Miracle-dz/UniFAR-FTUs huggingface dataset:
Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring

Early embryonic development is known to be susceptible to maternal undernutrition, leading to a disease‐related postnatal phenotype. To determine whether this sensitivity extended into oocyte development, we examined the effect of maternal normal protein diet (18% casein; NPD) or isocaloric low protein diet (9% casein; LPD) restricted to one ovulatory cycle (3.5 days) prior to natural mating in female MF‐1 mice. After mating, all females received NPD for the remainder of gestation and all offspring were litter size adjusted and fed standard chow. No difference in gestation length, litter size, sex ratio or postnatal growth was observed between treatments. Maternal LPD did, however, induce abnormal anxiety‐related behaviour in open field activities in male and female offspring (P < 0.05). Maternal LPD offspring also exhibited elevated systolic blood pressure (SBP) in males at 9 and 15 weeks and in both sexes at 21 weeks (P < 0.05). Male LPD offspring hypertension was accompanied by attenuated arterial responsiveness in vitro to vasodilators acetylcholine and isoprenaline (P < 0.05). LPD female offspring adult kidneys were also smaller, but had increased nephron numbers (P < 0.05). Moreover, the relationship between SBP and kidney or heart size or nephron number was altered by diet treatment (P < 0.05). These data demonstrate the sensitivity of mouse maturing oocytes in vivo to maternal protein undernutrition and identify both behavioural and cardiovascular postnatal outcomes, indicative of adult disease. These outcomes probably derive from a direct effect of protein restriction, although indirect stress mechanisms may also be contributory. Similar and distinct postnatal outcomes were observed here compared with maternal LPD treatment during post‐fertilization preimplantation development which may reflect the relative contribution of the paternal genome.
Hyperparathyroidism and Vitamin D Deficiency Predispose to Bone Loss in Renal Transplant Recipients

Background. Bone disease is common postrenal transplantation resulting in increased fracture rates and morbidity. The cause is multifactorial including hyperparathyroidism, corticosteroids, and possibly calcium and vitamin D deficiencies. The aim of this study was to identify modifiable factors contributing to bone disease in long-term renal transplant (RT) recipients. Methods. Ninety-seven RT recipients were prospectively recruited over a 6-month period from a single center. Bone-related parameters were collected including bone mineral density at lumbar spine and total hip sites, serum and urinary markers of bone-turnover and calcium metabolism, and intact parathyroid hormone levels. Results. The mean time posttransplant of RT recipients was 9.5 years and mean estimated glomerular filtration rate was 70.3 mL/min. Up to 50% of recipients had biochemical evidence of calcium and vitamin D deficiencies. In the multiple regression models, elevated intact parathyroid hormone levels and calcium deficiency, which are affected by estimated glomerular filtration rate and vitamin D levels, are significantly associated with reduction in bone mineral density measurements. Conclusions. Hyperparathyroidism and vitamin D deficiency are common and are likely to contribute to bone loss postrenal transplantation. Measures aim to correct these problems pre- and posttransplant may improve bone health in RT recipients.
Cognition and medial frontal cortex in health and disease

Purpose of reviewRecent work on the role of the medial frontal cortex in cognition and its involvement in neurological disorders is critically reviewed. Recent findingsThe highly influential notion of conflict monitoring by the anterior cingulate has been called into question by monkey single-cell neurophysiology and lesion studies in monkeys and humans. An alternative role for this region in adapting behaviour in response to changing demands over time is gaining support. By contrast, the more dorsally placed presupplementary motor area and supplementary eye field have been implicated in direct executive control in situations of response conflict. Although more rostral medial areas have been linked to complex cognitive operations involving references to the self, conceptual obstacles make the evidence difficult to interpret. The role of the orbitofrontal cortex in guiding action based on value has been reinforced. SummaryThe role of the medial frontal cortex in cognition continues to generate both interest and controversy. A few striking discrepancies between data from functional imaging and interventional techniques illustrate the hazards of drawing strong conclusions from merely correlative evidence. More broadly, a case can be made for tempering the empirical enthusiasm here with a little more theoretical restraint.
Parotid metastatic disease from cutaneous squamous cell carcinoma: Prognostic role of facial nerve sacrifice, lateral temporal bone resection, immune status and P‐stage

Recognized prognostic indicators for metastatic cutaneous squamous cell carcinoma (SCC) of the head and neck include facial nerve involvement, immune status, and “parotid” staging system (P‐stage). We sought to examine the impact of lateral temporal bone resection (LTBR) on prognosis.
Phenotypic distinctions between neural crest and placodal derived vagal C‐fibres in mouse lungs

Two major types of nociceptors have been described in dorsal root ganglia (DRGs). In comparison, little is known about the vagal nociceptor subtypes. The vagus nerves provide much of the capsaicin‐sensitive nociceptive innervation to visceral tissues, and are likely to contribute to the overall pathophysiology of visceral inflammatory diseases. The cell bodies of these afferent nerves are located in the vagal sensory ganglia referred to as nodose and jugular ganglia. Neurons of the nodose ganglion are derived from the epibranchial placodes, whereas jugular ganglion neurons are derived from the neural crest. In the adult mouse, however, there is often only a single ganglionic structure situated alone in the vagus nerve. By employing Wnt1Cre/R26R mice, which express β‐galactosidase only in neural crest derived neurons, we found that this single vagal sensory ganglion is a fused ganglion consisting of both neural crest neurons in the rostral portion and non‐neural crest (nodose) neurons in the more central and caudal portions of the structure. Based on their activation and gene expression profiles, we identified two major vagal capsaicin‐sensitive nociceptor phenotypes, which innervated a defined target, namely the lung in adult mice. One subtype is non‐peptidergic, placodal in origin, expresses P2X2 and P2X3 receptors, responds to α,β‐methylene ATP, and expresses TRKB, GFRα1 and RET. The other phenotype is derived from the cranial neural crest and does not express P2X2 receptors and fails to respond to α,β‐methylene ATP. This population can be further subdivided into two phenotypes, a peptidergic TRKA+ and GFRα3+ subpopulation, and a non‐peptidergic TRKB+ and GFRα1+ subpopulation. Consistent with their similar embryonic origin, the TRPV1 expressing neurons in the rostral dorsal root ganglia were more similar to jugular than nodose vagal neurons. The data support the hypothesis that vagal nociceptors innervating visceral tissues comprise at least two major subtypes. Due to distinctions in their gene expression profile, each type will respond to noxious or inflammatory conditions in their own unique manner.
What makes physicians go to work while sick: a comparative study of sickness presenteeism in four European countries (HOUPE).

QUESTIONS UNDER STUDY Sickness presenteeism is common in the health sector, especially among physicians, leading to high costs in terms of medical errors and loss in productivity. This study investigates predictors of sickness presenteeism in university hospitals, which might be especially exposed to competitive presenteeism. The study included comparisons of university hospitals in four European countries. METHODS A cross-sectional survey analysis of factors related to sickness behaviour and work patterns in the field of academic medicine was performed among permanently employed physicians from the HOUPE (Health and Organisation among University Physicians Europe) study: (Sweden n = 1,031, Norway n= 354, Iceland n = 242, Italy n = 369). The outcome measure was sickness presenteeism. RESULTS Sickness presence was more common among Italian physicians (86%) compared with physicians in other countries (70%‑76%). Country-stratified analyses showed that sickness presenteeism was associated with sickness behaviour and role conflicts in all countries. Competition in the form of publishing articles was a predictor in Italy and Sweden. Organisational care for physician well-being reduced sickness presenteeism in all countries. CONCLUSION Sickness presenteeism in university hospitals is part of a larger behavioural pattern where physicians seem to neglect or hide their own illness. Factors associated with competitive climate and myths about a healthy doctor might contribute to these behaviours. Importantly, it is suggested that managers and organisations should work actively to address these questions since organisational care might reduce the extent of these behaviours.
Interferon-dependent transcriptional activation: signal transduction without second messenger involvement?

Two specific macromolecular interactions are known to underlie the demonstrated transcriptional stimulation of different sets of genes incident to the binding of different polypeptide ligands to cells. The initial polypeptide-receptor interaction is widely recognized to be specific. It is also well established that the binding of specific transcription factors to well-defined DNA sites activates specific genes. In this paper, we suggest that a third, equally specific protein-protein interaction links the first two specific interactions and ensures the high specificity required in these pathways. We propose that a receptor-recognition protein is required to recognize the bound receptor. This receptor-recognition protein might itself be part of a transcription factor or might interact directly with a transcription factor that would thereby be activated and translocated to the nucleus to participate in gene activation. According to this hypothesis, no global changes in second messenger concentrations are necessary, and the enzymatic properties of the receptor-recognition protein(s) need not be specified. Phosphorylations of, or by, receptor-bound proteins would not, of course, be excluded. But such modifications during ligand-mediated signal transduction would not depend on global second messenger changes. This model is derived from studies of the proteins involved in interferon (IFN)-stimulated gene transcription. It is now established that interferon-alpha (IFN alpha) activates a multisubunit transcription factor in the cell cytoplasm, and that this factor then moves to the nucleus to activate a set of IFN-stimulated genes. (ABSTRACT TRUNCATED AT 250 WORDS)
Attention modulates the dorsal striatum response to love stimuli

In previous functional magnetic resonance imaging (fMRI) studies concerning romantic love, several brain regions including the caudate and putamen have consistently been found to be more responsive to beloved‐related than control stimuli. In those studies, infatuated individuals were typically instructed to passively view the stimuli or to think of the viewed person. In the current study, we examined how the instruction to attend to, or ignore the beloved modulates the response of these brain areas. Infatuated individuals performed an oddball task in which pictures of their beloved and friend served as targets and distractors. The dorsal striatum showed greater activation for the beloved than friend, but only when they were targets. The dorsal striatum actually tended to show less activation for the beloved than the friend when they were distractors. The longer the love and relationship duration, the smaller the response of the dorsal striatum to beloved‐distractor stimuli was. We interpret our findings in terms of reinforcement learning. By virtue of using a cognitive task with a full factorial design, we show that the dorsal striatum is not activated by beloved‐related information per se, but only by beloved‐related information that is attended. Hum Brain Mapp 35:503–512, 2014. © 2012 Wiley Periodicals, Inc.
Comparative Analysis of Apoptosis-inducing Activity of Codeine and Codeinone

Background There are relatively few studies about the antiproliferative effects of codeine-related compounds on human cancer cell lines, compared with those of morphine-related compounds. The authors previously found that codeinone, an oxidation metabolite of codeine, among 10 opioids, showed the highest cytotoxic activity (DNA fragmentation-inducing activity) against human promyelocytic leukemic cell lines (HL-60). This was counteracted by an antioxidant, N-acetyl-l-cysteine (NAC). These findings prompted us to perform a more detailed study of apoptosis induction after codeinone treatment. Methods Apoptosis was induced by treating HL-60 cells for 1–6 h with codeine or codeinone. DNA fragmentation was assessed by both agarose gel electrophoresis and fluorometric determination of the fragmented DNA after staining with diamidinophenylindole (DAPI). The appearance of apoptotic cells was monitored by microscopic observation after staining with Hoechst (H)-33342, and fluorescence activated cell sorter (FACS) after staining with Annexin. The release of cytochrome c and cytochrome oxidase from mitochondria and activation of caspase 3 were monitored by Western blot analysis. Intracellular caspase 3–like activity was confirmed by FACS, using cell permeable substrate. Mitochondrial manganese-containing superoxide dismutase (MnSOD) activity and mRNA expression were assayed by activity staining after separation on the polyacrylamide gel electrophoresis, and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. Results Codeinone induced internucleosomal DNA fragmentation and production of Annexin-positive apoptotic cells more potently than codeine in HL-60 cells. Codeinone stimulated the release of both cytochrome c and cytochrome oxidase, and cleavage of procaspase 3 without significant changes in both the activity and expression of MnSOD. Conclusions Codeinone was found to possess both apoptosis and necrosis-inducing activity, in addition to the reported antinociceptive activity, further substantiating its antitumor potential.
Combination Therapy with Sevelamer Hydrochloride and Calcium Carbonate in Japanese Patients with Long‐Term Hemodialysis: Alternative Approach for Optimal Mineral Management

Abstract: Calcium (Ca) overload by Ca‐containing phosphorus (P) binder has been suggested to be implicated in the pathogenesis of soft tissue and vascular calcification, which contribute to increased morbidity and mortality of cardiovascular disease in patients undergoing dialysis. Recently, a noncalcium P binder, sevelamer hydrochloride (sevelamer), has become available in Japan. However, Japanese patients undergoing dialysis might be less tolerant of sevelamer treatment, and it is likely to cause hypocalcemia because their dietary Ca intake is less than that in European and American patients. We evaluated the effects of combination therapy with sevelamer and calcium carbonate (CC) on mineral metabolism in Japanese hemodialysis patients, as an alternative form of P management. A total of 210 hemodialysis patients were enrolled, and were given a small dose of sevelamer (0.75–1.5 g/day) on CC treatment. Sevelamer dose was gradually increased, while CC decreased during 24 weeks. Five patients discontinued sevelamer treatment because of severe constipation, anorexia, and parathyroidectomy for severe secondary hyperparathyroidism. After 24 weeks, the dose of sevelamer was significantly increased to 3.29 g/day (initial dose: 1.47 g/day), while CC was decreased by 54%. Adjusted serum Ca significantly decreased (9.63 ± 0.57–9.45 ± 0.67 mg/dL; P = 0.0012), although serum P increased (5.89 ± 1.32–6.25 ± 1.32 mg/dL; P = 0.017). Serum intact PTH (iPTH) significantly increased in patients with a low or normal iPTH level (≤300 pg/mL), while it did not change in patients with secondary hyperparathyroidism (>300 pg/mL). The results suggest that the therapeutic regimen is more tolerant and reduces Ca load in Japanese hemodialysis patients while avoiding hypocalcemia. In addition, the mitigated Ca overload could improve PTH hyposecretion in patients with adynamic bone disease, which is associated with soft tissue calcification and higher mortality in uremia
Differences in global gene expression in peripheral blood mononuclear cells indicate a significant role of the innate responses in progression of dengue fever but not dengue hemorrhagic fever.

BACKGROUND Dengue virus infection causes an array of symptoms ranging from dengue fever (DF) to dengue hemorrhagic fever (DHF). The pathophysiological processes behind these 2 clinical manifestations are unclear. METHOD In the present study, genomewide transcriptomes of peripheral blood mononuclear cells (PBMCs) collected from children with acute-phase DF (i.e., DF PBMCs) or acute-phase DHF (i.e., DHF PBMCs) were compared using microarray analysis. Results of genome screening were validated at the genomic and proteomics levels. RESULTS DHF had stronger influences on the gene expression profile than did DF. Of the affected genes, metabolic gene expression was influenced the most. For the immune response category, 17 genes were more strongly up-regulated in DF PBMCs than in DHF PBMCs. Eight of the these 17 genes were categorized as belonging to the interferon (IFN) system. The up-regulation of IFN-related genes was accompanied by strong expression of CD59, a complement inhibitor. DHF PBMCs expressed genes involved in T and B cell activation, cytokine production, complement activation, and T cell apoptosis more strongly than did DF PBMCs. CONCLUSION We hypothesize that, during DF, genes in the IFN system and complement inhibitor play a role in lowering virus production and reducing tissue damage. In patients with DHF, the dysfunction of immune cells, complement, and cytokines increases viral load and tissue damage.
Hair cycle control by leptin as a new anagen inducer

Our purpose is to clarify the physiological role of leptin in hair cycle as leptin reportedly causes activation of Stat3, which is indispensable for hair cycling. While hair follicles in dorsal skin of 5‐week‐old C57/BL6 mice had progressed to late anagen phase, those in dorsal skin of 5‐week‐old leptin receptor deficient db/db mice remained in the first telogen and later entered the anagen at postnatal day 40, indicating that deficiency in leptin receptor signalling delayed the second hair cycle progression. Next, we shaved dorsal hairs on wild‐type mice at postnatal 7 weeks and injected skin with mouse leptin or a mock. After 20 days, although mock injection showed no effect, hair growth occurred around leptin injection area. Human leptin fragment (aa22–56) had similar effects. Although the hair cycle of ob/ob mice was similar to that of wild‐type mice, injection of mouse leptin on ob/ob mice at postnatal 7 weeks induced anagen transition. Immunohistochemically, leptin is expressed in hair follicles from catagen to early anagen in wild‐type mice, suggesting that leptin is an anagen inducer in vivo. Phosphorylation of Erk, Jak2 and Stat3 in human keratinocytes was stimulated by leptin and leptin fragment. In addition, RT‐PCR and ELISA showed that the production of leptin by human dermal papilla cells increased under hypoxic condition, suggesting that hypoxia in catagen/telogen phase promotes leptin production, preparing for entry into the next anagen. In conclusion, leptin, a well‐known adipokine, acts as an anagen inducer and represents a new player in hair biology.
Healing effects of foliage plants using physiological and psychological characteristics

Foliage plants serve as interior accessories and are placed in indoor spaces, such as offices, hotels, restaurants, and homes. Recently, their healing effects have attracted much attention. In this investigation, the healing effects of foliage plants on human subjects performing a computer task were examined by measuring salivary amylase activity, blood pressure, and pulse as physiological indices, and by using the profile of mood states (POMS, the Japanese edition) as a psychological index. The salivary amylase activities of the subjects working in a room with foliage plants were significantly decreased compared with those of the subjects working in a room without plants. When comparing average increase/decrease rate between cases immediately after and 30 min after task-loading, the rates of the salivary amylase activity, anger-hostility, vigor of the subjects in the cases with and without plants, are −11.1 and 3.5%, −3.4 and 0.3%, and 3.2 and −0.6%, respectively. It is evident that foliage plants have healing effects in workers.
Pneumococcal vaccines for sickle cell disease.

BACKGROUND People with sickle cell disease are particularly susceptible to pneumococcal infection, which may be fatal. Infants (children aged up to 23 months) are at particularly high risk, but conventional polysaccharide pneumococcal vaccines may be ineffective in this age group. New conjugate pneumococcal vaccines are now available, which may help to reduce the incidence of infection in people with sickle cell disease. OBJECTIVES To determine the efficacy of pneumococcal vaccines for reducing morbidity and mortality in people with sickle cell disease. SEARCH STRATEGY We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register, comprising of references identified from comprehensive electronic database searches and hand searching relevant journals and abstract books of conference proceedings. In addition, we contacted relevant pharmaceutical companies and experts in the field.Date of most recent search of Group's trials register: November 2003. SELECTION CRITERIA All randomised and quasi-randomised controlled trials comparing a polysaccharide or conjugate pneumococcal vaccine regimen with a different regimen or no vaccination in people with sickle cell disease. DATA COLLECTION AND ANALYSIS Two reviewers independently selected studies for inclusion, extracted data and assessed trial quality. MAIN RESULTS Nine trials were identified in the searches and five trials, with a total of 547 participants, met the inclusion criteria. Only one trial reported incidence of pneumococcal infection, and this demonstrated that the polysaccharide pneumococcal vaccine used (PPV14) failed to significantly reduce the risk of infection in children under three years of age, but was associated with only minor adverse events. Three trials of conjugate pneumococcal vaccines found that immune response was increased compared to control groups, including in infants, although clinical outcomes were not measured in these trials. REVIEWER'S CONCLUSIONS Previous trials have shown that conjugate pneumococcal vaccines are safe and effective in normal healthy patients, even those under the age of two years. The controlled trials included in this review have demonstrated immunogenicity (the body's response, without which there is no protection) of these vaccines, and observational studies in people with sickle cell disease support these findings. We therefore recommend that conjugate pneumococcal vaccines are used in people with sickle cell disease. Randomised trials in patients with sickle cell disease will be needed to determine the optimal vaccination regimen when further, potentially more effective vaccines become available. Such trials should measure clinical outcomes of effectiveness.