Miracle-dz/UniFAR-FTUs huggingface dataset:
Variation factors of paraoxonase in blood and in HDL lipoproteins in dairy cow

Paraoxonase-1 (PON) is an antioxidant enzyme synthesized by liver and mainly associated with high density lipoproteins (HDL). Aim of this study was to investigate the alterations of PON1 activity in plasma (pPON) or bound to HDL (HDL-PON) in relation to inflammatory conditions and physiological stages. Between -30 to +300 days from calving, 9 cows were monitored for metabolic and inflammatory profiles, milk yield, body condition score and feed intake. Cows were divided in 2 groups based on their response to postpartum inflammatory stimulus (high and low Liver Functionality Index: HI-LFI and LO-LFI). pPON decreased after calving (P<0.05) and was directly correlated with milk yield (r=0.48; P<0.01), albumins and other indirect indexes of negative acute phase proteins (-APP: cholesterol and retinol binding protein). On the contrary, pPON was inversely related with the +APP (haptoglobin, ceruloplasmin) and related indexes (bilirubin, ROM). The correlation between pPON and HDL-PON was low. After calving, the HI-LFI vs LO-LFI group had higher –APP and pPON levels, lower HDL-PON level and displayed better performances. Overall results demonstrated that pPON has a similar behavior in comparison to –APP, confirming previous data. The results suggested that pPON activity could represent an useful marker to assess the severity of postpartum inflammatory phenomena and their consequences. Fattori di variazione della paraoxonasi plasmatica e nelle lipoproteine HDL nella bovina da latte La paraoxonasi-1 (PON1) e un enzima antiossidante di sintesi epatica associato principalmente alle lipoproteine ad alta densita (HDL). Scopo dello studio e stato quello di valutare le variazioni di PON1 nel plasma (pPON) o nelle HDL (HDL-PON) in relazione allo stato infiammatorio ed allo stadio fisiologico. Nove bovine sono state controllate tra -30 e +300 giorni dal parto per: marcatori ematici dello stato infiammatorio, produzione di latte, stato di ingrassamento, ingestione di alimenti. Le bovine sono state divise in 2 gruppi sulla base della loro risposta allo stimolo infiammatorio post partum (alto e basso Liver Functionality Index: HI-LFI e LO-LFI). La pPON ha mostrato un calo temporaneo dopo il parto (P<0,05) e la sua attivita e risultata correlata con la produzione di latte (r=0,48; P<0,01), le albumine ematiche ed altri indici indiretti delle proteine negative di fase acuta (-APP: colesterolo, retinolo). Invece correlazioni inverse sono state osservate con le +APP (apto-globina e ceruloplasmina) ed altri indici correlati (es. bilirubina, ROM). La correlazione tra pPON e HDL-PON e risultata modesta. Dopo il parto le bovine HI-LFI (vs LO-LFI), oltre a livelli piu alti di -APP e di pPON, hanno mostrato migliori performance. Tali risultati confermano che nella bovina la pPON ha un andamento simile a quello delle –APP. Questa associazione supporta l’utilita della pPON per valutare la gravita della risposta infiammatoria nel postparto e le sue conseguenze.
A day at a time : a study of unsupported family carers of older people

Informal carers provide the majority of care for older people living in the community. The provision of care can be very stressful and is said to have an adverse affect on caregivers’ health. Policy has recognised the need to support carers and a key objective has been to improve service provision for them. Research has shown that service intervention can prevent the breakdown of care and admission to long term care. However, relatively few carers and older people use formal services. While the low uptake of support services is documented, it is not fully understood. The aim of this study was to explore the experiences of informal carers of older people who received no support services. It focused particularly on the question: why when caregiving is portrayed as being stressful, do carers continue without support from formal service providers? Purposive sampling was used to obtain a sample of unsupported carers of older people, who were interviewed three times over a period of two years. For this longitudinal study a predominantly qualitative approach underpinned by the principles of grounded theory was chosen with a quantitative component included in the second stage. The study used a range of methods including focus groups, interviews and self-completion questionnaires. The main source of data was individual in-depth interviews, while self-completion questionnaires and literature provided secondary and tertiary sources of data. Data were analysed according to the principles of grounded theory. The study found that carers were motivated by a strong sense of duty and a desire to maintain their independence and control over their lives and the caregiving situation. They regarded formal services as authoritarian and intrusive. Acceptance of support was associated with feelings of failure and a potential loss of control.
Paroxysmal nocturnal hemoglobinuria clones are not infrequent in patients with inherited bone marrow failure syndromes

The distinction of inherited bone marrow failure syndromes (IBMFS) from other acquired forms of aplastic anemia (AA) is very important for instituting proper therapy. However this is not often straight forward. A proper confirmatory genetic diagnosis is possible only in less than 50% of the patients even with the use of massive parallel sequencing (1). Moreover its application is still limited due to the cost and several logistical issues. Unfortunately, diethyl epoxy butane (DEB) or mitomycin C induced chromosome breakage studies (CBS) is the only test, which is widely employed, for the diagnosis of IBMFS in many resource-limited settings. This article is protected by copyright. All rights reserved.
Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism

BACKGROUND Although many patients with venous thromboembolism require extended treatment, it is uncertain whether it is better to use full‐ or lower‐intensity anticoagulation therapy or aspirin. METHODS In this randomized, double‐blind, phase 3 study, we assigned 3396 patients with venous thromboembolism to receive either once‐daily rivaroxaban (at doses of 20 mg or 10 mg) or 100 mg of aspirin. All the study patients had completed 6 to 12 months of anticoagulation therapy and were in equipoise regarding the need for continued anticoagulation. Study drugs were administered for up to 12 months. The primary efficacy outcome was symptomatic recurrent fatal or nonfatal venous thromboembolism, and the principal safety outcome was major bleeding. RESULTS A total of 3365 patients were included in the intention‐to‐treat analyses (median treatment duration, 351 days). The primary efficacy outcome occurred in 17 of 1107 patients (1.5%) receiving 20 mg of rivaroxaban and in 13 of 1127 patients (1.2%) receiving 10 mg of rivaroxaban, as compared with 50 of 1131 patients (4.4%) receiving aspirin (hazard ratio for 20 mg of rivaroxaban vs. aspirin, 0.34; 95% confidence interval [CI], 0.20 to 0.59; hazard ratio for 10 mg of rivaroxaban vs. aspirin, 0.26; 95% CI, 0.14 to 0.47; P<0.001 for both comparisons). Rates of major bleeding were 0.5% in the group receiving 20 mg of rivaroxaban, 0.4% in the group receiving 10 mg of rivaroxaban, and 0.3% in the aspirin group; the rates of clinically relevant nonmajor bleeding were 2.7%, 2.0%, and 1.8%, respectively. The incidence of adverse events was similar in all three groups. CONCLUSIONS Among patients with venous thromboembolism in equipoise for continued anticoagulation, the risk of a recurrent event was significantly lower with rivaroxaban at either a treatment dose (20 mg) or a prophylactic dose (10 mg) than with aspirin, without a significant increase in bleeding rates. (Funded by Bayer Pharmaceuticals; EINSTEIN CHOICE ClinicalTrials.gov number, NCT02064439.)
Cardiovascular Efficacy and Safety of Bococizumab in High‐Risk Patients

BACKGROUND Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin–kexin type 9 (PCSK9) and reduces levels of low‐density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow‐up was 10 months. RESULTS At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of ‐56.0% in the bococizumab group and +2.9% in the placebo group, for a between‐group difference of –59.0 percentage points (P<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower‐risk, shorter‐duration trial (in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [1.8 mmol per liter] and the median follow‐up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P=0.94). In the higher‐risk, longer‐duration trial (in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [2.6 mmol per liter] and the median follow‐up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P=0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P=0.08). Injection‐site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001). CONCLUSIONS In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower‐risk patients but did have a significant benefit in the trial involving higher‐risk patients. (Funded by Pfizer; SPIRE‐1 and SPIRE‐2 ClinicalTrials.gov numbers, NCT01975376 and NCT01975389.)
Prevalence of peripheral artery disease in adult hypertensive patients in Nnewi, Nigeria

Background: Peripheral artery disease (PAD) is usually due to artherosclerosis obliterans of the arteries of the lower limbs. Patients with PAD are at increased risk of mortality from major cardiovascular events, such as myocardial infarction and stroke. This study aims to find the prevalence of peripheral artery disease in adult hypertensive subjects in Nnewi. Materials and Methods : The study was carried out among adult hypertensive subjects in the medical outpatient clinics and the medical wards of the NnamdiAzikiwe University Teaching Hospital, Nnewi.Two-hundred and fifty subjects were recruited between August 2004 and December 2004 for this study. The Rose Intermittent Claudication Questionnaire was administered and the Ankle-Brachial Index (ABI) was assessed with a hand-held Doppler device. PAD was defined as ABI > 0.9. TheEpi info (2002 version) statistical software was used for statistical analysis. Results: The mean age of the study subjects was 58.9±8.9 years. They comprises106 (42.5%) males and 144 (57.6%) females. The overall prevalence of PAD was 24.8% in the total study group. The ratio of asymptomatic to symptomatic subjects was 3.4:1. Hypertensive subjects with diabetes mellitus had a slightly higher prevalence rate (26%), compared to those with hypertension only (24%). The prevalence of PAD was much higher in patients above 55 years (30.7%) than in those below 55 yearsof age (15.5%). Conclusion : Peripheral artery disease is common, though largely asymptomatic in Nigerian hypertensive subjects. More efforts at screening and unmasking subjects are required.
Effectiveness of a Third Dose of MMR Vaccine for Mumps Outbreak Control

BACKGROUND The effect of a third dose of the measles–mumps–rubella (MMR) vaccine in stemming a mumps outbreak is unknown. During an outbreak among vaccinated students at the University of Iowa, health officials implemented a widespread MMR vaccine campaign. We evaluated the effectiveness of a third dose for outbreak control and assessed for waning immunity. METHODS Of 20,496 university students who were enrolled during the 2015–2016 academic year, mumps was diagnosed in 259 students. We used Fisher's exact test to compare unadjusted attack rates according to dose status and years since receipt of the second MMR vaccine dose. We used multivariable time‐dependent Cox regression models to evaluate vaccine effectiveness, according to dose status (three vs. two doses and two vs. no doses) after adjustment for the number of years since the second dose. RESULTS Before the outbreak, 98.1% of the students had received at least two doses of MMR vaccine. During the outbreak, 4783 received a third dose. The attack rate was lower among the students who had received three doses than among those who had received two doses (6.7 vs. 14.5 cases per 1000 population, P<0.001). Students had more than nine times the risk of mumps if they had received the second MMR dose 13 years or more before the outbreak. At 28 days after vaccination, receipt of the third vaccine dose was associated with a 78.1% lower risk of mumps than receipt of a second dose (adjusted hazard ratio, 0.22; 95% confidence interval, 0.12 to 0.39). The vaccine effectiveness of two doses versus no doses was lower among students with more distant receipt of the second vaccine dose. CONCLUSIONS Students who had received a third dose of MMR vaccine had a lower risk of mumps than did those who had received two doses, after adjustment for the number of years since the second dose. Students who had received a second dose of MMR vaccine 13 years or more before the outbreak had an increased risk of mumps. These findings suggest that the campaign to administer a third dose of MMR vaccine improved mumps outbreak control and that waning immunity probably contributed to propagation of the outbreak. (Funded by the Centers for Disease Control and Prevention.)
The Most Common Contact Allergens

The 24 contact allergens are presented which produced positive patch test reactions in 3% or more of the patient population of the New York University Skin and Cancer Unit during the years 1968 to 1970. The ten most common among these were mercury bichloride, mercaptobenzothiazole, paraphenylenediamine, potassium dichromate, ethylenediamine, nickel sulfate, turpentine oil, formaldehyde solution, poison ivy, and bismarck brown. Some of the sources of exposure to these allergens and some of the known cross-sensitizing compounds are listed. The clinical significance of strong vs weak patch test reactions is discussed.
Histopathological Findings in Brain Tissue Obtained during Epilepsy Surgery

BACKGROUND Detailed neuropathological information on the structural brain lesions underlying seizures is valuable for understanding drug‐resistant focal epilepsy. METHODS We report the diagnoses made on the basis of resected brain specimens from 9523 patients who underwent epilepsy surgery for drug‐resistant seizures in 36 centers from 12 European countries over 25 years. Histopathological diagnoses were determined through examination of the specimens in local hospitals (41%) or at the German Neuropathology Reference Center for Epilepsy Surgery (59%). RESULTS The onset of seizures occurred before 18 years of age in 75.9% of patients overall, and 72.5% of the patients underwent surgery as adults. The mean duration of epilepsy before surgical resection was 20.1 years among adults and 5.3 years among children. The temporal lobe was involved in 71.9% of operations. There were 36 histopathological diagnoses in seven major disease categories. The most common categories were hippocampal sclerosis, found in 36.4% of the patients (88.7% of cases were in adults), tumors (mainly ganglioglioma) in 23.6%, and malformations of cortical development in 19.8% (focal cortical dysplasia was the most common type, 52.7% of cases of which were in children). No histopathological diagnosis could be established for 7.7% of the patients. CONCLUSIONS In patients with drug‐resistant focal epilepsy requiring surgery, hippocampal sclerosis was the most common histopathological diagnosis among adults, and focal cortical dysplasia was the most common diagnosis among children. Tumors were the second most common lesion in both groups. (Funded by the European Union and others.)
Sound‐specific plasticity in the primary auditory cortex as induced by the cholinergic pedunculopontine tegmental nucleus

Brain cholinergic modulation is essential for learning‐induced plasticity of the auditory cortex. The pedunculopontine tegmental nucleus (PPTg) is an important cholinergic nucleus in the brainstem, and appears to be involved in learning and subcortical plasticity. This study confirms the involvement of the PPTg in the plasticity of the auditory cortex in mice. We show here that electrical stimulation of the PPTg paired with a tone induced drastic changes in the frequency tunings of auditory cortical neurons. Importantly, the changes in frequency tuning were highly specific to the frequency of the paired tone; the best frequency of auditory cortical neurons shifted towards the frequency of the paired tone. We further demonstrated that such frequency‐specific plasticity was largely eliminated by either thalamic or cortical application of the muscarinic acetylcholine receptor antagonist atropine. Our finding suggests that the PPTg significantly contributes to auditory cortical plasticity via the auditory thalamus and cholinergic basal forebrain.
Lesion of medial prefrontal dopamine terminals abolishes habituation of accumbens shell dopamine responsiveness to taste stimuli

Taste stimuli increase extracellular dopamine (DA) in the nucleus accumbens (NAc) and in the medial prefrontal cortex (mPFC). This effect shows single‐trial habituation in NAc shell but not in core or in mPFC. Morphine sensitization abolishes habituation of DA responsiveness in NAc shell but induces it in mPFC. These observations support the hypothesis of an inhibitory influence of mPFC DA on NAc DA. To test this hypothesis, we used in vivo microdialysis to investigate the effect of mPFC 6‐hydroxy‐dopamine (6‐OHDA) lesions on the NAc DA responsiveness to taste stimuli. 6‐OHDA was infused bilaterally in the mPFC of rats implanted with guide cannulae. After 1 week, rats were implanted with an intraoral catheter, microdialysis probes were inserted into the guide cannulae, and dialysate DA was monitored in NAc shell/core after intraoral chocolate. 6‐OHDA infusion reduced tissue DA in the mPFC by 75%. Tyrosine hydroxylase immunohistochemistry showed that lesions were confined to the mPFC. mPFC 6‐OHDA lesion did not affect the NAc shell DA responsiveness to chocolate in naive rats but abolished habituation in rats pre‐exposed to the taste. In the NAc core, mPFC lesion potentiated, delayed and prolonged the stimulatory DA response to taste but failed to affect DA in pre‐exposed rats. Behavioural taste reactions and motor activity were not affected. The results indicate a top‐down control of NAc DA by mPFC and a reciprocal relationship between DA transmission in these two areas. Moreover, habituation of DA responsiveness in the NAc shell is dependent upon an intact DA input to the mPFC.
Endoscopic Treatment versus Shunting for Infant Hydrocephalus in Uganda

Background Postinfectious hydrocephalus in infants is a major health problem in sub‐Saharan Africa. The conventional treatment is ventriculoperitoneal shunting, but surgeons are usually not immediately available to revise shunts when they fail. Endoscopic third ventriculostomy with choroid plexus cauterization (ETV–CPC) is an alternative treatment that is less subject to late failure but is also less likely than shunting to result in a reduction in ventricular size that might facilitate better brain growth and cognitive outcomes. Methods We conducted a randomized trial to evaluate cognitive outcomes after ETV–CPC versus ventriculoperitoneal shunting in Ugandan infants with postinfectious hydrocephalus. The primary outcome was the Bayley Scales of Infant Development, Third Edition (BSID‐3), cognitive scaled score 12 months after surgery (scores range from 1 to 19, with higher scores indicating better performance). The secondary outcomes were BSID‐3 motor and language scores, treatment failure (defined as treatment‐related death or the need for repeat surgery), and brain volume measured on computed tomography. Results A total of 100 infants were enrolled; 51 were randomly assigned to undergo ETV–CPC, and 49 were assigned to undergo ventriculoperitoneal shunting. The median BSID‐3 cognitive scores at 12 months did not differ significantly between the treatment groups (a score of 4 for ETV–CPC and 2 for ventriculoperitoneal shunting; Hodges–Lehmann estimated difference, 0; 95% confidence interval [CI], ‐2 to 0; P=0.35). There was no significant difference between the ETV–CPC group and the ventriculoperitoneal‐shunt group in BSID‐3 motor or language scores, rates of treatment failure (35% and 24%, respectively; hazard ratio, 0.7; 95% CI, 0.3 to 1.5; P=0.24), or brain volume (z score, ‐2.4 and ‐2.1, respectively; estimated difference, 0.3; 95% CI, ‐0.3 to 1.0; P=0.12). Conclusions This single‐center study involving Ugandan infants with postinfectious hydrocephalus showed no significant difference between endoscopic ETV–CPC and ventriculoperitoneal shunting with regard to cognitive outcomes at 12 months. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01936272.)