Correlation of peak expiratory flow rate and single breath count in normal adults

Background: Spirometry mandates the requirement of equipments and skilled technicians which may be difficult to acquire in resource limited situations. Thus simple alternative tests like Peak Expiratory Flow Rate (PEFR) and Single Breath Count (SBC) can be used to assess the pulmonary functioning of an individual.Methods: Hundred healthy participants of both genders between the age group of 18-50 years were recruited for this study. They were asked to perform PEFR using the Mini Wright Peak Flow Meter and SBC using a metronome. Three reading were noted and the best of three readings were used for analysis.Results: The mean age and BMI of the participants were 31.54±10.42 years and 23.88±5.14 kg/m2 respectively. The Spearman’s correlation coefficient of PEFR and SBC was 0.7048 with p<0.001 indicating a strong positive correlation.Conclusions: SBC can be used as a simple, convenient and cost-effective alternative to PEFR to assess pulmonary function in adults.

Effect of physiotherapy on single breath count and breath holding time in COVID-19 patients

Background: The novel Coronavirus is known to primarily affect the respiratory system and physiotherapy treatment is integral to combat this infection. However, the assessment of pulmonary function poses a difficult challenge considering the risk of spread of infection and sanitisation of the devices used. Single breath count (SBC) and breath holding time (BHT) can be thus adopted as bedside assessment tests for pulmonary function following physiotherapy treatment.Method: In this a retrospective observational study of 51 COVID-19 patients, mean age 51.7±14.56 years, on room air, admitted in the step-down units of a tertiary care hospital. Patients received standard physiotherapy treatment, within safe hemodynamic limits. Pre and post treatment session SBC was recorded in 32 patients and BHT in 19 patients. Three reading were noted and the best of three readings were used for analysis.Results: The paired t test was used to analyse SBC and BHT. Mean pre and post SBC was 18.25±8.96 and 23.31±9.96 respectively with a mean difference of 5.06 and p<0.0001. Mean pre and post BHT were 19.37 and 23.05 seconds respectively with a mean difference of 3.68 and p<0.0001.  Statistically significant difference in the pre and post treatment session SBC and BHT was observed, indicating a positive effect of physiotherapy treatment on pulmonary function.Conclusion: Physiotherapy treatment shows significant improvement in the pulmonary function in COVID-19 patients. SBC and BHT tests can be used as assessment and prognostic tools for pulmonary function in COVID-19 patients

Molecular Defects of Vitamin B6 Metabolism Associated with Neonatal Epileptic Encephalopathy

Neonatal epileptic encephalopathy (NEE) is a seizure disorder that occurs within hours from birth and arises from central nervous system (CNS) dysfunctions of various origins, including metabolic or inflammatory conditions, abnormalities of brain structure and cerebrovascular diseases. In some rare circumstances, NEE is refractory to conventional antiepileptic drugs (AEDs) but responds very well to treatment with vitamin B6 in the form of either pyridoxine (PN) or pyridoxal 5’-phosphate (PLP). Vitamin B6-dependent NEE derives either from a deficiency of PLP, from inborn errors in enzymes, such as pyridoxine 5’-phosphate oxidase (PNPOx) and pyridoxal kinase (PL kinase) involved in the PLP salvage pathway or from inherited mutations of enzymes, such as -aminoadipic semialdehyde dehydrogenase (also known as antiquitin) involved in other metabolic pathways, which lead to the accumulation of intermediates that react with PLP, reducing its availability. Clinical phenotypes observed in vitamin B6-dependent NEE patients may include fetal distress, hypoglycemia, acidosis, anemia, and asphyxia. The health state of untreated patients may undergo progressive deterioration, which can lead to death within weeks. Surviving children are usually mentally retarded and are dependent on vitamin B6 to control the disease. Several known cases of B-dependent NEE, however do not or only mildly manifest some of the above clinical features, and are characterized by mild to moderate developmental delay. This chapter will review the molecular mechanism of how in-born errors in PNPOx or antiquitin affect PLP levels in the cell and lead to NEE. We will also review important clinical and general features associated with PLP dependent NEE, and provide some directions for clinicians to diagnose and treat or manage the diseas

Persistent elevation of urine aquaporin-2 during water loading in a child with nephrogenic syndrome of inappropriate antidiuresis (NSIAD) caused by a R137L mutation in the V2 vasopressin receptor

Nephrogenic Syndrome of Inappropriate Antidiuresis (NSIAD) is a novel disease caused by a gain-of-function mutation in the V2 vasopressin receptor (V2R), which results in water overload and hyponatremia. We report the effect of water loading in a 3-year old boy with NSIAD, diagnosed in infancy, to assess urine aquaporin-2 (AQP2) excretion as a marker for V2R activation, and to evaluate the progression of the disease since diagnosis. The patient is one of the first known NSIAD patients and the only patient with a R137L mutation. Patient underwent a standard water loading test in which serum and urine sodium and osmolality, serum AVP, and urine AQP2 excretion were measured. The patient was also evaluated for ad lib fluid intake before and after the test. This patient demonstrated persistent inability to excrete free water. Only 39% of the water load (20 ml/kg) was excreted during a 4-hour period (normal ≥ 80-90%). Concurrently, the patient developed hyponatremia and serum hypoosmolality. Serum AVP levels were detectable at baseline and decreased one hour after water loading; however, urine AQP2 levels were elevated and did not suppress normally during the water load. The patient remained eunatremic but relatively hypodipsic during ad lib intake. In conclusion, this is the first demonstration in a patient with NSIAD caused by a R137L mutation in the V2R that urine AQP2 excretion is inappropriately elevated and does not suppress normally with water loading. In addition, this is the first longitudinal report of a pediatric patient with NSIAD diagnosed in infancy who demonstrates the ability to maintain eunatremia during ad lib dietary intake

Shiga Toxin Binding to Glycolipids and Glycans

Background: Immunologically distinct forms of Shiga toxin (Stx1 and Stx2) display different potencies and disease outcomes, likely due to differences in host cell binding. The glycolipid globotriaosylceramide (Gb3) has been reported to be the receptor for both toxins. While there is considerable data to suggest that Gb3 can bind Stx1, binding of Stx2 to Gb3 is variable. Methodology: We used isothermal titration calorimetry (ITC) and enzyme-linked immunosorbent assay (ELISA) to examine binding of Stx1 and Stx2 to various glycans, glycosphingolipids, and glycosphingolipid mixtures in the presence or absence of membrane components, phosphatidylcholine, and cholesterol. We have also assessed the ability of glycolipids mixtures to neutralize Stx-mediated inhibition of protein synthesis in Vero kidney cells. Results: By ITC, Stx1 bound both Pk (the trisaccharide on Gb3) and P (the tetrasaccharide on globotetraosylceramide, Gb4), while Stx2 did not bind to either glycan. Binding to neutral glycolipids individually and in combination was assessed by ELISA. Stx1 bound to glycolipids Gb3 and Gb4, and Gb3 mixed with other neural glycolipids, while Stx2 only bound to Gb3 mixtures. In the presence of phosphatidylcholine and cholesterol, both Stx1 and Stx2 bound well to Gb3 or Gb4 alone or mixed with other neutral glycolipids. Pre-incubation with Gb3 in the presence of phosphatidylcholine and cholesterol neutralized Stx1, but not Stx2 toxicity to Vero cells

Loss of Niemann-Pick C1 or C2 Protein Results in Similar Biochemical Changes Suggesting That These Proteins Function in a Common Lysosomal Pathway

Niemann-Pick Type C (NPC) disease is a lysosomal storage disorder characterized by accumulation of unesterified cholesterol and other lipids in the endolysosomal system. NPC disease results from a defect in either of two distinct cholesterol-binding proteins: a transmembrane protein, NPC1, and a small soluble protein, NPC2. NPC1 and NPC2 are thought to function closely in the export of lysosomal cholesterol with both proteins binding cholesterol in vitro but they may have unrelated lysosomal roles. To investigate this possibility, we compared biochemical consequences of the loss of either protein. Analyses of lysosome-enriched subcellular fractions from brain and liver revealed similar decreases in buoyant densities of lysosomes from NPC1 or NPC2 deficient mice compared to controls. The subcellular distribution of both proteins was similar and paralleled a lysosomal marker. In liver, absence of either NPC1 or NPC2 resulted in similar alterations in the carbohydrate processing of the lysosomal protease, tripeptidyl peptidase I. These results highlight biochemical alterations in the lysosomal system of the NPC-mutant mice that appear secondary to lipid storage. In addition, the similarity in biochemical phenotypes resulting from either NPC1 or NPC2 deficiency supports models in which the function of these two proteins within lysosomes are linked closely

Rediscovery of Penicillium paradoxum (Ascomycete: Aspergillaceae) from Maharashtra, India

Penicillium paradoxum has an enigmatic Aspergillus-like anamorphic state; earlier named as Aspergillus paradoxus with a teleomorph state Hemicarpenteles paradoxus.  The present paper describes the rediscovery of this species from India after five decades and includes a phylogenetic study of this strain.  This is the first record of this strain from peninsular India including the Western Ghats. </div

Frequency and risk factors for liver disease following pancreatitis: A population-based cohort study

Background &amp; aimsBoth liver disease (LD) and pancreatitis pose substantial burdens. There have been no general population-based studies on frequency of LD after an episode of pancreatitis. The aim of this study was to investigate the occurrence of LD in a population-based cohort of patients following pancreatitis.MethodsNationwide data on the general population of nearly 3 million people were used to identify retrospectively diagnoses of acute pancreatitis, chronic pancreatitis (CP), LD and cirrhosis from 1998 to 2016. Acute pancreatitis was categorised as first (FAP) or recurrent (RAP) episode. Number of pancreatitis recurrences prior to LD diagnosis was determined.ResultsA total of 20,931 pancreatitis patients were included, of which 874 developed LD following pancreatitis. The incidence of LD in FAP was 115.59 (95% confidence interval 102.19-128.98), in RAP - 217.63 (95% confidence interval 173.31-261.94), and in CP - 539.43 (95% confidence interval 494.72-584.13) patients per 100,000 pancreatitis patients per year. There was a significant increase in the probability of LD with increasing number of pancreatitis recurrences and, for the same number of pancreatitis recurrences, LD was significantly more frequent after CP than RAP (hazard ratio 1.666 (95% confidence interval 1.322-2.098; p = &lt;0.001)).ConclusionsThe frequency of LD increases from FAP to RAP to CP. While number of pancreatitis recurrences is a significant risk factor for development of LD, there is a higher probability of LD following CP than RAP even for the same number of recurrences. Interventions preventing pancreatitis and its progression may lower the burden of LD