Analysis of thyroid function and related factors in narcolepsy patients.

The loss of hypocretin is thought to be the main pathophysiological mechanism of narcolepsy. There is strong evidence that hypocretin is related to the regulation of endocrine functions and depression. To explore thyroid hormone levels in narcolepsy patients was our aim. In addition, further is to analyze the relationship between thyroid hormone levels and sleep quality, anxiety, and depression in narcolepsy patients. There are 40 patients with narcolepsy and 40 healthy controls (HCs) were conducted. Blood samples were explored for thyroid function. Correlation analysis between thyroid hormones and clinical characteristics of narcolepsy was performed using Pearson or Spearman. Narcolepsy patients had significantly lower free thyroxine (FT4) levels in comparison to controls (p < 0.001). No subject was diagnosed with primary hypothyroidism. There were 4 (10%) subjects with subclinical hypothyroidism. The serum FT4 levels were positively correlated with HAMA14 score (r = - 0.343, p = 0.030) by Pearson correlation analysis. The serum TSH levels and HAMD24 score (r = - 0.807 p ˂0.001), and ESS score (r = - 0.317, p = 0.046) both showed a negative correction. Hypocretin deficiency may be associated with the regulation of thyroid hormones in narcolepsy patients. The serum thyroid hormones may affect the severity and neuropsychological functions of narcolepsy patients.

Clinical characteristics and phenotype distribution in 10 Chinese patients with X-linked adrenoleukodystrophy.

X-linked adrenoleukodystrophy (X-ALD) is the most frequent type of inherited demyelinating peroxisomal disease caused by mutations in the ATP binding cassette subfamily D member 1 (ABCD1) gene. The rate of early recognition and genetic diagnosis of X-ALD remains low due to its variable clinical manifestations. The present study summarized the clinical features Chinese X-ALD patients and performed a follow-up study to further precisely characterize this disease. A total of 10 patients diagnosed with X-ALD between 1994 and 2016 at Shandong Provincial Hospital Affiliated to Shandong University (Jinan, China) were included in the present study. Through reviewing their medical records and performing telephone follow-ups, the clinical features, biochemical laboratory data, brain images, treatments and long-term outcomes were retrospectively summarized. Mutation analysis of the ABCD1 gene was performed in certain patients. Most of the patients (8/10) had the childhood cerebral form of X-ALD. One patient presented with the olivo-ponto-cerebellar form, the rarest form of X-ALD. In all patients, brain magnetic resonance images revealed abnormalities with typical T2-weighted hyperintensity. Analysis of very long chain fatty acid revealed high plasma levels of hexacosanoic acid in all patients. Increased adrenocorticotropic hormone, decreased cortisol and neurophysiological manifestations were also observed. Three different mutations of the ABCD1 gene were identified in the 3 patients subjected to genotyping. During the follow-ups, most patients took neurotrophic drugs and received hydrocortisone replacement when required. One patient received a hematopoietic stem cell transplantation, but died 1 year following the transplantation. Chronic myelopathy and peripheral neuropathy progressed with time, gradually leading to a vegetative state or paralysis within several years of clinical symptom onset. In conclusion, male patients with adrenocortical insufficiency should be further investigated for X-ALD. Early detection is critical to prevent the progression of X-ALD with mutation analysis of ABCD1 the most accurate method to confirm diagnosis.

Influence of Straw Burning on Urban Air Pollutant Concentrations in Northeast China.

Northeast China is China's primary grain production base. A large amount of crop straw is incinerated every spring and autumn, which greatly impacts air quality. To study the degree of influence of straw burning on urban pollutant concentrations, this study used The Moderate-Resolution Imaging Spectroradiometer/Terra Thermal Anomalies & Fire Daily L3 Global 1 km V006 (MOD14A1) and The Moderate-Resolution Imaging Spectroradiometer/Aqua Thermal Anomalies and Fire Daily L3 Global 1 km V006 (MYD14A1) data from 2015 to 2017 to extract fire spot data on arable land burning and to study the spatial distribution characteristics of straw burning on urban pollutant concentrations, temporal variation characteristics and impact thresholds. The results show that straw burning in Northeast China is concentrated in spring and autumn; the seasonal spatial distributions of PM2.5, PM10 andAir Quality Index (AQI) in 41 cities or regions in Northeast China correspond to the seasonal variation of fire spots; and pollutants appear in the peak periods of fire spots. In areas where the concentration coefficient of rice or corn is greater than 1, the number of fire spots has a strong correlation with the urban pollution index. The correlation coefficient R between the number of burned fire spots and the pollutant concentration has a certain relationship with the urban distribution. Cities are aggregated in geospatial space with different R values.

The roles of special proresolving mediators in pain relief.

The resolution of acute inflammation, once thought to be a passive process, is now recognized as an active one. The productions of endogenous special proresolving mediators (SPMs) are involved in this process. SPMs, including lipoxins, resolvins, protectins, and maresins, are endogenous lipid mediators generated from ω-6 arachidonic acid or ω-3 poly-unsaturated fatty acids during the resolution phase of acute inflammation. They have potent anti-inflammatory and proresolving actions in various inflammatory disorders. Due to the potent proresolving and anti-inflammatory effects, SPMs are also used for pain relief. This review focuses on the mechanisms by which SPMs act on their respective G-protein-coupled receptors in immune cells and nerve cells to normalize pain via regulating inflammatory mediators, transient receptor potential ion channels, and central sensitization. SPMs may offer novel therapeutic approaches for preventing and treating pain conditions associated with inflammation.

Molecular epidemiology of swine influenza A viruses in the Southeastern United States, highlights regional differences in circulating strains.

Swine influenza A virus (IAV) can cause widespread respiratory disease with high morbidity, low mortality, and have a substantial economic impact to the swine industry. Swine infection may contribute to pandemic IAV given their susceptibility to both avian and human IAVs. Currently, three IAV subtypes (H1N1, H3N2 and H1N2) circulate in swine in North America frequently combining gene segments from avian or human viruses. This study investigated the prevalence of IAV in commercial swine herds. A total of 1878 oral fluid samples were collected from pigs of all ages from 201 commercial farms located in North Carolina and South Carolina. Sixty-eight oral fluid samples from 35 farms were positive by MP gene PCR with an overall IAV-positivity of 3.6%. On the herd level, the percentage of IAV positivity was 17.4%. Fifty-six viruses were subtyped, while 12 were partly subtyped or not subtyped at all. Using de novo assembly, complete sequences were obtained for 59 HA genes. The majority of IAVs subtyped had an H1 HA demonstrating a considerable prevalence over H3 viruses. Furthermore, only six out of eleven HA types were detected which has implications for the selection of vaccines used by swine producers in the region.

Confirmation of the pathogenicity of a mutation p.G337C in the COL1A2 gene associated with osteogenesis imperfecta.

Mutation analysis as the gold standard is particularly important in diagnosis of osteogenesis imperfecta (OI) and it may be preventable upon early diagnosis. In this study, we aimed to analyze the clinical and genetic materials of an OI pedigree as well as to confirm the deleterious property of the mutation.A pedigree with OI was identified. All family members received careful clinical examinations and blood was drawn for genetic analyses. Genes implicated in OI were screened for mutation. The function and structure of the mutant protein were predicted using bioinformatics analysis.The proband, a 9-month fetus, showed abnormal sonographic images. Disproportionately short and triangular face with blue sclera was noticed at birth. She can barely walk and suffered multiple fractures till 2-year old. Her mother appeared small stature, frequent fractures, blue sclera, and deformity of extremities. A heterozygous missense mutation c.1009G>T (p.G337C) in the COL1A2 gene was identified in her mother and her. Bioinformatics analysis showed p.G337 was well-conserved among multiple species and the mutation probably changed the structure and damaged the function of collagen.We suggest that the mutation p.G337C in the COL1A2 gene is pathogenic for OI by affecting the protein structure and the function of collagen.

Decoding noises in HIV computational genotyping.

Lack of a consistent and reliable genotyping system can critically impede HIV genomic research on pathogenesis, fitness, virulence, drug resistance, and genomic-based healthcare and treatment. At present, mis-genotyping, i.e., background noises in molecular genotyping, and its impact on epidemic surveillance is unknown. For the first time, we present a comprehensive assessment of HIV genotyping quality. HIV sequence data were retrieved from worldwide published records, and subjected to a systematic genotyping assessment pipeline. Results showed that mis-genotyped cases occurred at 4.6% globally, with some regional and high-risk population heterogeneities. Results also revealed a consistent mis-genotyping pattern in gp120 in all studied populations except the group of men who have sex with men. Our study also suggests novel virus diversities in the mis-genotyped cases. Finally, this study reemphasizes the importance of implementing a standardized genotyping pipeline to avoid genotyping disparity and to advance our understanding of virus evolution in various epidemiological settings.

TPH2 gene polymorphisms and bipolar disorder: A meta-analysis.

BACKGROUND: Disturbance of the serotonergic system contributes to the etiology of bipolar disorder (BD). Tryptophan hydroxylase-2 (TPH2) is an important rate-limiting enzyme in the synthetic pathway for brain serotonin and has been suggested to play a role in BD. MATERIALS AND METHODS: We performed a systematic review and meta-analysis of all studies to date investigating the association studies between TPH2 and BD published before Aug 2014. All studies were abstracted from PubMed, Embase, HuGNet, and China National Knowledge Infrastructure (CNKI). Manuscripts and the supplementary documents of published genome-wide association studies in the field were also included. Effect sizes of independent loci that have been studied in more than three articles were synthesized using fixed and random effects models. RESULTS: Eight eligible studies addressed association between 63 TPH2 gene single nucleotide polymorphisms (SNPs) with BD, after linkage disequilibrium analysis, 12 independent SNPs were identified. Finally, three SNPs (rs4760820, rs11178998, and rs7954758) were found associated with BD using fixed effects models, and rs4760820 and rs11178998 were still associated with BD even with the more conservative random effects models. CONCLUSIONS: rs4760820 and rs11178998 were identified to have strong genetic association with BD in present study though confirmation will require larger sample sizes and in additional populations.

Small interfering RNA-mediated knockdown of NF-κBp65 attenuates neuropathic pain following peripheral nerve injury in rats.

Recent reports show that the nuclear factor-κB (NF-κB) can control numerous genes encoding inflammatory and nociceptive mediators and play an important role in the development of central pain sensitization. The aim of the present study is to assess the role of NF-κB signal pathway and its downstream pro-inflammatory cytokines in the modulation of neuropathic pain, by using small interfering RNAs (siRNAs) technique, which has been shown to result in potent, long-lasting post-transcriptional silencing of specific genes. We developed a highly efficient method of lentivirus-mediated delivery of short-hairpin RNA (shRNA) targeting NF-κBp65 for gene silencing. This method successfully transduced LV-shNF-κBp65 into cultured spinal cord neurons in vitro and spinal cord cells in vivo, inhibited the expression of NF-κBp65 and pro-inflammatory factors (TNF-α, IL-1ß and IL-6) and alleviated mechanical allodynia and thermal hyperalgesia for more than 4weeks in chronic constriction injury (CCI) model of rats. Taken together, our results suggest that siRNA against NF-κBp65 is a potential strategy for analgesia. Furthermore, the lentiviral vector derived shRNA approach shows a great promise for the management of neuropathic pain and the study of functional NF-κBp65 gene expression.

[Expression of NF-kappaB and TNF-alpha in spinal dorsal horn in a rat model of neuropathic pain].

OBJECTIVE: To investigate the expressions of NF-kappaB and TNF-alpha in lumbar spinal cord in a rat model of chronic constrictive injury (CCI). METHODS: Seventy-six male SD rats were randomly divided into 2 groups (n = 38 each): CCI group receiving chronic constriction injury and sham group receiving sham operation as control. The mechanical and thermal nociceptive thresholds were assessed with paw withdrawal latency (PWL) to von Frey filaments and radiant heat at different time points. Five animals were sacrificed at each time point for real-time polymerase chain reaction (real-time PCR) and another three animals sacrificed at 7 d post-operation for double-immunofluorescence histochemical staining. Lumbar segments of spinal cord were removed. The expressions of NF-kappaB and TNF-alpha in spinal cord were examined by real-time PCR and double-immunofluorescence histochemical technique. RESULTS: The post-operative thresholds to mechanical and thermal stimuli decreased obviously. As compared with contralateral side and sham group, the expressions of NF-kappaB and TNF-alpha mRNA increased significantly in ipsilateral spinal dorsal horn. Their expressions began to increase at 4 d post-operation and peaked at 7 d. Then TNF-alpha began to decrease while NF-kappaB maintained at a high level throughout the experiment. Double-immunofluorescence histochemical staining revealed extensive co-localization of NF-kappaB with TNF-alpha on ipsilateral side of dorsal horn. CONCLUSION: The activation of NF-kappaB and its downstream inflammatory mediators may be involved in the regulation of neuropathic pain.