROI size. All LNs underwent core needle biopsy or were surgically removed. The 3 mm ROI for Mean-E in axial plane showed high interrater agreement [intraclass correlation coefficient (ICC) 0.899] with the cut-off value of 7.31 kPa resulting in 88.9% sensitivity and 60.9% specificity for differentiating malignant from benign LNs. In benign LNs, mean elasticity of the ROI was lower (7.68 ± 3.82 kPa; range, 3.41-15.40 kPa) compared to the malignant LNs (15.81 ± 10.61 kPa; range, 3.86-36.45 kPa). The most reproducible way to measure stiffness in inguinal LNs is a 3 mm circular ROI centered on the cortex of the LN in axial plane. Elasticity values were higher in the malignant LNs reflecting the stiffer nature of the metastatic LNs. 2D-SWE offers a noninvasive ultrasonographic tool to assess superficial inguinal lymph nodes with high reproducibility.


Accessory nerve injury after carotid endarterectomy. Case report.
Although cranial nerve injuries associated with carotid endarterectomy are well known, involvement of the accessory nerve is extremely rare. A case of partly reversible accessory nerve injury is described. Hitherto published cases are analyzed and possible pathogenetic mechanisms discussed.


[Otologic aspects of diving].
Ear diseases are the most common of all occupational diseases of diving. Otitis externa is the most frequent and troublesome infection in divers especially when the environment is humid. During compression, failure to equalize the pressure of the air-filled cavities surrounded by bone (middle ear, sinus) deprives the middle ear (or sinus) of aeration. Middle ear barotrauma is the most common barotrauma encountered in divers while external ear barotrauma (reversed ear) and inner ear barotrauma (with rupture of the round or oval window) are less common. Decompression sickness (Caisson disease) is primarily the result of inert gas bubbles; deafness and vertigo may result if the inner ear is involved. The most dramatic cause of disorientation under water is that due to vertigo. This vertigo is commonly a transient effect due to unequal caloric stimulation of the two labyrinths. The physical examination of the ear and nose necessary for assessment of diving fitness are discussed. A list of ENT contra-indications is presented which mandate temporary or permanent disqualification from diving.


Codelivery for Paclitaxel and Bcl-2 Conversion Gene by PHB-PDMAEMA Amphiphilic Cationic Copolymer for Effective Drug Resistant Cancer Therapy.
Antiapoptotic Bcl-2 protein's upregulated expression is a key reason for drug resistance leading to failure of chemotherapy. In this report, a series of biocompatible amphiphilic cationic poly[(R)-3-hydroxybutyrate] (PHB)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) copolymer, comprising hydrophobic PHB block and cationic PDMAEMA block, is designed to codeliver hydrophobic chemotherapeutic paclitaxel and Bcl-2 converting gene Nur77/ΔDBD with enhanced stability, due to the micelle formation by hydrophobic PHB segment. This copolymer shows less toxicity but similar gene transfection efficiency to polyethyenimine (25k). More importantly, this codelivery approach by PHB-PDMAEMA leads to increased drug resistant HepG2/Bcl-2 cancer cell death, by increased expression of Nur77 proteins in the Bcl-2 present intracellular mitochondria. This work signifies for the first time that cationic amphiphilic PHB-b-PDMAEMA copolymers can be utilized for the drug and gene codelivery to drug resistant cancer cells with high expression of antiapoptosis Bcl-2 protein and the positive results are encouraging for the further design of codelivery platforms for combating drug resistant cancer cells.


Microbiological investigations to validate the preparation of corneal transplants.
The globe and cornea are colonized by microorganisms and cannot be removed as sterile products. Antiseptic measures and storage of the cornea in medium containing antibiotics lead to an obvious reduction of the microbial flora. Unfortunately there is the possibility of secondary microbial contamination during the preparation. Large amounts of bacteria or resistant bacteria can ruin attempts to reduce the microbial flora. To validate the whole process of preparation we investigated the contamination of removed globes, environment, materials, instruments and media for each sequence of operation and eliminated sources of contamination. Recommendations are given to ensure a virtually sterile product at the end of preparation.


K-Box: automatic structuring and exchange of medical documents based on the clinical documentation architecture (CDA).
Sustainable health systems should understand information as a resource which also has to be managed efficiently. Today's electronic documentation is only the mandatory first step to automatic information exchange between hospitals, physician offices, pharmacies and other participants. The K-Box is a modular system which allows different monolithic information systems to be connected and integrated by using the clinical document architecture (CDA) as the standard document exchange format. A prototype K-Box has been implemented and a trial run is scheduled. The workflow selected for the trial produces discharge summaries in CDA format.


Mapping cover crop species in southeastern Michigan using Sentinel-2 satellite data and Google Earth Engine.
Cover crops are a critical agricultural practice that can improve soil quality, enhance crop yields, and reduce nitrogen and phosphorus losses from farms. Yet there is limited understanding of the extent to which cover crops have been adopted across large spatial and temporal scales. Remote sensing offers a low-cost way to monitor cover crop adoption at the field scale and at large spatio-temporal scales. To date, most studies using satellite data have mapped the presence of cover crops, but have not identified specific cover crop species, which is important because cover crops of different plant functional types (e.g., legumes, grasses) perform different ecosystem functions. Here we use Sentinel-2 satellite data and a random forest classifier to map the cover crop species cereal rye and red clover, which represent grass and legume functional types, in the River Raisin watershed in southeastern Michigan. Our maps of agricultural landcover across this region, including the two cover crop species, had moderate to high accuracies, with an overall accuracy of 83%. Red clover and cereal rye achieved F1 scores that ranged from 0.7 to 0.77, and user's and producer's accuracies that ranged from 63.3% to 86.2%. The most common misclassification of cover crops was fallow fields with remaining crop stubble, which often looked similar because these cover crop species are typically planted within existing crop stubble, or interseeded into a grain crop. We found that red-edge bands and images from the end of April and early July were the most important for classification accuracy. Our results demonstrate the potential to map individual cover crop species using Sentinel-2 imagery, which is critical for understanding the environmental outcomes of increasing crop diversity on farms.


Perception and production of /r/ allophones improve with hearing from a cochlear implant.
Tongue shape can vary greatly for allophones of /r/ produced in different phonetic contexts but the primary acoustic cue used by listeners, lowered F3, remains stable. For the current study, it was hypothesized that auditory feedback maintains the speech motor control mechanisms that are constraining acoustic variability of F3 in /r/; thus the listener's percept remains /r/ despite the range of articulatory configurations employed by the speaker. Given the potential importance of auditory feedback, postlingually deafened speakers should show larger acoustic variation in /r/ allophones than hearing controls, and auditory feedback from a cochlear implant could reduce that variation over time. To test these hypotheses, measures were made of phoneme perception and of production of tokens containing /r/, stop consonants, and /r/+stop clusters in hearing controls and in eight postlingually deafened adults pre- and postimplant. Postimplant, seven of the eight implant speakers did not differ from the control mean. It was also found that implant users' production of stop and stop+/r/ blend improved with time but the measured acoustic contrast between these was still better in the control speakers than for the implant group even after the implant users had experienced a year of improved auditory feedback.


Expression of monocyte chemoattractant protein-1 and macrophage colony-stimulating factor in normal and inflamed rat testis.
Macrophages are numerous in the testicular interstitial tissue under normal conditions and increase during inflammation. The mechanisms involved are poorly characterized. Expression of the macrophage-regulating cytokines monocyte chemoattractant protein (MCP)-1 and macrophage colony-stimulating factor (M-CSF) was examined in the adult rat testis before and after an i.p. injection of an inflammatory stimulus, lipopolysaccharide (LPS). In the normal testis, M-CSF was readily observed using Northern blot and Western blot analysis. In contrast, MCP-1 was not detectable by Northern blot in the normal testis, but was detected using RT-PCR amplification and a sensitive ELISA. After LPS treatment, testicular MCP-1 mRNA and protein expression increased dramatically (up to 400-fold). In-situ hybridization for MCP-1 revealed that production was confined to the interstitium of the inflamed testis, in Leydig cells, peritubular cells, perivascular cells and monocyte-like macrophages, but not in tissue-resident macrophages. Unlike MCP-1, M-CSF mRNA and protein expression in the testis increased only marginally, if at all, after LPS treatment. These results suggest that MCP-1 stimulates the increase in intratesticular macrophages that accompanies LPS-induced inflammation in vivo. Together with M-CSF, MCP-1 may also play a role in maintaining the resident macrophage population of the normal testis.


Identification of interleukin genes in Pogona vitticeps using a de novo transcriptome assembly from RNA-seq data.
Interleukins are a group of cytokines with complex immunomodulatory functions that are important for regulating immunity in vertebrate species. Reptiles and mammals last shared a common ancestor more than 350 million years ago, so it is not surprising that low sequence identity has prevented divergent interleukin genes from being identified in the central bearded dragon lizard, Pogona vitticeps, in its genome assembly. To determine the complete nucleotide sequences of key interleukin genes, we constructed full-length transcripts, using the Trinity platform, from short paired-end read RNA sequences from stimulated spleen cells. De novo transcript reconstruction and analysis allowed us to identify interleukin genes that are missing from the published P. vitticeps assembly. Identification of key cytokines in P. vitticeps will provide insight into the essential molecular mechanisms and evolution of interleukin gene families and allow for characterization of the immune response in a lizard for comparison with mammals.


Technique and use of "corrected-axis" tomograms of the mandibular condyles.
In diagnosing and treating temporomandibular joint (TMJ) dysfunctions, the oral and maxillofacial surgeon can use the radiographic technique of "corrected-axis" lateral tomography of the mandibular condyles. The theory, technique, and equipment necessary for making "corrected-axis" lateral tomograms of the mandibular condyles are presented. Once familiar with this technique, the surgeon can educate the radiologist and technician if it is one with which they are unfamiliar.


Identification and characterization of novel abdominal and pelvic brown adipose depots in mice.
Brown adipose tissue (BAT) generates heat through non-shivering thermogenesis, and increasing BAT amounts or activity could facilitate obesity treatment and provide metabolic benefits. In mice, BAT has been reported in perirenal, thoracic and cranial sites. Here, we describe new pelvic and lower abdominal BAT depots located around the urethra, internal reproductive and urinary tract organs and major lower pelvic blood vessels, as well as between adjacent muscles where the upper hind leg meets the abdominal cavity. Immunohistochemical, western blot and PCR analyses revealed that these tissues expressed BAT markers such as uncoupling protein 1 (UCP1) and CIDEA, but not white adipose markers, and β3-adrenergic stimulation increased UCP1 amounts, a classic characteristic of BAT tissue. The newly identified BAT stores contained extensive sympathetic innervation with high mitochondrial density and multilocular lipid droplets similar to interscapular BAT. BAT repositories were present and functional neonatally, and showed developmental changes between the neonatal and adult periods. In summary, several new depots showing classical BAT characteristics are reported and characterized in the lower abdominal/pelvic region of mice. These BAT stores are likely significant metabolic regulators in the mouse and some data suggests that similar BAT depots may also exist in humans.


Functional sensorial complementation during host orientation in an Asilidae parasitoid larva.
Changes in environmental conditions influence the performance of organisms in every aspect of their life. Being capable of accurately sensing these changes allow organisms to better adapt. The detection of environmental conditions involves different sensory modalities. There are many studies on the morphology of different sensory structures but not so many studies showing their function. Here we studied the morphology of different sensory structures in the larva of a dipteran parasitoid. We occluded the putative sensory structures coupling the morphology with their function. First, we could develop a non-invasive method in which we occluded the putative sensorial structures annulling their function temporarily. Regarding their functionality, we found that larvae of Mallophora ruficauda require simultaneously of the sensilla found both in the antennae and those of the maxillary palps in order to orient to its host. When either both antennae or both maxillary palps were occluded, no orientation to the host was observed. We also found that these structures are not involved in the acceptance of the host because high and similar proportion of parasitized hosts was found in host acceptance experiments. We propose that other sensilla could be involved in host acceptance and discuss how the different sensilla in the antennae and maxillary palps complement each other to provide larvae with the information for locating its host.


Prediction of blood lead by HPLC assay of erythrocyte pyrimidine 5'-nucleotidase.
A simplified preparation of erythrocytes (rbc) for rbc pyrimidine 5'-nucleotidase (P5N) is described and correlated with blood lead. Washed but unfiltered rbc are incubated with uridine monophosphate (UMP) and the amount of uridine liberated is measured by high performance liquid chromatography (HPLC). UMPase activity of unfiltered rbc of 20 normal subjects was 12.4 +/- 2.4 units, comparable to reported data obtained under varying conditions of preparation and P5N assay. In 20 lead-exposed adults and 20 controls, the regression coefficient for blood lead (PbB) predicted by rbc UMPase was In PbB = 4.77 - 0.22 UMPase; r2 = .61. If UMPase less than or equal to 7.6 units (mean, 2.0 SD) is considered abnormal, sensitivity for prediction of a blood lead greater than or equal to 40 micrograms/dL is 80%. Specificity, the percent of subjects with a UMPase greater than 7.6 units who had a blood lead less than 40 micrograms/dL, was 96%. Wider utilization of P5N, measured as UMPase, is proposed as a biologic correlate of blood lead.


[What is anomalous departure of the aorta and pulmonary artery from the right ventricle?].
Available literature data on terminological and anatomical definition of congenital combined valvular disease--anomalous right ventricular origin of the aorta and pulmonary artery--are reviewed. Not a single report analysed permitted an objective precise structural outline of the disease. The causes of this situation are elicited. The review of the 8 Soviet and 55 foreign original sources shows that the question of pathognomonicity of the anomaly anatomical signs remains disputable.


Right ventricular volume determination in isolated human hearts.
For right ventricular volume determination a new method was developed that took into account right ventricular imaging by apical two-dimensional echocardiography in the four- and two-chamber views. Right ventricular volume was calculated by subtraction of the partial volume of the left ventricle and interventricular septum from the total heart volume of the right and left ventricles including the interventricular septum. Accuracy of the subtraction method was evaluated in isolated human hearts by two-dimensional echocardiography and radiography. Regression analysis indicated that for both the echocardiographic and radiologic procedures, the subtraction method gave the best correlation with the right ventricular filling volume. The correlation coefficients obtained using the echocardiographic procedure were 0.964, 0.848, and 0.851 for the subtraction method, pyramid method, and Simpson's rule method, respectively. For the radiographic procedure, these values were 0.946, 0.860, and 0.872. Percentage difference calculations indicated that the subtraction method systematically underestimated (-7.4%) the filling volume in the echocardiographic procedure, but this was not seen with the radiologic procedures. The random error associated with the subtraction method was only half (10.5%, 13.9%) of that seen with the other two methods in both the echocardiographic and radiological procedures. These results indicate that right ventricular volume determination by the subtraction method seems to be suitable for apical two-dimensional echocardiography and is more accurate than the pyramid method and Simpson's rule method.


Genomic signatures reveal new evidences for selection of important traits in domestic cattle.
We investigated diverse genomic selections using high-density single nucleotide polymorphism data of five distinct cattle breeds. Based on allele frequency differences, we detected hundreds of candidate regions under positive selection across Holstein, Angus, Charolais, Brahman, and N'Dama. In addition to well-known genes such as KIT, MC1R, ASIP, GHR, LCORL, NCAPG, WIF1, and ABCA12, we found evidence for a variety of novel and less-known genes under selection in cattle, such as LAP3, SAR1B, LRIG3, FGF5, and NUDCD3. Selective sweeps near LAP3 were then validated by next-generation sequencing. Genome-wide association analysis involving 26,362 Holsteins confirmed that LAP3 and SAR1B were related to milk production traits, suggesting that our candidate regions were likely functional. In addition, haplotype network analyses further revealed distinct selective pressures and evolution patterns across these five cattle breeds. Our results provided a glimpse into diverse genomic selection during cattle domestication, breed formation, and recent genetic improvement. These findings will facilitate genome-assisted breeding to improve animal production and health.


Kinetics of Methylmercury Production Revisited.
Laboratory measurements of the biologically mediated methylation of mercury (Hg) to the neurotoxin monomethylmercury (MMHg) often exhibit kinetics that are inconsistent with first-order kinetic models. Using time-resolved measurements of filter passing Hg and MMHg during methylation/demethylation assays, a multisite kinetic sorption model, and reanalyses of previous assays, we show that competing kinetic sorption reactions can lead to time-varying availability and apparent non-first-order kinetics in Hg methylation and MMHg demethylation. The new model employing a multisite kinetic sorption model for Hg and MMHg can describe the range of behaviors for time-resolved methylation/demethylation data reported in the literature including those that exhibit non-first-order kinetics. Additionally, we show that neglecting competing sorption processes can confound analyses of methylation/demethylation assays, resulting in rate constant estimates that are systematically biased low. Simulations of MMHg production and transport in a hypothetical periphyton biofilm bed illustrate the implications of our new model and demonstrate that methylmercury production may be significantly different than projected by single-rate first-order models.


A short educational intervention diminishes causal illusions and specific paranormal beliefs in undergraduates.
Cognitive biases such as causal illusions have been related to paranormal and pseudoscientific beliefs and, thus, pose a real threat to the development of adequate critical thinking abilities. We aimed to reduce causal illusions in undergraduates by means of an educational intervention combining training-in-bias and training-in-rules techniques. First, participants directly experienced situations that tend to induce the Barnum effect and the confirmation bias. Thereafter, these effects were explained and examples of their influence over everyday life were provided. Compared to a control group, participants who received the intervention showed diminished causal illusions in a contingency learning task and a decrease in the precognition dimension of a paranormal belief scale. Overall, results suggest that evidence-based educational interventions like the one presented here could be used to significantly improve critical thinking skills in our students.


Ultrastructural characteristics of the blood cells of chickens commonly reared under backyard poultry farming in Mizoram, India.
The present study was undertaken to characterize the ultrastructural morphology of the blood cells of commonly reared chickens in the state of Mizoram, India under backyard poultry farming. For this study, 2 ml of whole blood was aseptically collected from the wings veins of 12 chickens of three different breeds namely the Zoar, Aseel and Rhode Island Red and processed for ultrastructural imaging under standard protocols. Under scanning electron microscopy (SEM) the matured erythrocytes of Zoar, Aseel and Rhode Island Red appeared elliptical in shape while the leukocytes and thrombocytes appeared round in shape with variable surface modifications. Under transmission electron microscopy (TEM) the granules of the heterophils of Zoar, Aseel and Rhode Island Red appeared predominantly fusiform in shape, the granules of the eosinophils appeared round in shape and that of the basophils appeared pleomorphic in shape. The cytoplasm of the monocytes, medium-to-large lymphocytes and thrombocytes of Zoar, Aseel and Rhode Island Red under TEM appeared to be vacuolated and granular while that of the small lymphocytes appeared to be granular but non-vacuolated. The study concluded that the ultrastructural characteristics of the blood cells of the three breeds of chicken studied were almost similar to the blood cells of other birds reported earlier.


Extracellular chloride is required for efficient platelet aggregation.
Anion channels perform a diverse range of functions and have been implicated in ATP release, volume regulation, and phosphatidylserine exposure. Platelets have been shown to express several anion channels but their function is incompletely understood. Due to a paucity of specific pharmacological blockers, we investigated the effect of extracellular chloride substitution on platelet activation using aggregometry and flow cytometry. In the absence of extracellular chloride, we observed a modest reduction of the maximum aggregation response to thrombin or collagen-related peptide. However, the rate of aggregation was substantially reduced in a manner that was dependent on the extracellular chloride concentration and aggregation in the absence of chloride was noticeably biphasic, indicative of impaired secondary signaling. This was further investigated by targeting secondary agonists with aspirin and apyrase or by blockade of the ADP receptor P2Y12. Under these conditions, the rates of aggregation were comparable to those recorded in the absence of extracellular chloride. Finally, we assessed platelet granule release by flow cytometry and report a chloride-dependent element of alpha, but not dense, granule secretion. Taken together these data support a role for anion channels in the efficient induction of platelet activation, likely via enhancement of secondary signaling pathways.


Clinical impact of chronic obstructive pulmonary disease on non-cystic fibrosis bronchiectasis. A study on 1,790 patients from the Spanish Bronchiectasis Historical Registry.
Few studies have evaluated the coexistence of bronchiectasis (BE) and chronic obstructive pulmonary disease (COPD) in series of patients diagnosed primarily with BE. The aim of this study was to analyse the characteristics of patients with BE associated with COPD included in the Spanish Bronchiectasis Historical Registry and compare them to the remaining patients with non-cystic fibrosis BE. We conducted a multicentre observational study of historical cohorts, analysing the characteristics of 1,790 patients who had been included in the registry between 2002 and 2011. Of these, 158 (8.8%) were registered as BE related to COPD and were compared to the remaining patients with BE of other aetiologies. Patients with COPD were mostly male, older, had a poorer respiratory function and more frequent exacerbations. There were no differences in the proportion of patients with chronic bronchial colonisation or in the isolated microorganisms. A significantly larger proportion of patients with COPD received treatment with bronchodilators, inhaled steroids and intravenous antibiotics, but there was no difference in the use of long term oral or inhaled antibiotherapy. During a follow-up period of 3.36 years, the overall proportion of deaths was 13.8%. When compared to the remaining aetiologies, patients with BE associated with COPD presented the highest mortality rate. The multivariate analysis showed that the diagnosis of COPD in a patient with BE as a primary diagnosis increased the risk of death by 1.77. Patients with BE related to COPD have the same microbiological characteristics as patients with BE due to other aetiologies. They receive treatment with long term oral and inhaled antibiotics aimed at controlling chronic bronchial colonisation, even though the current COPD treatment guidelines do not envisage this type of therapy. These patients' mortality is notably higher than that of remaining patients with non-cystic fibrosis BE.


[Multiple stepwise regression analysis of etiological factors of esophageal cancer in Cixian county].
Cixian county, one of the high-risk counties of esophageal cancer in the world, has a standardized mortality of 142.19/10(5) population, 1969-1971. The incidence of esophageal cancer had dropped year by year from 1974 to 1982. The significance of the incidence tendency was studied. The results are highly significant (P less than 0.001). The causative factors of esophageal cancer including five independent variables: X1 (number of people taking sanitized water), X2 (number of people on pickled Chinese cabbage), X3 (annual output of fruit), X4 (annual output of fresh vegetable) and X5 (annual output of sweet potato) and one dependent variable Y (morbidity of esophageal cancer) were studied by correlative analysis and multiple stepwise regression. Three correlative factors (X1, X2, and X5) with significant effect on the esophageal cancer were selected from the five suspected factors. The result indicated that taking sanitized water, reducing the number of people on pickled Chinese cabbage, changing the structure of food and keeping the nutrient balance, might decrease the incidence of esophageal cancer.


Treatment of biliary atresia by portoenterostomy and liver transplantation: The Queen Mary Hospital, Hong Kong experience.
Ninety three out of 96 patients with biliary atresia (BA) underwent Kasai 1 portoenterostomy and 11 children subsequently underwent 12 liver transplantation (LTX) procedures which included 8 living related liver transplants (LRLT), 3 reduced-size liver transplants (RSLT) and 1 orthotopic liver transplantation (OLT). During a follow-up period of 3-206 months (mean, 73 months) after portoenterostomy and 3-63 months after LTX, 50% of 96 patients are alive and well with total clearance of jaundice while 12% are mildly jaundiced, 10% are deeply jaundiced and 28% have died. Two of the 3 patients who did not undergo portoenterostomy and 25 from the portoenterostomy group have died. Of the latter group, 22 deaths occurred before, and 3 after the introduction of LTX therapy respectively. Of the 68 long-term survivors, 32 are less than 5, and 36 are 6-17 years old. Complete clearance of jaundice was achieved in 55% of patients irrespective of whether portoenterostomy was initially performed at < 10 or between 10 and 12 weeks. Portoenterostomy performed beyond 13 weeks was associated with declining results. We conclude that (1) portoenterostomy combined with liver transplantation, when indicated, has given patients with BA a much better prognosis and (2) pediatric LTX in our institute is a well established procedure with 100% patient and 88% primary graft survival.


MicroRNAs in disease and potential therapeutic applications.
MicroRNAs (miRNAs) are 21-24 nucleotide (nt) duplex RNAs that are created from precursor transcripts by subsequent processing steps mediated by members of the RNAseIII family, Drosha and Dicer. One of the two strands is incorporated into the active sites of the Argonaute family of proteins, where it serves as a guide for Watson-Crick base pairing with complementary sequences in target messenger RNAs (mRNAs). In mammals, the majority of miRNAs guide the RNA-induced silencing complex (RISC) to the 3' untranslated regions (UTRs) of mRNA targets, with the consequence that translation of the target mRNAs is inhibited. The importance of miRNAs in normal cellular development and metabolism is only now being realized. miRNA deficiencies or excesses have been correlated with a number of clinically important diseases ranging from myocardial infarction to cancers. The loss or gain of miRNA function can be caused by a single point mutation in either the miRNA or its target or by epigenetic silencing of primary miRNA transcription units. This review summarizes miRNA biogenesis and biology, explores the potential roles miRNAs can play in a variety of diseases, and suggests some therapeutic applications for restoring or inhibiting miRNA function.


Aberrant neutrophil degranulation in hospitalized patients with COVID-19 partially remains for 6 months.
Neutrophils are important players in COVID-19, contributing to tissue damage by release of inflammatory mediators, including ROS and neutrophil elastase. Longitudinal studies on the effects of COVID-19 on neutrophil phenotype and function are scarce. Here, we longitudinally investigated the phenotype and degranulation of neutrophils in COVID-19 patients (28 nonhospitalized and 35 hospitalized patients) compared with 17 healthy donors (HDs). We assessed phenotype, degranulation, CXCL8 (IL-8) release, and ROS generation within 8 days, at one or 6 month(s) after COVID-19 diagnosis. For degranulation and ROS production, we stimulated neutrophils, either with ssRNA and TNF or granulocyte-macrophage colony-stimulating factor and N-Formylmethionyl-leucyl-phenylalanine. During active COVID-19, neutrophils from hospitalized patients were more immature than from HDs and were impaired in degranulation and ROS generation, while neutrophils from nonhospitalized patients only demonstrated reduced CD66b+ granule release and ROS production. Baseline CD63 expression, indicative of primary granule release, and CXCL8 production by neutrophils from hospitalized patients were elevated for up to 6 months. These findings show that patients hospitalized due to COVID-19, but not nonhospitalized patients, demonstrated an aberrant neutrophil phenotype, degranulation, CXCL8 release, and ROS generation that partially persists up to 6 months after infection.


SEVERE INBREEDING DEPRESSION AND RAPID FITNESS REBOUND IN THE BUTTERFLY BICYCLUS ANYNANA (SATYRIDAE).
We established inbred laboratory lines of the satyrid Bicyclus anynana with one, three and 10 pairs of butterflies, which were subsequently allowed to increase freely to a maximum size of 300 butterflies. Minimally inbred control lines were established with 300 randomly selected virgin butterflies of equal sex ratio. We measured fecundity, egg weight, egg hatching, adult emergence, adult size, and the proportion of crippled adults in generations F2 , F3 , F5 , and F7 (the latter two for the one pair bottleneck lines only). The most striking result was an unexpectedly large decrease in egg hatching with increase in inbreeding (25% per 10% increase in inbreeding). Such a level of inbreeding depression has not been reported previously for any insect. The distribution of egg hatching rate for individual clutches within inbred lines was markedly skewed, with a large fraction of clutches producing no eggs at all. This is interpreted as a relatively lower ratio of detrimental to lethal (or sterile) mutation loads than is found in Drosophila, the only insects for which mutation loads have been well characterized. Possible explanations for this severe inbreeding depression include a relatively high rate of mutation to recessive alleles with substantial damaging effects and infrequent episodes of inbreeding in nature. In the experiments, average egg hatching rate recovered rapidly between F2 and F7 in three of the six one-pair lines. We discuss the implications of these results for survival of populations through extreme bottlenecks in nature and in captivity.