Miracle-dz/UniFAR-FTUs huggingface dataset:
Voltage‐dependent amplification of synaptic inputs in respiratory motoneurones

• The processes whereby various excitatory and inhibitory inputs are integrated in spinal motoneurones during naturally occurring motor acts are not well understood, largely because there are amplifying mechanisms within the motoneurone that can control the effective strengths of the inputs. • Knowledge of these processes is important in understanding conditions such as motoneurone disease, or the spasticity that can follow spinal cord injury or stroke • Respiration is a natural motor act that continues normally under experimental conditions, and this study investigated, for the first time, the likely amplifying processes at work in respiratory motoneurones. • In phrenic motoneurones, which control the most important respiratory muscle, the diaphragm, we found that the mechanism most favoured by investigations in other motoneurones, the activation of persistent inward currents via calcium channels, appears to make a very small contribution. Instead, modulation of synaptic currents (through NMDA channels) appears to be more important.
Screening for alcoholism in New Zealand prison inmates

The Michigan Alcoholism Screening Test (MAST) was administered to 129 male and 102 female prison inmates. Use of the usual classification rule for the MAST resulted in 71% and 65% of the samples classified as “alcoholic”, far higher than the incidence of alcoholism in studies which used overseas prisoners. Item analyses conducted with these data, and reconsideration of data from previous New Zealand studies using the MAST, indicate that it is a sound detection instrument. The high incidence of alcoholism here therefore probably reflects the high sensitivity of the MAST by comparison with assessment procedures based on traditional alcoholism criteria, although New Zealand offender groups seem to score higher than comparable overseas offenders and the classification rule may be slightly too liberal. Accordingly, the use of a higher cut-off score seems appropriate when using MAST score in classifying individuals. A higher cut-off score still resulted in around 50–60% of inmates being classified as alcoholics. The likely benefits of rehabilitative efforts within the criminal justice system focusing on alcohol abuse are discussed.
Respiration rate monitoring methods: A review

Respiration rate is an important indicator of a person's health, and thus it is monitored when performing clinical evaluations. There are different approaches for respiration monitoring, but generally they can be classed as contact or noncontact. For contact methods, the sensing device (or part of the instrument containing it) is attached to the subject's body. For noncontact approaches the monitoring is performed by an instrument that does not make any contact with the subject. In this article a review of respiration monitoring approaches (both contact and noncontact) is provided. Concerns related to the patient's recording comfort, recording hygiene, and the accuracy of respiration rate monitoring have resulted in the development of a number of noncontact respiration monitoring approaches. A description of thermal imaging based and vision based noncontact respiration monitoring approaches we are currently developing is provided. Pediatr. Pulmonol. 2011; 46:523–529. © 2011 Wiley‐Liss, Inc.
The roles of Clostridium difficile and norovirus among gastroenteritis-associated deaths in the United States, 1999-2007.

BACKGROUND Globally, gastroenteritis is recognized as an important contributor to mortality among children, but population-based data on gastroenteritis deaths among adults and the contributions of specific pathogens are limited. We aimed to describe trends in gastroenteritis deaths across all ages in the United States and specifically estimate the contributions of Clostridium difficile and norovirus. METHODS Gastroenteritis-associated deaths in the United States during 1999-2007 were identified from the National Center for Health Statistics multiple-cause-of-death mortality data. All deaths in which the underlying cause or any of the contributing causes listed gastroenteritis were included. Time-series regression models were used to identify cause-unspecified gastroenteritis deaths that were probably due to specific causes; seasonality of model residuals was analyzed to estimate norovirus-associated deaths. RESULTS Gastroenteritis mortality averaged 39/1000000 person-years (11 255 deaths per year) during the study period, increasing from 25/1 000 000 person-years in 1999-2000 to 57/1 000 000 person-years in 2006-2007 (P < .001). Adults aged ≥ 65 years accounted for 83% of gastroenteritis deaths (258/1 000 000 person-years). C. difficile mortality increased 5-fold from 10/1 000 000 person-years in 1999-2000 to 48/1 000 000 person-years in 2006-2007 (P < .001). Norovirus contributed to an estimated 797 deaths annually (3/1 000 000 person-years), with surges by up to 50% during epidemic seasons associated with emergent viral strains. CONCLUSIONS Gastroenteritis-associated mortality has more than doubled during the past decade, primarily affecting the elderly. C. difficile is the main contributor to gastroenteritis-associated deaths, largely accounting for the increasing trend, and norovirus is probably the second leading infectious cause. These findings can help guide appropriate clinical management strategies and vaccine development.
A Review of Home Visits by Occupational Therapists in a Geriatric Assessment Unit

A review of occupational therapy home visits carried out from a geriatric assessment unit over a 6-month period is reported. There were 179 non-respite admissions of patients previously living at home and 33% of these patients had a pre-discharge occupational therapy home visit. Almost 90% of visits led to discharge home, with the provision of additional aids in 63% and the recommendation of other additional support arrangements in almost 80%. Only one of the 54 patients discharged home was considered to have had a failed discharge.
Two types of extracellular action potentials recorded with narrow‐tipped pipettes in skeletal muscle of frog, Rana temporaria

• Two types of extracellular action potentials, bi‐ and tri‐phasic, were recorded within the same fibre of skeletal muscle of frog. • Unlike bi‐phasic, tri‐phasic action potentials were very sensitive to the potassium channel blocker barium, and to a frequency of stimulation of muscle preparation. • It is suggested that currents generated in a specialized t‐tubular compartment of a muscle fibre form the third phase of these action potentials and studies of tri‐phasic action potentials may provide a new tool for evaluating the role of t‐tubules in skeletal muscle contractility.
Early-onset liver fibrosis due to primary hepatitis C virus infection is higher over time in HIV-infected men.

To the Editor—We were pleased to read the recent report by Vogel et al [1] of their study undertaken in response to our findings of rapid onset fibrosis during primary hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)–infected men [2]. Their study, plus the recent publication of the liver biopsy results of Bottieau et al [3], seems to cement that this unexpected outcome is a true consequence of primary HCV infection in HIV-infected men. We disagree, however, that their results using transient elastography demonstrate a sharp decrease in the fibrosis progression rate (FPR) to a clinically unimportant level soon after the primary HCV infection period has waned.
Rhythmic dendritic Ca2+ oscillations in thalamocortical neurons during slow non‐REM sleep‐related activity in vitro

• Sensory thalamocortical (TC) neurons are thought to play a crucial role in oscillatory brain activity typical of slow wave sleep. • Intrinsic oscillations in TC neurons rely upon expression of T‐type voltage gated Ca2+ channels. • We show that during sleep like firing patterns in TC neurons in brain slices, low threshold spikes mediated by T‐type channels produce global and rhythmic dendritic Ca2+ signals. In particular we show Ca2+ elevations in dendritic spine like structures during slow oscillatory activity. • We find that the duration of dendritic Ca2+ signals and the mean level of Ca2+ in TC neuron dendrites varies with oscillation frequency. • This global repetitive Ca2+ entry in to TC cells during oscillations could have significant implications for synaptic signalling and biochemical processes in these important sensory neurons.
A role for ATP in bronchoconstriction‐induced activation of guinea pig vagal intrapulmonary C‐fibres

• Activation of bronchopulmonary C‐fibres can lead to parasympathetic reflex bronchoconstriction, mucus secretion, as well as sensations of dyspnea and urge‐to‐cough. • We show here that a subset of bronchopulmonary C‐fibres innervating the airways is stimulated when airways are exposed to either histamine or methacholine. • We provide evidence that supports the hypothesis that the C‐fibre activation is secondary to bronchoconstriction and the consequential release of ATP. It is the released ATP that then stimulates the C‐fibres. • This provides a mechanism by which bronchoconstriction itself can lead to certain sensations, as well as parasympathetic reflexes. Dysregulation of this process could contribute to symptoms of airway inflammatory diseases
An outbreak of wild poliovirus in the Republic of Congo, 2010-2011.

BACKGROUND The Republic of Congo has had no cases of wild poliovirus type 1 (WPV1) since 2000. In October 2010, a neurologist noted an abnormal number of cases of acute flaccid paralysis (AFP) among adults, which were later confirmed to be caused by WPV1. METHODS Those presenting with AFP underwent clinical history, physical examination, and clinical specimen collection to determine if they had polio. AFP cases were classified as laboratory-confirmed, clinical, or nonpolio AFP. Epidemiologic features of the outbreak were analyzed. RESULTS From 19 September 2010 to 22 January 2011, 445 cases of WPV1 were reported in the Republic of Congo; 390 cases were from Pointe Noire. Overall, 331 cases were among adults; 378 cases were clinically confirmed, and 64 cases were laboratory confirmed. The case-fatality ratio (CFR) was 43%. Epidemiologic characteristics differed among polio cases reported in Pointe Noire and cases reported in the rest of the Republic of Congo, including age distribution and CFR. The outbreak stopped after multiple vaccination rounds with oral poliovirus vaccine, which targeted the entire population. CONCLUSIONS This outbreak underscores the need to maintain high vaccination coverage to prevent outbreaks, the need to maintain timely high-quality surveillance to rapidly identify and respond to any potential cases before an outbreak escalates, and the need to perform ongoing risk assessments of immunity gaps in polio-free countries.
‘When Ovaries Retire’: Contrasting Women’s Experiences with Feminist and Medical Models of Menopause

Western biomedical paradigms tend to treat health as the absence of disease and the appropriate functioning of biologic and psychophysiologic processes in the individual. Non-biomedical or lay concepts of health often focus on ability to function, or on social or spiritual well-being evidenced by physical fitness, energy, vitality, absence of pain, feeling healthy and the ability to maintain social relationships (Calnan, 1987). Differences between biomedical and lay concepts of health and illness are most pronounced when symptoms are amorphous and ambiguous. Scholarly works on menopausal syndrome traditionally treat the symptoms profile as nonspecific and psychological or psychosomatic (Kaufert, 1982), thus suggesting that there will be little agreement in lay discussions of the experience of menopause. Support group discussions suggest exactly the reverse. Members demonstrate remarkable consistency and agreement in their notions of symptom clusters, cause, and relief, but symptom profiles frequently are presented in highly subjective terms more in keeping with folk medical under-standings of health and illness. This article hopes to demonstrate the importance of using self-help groups to understand experientially constructed notions of health and illness and to argue for greater biomedical attention to lay understandings of menopausal syndrome.
Revealing Medicinal Plants That Are Useful for the Comprehensive Management of Epilepsy and Associated Comorbidities through In Silico Mining of Their Phytochemical Diversity

Abstract In silico techniques in drug discovery may rationalise and speed up the identification of lead molecules from nature. Drug discovery from medicinal plants has mostly been confined to indications in accordance with their ethnical use only. However, the availability of multiple phytoconstituents in medicinal plants suggests that these may be much more useful beyond their traditional uses and in the management of chronic diseases, along with their comorbidities. In this study, the computer programmes PASS and PharmaExpert were used to reveal the medicinal plants useful in the comprehensive management of epilepsy and associated psychiatric disorders based on the pleiotropic effects predicted for their phytoconstituents. In silico analysis revealed that seven of 50 medicinal plants from traditional Indian medicine possessed the desired pleiotropic effect, i.e., anticonvulsant, antidepressant, and nootropic activities. The majority of phytoconstituents from Passiflora incarnata were concurrently predicted to have the desired pleiotropic effects. Therefore, P. incarnata was pharmacologically validated using the pentylenetetrazole kindling mouse model. Behavioural and neurochemical evaluations confirmed the ameliorative role of P. incarnata in epilepsy and the associated depression and memory deficit. The pharmacological findings from this study propose that PASS and PharmaExpert may serve as good tools for the optimisation of the selection of plants based on their phytoconstituents for the treatment of different ailments, even beyond their traditional use.
Preoperative Evaluation of Patients with Lung Cancer Undergoing Thoracic Surgery

Surgery is currently the only potentially curative treatment modality for patients with early-stage non–small-cell lung cancer. Because of a high prevalence of chronic obstructive pulmonary disease in patients with lung cancer, they represent a special subset of patients for whom preoperative evaluation of cardiopulmonary status is especially important. The goal of preoperative evaluation of patients with lung cancer is to assess whether the neoplasm is surgically resectable and to estimate the risk of perioperative morbidity and mortality. Screening spirometry should be obtained in all patients. If the preoperative FEV1 is less than 60% of the predicted normal, predicted postoperative FEV1 (PPO-FEV1) should be estimated based upon the preoperative value and the functional contribution of the lung to be resected. Patients with PPO-FEV1 of more than 40% of predicted normal can tolerate pneumonectomy. In patients who appear borderline candidates for surgery based on static lung function criteria, cardiopulmonary exercise testing with measurement of maximum oxygen consumption (V̇O2max) can further help stratify patients in terms of their risk for perioperative mortality or complications of surgical resection.
Activation of mouse bronchopulmonary C‐fibres by serotonin and allergen‐ovalbumin challenge

• Mast cell‐derived serotonin is a principal mediator of allergic reactions in rodents. Serotonin can also be released from platelets during various pathological conditions. • Vagal C‐fibres innervating the respiratory tract can be subdivided into nodose (placodal) C‐fibres or jugular (neural crest) C‐fibres). Activation of vagal placodal and/or neural crest vagal C‐fibres probably contributes to the dyspnoea, cough and reflex parasympathetic drive commonly associated with serotonin. • Serotonin used different receptor subtypes to evoke strong action potential discharge in placodal (5‐HT3 receptors) versus neural crest (non‐5‐HT3 receptors)‐derived vagal C‐fibres in the mouse lung. • Mast cell derived serotonin may activate neural crest C‐fibres, but did not stimulate placodal C‐fibres. • The effect of extracellular serotonin on vagal afferent activation therefore depends on its cellular source and the C‐fibre phenotype.
Electromagnetic inductance plethysmography to measure tidal breathing in preterm and term infants

Tidal breathing measurements which provide a non‐invasive measure of lung function in preterm and term infants are particularly useful to guide respiratory support. We used a new technique of electromagnetic inductance plethysmography (EIP) to measure tidal breathing in infants between 32 and 42 weeks postconceptional age (PCA). Tidal breathing was measured in 49 healthy spontaneously breathing infants between 32 and 42 weeks PCA. The weight‐corrected tidal volume (VT) and minute volume (MV) decreased with advancing PCA (VT 6.5 ± 1.5 ml/kg and MV 0.44 ± 0.04 L/kg/min at 32–33 weeks, respectively; 6.3 ± 0.9 ml/kg and 0.38 ± 0.02 L/kg/min at 34–36 weeks; and 5.1 ± 1.1 ml/kg and 0.28 ± 0.02 L/kg/min at term, VT P < 0.001 and MV P < 0.01 for 32–33 weeks PCA vs. term; VT P = 0.016 and MV P = 0.015 for 34–36 weeks PCA vs. term). Respiratory frequency and the phase angle decreased significantly with advancing PCA but the flow parameter tPTEF/tE did not change significantly. Using a new technique to measure tidal breathing parameters in newborn infants, our data confirms its usability in clinical practice and establishes normative data which can guide future respiratory management of newborn infants. Pediatr Pulmonol. 2013; 48:160–167. © 2012 Wiley Periodicals, Inc.
Ageing and cardiorespiratory response to hypoxia

• A previous study showed that an older age could be associated with a lower risk of severe altitude‐induced diseases. • This work combines a cross‐sectional study including 4675 subjects and a longitudinal study on 30 subjects. • It shows that ageing is associated with a blunting of cardiac chronotropic function and an increase in ventilatory response leading to maintenance of arterial O2 saturation in hypoxia. • These adaptive responses to hypoxia with ageing are blunted by menopause but can be maintained with endurance training. • The cardiac and ventilatory adaptations allow older people to challenge hypoxia similarly to younger ones when performing moderate exercise.
Evolution of gene expression changes in newborn rats after mechanical ventilation with reversible intubation

Mechanical ventilation (MV) is life‐saving but potentially harmful for lungs of premature infants. So far, animal models dealt with the acute impact of MV on immature lungs, but less with its delayed effects. We used a newborn rodent model including non‐surgical and therefore reversible intubation with moderate ventilation and hypothesized that there might be distinct gene expression patterns after a ventilation‐free recovery period compared to acute effects directly after MV. Newborn rat pups were subjected to 8 hr of MV with 60% oxygen (O2), 24 hr after injection of lipopolysaccharide (LPS), intended to create a low inflammatory background as often recognized in preterm infants. Animals were separated in controls (CTRL), LPS injection (LPS), or full intervention with LPS and MV with 60% O2 (LPS + MV + O2). Lungs were recovered either directly following (T:0 hr) or 48 hr after MV (T:48 hr). Histologically, signs of ventilator‐induced lung injury (VILI) were observed in LPS + MV + O2 lungs at T:0 hr, while changes appeared similar to those known from patients with chronic lung disease (CLD) with fewer albeit larger gas exchange units, at T:48 hr. At T:0 hr, LPS + MV + O2 increased gene expression of pro‐inflammatory MIP‐2. In parallel anti‐inflammatory IL‐1Ra gene expression was increased in LPS and LPS + MV + O2 groups. At T:48 hr, pro‐ and anti‐inflammatory genes had returned to their basal expression. MMP‐2 gene expression was decreased in LPS and LPS + MV + O2 groups at T:0 hr, but no longer at T:48 hr. MMP‐9 gene expression levels were unchanged directly after MV. However, at T:48 hr, gene and protein expression increased in LPS + MV + O2 group. In conclusion, this study demonstrates the feasibility of delayed outcome measurements after a ventilation‐free period in newborn rats and may help to further understand the time‐course of molecular changes following MV. The differences obtained from the two time points could be interpreted as an initial transitory increase of inflammation and a delayed impact of the intervention on structure‐related genes. Pediatr Pulmonol. 2012; 47:1204–1214. © 2012 Wiley Periodicals, Inc.
Peroxisome proliferator‐activated receptor γ coactivator 1‐α gene transfer restores mitochondrial biomass and improves mitochondrial calcium handling in post‐necrotic mdx mouse skeletal muscle

• Mitochondria are increasingly implicated in the pathogenesis of Duchenne muscular dystrophy (DMD). However, the extent to which the multiple facets of mitochondrial function are altered remains uncertain due to the lack of detailed assessment. • Peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC1α) was recently shown to improve muscle pathology in dystrophic muscle. However, the mechanisms are not fully elucidated. • This study provides novel information on mitochondrial dysfunction in DMD namely that (i) loss of mitochondrial biomass precedes overt respiratory abnormalities, (ii) mitochondrial H2O2 metabolism is improved at a time when no oxidative damage is detectable in the muscle, and (iii) susceptibility to permeability transition pore (PTP) opening is increased, which has only been inferred in the past, but never actually measured. • This study also provides new mechanistic information regarding the beneficial effects of PGC1α overexpression upon dystrophic muscles, namely that PGC1α not only increases mitochondrial biomass but also reduces PTP opening, improves mitochondrial Ca2+ handling and reduces the activation of Ca2+ and mitochondria‐dependent proteases in muscles of mdx mice. These mechanisms were not examined in previous investigations, which had largely attributed the improved histopathology after PGC1α therapy to utrophin upregulation.
Association of TMEM16A chloride channel overexpression with airway goblet cell metaplasia

• Chloride channels are important for proper hydration of the airway surface. • TMEM16A protein is an important component of calcium‐activated chloride channels. • Interleukin‐4, a cytokine that induces mucous cell metaplasia, also upregulates calcium‐dependent chloride secretion in human bronchial epithelial cells. • In bronchial epithelial cells treated with interleukin‐4, we found that TMEM16A protein becomes highly expressed in goblet but not in ciliated cells. • Upregulation of TMEM16A by interleukin‐4 may be important for secretion and proper expansion of mucins.
Expression of postsynaptic Ca2+‐activated K+ (SK) channels at C‐bouton synapses in mammalian lumbar α‐motoneurons

Spinal cord α‐motoneurons display strong membrane immunoreactivity (IR) against small‐conductance calcium‐activated potassium channel (SK) isoform SK2, and a specific subpopulation of motoneurons also express SK3‐IR. Rat α‐motoneurons expressing SK3‐IR are significantly smaller, have significantly longer after‐hyperpolarization half‐decay time, significantly larger after‐hyperpolarization amplitude and significantly slower axon conduction velocity than α‐motoneurons that lack SK3‐IR. Motoneuron pools innervating slow‐twitch muscles have a higher percentage of SK3‐IR α‐motoneurons than those innervating fast‐twitch muscles. Expression of SK3 may contribute to variability in after‐hyperpolarization duration and amplitude across different types of rat α‐motoneurons and may be a molecular factor differentiating between slow‐ and fast‐type motoneurons. In the soma and proximal dendrites of α‐motoneurons, large clusters of SK2 and SK3 channel subunits appose cholinergic C‐boutons and colocalize with muscarinic type 2 receptors and Kv2.1 channels, which suggests a novel cellular mechanism for state‐dependent regulation of neuronal excitability.