Miracle-dz/UniFAR-FTUs huggingface dataset:
Overcoming qEEG Abnormalities and Reward Gene Deficits during Protracted Abstinence in Male Psychostimulant and Polydrug Abusers Utilizing Putative Dopamine D2 Agonist Therapy: Part 2

Abstract Background: It is well established that in both food- and drug-addicted individuals there is “dopamine resistance” associated with the DRD2 gene A1 allele. Based on earlier studies, evidence is emerging wherein the potential of utilizing a natural, nonaddicting, safe, putative D2 agonist may play a significant role in the recovery of individuals with reward deficiency syndrome, including those addicted to psychoactive chemicals. Findings: Positive outcomes demonstrated by quantitative electroencephalographic (qEEG) imaging in a randomized, triple-blind, placebo-controlled, crossover study involving oral Synaptose Complex KB220Z™ showed an increase of alpha waves and low beta wave activity in the parietal brain region. Using t statistics, significant differences observed between placebo and Synaptose Complex KB220Z™ consistently occurred in the frontal regions after week 1 and then again after week 2 of analyses (P = 0.03). This is the first report to demonstrate involvement of the prefrontal cortex in the qEEG response to a natural putative D2 agonist (Synaptose Complex KB220Z™), especially evident in dopamine D2 A1 allele subjects. Independently, we have further supported this finding with an additional study of 3 serious polydrug abusers undergoing protracted abstinence who carried the DRD2 A1 allele. Significant qEEG differences were found between those who received 1 dose of placebo compared with those who were administered Synaptose Complex KB220Z™. Synaptose Complex KB220Z™ induced positive regulation of the dysregulated electrical activity of the brain in these addicts. The results are indicative of a phase change from low amplitude or low power in the brain to a more regulated state by increasing an average of 6.169 mV2 across the prefrontal cortical region. In the first experiment we found that while 50% of the subjects carried the DRD2 A1 allele, 100% carried ≥ 1 risk allele. Specifically, based on the proposed addiction risk score for these 14 subjects, 72% had moderate-to-severe addiction risk. Similar findings were obtained by repeating the experiment in 3 additional currently abstinent polydrug abusers carrying the DRD2 A1 allele. Conclusion: This seminal work will provide important information that may ultimately lead to significant improvement in the recovery of individuals with psychostimulant and polydrug abuse problems, specifically those with genetically induced dopamine deficiency. Based on this small sample size, we are proposing that with necessary large populations supporting these initial results, and possibly even additional candidate genes and single nucleotide polymorphisms, we may eventually have the clinical ability to classify severity according to genotype and possession of risk alleles, along with offering a safe, nonaddicting, natural dopaminergic receptor agonist that potentially upregulates instead of downregulates dopaminergic receptors, preferably the D2 subtype.
Management of severe acute to fulminant hepatitis B: to treat or not to treat or when to treat?

Despite a decline in cases of acute hepatitis B and the low hepatitis B virus (HBV) chronicity rates in adults, still some patients progress to HBV‐related fulminant liver failure. In this review, we discuss treatment options that may prevent the progression of severe acute hepatitis B to fulminant liver failure and death. In severe acute HBV with prolonged prothrombin time and increased bilirubin, interferon failed to be effective while antiviral treatment, particularly with lamivudine, appears to improve survival (mean survival almost 80%). Outcome without antiviral therapy has remained considerably poor, whereas there is no convincing evidence of amelioration of HBV‐targeted immunity. Of note, most patients who died or required transplantation despite lamivudine therapy, were started on lamivudine at advanced stages compared with those survived. This suggests that prompt and timely antiviral therapy is crucial. Owing to the abovementioned results the design of randomized placebo‐control trials in the setting of severe acute hepatitis B seems unethical. On the contrary, the design of multicentre double‐blind randomized trials to compare the efficacy between lamivudine and entecavir or even tenofovir in acute severe HBV cases is ideally needed, but these studies appear to be very difficult to perform considering that these cases are not frequent and therefore, it is almost impossible to have two arms adequately numerous and homogenous for statistical evaluation. Thus, in the absence of solid evidence based data, the hepatologists could treat their patients with severe acute hepatitis B with lamivudine or the most potent antivirals entecavir or tenofovir.
The Dyslexia-associated KIAA0319 Protein Undergoes Proteolytic Processing with γ-Secretase-independent Intramembrane Cleavage

The KIAA0319 gene has been associated with reading disability in several studies. It encodes a plasma membrane protein with a large, highly glycosylated, extracellular domain. This protein is proposed to function in adhesion and attachment and thought to play an important role during neuronal migration in the developing brain. We have previously proposed that endocytosis of this protein could constitute an important mechanism to regulate its function. Here we show that KIAA0319 undergoes ectodomain shedding and intramembrane cleavage. At least five different cleavage events occur, four in the extracellular domain and one within the transmembrane domain. The ectodomain shedding processing cleaves the extracellular domain, generating several small fragments, including the N-terminal region with the Cys-rich MANEC domain. It is possible that these fragments are released to the extracellular medium and trigger cellular responses. The intramembrane cleavage releases the intracellular domain from its membrane attachment. Our results suggest that this cleavage event is not carried out by γ-secretase, the enzyme complex involved in similar processing in many other type I proteins. The soluble cytoplasmic domain of KIAA0319 is able to translocate to the nucleus, accumulating in nucleoli after overexpression. This fragment has an unknown role, although it could be involved in regulation of gene expression. The absence of DNA-interacting motifs indicates that such a function would most probably be mediated through interaction with other proteins, not by direct DNA binding. These results suggest that KIAA0319 not only has a direct role in neuronal migration but may also have additional signaling functions.
Mental Health in American Colleges and Universities: Variation Across Student Subgroups and Across Campuses

Abstract We estimated the prevalence and correlates of mental health problems among college students in the United States. In 2007 and 2009, we administered online surveys with brief mental health screens to random samples of students at 26 campuses nationwide. We used sample probability weights to adjust for survey nonresponse. A total of 14,175 students completed the survey, corresponding to a 44% participation rate. The prevalence of positive screens was 17.3% for depression, 4.1% for panic disorder, 7.0% for generalized anxiety, 6.3% for suicidal ideation, and 15.3% for nonsuicidal self-injury. Mental health problems were significantly associated with sex, race/ethnicity, religiosity, relationship status, living on campus, and financial situation. The prevalence of conditions varied substantially across the campuses, although campus-level variation was still a small proportion of overall variation in student mental health. The findings offer a starting point for identifying individual and contextual factors that may be useful to target in intervention strategies.
Valuing recreational water clarity and quality: evidence from hedonic pricing models of lakeshore properties

ABSTRACT This study extends the economics literature on the relationship between recreational water quality and residential property pricing by separately testing the relationships between both water clarity and quality and the price of lakeshore residential properties in Ontario, Canada. Our econometric approach includes objective measures of both attributes: Secchi disk readings for water clarity and phosphorus concentrations for water quality. Econometric results presented in this study suggest that a one-metre improvement in water clarity results in an 8 per cent residential property price premium, while a one standard deviation improvement in water quality boosts lakeshore residence prices by 32 per cent.
Local ex vivo gene therapy with bone marrow stromal cells expressing human BMP4 promotes endosteal bone formation in mice

Bone loss in osteoporosis is caused by an imbalance between resorption and formation on endosteal surfaces of trabecular and cortical bone. We investigated the feasibility of increasing endosteal bone formation in mice by ex vivo gene therapy with bone marrow stromal cells (MSCs) transduced with a MLV‐based retroviral vector to express human bone morphogenetic protein 4 (BMP4).
Investigation of spatial correlation for two-user cooperative communication in indoor office environment

An experimental investigation of the spatial correlation for cooperative multiple-input multiple-output (MIMO) channel in an indoor environment is presented in this paper. The testbed is designed for a two-user cooperation channel sounding, operated at a carrier center frequency of 2.45GHz and a bandwidth of 100MHz. The measurements were conducted in a typical office environment. The spatial correlation is extracted based on the Kronecker channel model. The spatial correlation turns out to be surprisingly high for short-distance cooperative communication in a void office, and it drops rapidly with the increase of communication distance. Furthermore, the impact of environment itself on the spatial correlation was then studied by adding reflector and scatterers into the office. It shows that cooperation gets more benefits in the rich scattering and reflecting conditions.
Hyponatremia in Acute Decompensated Heart Failure: Mechanisms, Prognosis, and Treatment Options

Hyponatremia is common and is increasingly recognized as an independent prognostic marker that adversely affects morbidity and mortality in various disease states, including heart failure. In acute decompensated heart failure (ADHF), the degree of hyponatremia often parallels the severity of cardiac dysfunction and is further exacerbated by any reduction in glomerular filtration rate and arginine vasopressin dysregulation. A recent study showed that even modest improvement of hyponatremia may have survival benefits. Although management of hyponatremia in ADHF has traditionally focused on improving cardiac function and fluid restriction, the magnitude of improvement of serum sodium is fairly slow and unpredictable. In this article, we discuss the mechanisms of hyponatremia in ADHF, review its evolving prognostic significance, and evaluate the efficacy of various treatments for hyponatremia, including the recently approved vasopressin receptor antagonists for managing hyponatremia among patients hospitalized for ADHF. Copyright © 2008 Wiley Periodicals, Inc.
Rehabilitation of the Older Stroke Patient: Functional Outcome and Comparison with Younger Patients

Ergeletzis D, Kevorkian CG, Rintala D: Rehabilitation of the older stroke patient: Functional outcome and comparison with younger patients. Am J Phys Med Rehabil 2002;81:881–889. Objective To evaluate the inpatient rehabilitation progress and functional outcome of stroke patients aged 80 yr and over and make comparisons with a younger (<80 yr) stroke population receiving similar comprehensive rehabilitation therapies. Design A case series of 223 stroke patients consecutively admitted to the inpatient rehabilitation unit of a tertiary acute general hospital. A total of 44 patients with a first-time stroke were at least 80 yr old and over and 179 initial stroke patients were <80 yr old. The main outcome measures included admission and discharge scores of the FIM™ instrument, FIM gain and efficiency, and discharge disposition. Results The majority (72.7%) of the older stroke group (mean age, 84 yr; standard deviation, 3.7 yr; range, 80–94 yr) was able to return home, although to a lesser extent than the younger segment (90.5%). No continuous or categorical variable studied was related to discharge disposition in the older stroke patients. Admission FIM total was the most significant predictor of discharge FIM total and discharge FIM motor. The older group did have a lower FIM efficiency and made smaller FIM total and motor gains. In comparison with the younger stroke patients, the older stroke group was statistically more likely to be women (P < 0.001), unmarried (P < 0.001), living alone prestroke (P < 0.05), and unemployed (P < 0.001). Conclusion Most older stroke patients can successfully complete a rehabilitation program and return to the community. Demographic, functional, and outcome differences were found when comparing this population with younger counterparts.
Non-consulters and high consulters in general practice: cardio-respiratory health and risk factors.

The 1990 General Practitioner contract requires that health promotion and illness prevention services should be provided to all patients aged 16-74 years. Consultation rates over a period of three years were examined in 7010 middle-aged men in Great Britain to compare the cardio-respiratory health and risk factor status of non-consulters (men who did not consult in three years) with those of average consulters (men who consulted 3-5 times in three years) and high consulters (men who consulted 24 or more times in three years) to assess their relative need for health promotion and illness prevention services. The non-consulters (n = 1025) were remarkably similar to the average consulters (n = 1585) in health and lifestyle characteristics. The high consulters (n = 306) had a greater burden of ill-health and a less healthy lifestyle. Chest pain on exertion, chronic bronchitis, breathlessness or wheeze were present in 23 per cent of non-consulters, 27 per cent of average consulters and over 50 per cent of high consulters. Similarly, 48 per cent of the non-consulters smoked, drank heavily or were obese compared with 47 per cent of the average consulters and 61 per cent of the high consulters. The prevalence of recall of high blood pressure which had been diagnosed by a doctor rose from 6 per cent in non-consulters and 10 per cent in average consulters to 29 per cent in high consulters. (ABSTRACT TRUNCATED AT 250 WORDS)
Vaginal estrogen preparations: a review of safety and efficacy for vaginal atrophy.

BACKGROUND A theoretical advantage of local (i.e., vaginal) therapy of genitourinary symptoms could be avoidance of systemic adverse effects. Review of efficacy and adverse effects of commonly prescribed vaginal estrogens is of great clinical relevance. METHODS A Medline (1966-present) search was performed for randomized controlled trials involving vaginal estrogens. Reference lists of papers were reviewed for additional references. RESULTS Twenty-two references were randomized controlled trials of vaginal estrogens used by postmenopausal women with signs or symptoms of vaginal atrophy. Subject numbers ranged from 20 to 251. Duration ranged from 2 weeks to 1 year. Different preparations and schedules were used across the trials. All treatments alleviated signs and symptoms of atrophic vaginitis, regardless of whether objective signs of atrophy were required for study entry. Data for urinary symptoms was conflicting; the ring may prevent recurrent urinary tract infections (UTIs). The trials with endometrial scrutiny were less than one year and had mixed results. Nonhormonal lubricant is effective in improving some atrophic signs and symptoms. All preparations were associated with vaginal irritation. Bleeding with vaginal estradiol tablets may be less than that with CEE cream. Vaginal tablets or rings were preferred over other preparations. There were no serious adverse events reported. There was occasional expulsion of estradiol ring in the setting of prior hysterectomy. CONCLUSIONS All preparations are effective in decreasing signs and symptoms of vaginal atrophy, but they differ slightly in their adverse event profiles. Long-term safety of the preparations is best established for estradiol tablets (1 year), but is lacking for all preparations.
Functional genomics of Helicobacter pylori: identification of a β‐1,4 galactosyltransferase and generation of mutants with altered lipopolysaccharide

A previously annotated open reading frame (ORF) (HP0826) from Helicobacter pylori was cloned and expressed in Escherichia coli cells and determined to be a β‐1,4‐galactosyltransferase that used GlcNAc as an acceptor. Mutational analysis in H. pylori strains demonstrated that this enzyme plays a key role in the biosynthesis of the type 2 N‐acetyl‐lactosamine (LacNAc) polysaccharide O‐chain backbone, by catalysing the addition of Gal to GlcNAc. To examine the potential role of this O‐chain structure in bacterial colonization of the host stomach, the mutation was introduced into H. pylori strain SS1 which is known to be capable of colonizing the gastric mucosa of mice. Compared with the parental strain, mutated SS1 was less efficient at colonizing the murine stomach.
Osteopontin induces angiogenesis of murine neuroblastoma cells in mice

Angiogenesis is an essential process for tumor growth and is regulated by tumor‐derived angiogenic cytokines. Osteopontin (OPN) is one of the cytokines produced by various tumor cells and is suggested to be involved in angiogenesis by upregulating endothelial cell migration in cooperation with vascular endothelial cell growth factor (VEGF). To provide evidence of OPN involvement in a causal role in tumor angiogenesis, we generated a stable transfectant from murine neuroblastoma C1300 cells to constitutively secrete high levels of murine OPN. The OPN mRNA expression and protein secretion were confirmed by RT‐PCR and ELISA, respectively. The biological activity of secreted OPN was determined with migration assay by using human umbilical vein endothelial cells (HUVEC). Transfection with OPN gene did not increase VEGF production and did not affect gene expression of other angiogenic factors confirmed by complementary DNA macroarray system. To demonstrate the effect of OPN on tumor‐induced angiogenesis in vivo, millipore chambers containing OPN‐transfected or control cells were implanted to the dorsal air sac of mice. The OPN‐transfected cells significantly induced neovascularization in comparison to the control cells in mice. Conclusively, these results provide direct evidence of OPN involvement in the role of tumor angiogenesis. © 2002 Wiley‐Liss, Inc.
Guanethidine-mediated destruction of ovarian sympathetic nerves disrupts ovarian development and function in rats.

Immunosympathectomy produced by treatment of newborn rats with antibodies to nerve growth factor (NGF) delays ovarian development and disrupts estrous cyclicity. While these alterations have been ascribed to loss of sympathetic neurons innervating the ovary, the treatment also causes partial loss of ovarian sensory innervation. The present experiments were undertaken to determine if selective interference with ovarian noradrenergic/sympathetic action would result in alterations of ovarian development similar to those caused by NGF antibodies (NGF Ab). We have used two approaches to disrupt catecholamine action on ovarian cells: 1) inhibition of beta-adrenoreceptors by local delivery of receptor blockers to the ovaries of juvenile rats; and 2) elimination of the sympathetic innervation by long term postnatal treatment with guanethidine (GD), an adrenergic neuron blocking agent. When GD is administered chronically it produces an autoimmune-mediated destruction of peripheral sympathetic nerves, without affecting cholinergic or sensory neurons. Of the receptor blockers tested, FM-24, a nonreversible antagonist, resulted in a sustained 70% decrease in available receptors throughout the 10-day period studied. In spite of this, the timing of puberty, assessed by the age at vaginal opening and first ovulation, was not delayed, suggesting that activation of the remaining receptors by an intact innervation suffices to maintain a normal noradrenergic influence. GD treatment initiated at the end of the first week of postnatal life and maintained for three weeks slowed the juvenile-peripubertal rate of body growth, delayed the time of vaginal opening and first ovulation, and disrupted subsequent estrous cyclicity, but did not affect the animals' fertility. The ovaries of GD-treated rats exhibited a striking loss of sympathetic (norepinephrine and neuropeptide Y) nerves but a normal sensory innervation (represented by fibers containing calcitonin gene-related peptide). The concentration of beta-adrenoreceptors in granulosa cells was reduced, suggesting follicular immaturity. Direct assessment of this inference by morphometric analysis of the ovaries revealed that follicular development was retarded. The progesterone and estrogen response of juvenile ovaries to gonadotropins in vitro were also reduced. At this time, circulating LH levels were slightly decreased, but neither LHRH content in the median eminence nor the LHRH response to prostaglandin E2 in vitro were affected. (ABSTRACT TRUNCATED AT 400 WORDS)
Body shape index: Sex-specific differences in predictive power for all-cause mortality in the Japanese population

Background While body mass index (BMI) is the most widely used anthropometric measure, its association with all-cause mortality is generally J-shaped or U-shaped. A body shape index (ABSI) is a recently formulated anthropometric measure that shows linear relationship to all-cause mortality, especially in Caucasian cohorts. We aimed to address the relationship between ABSI and all-cause mortality in Asians and to assess the influence of sex difference and of chronic kidney disease (CKD) on this relationship. Methods This was a longitudinal cohort study assessing the association of ABSI, BMI, waist circumference (WC), and waist-to-height ratio (WHtR) with all-cause mortality in a Japanese nationwide Specific Health Checkup database. The study enrolled 160,625 participants followed-up between 2008 and 2012. We calculated the all-cause mortality risk associated with a 1-standard deviation increase (+1SD) in ABSI, BMI, WC, or WHtR in cohorts stratified by sex and the presence of CKD. Results During the 4-year follow up, 1.3% of participants died. In men, ABSI (+1SD) significantly increased the risk for all-cause mortality after adjusting for other known risk factors including CKD; hazard ratio (HR) and 95% confidence intervals (CI) of non-CKD cohort, 1.30 (1.18 to 1.43), p<0.01; HR and 95%CI of CKD cohort, 1.16 (1.01 to 1.34), p = 0.04. In women, ABSI (+1SD) did not show significant association with all-cause mortality, especially in the CKD cohort; HR and 95% CI of non-CKD cohort, 1.07 (0.99 to 1.17), p = 0.09; HR and 95%CI of CKD cohort, 0.98 (0.84 to 1.14), p = 0.78. Conversely, BMI (+1SD) was associated with significantly lower risk in men, although minimal association was found in women. WC and WHtR showed little association with all-cause mortality. On stratification per ABSI quartiles, mortality risk increased linearly and significantly with ABSI in men, but not in women with CKD. Both BMI and WC showed significant but U-shaped association with mortality in the non-CKD cohort and in men with CKD. WHtR also showed significant U-shaped association with mortality in men. Conclusions In the Japanese population, ABSI showed significant and linear correlation with mortality risk in men but not in women, especially in the presence of CKD.