Loss of the proprioception and touch sensation channel PIEZO2 in siblings with a progressive form of contractures.

Dominant mutations in PIEZO2, which codes for the principal mechanotransduction channel for proprioception and touch sensation, have been found to cause different forms of distal arthrogryposis. Some observations suggest that these dominant mutations induce a gain-of-function effect on the channel. Here, we report a consanguineous family with three siblings who showed short stature, scoliosis, gross motor impairment, and a progressive form of contractures involving the distal joints that is distinct from that found in patients with dominant mutations in PIEZO2. These siblings also displayed deficits in proprioception and touch sensation. Whole-exome sequencing performed in the three affected siblings revealed the presence of a rare homozygous variant (c.2708C>G; p.S903*) in PIEZO2. This variant is predicted to disrupt PIEZO2 function by abolishing the pore domain. Sanger sequencing confirmed that all three siblings are homozygous whereas their parents and an unaffected sibling are heterozygous for this variant. Recessive mutations in PIEZO2 thus appear to cause a progressive phenotype that overlaps with, while being mostly distinct from that associated with dominant mutations in the same gene.

Comparative analysis of serum malondialdehyde, antioxidant vitamins and immunoglobulin levels in patients suffering from generalized anxiety disorder.

The relationship between the elevated levels of serum malondialdehyde, depleted level of antioxidants (vitamin A, E and C) and altered level of immunoglobulins (IgA, IgG and IgM) in several psychiatric disorders has been established by various experimental evidences over the past few years. But previously no study was carried out to determine these components in patients suffering from generalized anxiety disorder (GAD) in Bangladesh. This study was conducted to compare the serum concentration of these components in GAD patients and healthy volunteers; matched by socioeconomic and sociodemographic parameters. Serum level of malondialdehyde and vitamin C were determined by UV spectrophotometric method, vitamins A and E were detected by RP-HPLC method whereas immunoglobulin levels were determined by turbidimetric method. Data were analyzed by independent t-test, Pearson's correlation and regression analysis. Significantly lower level of vitamin E (p<0.05) and significantly higher level of vitamin C were found in GAD patients than the healthy controls, whereas the change of vitamin A was insignificant. Serum malondialdehyde content was significantly higher (p<0.05) and IgM level was significantly (p<0.05) higher than that of the controls. Change in concentrations of IgG and IgA were insignificant (p>0.05). Pearson's correlation coefficient suggested that there were some significant positive and negative correlations among these tested components. Our study reveals that GAD patients have considerably higher level of malondialdehyde, immunoglobulins and altered level of antioxidant vitamins. These findings may play a key role in the diagnosis and treatment of GAD patients.

Determination of serum antioxidant vitamins, glutathione and MDA levels in panic disorder patients.

There are sufficient experimental evidences to establish the relationship between the elevated level of malondealdehyde (MDA)-the lipid peroxidation product and depleted level of antioxidants (Vitamin A, E, C and glutathione) in several psychiatric disorders. But previously no study was carried out to determine these components in panic disorder (PD) patients of Bangladesh. This study was conducted to assess the serum concentration of antioxidant vitamins, MDA and glutathione in 54 panic disorder patients and 52 healthy volunteers. Patients were recruited from Bangabandhu Sheikh Mujib Medical University, Bangladesh by random sampling. Serum level of MDA, glutathione and vitamin C were determined by UV spectrophotometric method whereas Vitamins A and E were detected by RP-HPLC method. Data were analyzed by independent t test and Pearson's correlation analysis. It had been found that the PD patients had low level of antioxidants like vitamin A (p=0.041) and vitamin E (p=0.018) than the healthy controls whereas the change of vitamin C is not significant. It had been found that the MDA content was significantly higher (p<0.05) in PD patients than that of controls. There was no significant difference for the glutathione content between the 2 groups. Pearson's correlation coefficient suggested that there were significant negative correlation between the glutathione level and vitamin C (p=0.013) and a positive correlation between the vitamin E and vitamin A (p=0.020) in patient group. Our study reveals that panic disorder patients have considerably higher level of MDA, lower level of antioxidant vitamins and glutathione than the healthy control subjects.

Molecular detection of noroviruses in hospitalized patients in Bangladesh.

From January 2004 to December 2005, a subset of stool specimens (n = 189) from patients who attended an urban hospital in Bangladesh, in which no pathogen was detected, was tested for the presence of noroviruses by conventional reverse transcription-polymerase chain reaction (RT-PCR). Norovirus RNA was detected in 37 samples (19.6%) in the no-pathogen-detected samples and the estimated overall norovirus detection rate was 8.5%. Diarrhea was generally moderate in the norovirus-infected patients and vomiting was the most common feature among them. Genetic analysis indicated that the GII genogroup was the most predominant norovirus strain (82.4%). The GI strain was found in 17.6% of samples and no cases of GIV were detected. This study indicates that a remarkable proportion of the diarrhea patients is hospitalized due to norovirus infection. Therefore, routine diagnosis of this virus in hospitalized patients is required. Since our study was based on hospitalized patients, community surveillance would be helpful to estimate the true burden of the virus in the country. The data regarding the genetic information of the circulating norovirus strains would be very useful for the norovirus vaccine development programs.

Malarigen malaria Pf/Pv antigen rapid test: a simple and effective tool for diagnosis of malaria in the far-flung hilly areas of Bangladesh.

Microscopic visualization of malarial parasites on thick and/or thin film is considered as "Gold Standard" for diagnosis of malaria. But it needs skilled microscopist as well as good laboratory set up, which are scarce in Chittagong Hill Tracts (CHT) in Bangladesh. A study was carried out to evaluate the efficacy of a newly introduced Rapid Diagnostic Test (RDT) device based on immunochromatographic test (ICT) format, for malarial parasite. This study was carried out at Balipara, a remote village 64 km away from Bandarban Hill District headquarters, during January 2007 to September 2007. A total 271 patients who reported to Sickbay of 37 Rifle Battalion, Balipara were tested by MALARIAGEN MALARIA Pf/Pv Antigen Rapid Test kit on the spot. Thick & thin blood films were prepared and stained by laboratory technician at the sick bay, properly labeled, preserved and sent to pathologist working at Armed Forces Medical College, Dhaka Cantonment, Dhaka for microscopy. Three (1.11%) cases were excluded as control band of RDT were negative or test band appeared after long incubation. Six (2.22%) were excluded for poor quality of staining blood film. Among 262 cases malarial parasites were detected in 74(28.24%). Of these 62(83.78%) were Plasmodium falciparum and 12(16.22%) were Plasmodium vivax. Parasite count ranged from 2500/mµL to 527500/mµL with mean 67400/mµL (+/-93400). Among 262 cases, 97(37.02%) were positive for malarial antigen(s) in RDT. Of these 74(76.29%) were P. falciparum and 23(23.71%) were P. vivax. Overall sensitivity and specificity of RDT for detection of malarial antigen(s) irrespective of their species were 95.95% and 86.71% respectively with positive and negative predictive value 73% & 98% respectively. Relative to microscopy, the device has shown sensitivity 94.6% and specificity 88.52% for detection of P. falciparum with positive and negative predictive value 72% and 98% respectively. The device sensitivity and specificity for detection of P. vivax were 100% and 93.1% with respective positive and negative predictive value 47% and 100%. Malariagen Malaria Pf/Pv Antigen Rapid Test (RDT) performs as a better sensor and discriminator of malarial parasites and their species and appears to be an acceptable tool for diagnosis of malaria in symptomatic patient.