Serum Electrolyte Status of Patients with Acute Stroke Admitted in a Tertiary Care Hospital.

Stroke, usually a focal rather than global neurological deficit resulting from vascular origin with sudden onset, may be with cerebral infarction or intracerebral haemorrhage. It results in brain oedema following vascular injury and electrolyte imbalance. A descriptive cross sectional study was carried out in the Department of Medicine, Mymensingh Medical College Hospital, Mymensingh, Bangladesh during March 2016 to May 2018 to assess the electrolyte levels among 220 purposively selected patients with stroke confirmed by CT scan. Data were collected by the principal investigator himself by using interview schedule and case record form after attaining consent. Blood samples were collected from the patients to carry out biochemical and haematological tests and to assess serum electrolyte levels. Data were cross-checked for completeness, consistency and relevancy, and were analyzed by computer software SPSS 20.0. Age was significantly higher in haemorrhagic stroke (64.88±13.00 years) than ischaemic stroke (60.92±13.96 years). Male (55.91%) were predominant than female (44.09%). One hundred nineteen (54.09%) patients had ischaemic stroke and 101(45.91%) patients had haemorrhagic stroke. The serum concentration of Na+, K+, Cl- and HCO3- were measured during acute period of stroke. Imbalance in serum Sodium, Chloride, Potassium and Bicarbonate level were observed in 37.27%, 29.55%, 23.18% and 6.36% patients respectively. Hyponatremia, hypokalemia, hypochloremia and acidosis were most common electrolyte imbalance in both ischaemic and haemorrhagic strokes. In ischaemic stroke hyponatremia was 35.29%, hypernatremia was 3.36%, hypokalemia 19.33%, hyperkalemia 0.84%, hypochloraemia 30.25%, hyperchloraemia 3.36%, acidosis was in 6.72% and alkalosdis in 1.68% patients while in haemorrhagic stroke hyponatremia 33.66%, hypernatremia 1.98%, hypokalaemia 22.77% hyperkalemia 3.96%, hypochloremia 19.80%, hyperchloraemia 4.95%, acidosis 2.97% and alkalosis was in 0.99% of patients. Mortality was more in hyponatremic, hypokalemic and in hypochloremic patients.

RSPO4 is a potential risk gene of stages III-IV, grade C periodontitis through effects on innate immune response and oral barrier integrity.

AIM: R-spondin 4 (RSPO4) is a suggestive risk gene of stage III-IV, grade C periodontitis and upregulated in gingiva of mice resistant to bacteria-induced alveolar bone loss. We aimed to replicate the association, identify and characterize the putative causal variant(s) and molecular effects, and understand the downstream effects of RSPO4 upregulation. MATERIALS AND METHODS: We performed a two-step association study for RSPO4 with imputed genotypes of a German-Dutch (896 stage III-IV, grade C periodontitis cases, 7104 controls) and Spanish sample (441 cases and 1141 controls). We analysed the allelic effects on transcription factor binding sites with reporter gene and antibody electrophoretic mobility shift assays. We used CRISPR/dCas9 activation and RNA sequencing to pinpoint RSPO4 as the target gene and to analyse downstream effects. RESULTS: RSPO4 was associated with periodontitis (rs6056178, pmeta  = 4.6 × 10-5 ). rs6056178 contains a GATA-binding motif. The rs6056178 T-allele abolished reporter activity (p = .004) and reduced GATA binding (-14.5%). CRISPRa of the associated region increased RSPO4 expression (25.8 ± 6.5-fold, p = .003). RSPO4 activation showed strongest induction of Gliomedin (439-fold) and Mucin 21 (178-fold) and of the gene set "response to interferon-alpha" (area under the curve [AUC] = 0.8, p < 5 × 10-6 ). The most repressed gene set was "extracellular matrix interactions" (AUC = 0.8, padj  = .00016). CONCLUSION: RSPO4 is a potential periodontitis risk gene and modifies host defence and barrier integrity.

Loss of the Nuclear Envelope Protein LAP1B Disrupts the Myogenic Differentiation of Patient-Derived Fibroblasts.

Lamina-associated polypeptide 1 (LAP1) is a ubiquitously expressed inner nuclear membrane protein encoded by TOR1AIP1, and presents as two isoforms in humans, LAP1B and LAP1C. While loss of both isoforms results in a multisystemic progeroid-like syndrome, specific loss of LAP1B causes muscular dystrophy and cardiomyopathy, suggesting that LAP1B has a critical role in striated muscle. To gain more insight into the molecular pathophysiology underlying muscular dystrophy caused by LAP1B, we established a patient-derived fibroblast line that was transdifferentiated into myogenic cells using inducible MyoD expression. Compared to the controls, we observed strongly reduced myogenic differentiation and fusion potentials. Similar defects were observed in the C2C12 murine myoblasts carrying loss-of-function LAP1A/B mutations. Using RNA sequencing, we found that, despite MyoD overexpression and efficient cell cycle exit, transcriptional reprogramming of the LAP1B-deficient cells into the myogenic lineage is impaired with delayed activation of MYOG and muscle-specific genes. Gene set enrichment analyses suggested dysregulations of protein metabolism, extracellular matrix, and chromosome organization. Finally, we found that the LAP1B-deficient cells exhibit nuclear deformations, such as an increased number of micronuclei and altered morphometric parameters. This study uncovers the phenotypic and transcriptomic changes occurring during myoconversion of patient-derived LAP1B-deficient fibroblasts and provides a useful resource to gain insights into the mechanisms implicated in LAP1B-associated nuclear envelopathies.

Knockout of zebrafish desmin genes does not cause skeletal muscle degeneration but alters calcium flux.

Desmin is a muscle-specific intermediate filament protein that has fundamental role in muscle structure and force transmission. Whereas human desmin protein is encoded by a single gene, two desmin paralogs (desma and desmb) exist in zebrafish. Desma and desmb show differential spatiotemporal expression during zebrafish embryonic and larval development, being similarly expressed in skeletal muscle until hatching, after which expression of desmb shifts to gut smooth muscle. We generated knockout (KO) mutant lines carrying loss-of-function mutations for each gene by using CRISPR/Cas9. Mutants are viable and fertile, and lack obvious skeletal muscle, heart or intestinal defects. In contrast to morphants, knockout of each gene did not cause any overt muscular phenotype, but did alter calcium flux in myofibres. These results point to a possible compensation mechanism in these mutant lines generated by targeting nonsense mutations to the first coding exon.

Platelet Count as a Severity of Chronic Obstructive Pulmonary Disease.

Chronic Obstructive Pulmonary disease (COPD) is a heterogenous respiratory disease characterized by a progressive, not fully reversible airflow limitation associated with an abnormal inflammatory response of the lung to noxious stimuli. It is a disease presenting with pulmonary inflammation as well as a systemic one. Measurement of inflammatory marker is difficult but platelet count estimation is easy and less costly. This descriptive, cross-sectional study was carried out at Department of Medicine, Mymensingh Medical college Hospital, Mymensingh, Bangladesh for a period of twelve months among fifty-nine COPD patients. Data were collected through interview, physical examination and laboratory investigations. Statistical analysis was performed using SPSS version 22.0 for consistency and completeness. Age range of the patients was 40 to 49 years with a mean of 56.3±10.9 years. Age group 40-49 years contained the highest number (19; 32.3%) of patients. Majority 57(96.6%) of the respondents were male. Thirty seven (62.7%) of patients were illiterate. Majority 56(94.9%) of patients resided in rural area, of them most 38(64.4%) were farmers. According to Spirometric measurement among 59 respondents of COPD patient, 3(5.1%) were in GOLD stage-I, 9(15.3%) in GOLD stage-II, 27(45.8%) in GOLD stage-III and 20(33.9%) in GOLD stage IV group. Mean platelet count (10³/µl), 241.6±86.5 was found in mild, whereas 315.0±47.7 in moderate, 337.2±76.3 in severe, and 412.4±67.5 in very severe group of COPD patients. So increase in platelet count is statistically significant in severity of COPD. In conclusion, platelet count measurement is less costly to categorize COPD and may be a diagnostic marker.

Loose cuff hypertension.

In this study, an analysis of the effects of cuff looseness on mean blood pressure readings was performed. Using a standard adult blood pressure cuff, pressure readings were taken on each arm at a cuff looseness of 0, 2, 4, and 6 cm beyond patient arm circumference. The cuff was then switched to the opposite arm and the procedure repeated. Blood pressure readings taken from the left arm with the cuff at an appropriately snug fit served as the reference. Increasing cuff looseness simulates the possibly incorrect blood pressure cuff placement by health care workers in the clinical setting. Data from 24 subjects support the claims that mean blood pressure increases with respect to increasing cuff looseness. It was shown that measurements taken on left and right arms will result in significantly different blood pressure readings (p < 0.001). It is therefore crucial to properly place the cuff at a snug fit on the patient's arm for each measurement procedure, to prevent false readings. Lack of consistent cuff size and snugness procedures can lead to misdiagnosis of hypertension, acute patient discomfort, and inconvenient costs to the patient and health care provider.

Chest compression force of trained and untrained CPR rescuers.

The objective of this study was to measure the force exerted by 83 trained CPR rescuers and 104 untrained adult laypersons (college students and staff). A bathroom scale was used to measure the force exerted by these subjects with their hands on the bathroom scale in the CPR position. The weight range for both groups was the same. Of the trained rescuers, 60% pressed with more than 125 lbs, whereas only 37% of the laypersons pressed with more than 125 lbs. In view of the American Heart Association (AHA) guidelines (2000) to depress the chest 1.5 to 2 inches, which requires 100-125 lbs, it would appear that most laypersons do not exert enough force for effective CPR.

Autosomal dominant carpal tunnel syndrome in a Karaite family.

A clinical examination and a history of 64 members belonging to four generations of a Karaite kindred revealed 11 patients with carpal tunnel syndrome (CTS). Bilateral involvement and early age of onset are salient features. The mutation may be traced in four generations. Hereditary primary CTS may be more prevalent than hitherto suspected.

Thrombin-induced degranulation of cultured bone marrow-derived mast cells: effect on calcium uptake.

The role of calcium in the mechanism of thrombin activation of bone marrow-derived mast cells (BMMC) was explored by measuring the changes in the uptake of 45Ca2+ into quiescent BMMC and into cells stimulated by thrombin or by IgE-antigen. The results indicate that activation of BMMC by either thrombin or IgE-antigen is Ca2+-dependent. One million BMMC, activated by 0.05-5 U thrombin, accumulated 45Ca2+ in a concentration-dependent manner, which levelled off at around 1 U thrombin. Extracellular 45Ca2+ uptake of thrombin-stimulated cells is saturable within 90 seconds and corresponds to the kinetics of histamine release, whereas that of IgE-antigen exposed cells continues unabated for over 5 min. The pattern of 45Ca2+ uptake of IgE-sensitized BMMC exposed to thrombin suggests that the pro-stimulatory locus of thrombin action on the surface membrane is distinct from that of IgE.