Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Rho kinase pathway in chondroitin sulfate proteoglycan‐mediated inhibition of neurite outgrowth in PC12 cells

Activation of the Rho kinase (ROCK) pathway has been associated with inhibition of neurite regeneration and outgrowth in spinal cord injury. Growth‐inhibitory substances present in the glial scar such as chondroitin sulfate proteoglycans (CSPGs) have been shown to create a nonpermissive environment for axon regeneration that results in growth cone collapse. In this study, an in vitro model was developed in nerve growth factor‐differentiated PC12 cells where the Rho/ROCK pathway was modulated by CSPG. CSPG elicited concentration‐dependent inhibition of neurite outgrowth in PC12 cells, which was reversed by ROCK inhibitors such as fasudil, dimethylfasudil, and Y27632. Further studies on the interactions of CSPG with ROCK inhibitors revealed that the modulation of ROCK by CSPG is noncompetitive in nature. It was also observed that ROCK inhibitors increased neurite outgrowth in undifferentiated PC12 cells, indicating constitutive ROCK activity in the cells. Analysis of signaling pathways demonstrated that the effect of CSPG increases the phosphorylation of myosin phosphatase, a substrate immediately downstream of ROCK activation. Fasudil, dimethylfasudil, and Y27632 inhibited the phosphorylation of myosin phosphatase induced by CSPG with rank order potencies comparable to those observed in the neurite outgrowth assay. In addition, ROCK inhibitors reversed cofilin phosphorylation induced by CSPG with similar rank order potencies. Taken together, our data demonstrate that the interaction of CSPG with the ROCK pathway involves downstream effectors of ROCK such as myosin phosphatase and cofilin. © 2008 Wiley‐Liss, Inc.
Improving Health Care for Mental and Substance Use Conditions: A Framework for Bridging the Quality Chasm

This article highlights selected findings of the 2005 Institute of Medicine (IOM) report on quality problems in health care for mental and substance use (M/SU) conditions and proposes a new framework for organizing and implementing recommendations of the IOM or any organization that would study and report on significant issues in health care administration, delivery, financing, policy, and research. The model, depicted as a "Quality Cube," proposes three essential axes of consideration for implementing broad-scale improvements in health care for M/SU and other health conditions: (a) quality-improvement aims (what goals need to be accomplished), (b) agents (who should take responsibility for their achievement), and (c) actions (how quality aims should be pursued).
Criteria for early onset of action of an antidepressant from the clinical trial logistics point of view – methodological considerations

Several authors have recommended various criteria for investigating the early onset of action (EOA) of an antidepressant. In this article some of the criteria that are most often mentioned were reviewed, considering clinical study design and logistics of the trial. The advantages and disadvantages of individual criteria are listed. Despite the existence of many recommendations, only a very limited number of them originate from scientific sources such as large databases. Moreover, some of the recommendations need to be viewed as suggestions as they do not originate from experience and data analysis. Individuals designing clinical trials to investigate EOA are left to try out different approaches, which are far from being internationally accepted and regulated. Copyright © 1999 Whurr Publishers, Ltd.
Global impact of antiretroviral therapy-associated diarrhea.

Dear Editor, Side effects of antiretroviral therapy (ART) still remain a formidable issue for patients globally. In resource-limited settings, side effects are a major risk for lack of treatment adherence. 1 Diarrhea remains one of the leading side effects seen in ART, and it contributes significantly to lack of treatment adherence in patients experiencing it. 2 Historically, diarrhea in HIV-positive patients was due to opportunistic infections or HIV itself. 3 However, since the advent of highly active antiretroviral therapy (HAART), diarrhea is now thought to be primarily due to antiretrovirals. 4 It is noted that among the major classes of antiretrovirals, protease inhibitors (and in particular ritonavir) seem to carry the greatest risk of for ART-induced diarrhea. 5 Two recent reviews highlight the importance of ART-associated diarrhea in HIV-infected patients, and focus on data regarding ritonavir-associated diarrhea. Macarthur and DuPont 6 found that up to 18% (range, 2‐18%) of patients on ritonavir-boosted protease inhibitor regimensexperiencegrade2‐4diarrhea(grade1 =mild;grade 2 =moderate; grade 3 =severe; grade 4 =life threatening). Wegzyn et al. 7 reported a diarrhea incidence of 15.5% in patients taking ritonavir-boosted lopinavir as part of their ART. These results mimic a previous review that demonstrated up to 19% (range, 2‐19%) of patients experience diarrhea on similar regimens. 2 Given that none of the current re
C‐terminal region‐dependent change of antibody‐binding to the Eighth Reelin repeat reflects the signaling activity of Reelin

Reelin is a secreted glycoprotein that plays pivotal roles in the development and function of the brain, but how it activates downstream intracellular signaling is not fully understood. We have recently reported that the highly conserved C‐terminal region (CTR) of Reelin is required for its full signaling activity, although the underlying mechanism remains unknown. During biochemical study of Reelin, we serendipitously found that one commercially available anti‐Reelin antibody G20 can bind to CTR‐lacking mutant Reelin proteins, but not wild‐type Reelin, on Western blotting. The G20 epitope resides in the last 19 residues of Reelin‐repeat 8 (RR8), and neither posttranslational modification nor proteolysis can explain this effect. Furthermore, when an unrelated sequence, such as FLAG‐tag, is inserted between RR8 and CTR, the reactivity of the corresponding antibody greatly decreases. These results suggest that RR8 and CTR form a tight structure that makes the surrounding sequence inaccessible to an antibody. Taking advantage of this phenomenon, we show the existence of CTR‐lacking Reelin isoform in vivo for the first time and estimate its contribution to the total amount of secreted Reelin. Importantly, the extent to which Reelin mutants react with G20 is inversely correlated with their signaling activity, indicating that the CTR‐induced structural change of RR8 is a prerequisite for downstream signaling activation, presumably via binding to a certain neuronal membrane molecule(s). © 2009 Wiley‐Liss, Inc.
Heart Rate Dynamics during Shambhavi Mahamudra- A Practice of Isha Yoga

This study was designed to quantify and compare the instantaneous changes of heart rate variability (HRV) during Shambhavi Mahamudra, a practice of Isha yoga. It includes major stages viz. Sukha pranayam, 'AUM' chanting, rapid breathing, and relaxed sitting. The standard lead II electrocardiogram (ECG) signals were acquired from eight healthy, yoga practitioners while performing various stages of Shambhavi Mahamudra. The short-term HRV were extracted from ECG, and analyzed using time, frequency-domain and Poincaré plot methods. The results showed a combination of increased sympathetic tone and withdrawal of vagal tone during Sukha pranayam, an increased sympathetic tone during `AUM' chanting, and withdrawal of vagal tone during rapid breathing. The HRV descriptors were not significantly different during relaxed sitting.
It's More Than Just Candy: Important Relationships Between Nutrition and Oral Health

Oral problems can affect and be affected by both diet and systemic nutrition. Dental caries (tooth decay) remains the most prevalent disease of children: 7 times more common than hay fever and five times more common than childhood asthma. The mouth is an early indicator of general health and nutritional status; clinical signs and symptoms of nutritional and other health problems frequently appear first in the oral cavity. Conversely, oral problems can have profound effects on nutritional status. Emerging research is revealing even more important relationships between nutrition and oral health issues and chronic health conditions such as heart disease, diabetes, and immune-compromising conditions. Health care professionals should help their patients by asking patients about oral health concerns and referring patients for dental consults when indicated. Promoting good oral health as well as good nutrition is essential to optimal overall health status
The quality of written instructions for dental prostheses in China.

PURPOSE To investigate the quality of written instructions for dental prostheses in China, including metal-ceramic fixed restorations and removable partial dentures (RPDs). MATERIALS AND METHODS A total of 1600 prepiloted questionnaires were distributed to five major commercial dental laboratories in different regions in China. The opinions of dental technicians on the written instructions provided by dentists were investigated. In addition, this study also revealed the technicians' responses to poorly written instructions. RESULTS Seven percent of the written instructions clarified the disinfection status of the impressions or casts, while 32% of the instructions provided general patient information (e.g., gender and age). In cases of metal-ceramic fixed restorations, percentages of written instructions specifying shade, ceramic veneering area, and margin design were 72%, 20%, and 9%, respectively. In fixed partial denture cases, 60% of written instructions provided the number of pontics, while 22% specified the pontic design. In the case of RPDs, 90% of instructions showed the type and position of clasps, 88% provided connector design, while 68% mentioned information regarding the artificial teeth. Dental technicians claimed that 78% of the written instructions involved were inadequately prescribed to some extent, but only about one-third of them would contact dentists for clarification. CONCLUSIONS Written instructions are not well prescribed in many cases. This situation may jeopardize the quality of prosthodontic treatment. It is necessary to shape responsible policy and mandatory professional guidelines for prosthodontic treatment procedures including dental laboratory services.
Candida albicans adherence to denture base material: chemical disinfection and the effect of acquired salivary pellicle formation.

PURPOSE The aim of this study was to evaluate the effect of 1% sodium hypochlorite (H1%) and 4% chlorhexidine gluconate (CG4%) on the adhesion of Candida albicans to denture base acrylic resins, as well as to verify the effect of the acquired salivary pellicle (ASP) formation on this process. MATERIALS AND METHODS A total of 300 acrylic specimens were immersed in distilled water (control) (n = 100), H1% (n = 100), or CG4% (n = 100) for 30 days. Twenty specimens were used in each experimental period (0, 1, 7, 15, 30 days). At the end of disinfection testing periods, 10 specimens of each group were exposed to human whole saliva to simulate ASP formation, and then all specimens were incubated with C. albicans ATTC 90028. Microorganism adhesion was analyzed by fluorescence microscopy, after staining with Acridine orange. RESULTS In the 30(th) disinfection cycle in relation to baseline, the H1% or CG4%, without ASP formation, reduced the C. albicans adhesion by approximately 80%; however, with ASP, this reduction after disinfection with H1% was higher (88%). The presence of ASP resulted in higher reduction of adhered fungal cells in comparison to resin without ASP, at the 1(st) H1% or CG4% disinfection cycle, as well as at 30(th) H1% disinfection cycles. CONCLUSIONS Our results suggest that the presence of saliva might influence the adhesion of C. albicans and improve the effectiveness of methods to reduce fungal adhesion.
Using the Biopsychosocial Model to Understand the Health Benefits of Yoga

Yoga is widely practiced as a means to promote physical, psychological and spiritual well-being. While a number of studies have documented the efficacy of yoga for functioning in healthy individuals and those experiencing illness or pain, biopsychosocial effects have not been detailed. We propose an analogue between the physical, psychological and spiritual effects of practice as espoused in yoga traditions, and the biopsychosocial model of health. To this end, we present a review and conceptual model of the potential biopsychosocial benefits of yoga, which may provide clues regarding the possible mechanisms of action of yoga upon well-being. Physical systems activated through yoga practice include musculoskeletal, cardiopulmonary, autonomic nervous system and endocrine functioning. Psychological benefits include enhanced coping, self-efficacy and positive mood. Spiritual mechanisms that can be understood within a Western medical model include acceptance and mindful awareness. We present empirical evidence that supports the involvement of these domains. However, additional well-conducted research is required to further establish the efficacy of yoga for health states, and to understand how posture, breath and meditative activity affect the body, mind and spirit.
Study of Lateral Epicondylitis (Tennis Elbow) Using the Health Improvement Network Database

Background Lateral epicondylitis has been studied mainly in work related and occupational groups, however little is known about the incidence or demographic associations in the general population. We have undertaken a large study using The Health Improvement Network (THIN) database to examine the epidemiology of lateral epicondylitis in the UK general population. Methods Diagnoses of lateral epicondylitis between 1987 and 2006 were used to calculate the incidence stratified by age, gender, deprivation score, UK health authority, and year. The age standardised rates for lateral epicondylitis in the UK were calculated with reference to the European Standard Population. Results The incidence rate of lateral epicondylitis was 2.45 per 1000 person-years. This was more common in males than females (males 2.63, females 2.55 per 1000 person-years, p < 0.001). After direct standardization, the age adjusted rates were 2.38 for males and 2.43 for females. The highest incidence rate of 7.35 per 1000 person-years was found in the age group 45-50 years. Regional distribution of the incidence rates showed a fairly even spread across 13 UK Health Authorities with the exception of London where incidence rates were significantly lower (1.75 per 1000 person-years, p < 0.001). Social deprivation was assessed using the Townsend score. The least deprived areas of the population had the highest incidence rates (2.86 per 1000 person years). Conclusions Our study represents the largest general population study of lateral epicondylitis reported to date. The results obtained provide the clinician with a better understanding of the epidemiology of lateral epicondylitis in the community.
Adolescent and Adult HIV Providers ’ Definitions of HIV-Infected Youths ’ Successful Transition to Adult Care in the United States

It is important for both individualand population-level health that HIV-infected individuals progress through the Care Continuum. However, HIV-infected youth frequently disengage from care during transition from pediatric/ adolescent to adult care; only 50% remain in adult care after 1 year. Understanding how providers define and approach a successful healthcare transition can improve the delivery of HIV-related services during critical years of HIV treatment. We conducted 58 staff interviews across 14 Adolescent Trials Network clinics (n = 30) and 20 adult clinics (n = 28). We used the constant comparative method to examine how providers defined and approached youths’ successful transition. Providers identified four components critical to successful transition: (1) clinical outcomes (e.g., medication adherence and viral suppression); (2) youth knowing how to complete treatment-related activities (e.g., refilling prescriptions and making appointments); (3) youth taking responsibility for treatment-related activities and their overall health (e.g., ‘‘when they stop reaching out to the adolescent [clinic] to solve all their problems.’’); and (4) youth feeling a connection and trust toward the adult clinic (e.g., ‘‘they feel safe here’’), with some providers even prioritizing connectedness over clinical outcomes (e.g., ‘‘Even if they’re not taking meds but are connected [to care], .that’s a success.’’). The identification of key components of successful transition can guide focused interventions and resources to improve youth maintenance in the HIV Care Continuum as they transition to adult care. Identifying what facilitates successful transitions, and the gaps that interventions can target, will help to ensure HIV-infected youth remain healthy across their lifespan.
Atypical Antipsychotics in the Treatment of Posttraumatic Stress Disorder

ObjectivesThis study reviewed extant published articles on the efficacy and safety of atypical antipsychotics for the treatment of posttraumatic stress disorder (PTSD). MethodsWe performed a literature search using PubMed, EMBASE, and the Cochrane database in January 2013. Selection criteria for this review included prospective, controlled studies using validated rating scales of PTSD symptoms in the management of PTSD. ResultsA total of 12 prospective, controlled studies were included in this review. This review found that atypical antipsychotics are effective and safe in treating PTSD, although there were some negative findings. In particular, atypical antipsychotics also seem to be effective in treating anxiety, depression, and psychotic symptoms frequently accompanied by PTSD. ConclusionsThis review found that atypical antipsychotics seemed to be effective and tolerable in the management of PTSD, although the evidence was limited.
Dasatinib sensitizes primary chronic lymphocytic leukaemia lymphocytes to chlorambucil and fludarabine in vitro

The dual c‐abl/Src kinase inhibitor, dasatinib, utilized to treat chronic myeloid leukaemia (CML) when used at clinically attainable sublethal concentrations, synergistically sensitized primary chronic lymphocytic leukaemia (CLL) lymphocytes to chlorambucil and fludarabine. In contrast, dasatinib alone demonstrated toxicity to CLL lymphocytes at concentrations that are generally not clinically attainable. Dasatinib resistance and poorer dasatinib‐mediated sensitization to chlorambucil and fludarabine was associated with higher expression of c‐abl protein levels. In contrast, chlorambucil and fludarabine resistance correlated with basal p53 protein levels. Moreover, Western blot analysis after in vitro treatment of primary CLL lymphocytes with dasatinib, chlorambucil and/or fludarabine, showed that dasatinib: (i) inhibited c‐abl function (e.g. downregulation of c‐abl protein levels and decreased the phosphorylation of a c‐abl downstream target, Dok2), (ii) decreased chlorambucil/fludarabine induced accumulation of p53 protein levels, (iii) altered the response to chlorambucil/fludarabine induced DNA‐damage as evidenced by an increase in chlorambucil/fludarabine‐induced H2AX phosphorylation, and (iv) accentuated the c‐abl downregulation induced by chlorambucil/fludarabine. Our results suggest that dasatinib in combination with chlorambucil or fludarabine may improve the therapy of CLL.
The Relevance of Smoking and Nicotine to Clinical Psychiatry

The recent World Bank report fl] noted the important role of tobacco as a cause of mortality and morbidity, and also predicted that tobacco will become the greatest contributing risk factor to mortality over the next decades. While these trends are alarming enough, the issues concerning tobacco use are of even greater importance to people with many of the major psychiatric disorders (such as depression, bipolar disorder and schizophrenia) as cigarette consumption tends to be both more common and higher than in the general population [2].
THE PHARMACOLOGY OF MERCURY

A considerable volume of information has been accumulated on the behavior of mercury in the body. Valuable contributions to the pathologic changes produced in the liver, kidney and other organs have also been made by cases of poisoning in man and by experimental studies on animals. Very few reports, however, have appeared on the pharmacologic action of mercury. Dreser 1 studied the action of various compounds of mercury on the isolated heart. More recently Mueller, Schoeler and Schrauth 2 reported experiments on the effects of several organic preparations on the circulation and respiration in cats in which injection was made intravenously. During the past year Kleitman and I carried out experiments with compounds of mercury on different animals and on the isolated heart of the frog and turtle. We have also studied the effect of different substances on the action of mercury, giving some attention to its absorption from the
Ischemia‐induced changes in glucagon‐like peptide‐1 receptor and neuroprotective effect of its agonist, exendin‐4, in experimental transient cerebral ischemia

Glucagon‐like peptide‐1 receptor (GLP‐1R) protects against neuronal damages in the brain. In the present study, ischemia‐induced changes in GLP‐1R immunoreactivity in the gerbil hippocampal CA1 region were evaluated after transient cerebral ischemia; in addition, the neuroprotective effect of the GLP‐1R agonist exendin‐4 (EX‐4) against ischemic damage was studied. GLP‐1R immunoreactivity and its protein levels in the ischemic CA1 region were highest at 1 day after ischemia/reperfusion (I/R). At 4 days after I/R, GLP‐1R immunoreactivity was hardly detected in CA1 pyramidal neurons, and its protein level was lowest. GLP‐1R protein level was increased again at 10 days after I/R, and GLP‐1R immunoreactivity was found in astrocytes and GABAergic interneurons. In addition, EX‐4 treatment attenuated ischemia‐induced hyperactivity, neuronal damage, and microglial activation in the ischemic CA1 region in a dose‐dependent manner. EX‐4 treatment also induced the elevation of GLP‐1R immunoreactivity and protein levels in the ischemic CA1 region. These results indicate that GLP‐1R is altered in the ischemic region after an ischemic insult and that EX‐4 protects against ischemia‐induced neuronal death possibly by increasing GLP‐1R expression and attenuating microglial activation against transient cerebral ischemic damage. © 2011 Wiley‐Liss, Inc.
Successful Disinfection of Needleless Access Ports: A Matter of Time and Friction

Abstract Background There is controversy as to whether the design of the needleless access port or the method used to clean it prior to access impacts successful disinfection. The authors studied the disinfection effectiveness for needleless access ports. Method The ports of 4 models of needleless access ports were inoculated with bacteria. The ports were disinfected for 15 seconds with 70% alcohol alone or 3.15% chlorhexidine/70% alcohol (Chlorascrub, PDI, Orangeburg, NY). Saline flush solutions were collected and cultured. Results Disinfection with either 70% alcohol alone or with 3.15% chlorhexidine/70% alcohol for 15 seconds was effective. Conclusions All models of needleless access ports were effectively disinfected using these two methods.