Miracle-dz/UniFAR-FTUs huggingface dataset:
Folate status and health: challenges and opportunities

Abstract Each year approximately 2400 pregnancies develop folic acid-preventable spina bifida and anencephaly in Europe. Currently, 70% of all affected pregnancies are terminated after prenatal diagnosis. The prevalence of neural tube defects (NTDs) has been significantly lowered in more than 70 countries worldwide by applying fortification with folic acid. Periconceptional supplementation of folic acid also reduces the risk of congenital heart diseases, preterm birth, low birth weight, and health problems associated with child mortality and morbidity. All European governments failed to issue folic acid fortification of centrally processed and widely eaten foods in order to prevent NTDs and other unwanted birth outcomes. The estimated average dietary intake of folate in Germany is 200 μg dietary folate equivalents (DFE)/day. More than half of German women of reproductive age do not consume sufficient dietary folate to achieve optimal serum or red blood cell folate concentrations (>18 or 1000 nmol/L, respectively) necessary to prevent spina bifida and anencephaly. To date, targeted supplementation is recommended in Europe, but this approach failed to reduce the rate of NTDs during the last 10 years. Public health centers for prenatal care and fortification with folic acid in Europe are urgently needed. Only such an action will sufficiently improve folate status, prevent at least 50% of the NTD cases, reduce child mortality and morbidity, and alleviate other health problems associated with low folate such as anemia.
Distinct Phenotype and Function of NK Cells in the Pancreas of Nonobese Diabetic Mice

Little is known about target organ-infiltrating NK cells in type 1 diabetes and other autoimmune diseases. In this study, we identified NK cells with a unique phenotype in the pancreas of NOD mice. Pancreatic NK cells, localized to the endocrine and exocrine parts, were present before T cells during disease development and did not require T cells for their infiltration. Furthermore, NK cells, or NK cell precursors, from the spleen could traffic to the pancreas, where they displayed the pancreatic phenotype. Pancreatic NK cells from other mouse strains shared phenotypic characteristics with pancreatic NK cells from NOD mice, but displayed less surface killer cell lectin-like receptor G1, a marker for mature NK cells that have undergone proliferation, and also did not proliferate to the same extent. A subset of NOD mouse pancreatic NK cells produced IFN-γ spontaneously, suggesting ongoing effector responses. However, most NOD mouse pancreatic NK cells were hyporesponsive compared with spleen NK cells, as reflected by diminished cytokine secretion and a lower capacity to degranulate. Interestingly, such hyporesponsiveness was not seen in pancreatic NK cells from the nonautoimmune strain C57BL/6, suggesting that this feature is not a general property of pancreatic NK cells. Based on our data, we propose that NK cells are sentinel cells in a normal pancreas. We further speculate that during inflammation, pancreatic NK cells initially mediate proinflammatory effector functions, potentially contributing to organ-specific autoimmunity, but later become hyporesponsive because of exhaustion or regulation.
The Transition from Acute to Subacute and Chronic Low Back Pain: A Study Based on Determinants of Quality of Life and Prediction of Chronic Disability

Study Design. Follow-up study. Objectives. To document differences between acute and subacute low back pain (LBP) based on the risk of developing chronic disability and on the correlation between pain, disability, and quality of life. Summary of Background Data. The subacute stage should identify the time in which the risk of developing chronic disability increases and specific measures should be considered, but its definition is currently inconsistent. Methods. 366 patients were given Visual Analog Scales (VAS) for LBP and referred pain (RP), Roland-Morris questionnaires (RMQs), and EuroQol (EQ) questionnaires on their first visit and 14 and 59 days later. Results. Median duration of pain when entering the study was 4 days (P25, P75: 2,10). Simple correlations among LBP, VAS, and RMQ were r = 0.407 (day 1), 0.688 (day 15), and 0.739 (day 60). Among LBP, VAS, and EQ, r = −0.523, r = −0.701, and r = −0.760. Among RP, VAS, and RMQ, r = 0.280, r = 0.561, and r = 0.583. Between RP, VAS, and EQ, r = −0.306, r = −0.534 and r = −0.600. Between RMQ and EQ, r = −0.650, r = −0.765 and r = −0.815. In 42 patients, disability did not improve throughout the study period, and a prestudy duration of ≥14 days was the only independent predictor. All these models were significant at the P < 0.007 level. Improvement in quality of life was more likely to occur in patients in which disability improved [odds ratio (OR), 18.29; 95% CI; 8.64, 38.73; P < 0.001]. As opposed to acute patients, in those with a prestudy duration of pain of ≥14 days, on day 60 RP had no influence on disability, and LBP had no influence on quality of life. Conclusion. LBP influences disability and quality of life more than RP. Disability is predicted by pain duration and quality of life is predicted by disability, but pain severity predicts neither one of them. Changes related to determinants of disability and quality of life, and to the prediction of chronic disability, appear 14 days after the onset of pain, supporting that cutoff point for considering a patient as being subacute.
Functional behavior of patients with conventional pacemakers undergoing cardiac resynchronization.

BACKGROUND Cardiac resynchronization therapy (CRT) is an efficient treatment for patients with heart failure (HF), severe ventricular dysfunction and intraventricular block. Conventional pacemakers (CPM) implanted in the right ventricular apical area cause alterations in the normal sequence of cardiac activation similar to those induced by LBBB (left bundle-branch block). Therefore, patients with CPM and advanced HF could be candidates to undergo CRT, but as only small numbers of patients have been evaluated so far, definitive conclusions are lacking. OBJECTIVE To assess the clinical and functional outcome of cardiac resynchronization therapy (CRT) in patients with conventional pacemakers. METHODS Patients with CPM, who were in NYHA HF functional class III/IV class refractory to drug therapy, and left ventricular ejection fraction (LVEF) ) <35% underwent CRT. Patients clinical-functional behavior was assessed prospectively six months after the procedure. The improvement of one HF-functional class was set as an effective response to the procedure. The following was assessed: QRS duration (ECG), diastolic diameter (LVDd), left ventricular systolic diameter (LVSd) and LVEF seen on the echocardiogram. For the statistical analysis, Students paired t test and Spearmans correlation were used. RESULTS Twenty-nine patients (mean age 61.5) were evaluated. Of these, six were females, and chagasic cardiomyopathy was predominant. During the clinical follow-up of 22.7+/-13 months, 86.2% of the patients benefited from CRT. Within this group, the mean LVEF increased by 18% (p=0.013), QRS duration dropped by 11.8% (p=0.002) and no significant reduction in left ventricular intracavitary diameters was observed. CONCLUSION CRT is effective for patients with CPM and advanced HF as it yields a high rate of response (86.2%), significantly improves LVEF and reduces QRS duration.
A case of Mikulicz’s disease with Th2-biased cytokine profile: possible feature discriminable from Sjögren’s syndrome

This article concerns a male patient with Mikulicz’s disease (MD) accompanied with marked elevation of serum immunoglobulin (Ig)G4 and IgE levels. His peripheral blood mononuclear cells (PBMC) showed markedly enhanced in vitro production of interleukin (IL)-4, IL-5, IL-13, but not interferon gamma (IFN-γ) compared with patients with Sjögren’s syndrome (SS) and healthy donors, suggesting distinct Th2 bias in this MD patient. Besides the prominent infiltration of IgG4-producing plasma cells, the enhanced expression of both CD40 and CD40 ligand (CD40L) were observed in the swollen salivary gland of the MD patient, suggesting enhanced signaling pathways for the induction of IgG4 and IgE switching. Possible differences between MD and SS in light of their underlying pathogenesis are discussed.
Hyperbaric oxygen therapy for wound healing in diabetic rats: Varying efficacy after a clinically-based protocol

Hyperbaric oxygen therapy (HBOT) is a clinical treatment in which a patient breathes pure oxygen for a limited period of time at an increased pressure. Although this therapy has been used for decades to assist wound healing, its efficacy for many conditions is unproven and its mechanism of action is not yet fully clarified. This study investigated the effects of HBOT on wound healing using a diabetes-impaired pressure ulcer rat model. Seven weeks after streptozotocin-induced diabetes in rats (n = 55), a pressure ulcer was created on dorsal skin. Subsequently, animals received HBOT during 6 weeks following a standard clinical protocol (HBOT group with varying endpoints up to 42 days post-wounding) versus controls without HBOT. Capillary venous oxygen saturation (SO2) showed a significant increase in the HBOT group on day 24; however, this increase was significant at this time point only. The quantity of hemoglobin in the micro-blood vessels (rHB) showed a significant decrease in the HBOT group on days 21 and 42, and showed a trend to decrease on day 31. Blood flow in the microcirculation showed a significant increase on days 17, 21 and 31 but a significant decrease on days 24 and 28. Inflammation scoring showed significantly decreased CD68 counts in the HBOT group on day 42, but not in the early stages of wound healing. Animals in the HBOT group showed a trend for an increase in mean wound breaking strength on day 42.
Identification of a major I-Ek-restricted determinant of hen egg lysozyme: limitations of lymph node proliferation studies in defining immunodominance and crypticity.

We have chemically analyzed the peptides presented by I-Ek molecules after processing of hen egg lysozyme (HEL) by a murine B-lymphoma line or by splenocytes. In both cases, the identified peptides were derived from a single region of HEL, containing the core residues 85-96 with heterogeneous N and C termini. This was a surprising result because this determinant had previously been described as cryptic--i.e., not presented after processing of intact HEL. Examination of the specificities of T hybridomas isolated after immunization with either HEL or 84-96 peptide (p84-96) provided an explanation for this controversy. Whereas hybridomas induced by immunization with HEL responded equally well to HEL and p84-96, those induced by peptide immunization showed a marked preference for p84-96 over intact HEL. In other words, hybridomas isolated after p84-96 immunization responded poorly to forms of the 84-96 determinant produced by natural processing, leading to the possible erroneous interpretation that 84-96 is a hidden determinant. We conclude that (i) p84-96 is efficiently presented on I-Ek molecules after processing of HEL, (ii) the explanation for the weak lymph node response to this epitope after immunization with HEL lies at the level of the T cell, not the antigen-presenting cell, and (iii) crypticity cannot be defined on the basis of T-cell proliferation studies alone.
Immunohistochemical distribution and biological activity of pituitary adenylate cyclase‐activating polypeptide (PACAP) in the central nervous system of the frog Rana ridibunda

The primary structure of frog pituitary adenylate cyclase‐activating polypeptide (PACAP) has recently been determined and the results show that the sequence of PACAP has been highly conserved during evolution. In particular, the structure of the 1–27 fragment of PACAP is identical in frog and mammals. Using an antiserum raised against PACAP27, we have investigated the distribution of PACAP‐containing neurons in the central nervous system of the frog Rana ridibunda by the immunofluorescence technique. The main populations of immunoreactive perikarya were located in the medial and ventral diencephalon, i.e., the preoptic nucleus, the ventral and dorsal infundibular nuclei, the nucleus posterocentralis thalami, and the ventral and ventrolateral areas of the thalamus. In the telencephalon, sparse cell bodies were found in the nucleus accumbens septi, the amygdala, the pallial commissure, and the bed nucleus of the pallial commissure. In the hindbrain, the torus semicircularis, the nucleus profundus and the nucleus anteroventralis tegmenti of the mesencephalon also contained populations of PACAP‐immunoreactive perikarya. Beaded nerve fibers were observed throughout the brain. Occasionally they formed bundles, e.g., from the ventral infundibulum to the external vascular layer of the median eminence, from the central thalamus to the optic tectum, and rostrocaudally, from the nucleus accumbens septi to the nucleus entopeduncularis. Other areas, such as the interpeduncular nucleus, the nucleus isthmi and the roots of cranial nerves V and VIII in the medulla oblongata, were also densely innervated. The adenylate cyclase‐stimulating activity of PACAP was tested by using a static incubation technique for hypothalamic slices. Synthetic PACAP27 (lO−10 to 3 · 10−6 M) induced a dose‐dependent stimulation of cAMP production. The half‐maximum effective dose (ED50) of PACAP27was3.5 · 10−7 M.
An early diagnostic tool for diabetic neuropathy: Conduction velocity distribution

Diabetes is a metabolic disorder that affects much of the human population. As a secondary complication, diabetic neuropathy causes time‐dependent damage to peripheral nerves. In this study, experimental diabetes was induced by streptozotocin (STZ; 50 mg/kg intraperitoneally) in rats. Diabetic animals were grouped into those with 2 or 4 weeks of diabetes, whereas a control group received only the STZ vehicle (0.1 M citrate). Sciatic nerves were dissected, and compound action potentials (CAPs) were recorded. Results deduced by conventional calculation carried less information when compared with conduction velocity distribution (CVD) obtained by a computer‐based mathematical model. Using the conventional approach, statistically significant changes were first seen in the fourth week of diabetes, whereas results deduced by CVD measurement could be seen in the second week. Consequently, the CVD calculation provides more information for the early diagnosis of neuropathies compared with classical conduction velocity measurements. Muscle Nerve 43: 237–244, 2011
Treatment of cervical spine fractures with halo vest method in children and young people.

BACKGROUND The Halo Vest method is a non-invasive treatment of cervical spine fractures. It is successfully applied in adults, which is supported by numerous studies, but has rarely been used among children and young people. There is little published research in this field. The aim of the paper is to present the effectiveness of Halo Vest external fixation in children and to evaluate the complication rate of this method. MATERIAL AND METHODS A retrospective study of 6 patients with cervical spine fractures with an average age of 13.3 years (range: 10 to 17 years) treated with Halo Vest external fixation between 2004 and 2013. The type and cause of fracture, treatment outcome and complications were evaluated. RESULTS The average duration of follow-up was 55 months. In 5 cases, the treatment result was satisfactory. In one case, there were complications in the form of an external infection around the cranial pins. CONCLUSIONS 1. The Halo Vest system can be applied as a non-operative method of treating cervical spine fractures in children and young people. 2. The criteria of eligibility for specific types of cervical spine fracture treatment in children and young people require further investigation, especially with regard to eliminating complications.
Type-specific HPV prevalence in invasive cervical cancer in the UK prior to national HPV immunisation programme: baseline for monitoring the effects of immunisation

Aims To establish the human papillomavirus (HPV) type-specific prevalence in cervical cancer and high-grade cervical lesions in the UK prior to the introduction of national HPV vaccination. Methods Specimens of cervical cancer (n=1235) and cervical intraepithelial neoplasia (CIN)3 (n=2268) were tested for HPV genotypes in England, Scotland, Wales and Northern Ireland. Data were pooled and weighted estimates presented. Results Among cervical cancer cases, 95.8% were positive for at least one high-risk (HR) HPV type. Restricting to those with HR HPV, the proportion positive for HPV16 and/or HPV18 was similar across countries (weighted overall prevalence 83.0%). This proportion decreased with increasing age at diagnosis (p=0.0005). HPV31, HPV33, HPV45, HPV52 and/or HPV58 were detected in 16.1% of HR HPV-positive cervical cancers and there was no significant association with age for these types. For HR HPV-positive CIN3 cases, there was a similar age-specific pattern with the highest positivity of HPV16 and/or HPV18 in the youngest age group (77.2%). The proportion of HR HPV CIN3 cases positive for HPV31, HPV33, HPV45, HPV52 and/or HPV58 was 36.3% in those aged <30 years at diagnosis. Conclusions The prevalence of HPV 16 and/or 18 was high in all UK countries and highest in those diagnosed at a younger age. The UK is well placed to monitor the impact of HPV vaccination on type-specific HPV prevalence in cervical disease.
Skeletal development in the meat-type chicken

1. This study ascertained how bone of modern meat-type chickens develops under typical commercial conditions and compares development with that in genetic precursor stock. 2. A modern fast-growing selected strain and a slower-growing control strain were used. Birds were weighed weekly. A random sample was taken from each population at a range of ages up to 39 d. 3. A tibiotarsus from each bird was X-rayed and its dimensions and estimated resistance to bending were determined. Cortical bone samples were ashed to measure total mineral, calcium and phosphorus content. Cortical samples were also taken for porosity assessment. 4. As expected, the selected strain grew faster and heavier than the control strain. Despite this, both strains demonstrated similar periods of rapid bone formation (days 4 to 18) and mineralisation (days 4 to 11), and achieved similar estimates of resistance to bending. 5. However, cortical bone of the selected strain was less well mineralised and more porous than that of the control strain and showed a significant increase in the molar Ca:P ratios above the expected range of values during the first 2 to 3 weeks of life. 6. Despite production of bones with the correct dimensions for load support, the relatively poor density and mineral content of bone in the selected strain is likely to reduce effective breaking strength of the tibiotarsus. Possible reasons may be either inadequate dietary supply of Ca and P or impaired utilisation of the minerals due to a rapid growth rate or genetic factors.
Sleep Hygiene and Migraine in Children and Adolescents

Although sleep problems are a common complaint in migraine patients, the role of sleep habits and hygiene as triggering factors of head pain attacks has been poorly analyzed. The aim of this study was to evaluate the effect of modifying bad sleep habits across several headache parameters. Based on our previous study, we selected 70/164 migraineurs (42.7%) with poor sleep hygiene and randomly assigned them to two groups: group A migraineurs, who were instructed to follow directions to improve sleep hygiene; and group B migraineurs who were not given instructions on improving sleep hygiene. Mean duration and frequency of migraine attacks were significantly reduced at follow-up in group A, while group B showed only an insignificant initial reduction. No differences were found in the severity of migraine attacks that seemed related to a higher prevalence of nocturnal symptoms such as bedtime struggles, hypnic jerks, nightmares, and restless sleep. Our study is an alternative approach to the treatment of migraine, i.e. treatment through a simple modification of sleep behavior without recurring to pharmacological treatment.
Feeding kinematics and performance of Hawaiian stream gobies, Awaous guamensis and Lentipes concolor: Linkage of functional morphology and ecology

Distributions of Hawaiian stream fishes are typically interrupted by waterfalls that divide streams into multiple segments. Larvae hatch upstream, are flushed into the ocean, and must climb these waterfalls to reach adult habitats when returning back to freshwater as part of an amphidromous life cycle. Stream surveys and studies of climbing performance show that Lentipes concolor Gill can reach fast‐flowing upper stream segments but that Awaous guamensis Valenciennes reaches only slower, lower stream segments. Gut content analyses for these two species indicate considerable overlap in diet, suggesting that feeding kinematics and performance of these two species might be comparable. Alternatively, feeding kinematics and performance of these species might be expected to differ in relation to the different flow regimes in their habitat (feeding in faster stream currents for L. concolor versus in slower currents for A. guamensis). To test these alternative hypotheses, we compared food capturing kinematics and performance during suction feeding behaviors of A. guamensis and L. concolor using morphological data and high‐speed video. Lentipes concolor showed both a significantly larger gape angle and faster jaw opening than A. guamensis. Geometric models calculated that despite the inverse relationship of gape size and suction pressure generation, the fast jaw motions of L. concolor allow it to achieve higher pressure differentials than A. guamensis. Such elevated suction pressure would enhance the ability of L. concolor to successfully capture food in the fast stream reaches it typically inhabits. Differences in jaw morphology may contribute to these differences in performance, as the lever ratio for jaw opening is about 10% lower in L. concolor compared with A. guamensis, suiting the jaws of L. concolor better for fast opening. J. Morphol. 2009. © 2008 Wiley‐Liss, Inc.