Synthesis and biological characterization of an orally bioavailable lactate dehydrogenase-A inhibitor against pancreatic cancer.

Lactate dehydrogenase-A (LDHA) is the major isoform of lactate dehydrogenases (LDH) that is overexpressed and linked to poor survival in pancreatic ductal adenocarcinoma (PDAC). Despite some progress, current LDH inhibitors have poor structural and physicochemical properties or exhibit unfavorable pharmacokinetics that have hampered their development. The present study reports the synthesis and biological evaluation of a novel class of LDHA inhibitors comprising a succinic acid monoamide motif. Compounds 6 and 21 are structurally related analogs that demonstrated potent inhibition of LDHA with IC50s of 46 nM and 72 nM, respectively. We solved cocrystal structures of compound 21-bound to LDHA that showed that the compound binds to a distinct allosteric site between the two subunits of the LDHA tetramer. Inhibition of LDHA correlated with reduced lactate production and reduction of glycolysis in MIA PaCa-2 pancreatic cancer cells. The lead compounds inhibit the proliferation of human pancreatic cancer cell lines and patient-derived 3D organoids and exhibit a synergistic cytotoxic effect with the OXPHOS inhibitor phenformin. Unlike current LDHA inhibitors, 6 and 21 have appropriate pharmacokinetics and ligand efficiency metrics, exhibit up to 73% oral bioavailability, and a cumulative half-life greater than 4 h in mice.

Primary antiphospholipid syndrome in a male presents with acute digital ischemia: Dramatic response to glucocorticoid.

We present a rare case of primary antiphospholipid syndrome in a 38-year-old male who presented with painful digital ischemia. Early initiation of anticoagulation and addition of glucocorticoid led to a significant improvement in the patient.

Acute non-immune hemolytic anemia in enteric fever due to nalidixic acid-resistant Salmonella enterica serotype Typhi: A case report.

Nalidixic acid-resistant Salmonella enterica serotype Typhi is a well-known cause of enteric fever, and its prevalence is increasing worldwide. However, the incidence of enteric fever complicated by non-immune hemolytic anemia without co-existing thalassemia or glucose-6-phosphate dehydrogenase deficiency is rare. In this case report, we present a case of acute non-immune hemolytic anemia in enteric fever caused by nalidixic acid-resistant Salmonella enterica serotype Typhi.

Bardet-Biedl syndrome: Delayed diagnosis in a 14-year-old child with end-stage renal disease.

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive ciliopathic disorder. Because of its low prevalence and wide spectrum of clinical features, many patients remain undiagnosed. We report a case of a 14-year-old boy with a typical phenotype of BBS who remains undiagnosed until the development of end-stage renal disease.

Grant Report on mCARE: Mobile-Based Care for Children with Autism Spectrum Disorder (ASD) for Low- and Middle-Income Countries (LMICs).

In low- and middle-income countries, especially in Bangladesh, Autism Spectrum Disorder (ASD) may be considered an anathema, and social-cultural-financial constraints mean that there are few facilities available for treatment for ASD children. The revolution in the use of the mobile phone (~80%) by the majority of people in Bangladesh in recent years has created an opportunity to improve the overall scenario in the treatment or remote monitoring process for children with ASD. In this grant project, we planned and developed a mobile phone-based system to remotely monitor children with ASD and help their treatment process both at the caregiver and care practitioner ends. In developing mCARE, we utilized a Remote Experience Sampling Method to design, build, deploy, and study the impact of mobile based monitoring and treatment of children with ASD in Bangladesh. We developed a mobile application using the Experience Sampling Method (ESM). A caregiver routinely reported the behavioral and milestone parameters of their children with ASD. The care practitioners monitored the longitudinal data that helped them in decision-making in a particular patient's treatment process. The Value Sensitive Design (VSD) was used to make this mobile application more user friendly with consideration of the local economic, social, and cultural values in Bangladesh.

Vanadyl ß-tetrabromoporphyrin: synthesis, crystal structure and its use as an efficient and selective catalyst for olefin epoxidation in aqueous medium.

We hereby report the synthesis, characterization and catalytic applications in the epoxidation of alkenes by a vanadyl porphyrin having bulky bromo substituents at the ß-positions viz. vanandyltetrabromotetraphenylporphyrin (1). The synthesized porphyrin was characterized by various spectroscopic techniques like UV-visible, FT-IR, EPR, MALDI-TOF mass spectrometry and single crystal X-ray analysis. Porphyrin 1 has a nonplanar structure as indicated by its X-ray structure, DFT and electrochemical studies. 1 was analyzed for its catalytic application in the epoxidation of various alkenes. The catalytic reactions were carried out in CH3CN/H2O mixture in 3 : 1 (v/v) ratio. 1 displayed good efficiency in terms of mild reaction conditions, lower reaction temperature and minimal catalyst amount consumption. 1 exhibited excellent selectivity, high conversion efficiency and huge TOF (7600-9800 h-1) in a significantly low reaction time of 0.5 h. Catalyst 1 was regenerated at the end of various catalytic cycles making it reusable and industrially important.

Live fish in the trachea and bronchus: a case report.

BACKGROUND: A live foreign body in trachea or bronchus is a very rare as well as life threatening condition. A bigger fish with irregular shape usually impacts at the oropharynx, hypopharynx or inlet of the larynx. But a small or flat, elongated foreign body may cross the glottis and enter into trachea and bronchus. We report a rare type of very long live fish in trachea and bronchus. CASE PRESENTATION: A 16-year-old Bangladeshi boy presented with severe respiratory distress and cyanosis with a history of live fish impaction in the throat. To relieve respiratory distress and secure life an emergency tracheostomy was carried out while a tail fin of a fish was seen through tracheostome directed to the right bronchus which was grasped with an artery forceps and pulled out of the trachea. Respiratory distress was relieved immediately. The fish removed from the trachea was locally known as Guchi Baim Fish (Macrognathus pancalus). It was about 16 cm long and about 2 cm wide at its central region. CONCLUSION: Live fish lodging in the trachea and bronchus is an acute emergency condition. It is very difficult to diagnose and manage because of its presence in critical anatomical location. So a quick short history from accompanying persons especially about the type of fish is crucial to predicting the site of its lodgement in the airway as well as management plan. Avoidance of the tendency of holding the fish between teeth during fishing can prevent this life threatening condition.