Pre-hibernation diet alters skeletal muscle relaxation kinetics, but not force development in torpid arctic ground squirrels.

During the hibernation season, Arctic ground squirrels (AGS) experience extreme temperature fluctuations (body temperature, Tb, as low as - 3 °C), during which they are mostly physically inactive. Once Tb reaches ~ 15 °C during interbout arousals, hibernators recruit skeletal muscle (SkM) for shivering thermogenesis to reach Tb of ~ 35 °C. Polyunsaturated fatty acids (PUFA) in the diet are known to influence SkM function and metabolism. Recent studies in the cardiac muscle of hibernators have revealed that increased levels of ω-6 and the ω-6:ω-3 PUFA ratio correlate with sarco/endoplasmic reticulum calcium ATPase (SERCA) activity and hibernation status. We hypothesized that diet (increased ω-6:ω-3 PUFA ratio) and torpor status are important in the regulation of the SERCA pump and that this may improve SkM performance during hibernation. Ex vivo functional assays were used to characterize performance changes in SkM (diaphragm) from AGS fed the following diets. (1) Standard rodent chow with an ω-6:ω-3 ratio of 5:1, or (2) a balanced diet with an ω-6:ω-3 ratio of 1:1 that roughly mimics wild diet. We collected diaphragms at three different stages of hibernation (early torpor, late torpor, and arousal) and evaluated muscle function under hypothermic temperature stress at 4 °C, 15 °C, 25 °C, and 37 °C to determine functional resilience. Our data show that torpid animals fed standard rodent chow have faster SkM relaxation when compared to the balanced diet animals. Furthermore, we discovered that standard rodent chow AGS during torpor has higher SkM relaxation kinetics, but this effect of torpor is eliminated in balanced diet AGS. Interestingly, neither diet nor torpor influenced the rate of force development (rate of calcium release). This is the first study to show that increasing the dietary ω-6:ω-3 PUFA ratio improves skeletal muscle performance during decreased temperatures in a hibernating animal. This evidence supports the interpretation that diet can change some functional properties of the SkM, presumably through membrane lipid composition, ambient temperature, and torpor interaction, with an impact on SkM performance.

Cardiac Rhythms and Variation in Hibernating Arctic Ground Squirrels.

AbstractThe dramatic decrease in heart rate (HR) during entrance into hibernation is not a mere response to the lowering of core body temperature (Tb) but a highly regulated fall, as the decrease in HR precedes the drop in Tb. This regulated fall in HR is thought to be mediated by increased cardiac parasympathetic activity. Conversely, the sympathetic nervous system is thought to drive the increase of HR during arousal. Despite this general understanding, we lack temporal information on cardiac parasympathetic regulation throughout a complete hibernation bout. The goal of this study was to fill this gap in knowledge by using Arctic ground squirrels implanted with electrocardiogram/temperature telemetry transmitters. Short-term HR variability (root mean square of successive differences [RMSSD]), an indirect measure of cardiac parasympathetic regulation, was calculated in 11 Arctic ground squirrels. RMSSD, normalized as RMSSD/RR interval (RRI), increased fourfold during early entrance (from 0.2±0.1 to 0.8±0.2, P<0.05). RMSSD/RRI peaked after HR dropped by over 90% and Tb fell by 70%. Late entrance was delineated by a decline in RMSSD/RRI while Tb continued to decrease. During arousal, HR started to increase 2 h before Tb, with a concurrent decrease in RMSSD/RRI to a new minimum. As Tb increased to a maximum during interbout arousal, HR declined, and RMSSD/RRI increased. These data suggest that activation of the parasympathetic nervous system initiates and regulates the HR decrease during entrance into hibernation and that withdrawal of parasympathetic activation initiates arousal. We conclude that cardiac parasympathetic regulation persists throughout all phases of a hibernation bout-a feature of the autonomic nervous system's regulation of hibernation that was not appreciated previously.

Opportunities and barriers to translating the hibernation phenotype for neurocritical care.

Targeted temperature management (TTM) is standard of care for neonatal hypoxic ischemic encephalopathy (HIE). Prevention of fever, not excluding cooling core body temperature to 33°C, is standard of care for brain injury post cardiac arrest. Although TTM is beneficial, HIE and cardiac arrest still carry significant risk of death and severe disability. Mammalian hibernation is a gold standard of neuroprotective metabolic suppression, that if better understood might make TTM more accessible, improve efficacy of TTM and identify adjunctive therapies to protect and regenerate neurons after hypoxic ischemia brain injury. Hibernating species tolerate cerebral ischemia/reperfusion better than humans and better than other models of cerebral ischemia tolerance. Such tolerance limits risk of transitions into and out of hibernation torpor and suggests that a barrier to translate hibernation torpor may be human vulnerability to these transitions. At the same time, understanding how hibernating mammals protect their brains is an opportunity to identify adjunctive therapies for TTM. Here we summarize what is known about the hemodynamics of hibernation and how the hibernating brain resists injury to identify opportunities to translate these mechanisms for neurocritical care.

Psoriasis associated with ACE inhibitors: an analysis of the FAERS database.

Many case reports have been published concerning the development or exacerbation of psoriasis after administration of angiotensin-converting enzyme (ACE) inhibitors. The aim of the present study was to investigate the association between psoriasis and ACE inhibitors using the US Food and Drug Administration Adverse Event Reporting System (FAERS) data. After excluding patients with psoriasis-related primary diseases, the association of psoriasis with 14 ACE inhibitors was examined using disproportional analyses reporting odds ratio (ROR) and information component (IC). Signals were detected for all 14 ACE inhibitors combined (ROR: 1.25, 95% confidence interval [CI]: 1.14-1.37; IC: 0.31, 95% CI: 0.17-0.44) and individually for lisinopril (ROR: 1.20, 95% CI: 1.05-1.37; IC: 0.25, 95% CI: 0.06-0.45), perindopril (ROR: 1.86, 95% CI: 1.38-2.52; IC: 0.86, 95% CI: 0.43-1.30), and ramipril (ROR: 1.63, 95% CI: 1.36-1.96; IC: 0.69, 95% CI: 0.42-0.96). ACE inhibitors are widely used in patients with hypertension, heart failure, and diabetes mellitus, which are considered comorbidities of psoriasis. Our results suggest that the involvement of ACE inhibitors should be considered in patients on ACE inhibitor therapy who have developed (or show exacerbated) psoriasis.

Evaluation of syncope association with α1-adrenoceptor blockers in males using the FAERS database: impact of concomitant hypertension.

Previous studies have revealed an association between the administration of α1-adrenoceptor blockers (α1Bs) and episodes of syncope in patients with benign prostatic hyperplasia (BPH). The objective of the present study was to evaluate the association between α1Bs and syncope in BPH patients with hypertension using two different pharmacoepidemiological indices. Using the US Food and Drug Administration Adverse Event Reporting System, we analyzed the whole dataset and subsets for specific indications, including hypertension, diabetes, and dyslipidemia, for males older than 40 years. The drugs of interest were alfuzosin, doxazosin, and terazosin as non-selective α1Bs and silodosin and tamsulosin as selective α1Bs. The reporting odds ratio (ROR) and information component (IC) were used for signal detection. The association between the non-selective α1Bs and syncope was observed for all the items examined. The results obtained using the whole dataset, as well as the diabetes and dyslipidemia subsets, were same for the selective and non-selective α1Bs in terms of the association with syncope, while no association with syncope was observed for both silodosin [ROR: 1.09, 95% confidence interval (CI): 0.61-1.93; IC: 0.10, 95% CI: -0.72-0.92] and tamsulosin (ROR: 1.08, 95% CI: 0.90-1.30; IC: 0.10, 95% CI: -0.17-0.37) in patients with hypertension. The data suggested that α1Bs, even those with receptor subtype selectivity, were associated with syncope. Thus, careful attention should be paid when prescribing α1Bs, especially to patients who do not take medications for hypertension.

Serum ß-cryptoxanthin and ß-carotene derived from Satsuma mandarin and brachial-ankle pulse wave velocity: The Mikkabi cohort study.

BACKGROUND AND AIMS: Findings of observational studies suggest cardioprotective effects of antioxidant vitamins and carotenoids. However, recent meta-analyses failed to show the beneficial effects of supplemental intake of antioxidants on cardiovascular disease (CVD). We aimed to assess the association between CVD risk and ß-cryptoxanthin in Japan, where Satsuma mandarin, a major source of ß-cryptoxanthin, is widely consumed. METHODS AND RESULTS: This was part of the Mikkabi cohort study. Surveys were conducted at baseline, in 2003 and 2005, and on follow-up in 2006, 2009, and 2013. We examined brachial-ankle pulse wave velocity (baPWV) with a high cut-off value set at 18.3 m s(-1). Hazard ratios (HR) and 95% confidence intervals for high baPWV were estimated using a Cox proportional hazards model with adjustment for potential confounders. A total of 635 participants with baPWV of less than 18.3 m s(-1) at baseline were included in the analysis. During the follow-up period of 57,921 person-months, 99 subjects developed high baPWV. After multivariate adjustment, the HR for high baPWV in the highest tertile compared with the lowest tertile was significantly low for ß-cryptoxanthin, ß-carotene, and total carotenoids. Serum concentrations of ß-cryptoxanthin and ß-carotene were higher in people who ate Satsuma mandarin frequently. Compared with <1/d intake of Satsuma mandarin, 3-4/d was associated with a low risk of high PWV. CONCLUSION: This study indicated that ß-cryptoxanthin and ß-carotene derived from Satsuma mandarin are candidate micronutrients for preventing arteriosclerosis development. Further longitudinal and interventional studies will be required to validate the effect on CVD.

A patient with elderly-onset atypical hydroa vacciniforme with an indolent clinical course.

Hydroa vacciniforme (HV) is a rare photodermatosis that mainly affects children and manifests as vesiculopapular eruptions in sun-exposed areas without systemic symptoms. HV-like lymphoma (HVLL) is one of the Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPD) of childhood. Its diagnosis is based on monoclonal T-cell proliferation; however, its degree of malignancy is controversial owing to its variable prognosis. Elderly-onset cases of these diseases are extremely rare, and the clinical features remain unknown. It has been shown that late onset is closely associated with a severe phenotype in EBV-associated LPD including atypical HV. Here we describe a case of elderly-onset atypical HV accompanied by T-cell monoclonality, but with a very indolent clinical course. Our patient indicates a possible case with elderly-onset atypical HV manifesting a favourable course, and that T-cell monoclonality and age of onset cannot always predict the disease severity, and highlights the difficulty of prognosis prediction in elderly-onset atypical HV.

Brain structural changes as vulnerability factors and acquired signs of post-earthquake stress.

Many survivors of severe disasters, even those without posttraumatic stress disorder (PTSD), need psychological support. To understand the pathogenesis of PTSD symptoms and prevent the development of PTSD, the critical issue is to distinguish neurological abnormalities as vulnerability factors from acquired signs of PTSD symptoms in the early stage of adaptation to the trauma in the normal population. The neurological underpinnings of PTSD have been well characterized, but the causal relationships with the traumatic event are still unclear. We examined 42 non-PTSD subjects to find brain morphometric changes related to the severity of PTSD symptoms in a longitudinal magnetic resonance imaging study extending through the Great East Japan Earthquake. We found that regional grey matter volume (rGMV) in the right ventral anterior cingulate cortex (ACC) before the earthquake, and decreased rGMV in the left orbitofrontal cortex (OFC) through the earthquake were negatively associated with PTSD symptoms. Our results indicate that subjects with smaller GMV in the ACC before the earthquake, and subjects with decreased GMV in the OFC through the earthquake were likely to have PTSD symptoms. As the ACC is involved in processing of fear and anxiety, our results indicate that these processing are related to vulnerability for PTSD symptoms. In addition, decreased OFC volume was induced by failing to extinct conditioned fear soon after the traumatic event. These findings provide a better understanding of posttraumatic responses in early stage of adaptation to the trauma and may contribute to the development of effective methods to prevent PTSD.

Association of interleukin-1 gene polymorphisms with sudden sensorineural hearing loss and Ménière's disease.

Sudden sensorineural hearing loss (SSNHL) and Ménière's disease are the most common inner ear diseases in which the causes are unknown. As recent magnetic resonance imaging has demonstrated disruption of the blood-labyrinth barrier in these inner ear diseases, inflammatory reaction associated with increased permeability of the blood vessels may be involved. The genotypes of interleukin 1A (IL1A) (-889C/T; rs1800587) and interleukin 1B (IL1B) (-511C/T; rs16944) were determined using an allele-specific primer-polymerase chain reaction method in 72 patients with SSNHL, 68 patients with Ménière's disease, and 2202 control subjects living almost in the same area as the patients. A significantly higher prevalence of the IL1A-889T allele was observed in SSNHL and Ménière's disease compared with controls, although no significant difference in distribution of IL1B-511C/T genotypes was observed between the patients and controls. Adjusted odd ratios for SSNHL and Ménière's disease risks in the -889TT genotypes were 25.89 (95% confidence interval (CI) 12.19-54.98) and 18.20 (95% CI 7.80-42.46), respectively, after age and gender were taken as moderator variables. Our results suggested that IL1A is closely associated with susceptibility of SSNHL and Ménière's disease.

Dietary patterns of antioxidant vitamin and carotenoid intake associated with bone mineral density: findings from post-menopausal Japanese female subjects.

UNLABELLED: Recent studies show that antioxidants may reduce the risk of osteoporosis. This study showed the associations of bone mineral density with dietary patterns of antioxidant vitamins and carotenoids. The findings suggest the combination of vitamin C and ß-cryptoxanthin intakes might provide benefit to bone health in post-menopausal Japanese female subjects. INTRODUCTION: Recent epidemiological studies show antioxidants may reduce the risk of osteoporosis, but little is known about the dietary patterns of antioxidant vitamin and carotenoid intakes and their relation with bone mineral density (BMD). METHODS: A total of 293 post-menopausal female subjects who had received health examinations in the town of Mikkabi, Shizuoka Prefecture, Japan, participated in the study. Radial BMD was measured using dual-energy X-ray absorptiometry. Dietary intakes of antioxidant vitamins and carotenoids were assessed by using a validated food-frequency questionnaire. Dietary patterns were identified on a selected set of antioxidants through principal component factor analysis. RESULTS: Three dietary patterns were identified. The "retinol" pattern, characterized by notably high intakes of preformed retinol, zeaxanthin, and vitamin E, was positively associated with the risk for low BMD. In contrast, the "ß-cryptoxanthin" pattern, characterized by notably high intakes of ß-cryptoxanthin and vitamin C, was negatively associated with low BMD. The odds ratios for low BMD in the highest tertiles of dietary intakes of preformed retinol, vitamin C, and ß-cryptoxanthin against the lowest tertiles were 3.22 [95% confidence interval (CI), 1.38-7.51], 0.25 (CI, 0.10-0.66), and 0.40 (CI, 0.17-0.92), respectively, after adjustments for confounders. However, negative associations of vitamin C and ß-cryptoxanthin with low BMD were not significant after further adjustment for intake of ß-cryptoxanthin or vitamin C, respectively. Higher intakes of both vitamin C and ß-cryptoxanthin were significantly associated with low BMD (P < 0.05). CONCLUSIONS: The combination of vitamin C and ß-cryptoxanthin may be associated with radial BMD in post-menopausal Japanese female subjects.

Analysis of VH gene rearrangement and somatic hypermutation in Sjogren's syndrome and IgG4-related sclerosing sialadenitis.

IgG4-related sclerosing sialadenitis is currently considered as an autoimmune disease distinct from Sjogren's syndrome (SS) and responds extremely well to steroid therapy. To further elucidate the characteristics of IgG4-related sclerosing sialadenitis, we analysed VH fragments of IgH genes and their somatic hypermutation in SS (n = 3) and IgG4-related sclerosing sialadenitis (n = 3), using sialolithiasis (n = 3) as a non-autoimmune control. DNA was extracted from the affected inflammatory lesions. After PCR amplification of rearranged IgH genes, at least 50 clones per case (more than 500 clones in total) were sequenced for VH fragments. Monoclonal IgH rearrangement was not detected in any cases examined. When compared with sialolithiasis, there was no VH family or VH fragment specific to SS or IgG4-related sclerosing sialadenitis. However, rates of unmutated VH fragments in SS (30%) and IgG4-related sclerosing sialadenitis (39%) were higher than that in sialolithiasis (14%) with statistical significance (P = 0.0005 and P < 0.0001, respectively). This finding suggests that some autoantibodies encoded by germline or less mutated VH genes may fail to be eliminated and could play a role in the development of SS and IgG4-related sclerosing sialadenitis.

Soy sauce allergy.

BACKGROUND: Soy sauce is well-known as a Japanese traditional seasoning, namely shoyu. Usually, shoyu means sauce made from soy. Shoyu does have not only benefits but also adverse effects. Soy sauce allergy which is not caused by soy or wheat allergy is rare. PATIENTS: Our four patients developed cellulites and dermatitis around lips with irritation after a meal with shoyu. The age of the patients was 10, 35, 46 and 51 years; they were all female. OBJECTIVES: These inflammations can be developed by two causes; first it can be caused by allergic reactions to shoyu; the second, it can be caused by histamine poisoning. It is important to determine whether inflammation is caused by allergic reactions or histamine poisoning. METHODS: We determined the volume of histamine in some sauces and performed prick test and laboratory tests. RESULTS: Four patients had positive reactions by prick test after using some sauces. We suspected that histamine caused their symptoms, but nine normal volunteers had negative reactions. Patient's specific IgE score to soy and wheat was class 0. The results showed that the sauce made from soybean and broad bean contained histamine, but histamine in other sauces was not detected. CONCLUSIONS: In this study, we confirmed by prick test, four cases of soy sauce allergy, which was caused by some products during brewing. When patients with inflammations around mouth, after a meal containing or using soy sauce, are examined, it should be considered whether dermatitis or cellulites were developed by allergic reaction or by histamine poisoning.

Anatomy-based surgery to remove thyroglossal duct cyst: two anomalous cases.

OBJECTIVE: To review previous reports and to discuss the management of branching polycystic and giant thyroglossal duct cysts. CASE REPORT: We present two cases of thyroglossal duct cyst: one a branching, polycystic thyroglossal duct cyst in an 11-year-old boy, and the other a giant thyroglossal cyst in a 41-year-old man. Such cysts are rare. Both patients were operated upon according to the methods of Sistrunk and Horisawa, and both had a satisfactory post-operative course. DISCUSSION: We discuss the most important aspects of such cyst removal procedures. CONCLUSION: Our experience suggests that surgery to remove an anomalous thyroglossal duct cyst should be performed using a technique based on the anatomy of the hyoid bone region.

[Lung cancer operation in situs inversus totalis patient].

Situs inversus totalis represents a complete mirror image anatomy of the normal arrangement of the thoracic and abdominal viscera. This rare condition may pose possible surgical problems due to anatomical abnormality. There were few reports of surgical treatment for lung cancer patient with situs inversus totalis. In this case report, we describe a 74-year-old patient with situs inversus totalis and primary lung cancer who underwent successful left upper lobectomy and systemic lymph node dissection. For this rare condition, detail preoperative evaluation of mirror image anatomy with computed tomography and bronchofiber optic examination was thought to be a key to carry out safe operative procedure.