Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalence, correlates, and outcomes of cryptococcal antigen positivity among patients with AIDS, United States, 1986-2012.

BACKGROUND Cryptococcal meningitis (CM) is one of the most common causes of AIDS-related mortality worldwide, accounting for 33%-63% of all cases of adult meningitis in sub-Saharan Africa and >500 000 deaths annually. In sub-Saharan Africa, the World Health Organization recommends routinely screening AIDS patients with a CD4 count ≤100 cells/µL for cryptococcal infection. In the United States, there are no recommendations for routine screening. We aimed to determine the prevalence of cryptococcal infection and outcomes of those infected among people living with advanced AIDS in the United States, to inform updates in the prevention and management of CM. METHODS Using stored sera from participants in the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study from 1986 to 2012, we screened 1872 specimens with CD4 T-cell counts ≤100 cells/µL for cryptococcal antigen (CrAg) using the CrAg lateral flow assay. RESULTS The overall prevalence of CrAg positivity within the study population was 2.9% (95% confidence interval, .2%-3.8%). Results from multivariable analysis revealed that a previous diagnosis with CM and a CD4 count ≤50 cells/µL were significantly associated with CrAg positivity. Participants who were CrAg positive had significantly shorter survival (2.8 years) than those who were CrAg negative (3.8 years; P = .03). CONCLUSIONS The prevalence of cryptococcal infection among advanced AIDS patients in the United States was high and above the published cost-effectiveness threshold for routine screening. We recommend routine CrAg screening among human immunodeficiency virus-infected patients with a CD4 count ≤100 cells/µL to detect and treat early infection.
Intramural Injection with Botulinum Toxin Type A in Piglet Esophagus. The Influencer on Maximum Load and Elongation: A Dose Response Study

Abstract Introduction The treatment of esophageal atresia (OA) is challenging. The main goal is to achieve primary anastomosis. We have previously demonstrated in a pig model that intramural injection of botulinum toxin type A (BTX-A) resulted in significant elongation of the esophagus during tensioning until bursting point. The objectives of the present study were to investigate the influence of different amounts of intramural BTX-A on the stretch–tension characteristics and histological changes of the esophagus in piglets. Materials and Methods A total of 52 piglets were randomized to four groups receiving 2, 4, or 8 units/kg of BTX-A or isotonic saline (placebo). After a 1-hour of rest the esophagus was harvested and subjected to a stretch–tension test and histological examination to assess changes in the density of presynaptic vesicles in the nerve cells. Results Overall, 9 of the 52 animals were excluded from analysis due to problems with the stretch–tension test or death from anesthesia. The maximum loads were higher in the BTX-A groups (2 units/kg: +2.1 N; 4 units/kg: +1.3 N; 8 units/kg: +1.9 N) than the placebo (p = 0.046). There were no significant differences in percentage elongation, or histology. Conclusions This study demonstrated that injection of 2 units/kg BTX-A into a nonanastomosed esophageal wall resulted in a modest increase in the maximum load achieved before bursting; this may be due to the muscle-relaxant effect of BTX-A. BTX-A injection produced no significant effects on elongation or esophageal histology. The clinical usefulness of BTX-A in treatment of OA is still unclear.
Clinical Characteristics of Posterior and Lateral Semicircular Canal Dehiscence

Abstract The objective of this study was to evaluate the characteristic symptoms of and treatments for lateral semicircular canal dehiscence (LSCD) and posterior semicircular canal dehiscence (PSCD) and its proposed mechanism. A dehiscence acquired in any of the semicircular canals may evoke various auditory symptoms (autophony and inner ear conductive hearing loss) or vestibular symptoms (vertigo, the Tullio phenomenon, and Hennebert sign) by creating a “third mobile window” in the bone that enables aberrant communication between the inner ear and nearby structures. A PubMed search was performed using the keywords lateral, posterior, and semicircular canal dehiscence to identify all relevant cases. Our data suggest that PSCD, although clinically rare, is most likely associated with a high-riding jugular bulb and fibrous dysplasia. Patients may experience auditory manifestations that range from mild conductive to extensive sensorineural hearing loss. LSCD is usually associated with chronic otitis media with cholesteatoma.
Cardiovascular health of immigrant women: implications for evidence‐based practice

There is a dearth of information on the cardiovascular health of immigrant women. The present study analyzed the dataset from the National Population Health Survey to describe the modifiable CVD risk factors of Canadian immigrant women. Results indicated a statistically significant difference in modifiable CVD risk factors with respect to the country of birth, spoken language, and the length of time in Canada. The prevalence of smoking was significantly different across all income groups, with the lowest and middle income groups having the highest prevalence rate. Compared with their non‐white counterparts, the white immigrant women had a greater prevalence of obesity, hypertension, and smoking. Irrespective of race and country of birth, immigrant women tended to have worse CVD risk factors than non‐immigrant women. Age was the most important predictor of heart disease and hypertension. Implications of the study results for evidence‐based practice are discussed.
Prevalence of migraine and other headache in Finnish children starting school.

SYNOPSIS The prevalence of migraine and other headaches are assessed in Finnish seven year old school children. Four thousand two hundred thirty-five children were examined. 37.7% had headaches before starting school. Initially headaches occurred occasionally and were most often associated with febrile episodes. 3.2% of children had migraine.
Intracranial Vascular Malformations and Epilepsy

Abstract Among the spectrum of intracranial vascular malformations (IVMs), arteriovenous malformations (AVMs), and cavernous malformations (CCMs) are of particular importance for epilepsy. Seizures are a common mode of presentation for both conditions. Seizures may occur de novo or secondary to intracerebral hemorrhage. Timely imaging is thus crucial for patients with seizures and AVMs or CCMs. Patients with a first-ever AVM- or CCM-related seizure can now be considered to have epilepsy according to the International League Against Epilepsy criteria. Observational studies and case series suggest that between 45 to 78% of patients with AVM-related epilepsy and 47 to 60% of patients with CCM-related epilepsy may achieve seizure freedom through antiepileptic drugs (AEDs) alone. Invasive procedures are available although current evidence suggests that epilepsy-specific preintervention evaluations are underused. Randomized controlled trials and population-based studies have demonstrated worse short-term functional outcomes after routine intervention on unruptured AVMs or CCMs when compared with conservative management. The role of invasive therapy for IVM-related epilepsy has yielded mixed results. Case series have reported high estimates of seizure freedom although these results have not been replicated in controlled observational studies. Randomized controlled trials of immediate invasive therapy versus conservative management, in addition to usual care with AEDs and of different types of treatment and their timing, are warranted for AVMs and CCM-related epilepsy.
Cannabis Use and Reduced Risk of Insulin Resistance in HIV-HCV Infected Patients: A Longitudinal Analysis (ANRS CO13 HEPAVIH).

BACKGROUND Diabetes and insulin resistance (IR) is common in human immunodeficiency virus-hepatitis C virus (HIV-HCV)-coinfected patients, a population also concerned with elevated cannabis use. Cannabis has been associated with reduced IR risk in some population-based surveys. We determined whether cannabis use was consistently associated with reduced IR risk in HEPAVIH, a French nationwide cohort of HIV-HCV-coinfected patients. METHODS HEPAVIH medical and sociobehavioral data were collected (using annual self-administered questionnaires). We used 60 months of follow-up data for patients with at least 1 medical visit where IR (using homeostatic model assessment of insulin resistance [HOMA-IR]) and cannabis use were assessed. A mixed logistic regression model was used to evaluate the association between IR risk (HOMA-IR > 2.77) and cannabis use (occasional, regular, daily). RESULTS Among the 703 patients included in the study (1287 visits), 323 (46%) had HOMA-IR > 2.77 for at least 1 follow-up visit and 319 (45%) reported cannabis use in the 6 months before the first available visit. Cannabis users (irrespective of frequency) were less likely to have HOMA-IR > 2.77 (odds ratio [95% confidence interval], 0.4 [.2-.5]) after adjustment for known correlates/confounders. Two sensitivity analyses with HOMA-IR values as a continuous variable and a cutoff value of 3.8 confirmed the association between reduced IR risk and cannabis use. CONCLUSIONS Cannabis use is associated with a lower IR risk in HIV-HCV-coinfected patients. The benefits of cannabis-based pharmacotherapies for patients concerned with increased risk of IR and diabetes need to be evaluated in clinical research and practice.
How Is Baby Doing?: Growth of US and Canadian Infants Using the Centers for Disease Control and Prevention and World Health Organization Charts

Pediatricians typically use Centers for Disease Control and Prevention 2000 growth charts as reference tools to monitor and assess infant health and nutritional status. The World Health Organization 2006 growth charts, defined as a global growth standard, have been proposed for this use. To date, there are no longitudinal, prospective published data analyses for US and Canadian infants to evaluate the impact of adopting the World Health Organization charts. Because interventions are often driven by interpretation of weight percentiles, healthcare professionals need to be aware that the adoption of the World Health Organization 2006 growth charts may result in differences in infant weight categorization. The World Health Organization 2006 growth charts also include a body mass index chart for infants. Body mass index provides a reference used worldwide for classifying weight status in the older child and adult. However, it is not clear whether the body mass index chart is an appropriate screening tool to define infants younger than 2 years at risk for overweight and/or obesity.
Cortical HCN channels: function, trafficking and plasticity

The hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channels belong to the superfamily of voltage‐gated potassium ion channels. They are, however, activated by hyperpolarizing potentials and are permeable to cations. Four HCN subunits have been cloned, of which HCN1 and HCN2 subunits are predominantly expressed in the cortex. These subunits are principally located in pyramidal cell dendrites, although they are also found at lower concentrations in the somata of pyramidal neurons as well as other neuron subtypes. HCN channels are actively trafficked to dendrites by binding to the chaperone protein TRIP8b. Somato‐dendritic HCN channels in pyramidal neurons modulate spike firing and synaptic potential integration by influencing the membrane resistance and resting membrane potential. Intriguingly, HCN channels are present in certain cortical axons and synaptic terminals too. Here, they regulate synaptic transmission but the underlying mechanisms appear to vary considerably amongst different synaptic terminals. In conclusion, HCN channels are expressed in multiple neuronal subcellular compartments in the cortex, where they have a diverse and complex effect on neuronal excitability.
Prophylactic erythropoietin exacerbates ventilation‐induced lung inflammation and injury in preterm lambs

Erythropoietin (EPO) has been suggested as a potential treatment for bronchopulmonary dysplasia (BPD) in preterm infants. Ventilation‐induced lung injury (VILI) is a major cause of BPD in preterm neonates. We investigated whether early high‐dose EPO (i.v. 5000 IU kg−1) administration can reduce lung inflammation and injury resultant from VILI in ventilated preterm lambs. Early high‐dose EPO administration increased mRNA expression of early markers of lung inflammation and injury and systemic injury controls. Early high‐dose EPO worsened histological assessment of inflammation, airway wall thickness, haemorrhage and total injury compared to controls. Early high‐dose EPO may increase the incidence and severity of respiratory disease in ventilated, preterm neonates.
Cholinergic involvement in control of REM sleep paralysis

REM sleep, also known as dreaming sleep, is marked by intense cortical activation and absence of skeletal muscle tone, so-called REM sleep paralysis (atonia). It is commonly believed that REM sleep paralysis functions to prevent movement during vivid dreams. Indeed, REM sleep behaviour disorder – a neurological condition marked by violent dream enactment – results from loss of REM sleep paralysis. For the last 50 years, biologists have focused on the identification of brain mechanisms responsible for REM sleep. A majority of evidence suggests that a brainstem region known as the sublaterodorsal nucleus (SLD), also called the subcoeruleus, is important for REM sleep generation (Jouvet 1962). However, there is uncertainty concerning the chemical mechanisms by which the SLD triggers REM sleep phenomena. For example, some data suggest that cholinergic modulation of SLD cells underlies REM sleep generation, whereas, other data suggest that GABAergic disinhibition and glutamatergic excitation of SLD cells are critical for REM sleep control (Boissard et al. 2002; Lu et al. 2006). The recent study by Weng et al. (2014) provides a potentially new framework for understanding REM sleep control by showing that both cholinergic and glutamatergic processes operating within the SLD could be important for triggering REM sleep paralysis.
Diurnal inhibition of NMDA‐EPSCs at rat hippocampal mossy fibre synapses through orexin‐2 receptors

Orexins are well described for their excitatory actions on feeding‐ and arousal‐promoting brain centres; we describe here an inhibitory action of orexin‐A on synaptic NMDA receptors in hippocampus, a key area for synaptic plasticity and memory formation. Orexin‐A inhibited NMDA receptor responses at mossy fibre–CA3 connections through postsynaptically expressed orexin‐2 receptors, whereas a minor inhibition was observed at Schaffer collateral–CA1 connections, and no effect occurred at non‐mossy‐fibre excitatory synapses in CA3. Exogenously applied orexin‐A inhibited NMDA receptors in slices prepared during the rats’ resting phase, when endogenous orexin levels are low, but not in slices prepared in the active phase, when endogenous orexins peak. Through intraperitoneal administration of an orexin receptor antagonist during the active period, exogenous orexin‐A‐mediated inhibition was restored in the slice. Endogenous orexins suppress hippocampal synaptic NMDA receptor function in a diurnally cyclic manner, probably restraining synaptic plasticity and learning during certain periods of waking.
Tolerability of Fluoroquinolones in Management of Latent Tuberculosis in Liver Transplant Candidates.

TO THE EDITOR—Recently, Torre-Cisneros and colleagues [1] raised concerns about the safety of using levofloxacin for tuberculosis prophylaxis in liver transplant patients. In their study, 11 out of 33 patients in the levofloxacin arm developed adverse effects, including 5 with tenosynovitis. Only 18 (54.5%) of the patients completed tuberculosis prophylaxis with levofloxacin, and the study was suspended due to safety concerns. Their findings differ from our experience, which we would like to share here. At Stanford, our standard of care is to treat latent tuberculosis prior to liver transplant whenever possible. Regimens include isoniazid (INH) × 9 months, rifampin (RIF) × 4 months, or a fluoroquinolone (FQ) × 9 months when there is concern for potential INH or RIF hepatotoxicity. Per our retrospective chart review, 44 liver transplant candidates with positive tuberculosis interferon-gammarelease-assays were started on tuberculosis prophylaxis during the pretransplant period from 2006 to 2014. Twenty-five patients received FQ (17 levofloxacin and 8 moxifloxacin), 10 received INH, and 9 received RIF (Table 1). Adverse events were observed in 14 of 25 FQtreated patients, including 4 (16%) that developed musculoskeletal symptoms ranging from diffuse joint pain to unilateral tendinopathy. Importantly, only one patient with musculoskeletal symptoms required permanent discontinuation of the drug. In the other 3 cases, symptoms resolved after a temporary hold of the FQ, close monitoring, and rechallenge; these patients subsequently completed the full 9-month course of prophylaxis. One additional patient required discontinuation of FQ due to severe fatigue. An additional 6 patients received FQs post-transplant for tuberculosis prophylaxis; of these, only one reported diffuse joint pain but was ultimately one of 5 patients that completed prophylaxis; one did not complete prophylaxis due to death unrelated to tuberculosis (data not shown). We did not observe hepatotoxicity (defined as liver enzyme abnormalities greater than twice the upper limit of normal) linked to FQ use, either preor post-transplant. None of the treated patients have developed tuberculosis reactivation with a median follow-up time of 46 months (range 21–75). As Torre-Cisneros et al have noted [1], levofloxacin, although linked to tendinitis and tendon rupture, is generally a safe drug. Adverse drug reactions linked to FQs do not always require discontinuation of therapy [2]. In fact, previous studies record the discontinuation rate of levofloxacin in clinical trials at approximately 4% [3]. Our experience is that some adverse effects reported by patients on FQ may be nonspecific and, although they require an abundance of caution, may not always necessitate cessation of the Table 1. Outcomes and Adverse Events Associated With Latent Tuberculosis Treatment in Liver Transplant Candidates
The impact of national cultures on structured knowledge transfer

Purpose – The purpose of this paper is to explore the impact of national culture on the structured knowledge transfer from a US‐based (onshore) technical support center to an offshore support center in China.Design/methodology/approach – The research was conducted as an interpretive case study. Three techniques (i.e. document review, participant observation, and semi‐structured interviews) were employed for data collection in the field.Findings – The findings identify that knowledge tacitness, knowledge gaps, cultural and communication difficulties and weak relationships were the critical barriers to successful knowledge transfer in a cross‐cultural knowledge transfer context. It was found that, when a provider and a recipient are located in different individualism/collectivism, power distance, and uncertainty avoidance cultural dimensions, there will be a reduced likelihood of successful knowledge transfer in a structured knowledge transfer process. However, peer‐to‐peer help, close relationships and pro.
Native store‐operated calcium channels are functionally expressed in mouse spinal cord dorsal horn neurons and regulate resting calcium homeostasis

A previous study indicates that store‐operated calcium channels (SOCs) play a role in pain hypersensitivity. Here we report for the first time that SOCs are expressed and functional in spinal cord dorsal horn neurons. Using the small inhibitory RNA knockdown approach, we have demonstrated that Orai1 is necessary, and both STIM1 and STIM2 are important for SOC entry and SOC current in dorsal horn neurons. Our findings demonstrate that STIM1, STIM2 and Orai1 play an important role in resting Ca2+ homeostasis. Our results also indicate that SOCs are involved in the function of neurokinin 1 receptors and activation of SOCs produces an excitatory action in dorsal horn neurons. The present study reveals that a novel calcium signal mediated by SOCs is present in dorsal horn neurons and provides a potential mechanism for SOC inhibition‐induced central analgesia.
Direct inhibition of hypothalamic proopiomelanocortin neurons by dynorphin A is mediated by the μ‐opioid receptor

Dynorphin A inhibits anorexigenic hypothalamic proopiomelanocortin neurons by activating a potassium conductance. Although dynorphin A is considered selective for κ‐opioid receptors, the present data show that the dynorphin A‐induced potassium conductance is reversed by a μ‐opioid receptor‐selective antagonist and is absent in mice lacking functional μ‐opioid receptors. Thus, μ‐opioid receptors mediate the inhibition of proopiomelanocortin neurons caused by dynorphin A, consistent with other studies showing that κ‐opioid receptor‐selective agonists and antagonists can act at the μ‐opioid receptor when used at sufficiently high concentrations. The results indicate that if dynorphin A inhibits proopiomelanocortin neurons to increase food intake, it does so either by activating μ‐opioid receptors on these neurons or by inhibiting κ‐opioid receptors located in the presynaptic compartment of proopiomelanocortin neurons.
Direct excitation of parvalbumin‐positive interneurons by M1 muscarinic acetylcholine receptors: roles in cellular excitability, inhibitory transmission and cognition

Parvalbumin‐containing (PV) neurons from mouse CA1 hippocampus (HC) and prefrontal cortex exhibit a fast spiking phenotype in vitro. Within CA1, HC PV cells are mainly comprised of basket and bistratified cell types. Direct activation of muscarinic acetylcholine receptors (mAChRs) enhances excitability more in CA1 HC than in prefrontal cortex PV cells. mAChR‐induced excitation of CA1 PV cells occurs through direct activation of M1 mAChRs. Transgenetic deletion of M1 mAChRs from PV cells diminishes M1 mAChR expression and cholinergic excitation of CA1 PV cells. mAChR‐induced excitation exclusively in PV cells enhances GABAergic transmission in CA1 pyramidal cells. In vivo activation of M1 mAChRs in PV cells is important in recognition and working memory but not spatial memory.
PGC1‐α over‐expression prevents metabolic alterations and soleus muscle atrophy in hindlimb unloaded mice

Oxidative stress is widely considered a major cause of muscle loss not only in disuse but also in most chronic diseases, triggering carbonylation of proteins and activation of catabolic pathways involved in their degradation. Here we show that administration of an antioxidant prevents redox imbalance, but does not prevent activation of catabolic pathways and muscle atrophy. We indicate that alterations of oxidative metabolism, occurring in slow soleus muscle, are not just a consequence of disuse, but a major cause of activation of catabolic pathways and loss of mass. This conclusion is confirmed by the observation that muscle‐specific overexpression of PGC‐1α, a master regulator of mitochondrial biogenesis, prevents activation of catabolic systems and disuse muscle atrophy. These findings contribute to a better mechanistic understanding of disuse muscle loss.