Clinical effectiveness and safety of escitalopram and desvenlafaxine in patients of depression with anxiety: A randomized,open-label controlled trial

Aim:

Selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) are effective in treating anxiety disorders associated with major depressive disorder (MDD). This randomized, controlled, parallel-group, open-label, phase 4 trial (CTRI/2012/08/002895) was undertaken to compare the effectiveness and safety of desvenlafaxine versus escitalopram, a standard antidepressant.

Materials and Methods:

Effectiveness was assessed using the Hamilton Depression Rating Scale (HAM-D₁₇) and Hamilton Anxiety Rating Scale (HAM-A). Response to treatment was assessed by ≥50% decrease of baseline scores (responder rate). Safety and tolerability was evaluated by changes in routine laboratory parameters, vital signs, and adverse events reported by the subject and/or observed by the clinician.

Results:

Responder rates for both HAM-A and HAM-D scores at 8 weeks were better in the escitalopram group compared to the desvenlafaxine group (HAM-A 76.92% vs. 71.05%; HAM-D 79.48% vs 73.68%) but the differences were not statistically significant (P = 0.59 and P = 0.61). Within group changes of both scores, from baseline to subsequent visits in both treatment arms were statistically significant (P < 0.01).

Conclusion:

The effectiveness of desvenlafaxine was comparable to escitalopram, but escitalopram was better tolerated.KEY WORDS: Anxiety, clinical trial, desvenlafaxine, escitalopram, major depressive disorder     

Reversible bilateral sensori-neural hearing loss due to olanzapine in a male suffering from bipolar affective disorder

An elderly male with Bipolar Affective Disorder (BPAD) developed reversible ototoxicity, manifesting as bilateral sensory-neural hearing loss (SNHL) with administration of olanzapine.KEY WORDS: Olanzapine, bipolar affective disorder, ototoxicity     

Mercury accumulation in bats near hydroelectric reservoirs in Peninsular Malaysia

In large man-made reservoirs such as those resulting from hydroelectric dam construction, bacteria transform the relatively harmless inorganic mercury naturally present in soil and the submerged plant matter into toxic methylmercury. Methylmercury then enters food webs and can accumulate in organisms at higher trophic levels. Bats feeding on insects emerging from aquatic systems can show accumulation of mercury consumed through their insect prey. In this study, we investigated whether the concentration of mercury in the fur of insectivorous bat species was significantly higher than that in the fur of frugivorous bat species, sampled near hydroelectric reservoirs in Peninsular Malaysia. Bats were sampled at Temenggor Lake and Kenyir Lake and fur samples from the most abundant genera of the two feeding guilds—insectivorous (Hipposideros and Rhinolophus) and frugivorous (Cynopterus and Megaerops) were collected for mercury analysis. We found significantly higher concentrations of total mercury in the fur of insectivorous bats. Mercury concentrations also differed significantly between insectivorous bats sampled at the two sites, with bats from Kenyir Lake, the younger reservoir, showing higher mercury concentrations, and between the insectivorous genera, with Hipposideros bats showing higher mercury concentrations. Ten bats (H. cf. larvatus) sampled at Kenyir Lake had mercury concentrations approaching or exceeding 10 mg/kg, which is the threshold at which detrimental effects occur in humans, bats and mice.     

Effect of Ankle Torque on the Ankle–Foot Orthosis Joint Design Sustainability

The ankle joint of a powered ankle–foot orthosis (PAFO) is a prominent component, as it must withstand the dynamic loading conditions during its service time, while delivering all the functional requirements such as reducing the metabolic effort during walking, minimizing the stress on the user’s joint, and improving the gait stability of the impaired subjects. More often, the life of an AFO is limited by the performance of its joint; hence, a careful design consideration and material selection are required to increase the AFO’s service life. In the present work, a compact AFO joint was designed based on a worm gear mechanism with steel and brass counterparts due to the fact of its large torque transfer capability in a single stage, enabling a compact joint. Further, it provided an added advantage of self-locking due to the large friction that prevents backdrive, which is beneficial for drop-foot recovery. The design was verified using nonlinear finite element analysis for maximum torque situations at the ankle joint during normal walking. The results indicate stress levels within its design performance; however, it is recommended to select high-grade structural steel for the ankle shaft as the highest stresses in AFO were located on it.     

Structure-Function Analyses of New SARS-CoV-2 Variants B.1.1.7, B.1.351 and B.1.1.28.1: Clinical,Diagnostic, Therapeutic and Public Health Implications

SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus 2) has accumulated multiple mutations during its global circulation. Recently, three SARS-CoV-2 lineages, B.1.1.7 (501Y.V1), B.1.351 (501Y.V2) and B.1.1.28.1 (P.1), have emerged in the United Kingdom, South Africa and Brazil, respectively. Here, we have presented global viewpoint on implications of emerging SARS-CoV-2 variants based on structural–function impact of crucial mutations occurring in its spike (S), ORF8 and nucleocapsid (N) proteins. While the N501Y mutation was observed in all three lineages, the 501Y.V1 and P.1 accumulated a different set of mutations in the S protein. The missense mutational effects were predicted through a COVID-19 dedicated resource followed by atomistic molecular dynamics simulations. Current findings indicate that some mutations in the S protein might lead to higher affinity with host receptors and resistance against antibodies, but not all are due to different antibody binding (epitope) regions. Mutations may, however, result in diagnostic tests failures and possible interference with binding of newly identified anti-viral candidates against SARS-CoV-2, likely necessitating roll out of recurring “flu-like shots” annually for tackling COVID-19. The functional relevance of these mutations has been described in terms of modulation of host tropism, antibody resistance, diagnostic sensitivity and therapeutic candidates. Besides global economic losses, post-vaccine reinfections with emerging variants can have significant clinical, therapeutic and public health impacts.     

An efficient and environmentally sustainable domino protocol for the synthesis of structurally diverse spiroannulated pyrimidophenazines using erbium doped TiO2 nanoparticles as a recyclable and reusable heterogeneous acid catalyst

An efficient and environmentally sustainable domino protocol has been presented for the synthesis of structurally diverse spiroannulated pyrimidophenazines involving a four component reaction of 2-hydroxynaphthalene-1,4-dione, benzene-1,2-diamine, cyclic ketones and amino derivatives in the presence of erbium doped TiO₂ nanoparticles as a recyclable and reusable heterogeneous acid catalyst. The present synthetic protocol features mild reaction conditions with operational simplicity, excellent yield with high purity, short reaction time and high atom economy with the use of a recoverable and reusable environmentally sustainable heterogeneous catalyst.

An efficient and environmentally sustainable domino protocol has been presented for the synthesis of structurally diverse spiroannulated pyrimidophenazines using erbium doped TiO₂ nanoparticles as a recyclable and reusable heterogeneous acid catalyst.     

A dipodal molecular probe for naked eye detection of trivalent cations (Al3+, Fe3+and Cr3+) in aqueous medium and its applications in real sample analysis and molecular logic gates

A simple and low cost multifunctional colorimetric receptor L has been designed, synthesized and characterized by ¹H-NMR, IR spectroscopy, ESI-MS spectrometry and elemental analysis. The chemosensor L can selectively detect three biologically and environmentally important trivalent metal ions (Al³⁺, Fe³⁺and Cr³⁺) both visually and spectrophotometrically in CH₃CN–H₂O (1 : 1, v/v) solution in the presence of other biologically relevant metal ions. The Job''s plot analyses indicate the 2 : 2 binding stereochemistry for Al³⁺, Fe³⁺ and Cr³⁺ ions with L, which was further confirmed by ¹H-NMR and ESI-MS studies. The binding constant values were found to be 2.9 × 10⁴ M⁻¹ for Al³⁺, 1.079 × 10⁵ M⁻¹ for Fe³⁺ and 1.366 × 10⁵ M⁻¹ for Cr³⁺ respectively. The detections limits of the sensor for Al³⁺ (2.8 × 10⁻⁷ M), Fe³⁺ (1.9 × 10⁻⁷ M) and Cr³⁺ (2.5 × 10⁻⁷ M) are far below than the limit set by the World Health Organization (WHO) for drinking water. Moreover, colorimetric test kits for rapid detection of Al³⁺, Fe³⁺, and Cr³⁺ could be successively applied for all practical purposes, indicating its potential use in environmental samples. It has also been used in building molecular logic gates.

A dipodal reversible colorimetric trivalent metal ion chemosensor (L) has been designed and synthesized. The chemosensor L successfully detects Al³⁺, Fe³⁺ and Cr³⁺ based on binding site-signaling approach and it has practical application.     

Early- and late-onset pancreatic adenocarcinoma: A population-based comparative study

BackgroundPancreatic cancer is projected to become the second leading cause of cancer related death in the US. We aim to investigate the demographics, clinical outcomes and survival outcomes of patients diagnosed with early-onset (<40 years) and late-onset (>40 years) pancreatic adenocarcinoma (PAC).MethodsData on PAC between 1975 and 2016 were extracted from the Surveillance, Epidemiology, and End Results Registry.ResultsWithin the study period, 136,100 patients were identified which included 1181 patients with early-onset PAC and 134,919 patients with late-onset PAC. Both cohorts tend to present with distant metastasis (70.3% vs 57.9%). Both groups also showed an exponential rise in incidence (early-onset 3.69% annual change vs late-onset 6.25% annual change). When stratified by anatomical location, there was a trend of increasing cancer in the head of the pancreas for patients <40 years (3.63% annual change). While late PAC showed increasing cancer in all anatomical locations, the largest increase was observed in the tail of the pancreas (8.62% annual change). Overall, there was a mild difference in survival for early- and late-onset PAC (7 months vs 6 months, respectively, log rank p = 0.004). Both age groups showed the worse prognosis when cancer occurred in the tail of the pancreas (6 months vs 4 months, respectively). On cox proportion analysis, patients with late-onset PAC had twice the risk of mortality compared to early-onset PAC (HR 2.06, CI: 1.788–2.370, P = 0.001).ConclusionsOur study showed that both early- and late-onset PAC are increasing and while prognosis remains poor. Tumor anatomy showed a growing incidence of early-onset PAC in the head of the pancreas while late-onset PAC showed a rising incidence in the body and tail of the pancreas.