Physical frailty trajectories in older stroke survivors: Findings from a national cohort study.

BACKGROUND: Physical frailty (PF) is highly prevalent and associated with undesirable outcomes in stroke survivors aged 65 years or older. However, the long-term trajectories of PF are understudied in those older stroke survivors. AIMS: To identify PF trajectories and relative predictors associated with the PF trajectories in older stroke survivors. DESIGN: This is a secondary analysis of a population-based cohort study in the United States. METHODS: Six hundred and sixty-three older stroke survivors from the National Health and Ageing Trends Study from 2015 to 2021 were included. PF was operationally assessed based on the Fried Frailty Phenotype. Trajectories were identified by group-based trajectory modelling. The associations between sociodemographic characteristics, clinical factors, symptoms, cognitive factors and PF trajectories were examined using the design-based logistic regression method. RESULTS: Most older stroke survivors were 75 and older (63.32%), female (53.99%), white (80.54%) and partnered (50.64%). Two PF trajectory groups were identified (Group 1: low risk, robust; 49.47%; Group 2: high risk, deteriorating; 50.53%). Individuals were at a higher risk to be assigned to Group 2 if they were 75-84 years (adjusted odds ratio [aOR]: 2.16, 95% CI: 1.23-3.80) or 85+ years (aOR: 2.77, 95% CI: 1.52-5.04), had fair self-reported health (aOR: 2.78, 95% CI: 1.53-5.07) or poor self-reported health (aOR: 3.37, 95% CI: 1.51-7.52), had comorbidities (aOR: 8.44, 95% CI: 1.31-54.42), had breathing problems (aOR: 2.18, 95% CI: 1.18-4.02) and had balance problems (aOR: 1.70, 95% CI: 1.06-2.73). CONCLUSION: PF trajectories in older stroke survivors were heterogeneous and were associated with age, self-rated health status, comorbidities, breathing problems and balance problems. IMPLICATION TO CLINICAL PRACTICE: Early, routine, dynamic screening for stroke-related physical frailty (PF) and relative predictors might be beneficial for identifying the most vulnerable individuals. Our findings might help develop strategies to manage PF progression. REPORTING METHOD: The reporting followed the STROBE guideline.

Profile of Chinese Cluster Headache Register Individual Study (CHRIS): Clinical characteristics, diagnosis and treatment status data of 816 patients in China.

BACKGROUND: The clinical profile of cluster headache may differ among different regions of the world, warranting interest in the data obtained from the initial Chinese Cluster Headache Register Individual Study (CHRIS) for better understanding. METHODS: We conducted a multicenter, prospective, longitudinal cohort study on cluster headache across all 31 provinces of China, aiming to gather clinical characteristics, treatment approaches, imaging, electrophysiological and biological samples. RESULTS: In total 816 patients were enrolled with a male-to-female ratio of 4.33:1. The mean age at consultation was 34.98 ± 9.91 years, and 24.89 ± 9.77 years at onset. Only 2.33% were diagnosed with chronic cluster headache, and 6.99% had a family history of the condition. The most common bout was one to two times per year (45.96%), lasting two weeks to one month (44.00%), and occurring frequently in spring (76.23%) and winter (73.04%). Of these, 68.50% experienced one to two attacks per day, with the majority lasting one to two hours (45.59%). The most common time for attacks was between 9 am and 12 pm (75.86%), followed by 1 am and 3 am (43.48%). Lacrimation (78.80%) was the most predominant autonomic symptom reported. Furthermore, 39.22% of patients experienced a delay of 10 years or more in receiving a correct diagnosis. Only 35.67% and 24.26% of patients received common acute and preventive treatments, respectively. CONCLUSION: Due to differences in ethnicity, genetics and lifestyle conditions, CHRIS has provided valuable baseline data from China. By establishing a dynamic cohort with comprehensive multidimensional data, it aims to advance the management system for cluster headache in China.

Verification of a clinical decision support system for the diagnosis of headache disorders based on patient-computer interactions: a multi-center study.

BACKGROUND: Although headache disorders are common, the current diagnostic approach is unsatisfactory. Previously, we designed a guideline-based clinical decision support system (CDSS 1.0) for diagnosing headache disorders. However, the system requires doctors to enter electronic information, which may limit widespread use. METHODS: In this study, we developed the updated CDSS 2.0, which handles clinical information acquisition via human-computer conversations conducted on personal mobile devices in an outpatient setting. We tested CDSS 2.0 at headache clinics in 16 hospitals in 14 provinces of China. RESULTS: Of the 653 patients recruited, 18.68% (122/652) were suspected by specialists to have secondary headaches. According to "red-flag" responses, all these participants were warned of potential secondary risks by CDSS 2.0. For the remaining 531 patients, we compared the diagnostic accuracy of assessments made using only electronic data firstly. In Comparison A, the system correctly recognized 115/129 (89.15%) cases of migraine without aura (MO), 32/32 (100%) cases of migraine with aura (MA), 10/10 (100%) cases of chronic migraine (CM), 77/95 (81.05%) cases of probable migraine (PM), 11/11 (100%) cases of infrequent episodic tension-type headache (iETTH), 36/45 (80.00%) cases of frequent episodic tension-type headache (fETTH), 23/25 (92.00%) cases of chronic tension-type headache (CTTH), 53/60 (88.33%) cases of probable tension-type headache (PTTH), 8/9 (88.89%) cases of cluster headache (CH), 5/5 (100%) cases of new daily persistent headache (NDPH), and 28/29 (96.55%) cases of medication overuse headache (MOH). In Comparison B, after combining outpatient medical records, the correct recognition rates of MO (76.03%), MA (96.15%), CM (90%), PM (75.29%), iETTH (88.89%), fETTH (72.73%), CTTH (95.65%), PTTH (79.66%), CH (77.78%), NDPH (80%), and MOH (84.85%) were still satisfactory. A patient satisfaction survey indicated that the conversational questionnaire was very well accepted, with high levels of satisfaction reported by 852 patients. CONCLUSIONS: The CDSS 2.0 achieved high diagnostic accuracy for most primary and some secondary headaches. Human-computer conversation data were well integrated into the diagnostic process, and the system was well accepted by patients. The follow-up process and doctor-client interactions will be future areas of research for the development of CDSS for headaches.

Health status and public health education for internal older migrants in China: Evidence from a nationally representative survey.

Background: Self-rated health has been widely used as a useful screening tool to subjectively evaluate individuals' health status. Under the context of the rapid growth of aging, there was a dramatic rapid expansion in internal older migrants in China. Serious concerns on the issues of health status continue to attract quite a lot of attention over the past decades. Public health education is one of the most important health care services and methods to improve individuals' health status. However, most previous studies focus on the utilization of public health services such as visiting to doctors, physical examination, and hospitalization. There was limited evidence on the self-rated health and public health education of older migrants. Objectives: The study aimed to evaluate self-rated health and the associated determinants in older migrants, as well as to gain a deeper insight into the current status of public health education received by older migrants. Methods: We derived the data from the National Migrants Population Health and Family Planning Dynamic Monitor Survey 2018, a cross-sectional study, for secondary analysis. Internal migrants aged 60 years old or over were included in the study. Self-rated health was the dependent variable, while sociodemographic characteristics were the independent variable. The univariate and multivariate analyses were performed by Stata 15.1. Results: A total of 5,589 older migrants were included in the study. Eighty-two percentage of older migrants reported healthy self-rated health. There was a significant association between age, gender, minzu, education level, monthly income, public health education, and self-rated health (P < 0.5). However, the proportion of older migrants that received specific public health education was <50%. The most common approach to receiving public health education was through the leaflet, while <20% of older migrants received public health education through public consultation and one-to-one education. Conclusions: It was necessary to promote the publicity of public health education in older migrants through easy access and diverse approaches in order to effectively spread health-related knowledge to older migrants to satisfy their health needs and maintain their health.

Perceived Family Function and Associated Predictors in Nurses: A Cross-Sectional Study.

Background: Nurses play a key role in the health care system. However, clinical nurses experience different kinds of stressors that might impact the nurses' quality of life or quality of care. Family is one of the main social support resources, and quality family function might improve the quality of care provided by nurses. However, evidence on family function in Chinese clinical nurses is quite limited. Objectives: The current study was to evaluate the family function of the Chinese clinical nurses, and to explore associated predicting factors. Methods: A multi-center cross-sectional anonymous online survey was carried out. Chinese Family Function Scale was used in the study. Spearman's rank correlation analysis, Mann-Whitney U test, or Kruskal-Wallis H test was performed in the univariate analysis. The pairwise comparison method was used to determine whether the difference was significant between pair groups. Categorical regression (optimal scaling regression) was the main method to analyze factors that had been confirmed to be statistically significant in the univariate analysis. Results: Nineteen thousand four hundred and twenty-two nurses completed the online questionnaires. The median of the nurse's perceived family function score was three (Inter-quartile Range: IQR 2-5). The multivariate analysis showed that the highest education level (P <0.001), the hospital level (P <0 .001), rotation shift status (P <0.001), working department (P < 0.001), number of children (P < 0.001), monthly income per family member (P < 0.001) were significantly associated with family function. Moreover, the importance of the factors was the number of children (49.1%), monthly income per family member (20.7%), rotation shift status (12.4%), the highest education level (8.0%), the hospital level (7.6%), and working department (2.4%) in turn. Conclusions: The family function was associated with multiple factors, which hints that managers, leaders, and government could make strategies to improve nurses' family function in order to lead nurses to make a balance between family and work. Policymakers, nursing managers, and employers should make strategies such as promoting children-care services, increasing nurses' income, educating and training enough nurses, and building a well-established system of career development to help clinical nurses improve their family function so that to improve the quality of care.

Upregulation of N-Type Voltage-Gated Calcium Channels Induces Neuropathic Pain in Experimental Autoimmune Neuritis.

Objective: Guillain-Barré syndrome (GBS) is a common autoimmune disease of the peripheral nervous system, and there is still no effective treatment for GBS. This investigation intends to figure out the effect and mechanism of N-type voltage-gated calcium (Cav2.2) channels on neuropathic pain in GBS. Methods: An experimental autoimmune neuritis (EAN) model was established in Lewis rats induced by myelin P253-78 peptide and complete Freund's adjuvant. Luxol fast blue (LFB) staining was used for observing the degree of cell infiltration and demyelination in the sciatic nerve of rats, ELISA for detecting IL-6 and TNF-α expression in the serum, qRT-PCR, and Western blot for measuring the expression of iNOS, MCP-1, and Cav2.2 in the sciatic nerve, respectively. Results: EAN led to significant decreases in the mechanical withdrawal threshold, thermal withdrawal threshold, and mechanical hyperalgesia threshold and an increase in the withdrawal threshold to cold stimulation. The serum IL-6 and TNF-α expression was significantly increased, and the mRNA and protein expression of iNOS, MCP-1, and Cav2.2 in the sciatic nerve were significantly increased in the EAN rats. However, silencing Cav2.2 expression could significantly reverse the above EAN-caused results. Conclusion: Silencing Cav2.2 expression can significantly reduce the clinical score, pathological injury, and mechanical allodynia, reducing the release of inflammatory factors, thus improving neuropathic pain in EAN rats.

Health promoting lifestyle behaviors and associated predictors among clinical nurses in China: a cross-sectional study.

BACKGROUND: Nurses play a core role and encompass the main workforce in health care systems. Their role model of health promoting lifestyle behaviors (HPLB) would directly or indirectly affect their clients' beliefs or attitudes of health promotion. There is limited evidence on HPLB in clinical registered nurses. The current study aimed to explore the HPLB and associated influencing factors among clinical registered nurses in China. METHODS: A multi-center cross-sectional anonymous online survey was conducted in 2020. Participants were asked to complete social demographic information as well as the revised Chinese edition of Health Promoting Lifestyle Profile (HPLP). Independent-Sample T-Test, One-Way ANOVA, and categorical regression (optimal scaling regression) were the main methods to analyze the relationship between demographic data and the score of HPLB. RESULTS: 19,422 nurses were included in the study. The mean score of self-actualization, health responsibility/physical activity, nutrition, job safety, interpersonal support, and overall Health Promoting Lifestyle Profile were, 27.61(5.42) out of a score of 36, 22.71(7.77) out of a score of 44, 10.43(2.97) out of a score of 16, 22.05(3.97) out of a score of 28, 20.19(4.67) out of a score of 28, and 102.99 (19.93) out of a score of 144, respectively. There was a significant relationship among Hospital levels, working years, nightshift status, and monthly income per person, and mean score of all subscales and the overall HPLP (P < 0.05). CONCLUSIONS: Nurses who participated in the study presented a moderate level of health promoting lifestyle behaviors. Hospital levels, working years, nightshift status, and monthly income per person were predictors for all subscales and overall HPLP.

Recommendations for the diagnosis and treatment of paroxysmal kinesigenic dyskinesia: an expert consensus in China.

Paroxysmal dyskinesias are a group of neurological diseases characterized by intermittent episodes of involuntary movements with different causes. Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesia and can be divided into primary and secondary types based on the etiology. Clinically, PKD is characterized by recurrent and transient attacks of involuntary movements precipitated by a sudden voluntary action. The major cause of primary PKD is genetic abnormalities, and the inheritance pattern of PKD is mainly autosomal-dominant with incomplete penetrance. The proline-rich transmembrane protein 2 (PRRT2) was the first identified causative gene of PKD, accounting for the majority of PKD cases worldwide. An increasing number of studies has revealed the clinical and genetic characteristics, as well as the underlying mechanisms of PKD. By seeking the views of domestic experts, we propose an expert consensus regarding the diagnosis and treatment of PKD to help establish standardized clinical evaluation and therapies for PKD. In this consensus, we review the clinical manifestations, etiology, clinical diagnostic criteria and therapeutic recommendations for PKD, and results of genetic analyses in PKD patients performed in domestic hospitals.

Quantitative Study of the Changes in Cerebral Blood Flow and Iron Deposition During Progression of Alzheimer's Disease.

BACKGROUND: Advanced Alzheimer's disease (AD) has no effective treatment, and identifying early diagnosis markers can provide a time window for treatment. OBJECTIVE: To quantify the changes in cerebral blood flow (CBF) and iron deposition during progression of AD. METHODS: 94 subjects underwent brain imaging on a 3.0-T MRI scanner with techniques of three-dimensional arterial spin labeling (3D-ASL) and quantitative susceptibility mapping (QSM). The subjects included 22 patients with probable AD, 22 patients with mild cognitive impairment (MCI), 25 patients with subjective cognitive decline (SCD), and 25 normal controls (NC). The CBF and QSM values were obtained using a standardized brain region method based on the Brainnetome Atlas. The differences in CBF and QSM values were analyzed between and within groups using variance analysis and correlation analysis. RESULTS: CBF and QSM identified several abnormal brain regions of interest (ROIs) at different stages of AD (p < 0.05). Regionally, the CBF values in several ROIs of the AD and MCI subjects were lower than for NC subjects (p < 0.001). Higher QSM values were observed in the globus pallidus. The CBF and QSM values in multiple ROI were negatively correlated, while the putamen was the common ROI of the three study groups (p < 0.05). The CBF and QSM values in hippocampus were cross-correlated with scale scores during the progression of AD (p < 0.05). CONCLUSION: Iron deposition in the basal ganglia and reduction in blood perfusion in multiple regions existed during the progression of AD. The QSM values in putamen can be used as an imaging biomarker for early diagnosis of AD.

Case 259: Primary Central Nervous System Lymphomatoid Granulomatosis Mimicking Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS).

History In November 2012, a previously healthy 31-year-old woman was admitted to our hospital with a 2-month history of right-sided numbness, diplopia, and intermittent nausea and dizziness. She did not have a history of fever, weight loss, headache, photophobia, seizure, or extremity weakness. Physical examination revealed left abduction limitation and right-sided hypoesthesia. Kernig and Brudzinski signs were absent, and pathergy test results were negative. Laboratory evaluation revealed normal complete and differential blood counts, normal serum chemistry, and normal immune function. Analysis of her serum was negative for antiaquaporin 4 antibody, rheumatism antibody profile, and paraneoplastic profile. Serum analysis was also negative for human immunodeficiency virus type 1 and 2 RNA, hepatitis B and C antigen or antibody profile, and fluorescent treponemal antibody absorption. Cerebrospinal fluid (CSF) analysis revealed clear fluid, a normal glucose level, an elevated protein level (45 mg/dL; normal range, 20-40 mg/dL), and an elevated white blood cell count (10/mm3 [0.01 ×109/L]; normal range, 0-8/mm3 [{0-0.008} ×109/L]; 81% lymphocytes, 19% monocytes). No CSF-specific oligoclonal bands were detected. Gram staining, acid-fast staining, and lactic acid and cryptococcal antigen test results were negative. CSF did not grow any bacteria, fungus, or acid-fast bacillus at culture. Spinal cord MRI, brain MR angiography, and CT of the chest, abdomen, and pelvis revealed normal findings (images not shown). Brain MRI and gadolinium-enhanced (20 mL gadopentetate dimeglumine, BeiLu Pharmaceutical, Beijing, China) MRI were performed. The patient's clinical symptoms and imaging findings responded to treatment with a high dose of steroids. However, the patient's symptoms exhibited clinical and radiologic progression as she attempted to taper the steroid dose. She arbitrarily stopped taking the steroids and started traditional Chinese treatment instead. However, her condition was not controlled. In November 2013, she was readmitted with worsening dizziness and diplopia accompanied by hearing loss, tinnitus, slurred speech, drinking-induced cough, walking instability, and involuntary outbursts of laughter and crying. Dysmetria, ataxia, brisk tendon reflexes, pathologic reflexes, and pseudobulbar signs were observed bilaterally. Repeated biochemical and immune tests did not yield positive findings. CSF analysis revealed mild lymphocytic pleocytosis (white blood cell count, 8/mm3 [0.008 ×109/L]; 83% lymphocytes, 17% monocytes) and a slightly elevated total protein level (46 mg/dL). Brain PET revealed diffuse high metabolism in the midbrain and pons (images not shown). Whole-body PET was negative for malignancy (images not shown). Brain MRI and gadolinium-enhanced MRI were performed. The patient's clinical symptoms and imaging findings improved after treatment with a high dose of steroids. Thereafter, intravenous cyclophosphamide therapy was added after her condition deteriorated again when the prednisone dose was tapered to 20 mg per day in March 2014. Her pontocerebral symptoms were relatively stable in the following year, with apparent diminishment of lesions in the brainstem and cerebellum observed at brain PET (images not shown). Follow-up MR images were obtained in July 2014. Subsequently, the patient exhibited clinical and radiologic aggravation. MR images were obtained again in July 2015 and February 2016. The patient underwent biopsy of the right frontal lobe, and a histopathologic examination was performed in August 2015. Afterward, her condition worsened, and she died in September 2016.

Case 259.

History In November 2012, a previously healthy 31-year-old woman was admitted to our hospital with a 2-month history of right-sided numbness, diplopia, and intermittent nausea and dizziness. She did not have a history of fever, weight loss, headache, photophobia, seizure, or extremity weakness. Physical examination revealed left abduction limitation and right-sided hypoesthesia. Kernig and Brudzinski signs were absent, and pathergy test results were negative. Laboratory evaluation revealed normal complete and differential blood counts, normal serum chemistry, and normal immune function. Analysis of her serum was negative for antiaquaporin 4 antibody, rheumatism antibody profile, and paraneoplastic profile. Serum analysis was also negative for human immunodeficiency virus type 1 and 2 RNA, hepatitis B and C antigen or antibody profile, and fluorescent treponemal antibody absorption. Cerebrospinal fluid (CSF) analysis revealed clear fluid, a normal glucose level, an elevated protein level (45 mg/dL; normal range, 20-40 mg/dL), and an elevated white blood cell count (10/mm3 [0.01 ×109/L]; normal range, 0-8/mm3 [{0-0.008} ×109/L]; 81% lymphocytes, 19% monocytes). No CSF-specific oligoclonal bands were detected. Gram staining, acid-fast staining, and lactic acid and cryptococcal antigen test results were negative. CSF did not grow any bacteria, fungus, or acid-fast bacillus at culture. Spinal cord MRI, brain MR angiography, and CT of the chest, abdomen, and pelvis revealed normal findings (images not shown). Brain MRI and gadolinium-enhanced (20 mL gadopentetate dimeglumine, BeiLu Pharmaceutical, Beijing, China) MRI were performed ( Fig 1 ). The patient's clinical symptoms and imaging findings responded to treatment with a high dose of steroids. However, the patient's symptoms exhibited clinical and radiologic progression as she attempted to taper the steroid dose. She arbitrarily stopped taking the steroids and started traditional Chinese treatment instead. However, her condition was not controlled. [Figure: see text][Figure: see text][Figure: see text] In November 2013, she was readmitted with worsening dizziness and diplopia accompanied by hearing loss, tinnitus, slurred speech, drinking-induced cough, walking instability, and involuntary outbursts of laughter and crying. Dysmetria, ataxia, brisk tendon reflexes, pathologic reflexes, and pseudobulbar signs were observed bilaterally. Repeated biochemical and immune tests did not yield positive findings. CSF analysis revealed mild lymphocytic pleocytosis (white blood cell count, 8/mm3 [0.008 ×109/L]; 83% lymphocytes, 17% monocytes) and a slightly elevated total protein level (46 mg/dL). Brain PET revealed diffuse high metabolism in the midbrain and pons (images not shown). Whole-body PET was negative for malignancy (images not shown). Brain MRI and gadolinium-enhanced MRI were performed ( Fig 2 ). The patient's clinical symptoms and imaging findings improved after treatment with a high dose of steroids. Thereafter, intravenous cyclophosphamide therapy was added after her condition deteriorated again when the prednisone dose was tapered to 20 mg per day in March 2014 ( Fig 3a ). Her pontocerebral symptoms were relatively stable in the following year, with apparent diminishment of lesions in the brainstem and cerebellum observed at brain PET (images not shown). Follow-up MR images were obtained in July 2014 ( Fig 3b ). Subsequently, the patient exhibited clinical and radiologic aggravation. MR images were obtained again in July 2015 ( Fig 4 ) and February 2016 ( Fig 5 ). The patient underwent biopsy of the right frontal lobe, and a histopathologic examination was performed in August 2015. Afterward, her condition worsened, and she died in September 2016. [Figure: see text][Figure: see text][Figure: see text] [Figure: see text][Figure: see text].

Contact heat-evoked potentials as a useful means in patients with Guillain-Barré syndrome.

Few objective methods have been utilized to identify the small myelinated fiber impairment causing neuropathic pain in Guillain-Barré syndrome (GBS). In this study, contact heat-evoked potentials (CHEPs) were applied to study the nociceptive pathway in GBS. Sixty GBS patients and fifty healthy controls were enrolled. The 60 GBS patients were divided into two subgroups presenting with or without subjective lower limb paresthesia (21/39). CHEPs were recorded at Cz and Pz with a peak thermal stimuli of 47 °C applied to the skin of the leg above the internal malleolus (AIM) and of the waist at the anterior superior iliac spine (ASIS) level. The N2 latency and N2-P2 amplitude of CHEPs were compared. When the skin of the leg AIM was stimulated, the N2 latency was significantly postponed (425.23 ± 28.66 vs. 402.30 ± 19.48 ms, P < 0.05) and the N2-P2 amplitude significantly decreased in GBS patients as compared to controls (32.71 ± 7.49 vs. 42.77 ± 8.71 µV, P < 0.05). Slower nerve conduction velocity was observed in GBS patients (11.84 ± 1.45 vs. 13.28 ± 0.66 ms, P < 0.05). However, no differences in N2 latency or N2-P2 amplitude were detected between the two subgroups of GBS patients with or without subjective lower limb paresthesia (P all >0.05). Moreover, there were no differences in N2 latency and N2-P2 amplitude among different groups when the waist was stimulated at the ASIS level. Our study suggested that CHEPs could be utilized as an objective and non-invasive tool to detect small myelinated fiber damage in GBS patients, especially for those without subjective paresthesia.

Neurosyphilis presenting with psychotic symptoms and status epilepticus.

The widespread use of antibiotics in recent years has considerably modified the clinical features of neurosyphilis. Presently, atypical or masked forms of this disease often occur and obscure diagnosis, despite a thorough history and clinical work-up. Here, we report a patient with neurosyphilis presenting with psychotic symptoms who then developed status epilepticus and left limb weakness. Diffusion-weighted magnetic resonance imaging showed hyperintensity involving the right parietal, occipital and temporal lobes and the thalamus. Subsequent serological and cerebrospinal fluid tests confirmed the diagnosis of neurosyphilis. The coexistence of meningovascular syphilis, syphilitic meningitis, and general paresis resulted in the complex manifestation of this patients' condition, as described here in terms of the unusual presentation, evolution, and final diagnosis.

Verification of proposed peripheral biomarkers in mononuclear cells of individuals with schizophrenia.

Recent studies reported gene expression alterations in peripheral blood cells (PBC) obtained from patients with schizophrenia as compared to healthy controls. These alterations can not only be regarded as potential biomarkers but can also further our understanding of the disease. In light of previous reports, expression levels of the following genes: APOBEC3B, CXCL1, DRD2, GNAO1, Kir2.3, S100A9, and SELENBP1 in PBCs were compared between 30 first-hospitalized patients with schizophrenia and 26 healthy controls using quantitative real-time PCR. A significant elevation (2.6-fold; p<0.05) was confirmed for transcripts from the gene CXCL1 but not from the other genes investigated. Within the patients group, APOBEC3B expression was inversely correlated with duration of neuroleptic treatment. These findings indicate that gene expression in PBC from patients with schizophrenia may not only vary with the methods used for analysis but also with state-related differences in gene expression.

Elevated levels of transcripts encoding a human retroviral envelope protein (syncytin) in muscles from patients with motor neuron disease.

Retroviral components of both exogenous and endogenous origins have been associated with nervous system diseases in both animals and humans. In the present study, the levels of transcripts from elements in the human endogenous retrovirus (HERV) W family were determined in muscle biopsies from patients with motor neuron disease (MND) and control subjects. Transcripts from the HERV-W element on chromosome 7q21.2 encoding syncytin and from the SOD1 gene were detected at elevated levels in biopsies from the most affected muscles from MND patients compared to biopsies from control individuals. According to a recent study, syncytin is expressed in microglia in normal brain and can be up-regulated in macrophages/microglia during inflammation. Although syncytin may have cytotoxic effects, it is therefore more likely that the present findings reflect a macrophage response in the muscles undergoing neurogenic atrophy than a primary pathogenetic event in MND.

Transactivation of elements in the human endogenous retrovirus W family by viral infection.

BACKGROUND: Aberrant expression of human endogenous retrovirus (HERV) elements in the W family has previously been associated with schizophrenia, multiple sclerosis and preeclampsia. Little is know regarding the basal expression, transcriptional regulation and functional significance of individual HERV-elements. Since viral infections have previously been reported to transactivate retroviral long terminal repeat regions we examined the basal expression of HERV-W elements and following infections by influenza A/WSN/33 and Herpes simplex 1 viruses in human cell-lines. METHODS: Relative levels of transcripts encoding HERV-W elements and cellular genes were analyzed by qPCR methods. An analysis of amplicon melting temperatures was used to detect variations in the frequencies of amplicons in discrete ranges of such melting temperatures. These frequency-distributions were taken as proxy markers for the repertoires of transcribed HERV-W elements in the cells. RESULTS: We report cell-specific expression patterns of HERV-W elements during base-line conditions. Expressed elements include those with intact regulatory long terminal repeat regions (LTRs) as well as elements flanked by truncated LTRs. Subsets of HERV-W elements were transactivated by viral infection in the different cell-lines. Transcriptional activation of these elements, including that encoding syncytin, was dependent on viral replication and was not induced by antiviral responses. Serum deprivation of cells induced similar changes in the expression of HERV-W elements suggesting that the observed phenomena are, in part, an effect of cellular stress. CONCLUSION: We found that HERV-W elements, including elements lacking regulatory LTRs, are expressed in cell-specific patterns which can be modulated by environmental influences. This brings into light that mechanisms behind the regulation of expression of HERV-W elements are more complex than previously assumed and suggests biological functions of these transcripts.

Evaluation of minor groove binding probe and Taqman probe PCR assays: Influence of mismatches and template complexity on quantification.

Real-time PCR assays using 3'-minor groove binder (MGB) or Taqman probes are widely used for clinical virological testing and mutation/polymorphism detection. We compared a 3'-MGB probe to a conventional Taqman probe for linearity, sensitivity, specificity and dynamic range. The performance of the two assays was compared using plasmids containing different mismatches or using human genomic DNA as a template. Comparable linearity and sensitivity were observed for the MGB and the Taqman probe assays. Using standard conditions, none of the assays were sequence-specific. Up to five mismatches generated a detectable signal in the Taqman probe assay. The performance of the Taqman as well as the MGB probe assay was influenced by the complexity of the template, the latter, however, to a lesser degree. Overall, these results highlight the advantages of the MGB probe over the Taqman probe regarding mismatch discrimination, but suggest that optimization of reaction conditions and verification of the specificity are necessary also for MGB probes.