Effectiveness of two annual, single-dose mass drug administrations of diethylcarbamazine alone or in combination with albendazole on soil-transmitted helminthiasis in filariasis elimination programme

A longitudinal community-trial on the control of soil-transmitted helminths (STHs), as part of a lymphatic filariasis elimination campaign, was taken up in two revenue blocks of southern India in the years 2001 and 2002 to assess the impact of two annual single-dose mass drug administration (MDA) of diethylcarbamazine (DEC) + albendazole (ALB) with that of DEC alone. The prevalences and intensities of STHs were studied among cross-sectional samples of school children aged 9-10 years by using the Kato-Katz technique at baseline and 11 months after each MDA. The combined drug mass treatment produced a higher reduction in the prevalence (RIP) (51-77%) and the egg reduction rate (ERR) (92-98%) compared with 12-15% RIP and 58-62% ERR of DEC alone mass treatment. The effect of two-drug therapy after two annual treatments was relatively long lasting as shown by RIP and ERR indicating that the reinfection rates were relatively lower in this approach than single-drug therapy. This study demonstrates that mass drug co-administration of DEC + ALB in Global Programme for Elimination of Lymphatic Filariasis (GPELF) targeted at the community had a synergistic and sustainable effect against soil-transmitted helminthiasis and provided considerable 'beyond filariasis' benefits. The additional advantages accrued to the community underscore the importance of scaling-up GPELF to cover the entire population at risk.     

Role of retrograde dilatation in the management of pharyngo-esophageal corrosive strictures

Pharyngo-esophageal corrosive stricture is a complex clinical scenario. If an esophageal opening cannot be found orally through endoscopy, a retrograde approach with a mini-laparotomy and gastrostomy should be attempted. This study primarily aimed at defining the role of preoperative retrograde dilatation of pharyngo-esophageal corrosive strictures. A retrospective analysis of 51 cases of pharyngo-esophageal corrosive strictures identified between 1997-2005 was performed. The demographic details were analyzed. The details of the injury to the pharynx either in isolation or in combination were noted and the management details were recorded. In 21 patients preoperative retrograde dilatation was considered and the technique was successful in 14 (Group I). In seven the technique failed (Group II) and these patients underwent transhiatal resection and gastric pull-through and/or retrosternal pharyngocoloplasty. In Group I patients the postoperative stay was significantly less than in Group II (12 +/- 2.03 days vs. 18 +/- 4.32 days; p = 0.001) Recurrent aspiration, respiratory tract infections, choking sensation and the need for tracheostomy were less frequent in Group I. The overall functional assessment was good in Group I. For treatment of pharyngo-esophageal obstruction, if antegrade dilatation is not possible due to technical reasons, retrograde dilatation is a viable option before opting for organ replacement/bypass procedures. There is no best replacement of the native organ to maintain quality of life.     

High-dose radioimmunotherapy versus conventional high-dose therapy and autologous hematopoietic stem cell transplantation for relapsed follicular non-Hodgkin lymphoma: a multivariable cohort analysis

We performed a multivariable comparison of 125 consecutive patients with follicular lymphoma (FL) treated at our centers with either high-dose radioimmunotherapy (HD-RIT) using 131I-anti-CD20 (n = 27) or conventional high-dose therapy (C-HDT) (n = 98) and autologous hematopoietic stem cell transplantation. The groups were similar, although more patients treated with HD-RIT had an elevated pretransplantation level of lactate dehydrogenase (41% versus 20%, P =.03) and elevated international prognostic score (41% versus 19%, P =.02). Patients treated with HD-RIT received individualized therapeutic doses of 131I-tositumomab (median, 19.7 GBq [531 mCi]) to deliver 17 to 31 Gy (median, 27 Gy) to critical organs. Patients treated with C-HDT received total body irradiation plus chemotherapy (70%) or chemotherapy alone (30%). Patients treated with HD-RIT experienced improved overall survival (OS) (unadjusted hazard ratio [HR] for death = 0.4 [95% confidence interval (95% CI), 0.2-0.9], P =.02; adjusted HR, 0.3, P =.004) and progression-free survival (PFS) (unadjusted HR =.6 [95% C.I., 0.3-1.0], P =.06; adjusted HR, 0.5, P =.03) versus patients treated with C-HDT. The estimated 5-year OS and PFS were 67% and 48%, respectively, for HD-RIT and 53% and 29%, respectively, for C-HDT. One hundred-day treatment-related mortality was 3.7% in the HD-RIT group and 11% in the C-HDT group. The probability of secondary myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) was estimated to be.076 at 8 years in the HD-RIT group and.086 at 7 years in the C-HDT group. HD-RIT may improve outcomes versus C-HDT in patients with relapsed FL.     

Molecular typing of Neisseria gonorrhoeae from hospital and community isolates by restriction fragment length polymorphism

Strains of Neisseria gonorrhoeae are generally characterized by auxotyping, serotyping, plasmid profile, antibiotic sensitivity and deoxyribonucleic acid (DNA) amplification fingerprinting. The aim of this study was to analyse the generation of restriction fragment length polymorphism (RFLP) patterns by BgIII digestion of total genomic DNA of N. gonorrhoeae isolated from the community (n =30) and the hospital (n =15) and to establish an association with serogrouping and antibiogram. The RFLP patterns produced by BgIII restriction digestion showed 7 different patterns among 30 community isolates and 9 different patterns among 15 hospital isolates. 66.7% of isolates belonged to serogroup WI. Penicillin resistance was observed in 46.7% of community isolates and 66.7% hospital isolates. However, penicillinase producing N. gonorrhoeae (PPNG) were lower in the community (6.6%) than in the hospital isolates (53.3%). PPNG strains were more often seen in serogroup WI. This is the first Indian report on RFLP genotype pattern in N. gonorrhoeae. We noted differences in RFLP genotypes of the community (RFLP types 1, 2, 3, 4, 5 and 7) and hospital strains (RFLP types 6 and 8), while no differences in the serogroup were observed. Ciprofloxacin resistance was 20.0% and 26.6% in the community and hospital isolates, respectively. Ceftriaxone emerges as the current drug of choice for an effective policy of antibiotic treatment of gonorrhoea through syndromic management in developing countries.     

A phase II trial evaluating the efficacy of high-dose Radioiodinated Tositumomab (Anti-CD20) antibody,etoposide and cyclophosphamide followed by autologous transplantation,for high-risk relapsed or refractory non-hodgkin lymphoma

Radiation is the most effective treatment for localized lymphoma, but treatment of multifocal disease is limited by toxicity. Radioimmunotherapy (RIT) delivers tumoricidal radiation to multifocal sites, further augmenting response by dose-escalation. This phase II trial evaluated high-dose RIT and chemotherapy prior to autologous stem-cell transplant (ASCT) for high-risk, relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (NHL). The primary endpoint was progression free survival (PFS). Secondary endpoints were overall survival (OS), toxicity, and tolerability. Patients age < 60 years with R/R NHL expressing CD20 were eligible. Mantle cell lymphoma (MCL) patients could proceed to transplant in first remission. Patients received I-131-tositumomab delivered at ≤25Gy to critical normal organs, followed by etoposide, cyclophosphamide and ASCT. A group of 107 patients were treated including aggressive lymphoma (N = 29), indolent lymphoma (N = 45), and MCL (N = 33). After a median follow-up of 10.1 years, the 10-year PFS for the aggressive, indolent, and MCL groups were 62%, 64%, 43% respectively. The 10-year OS for the aggressive, indolent, and MCL groups were 61%, 71%, 48% respectively. Toxicities were similar to standard conditioning regimens and non-relapse mortality at 100 days was 2.8%. Late myeloid malignancies were seen in 6% of patients. High-dose I-131-tositumomab, etoposide and cyclophosphamide followed by ASCT appeared feasible, safe, and effective in treating NHL, with estimated PFS at 10-years of 43%-64%. In light of novel cellular therapies for R/R NHL, high-dose RIT-containing regimens yield comparable efficacy and safety and could be prospectively compared.     

Analysis of mtCOI and 18S rRNA Sequence-Based Characterization of Recently Commercialized Marine Edible Pufferfishes

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - The pufferfishes are considered as a serious hazard to consumers since it contains a strong marine toxin...     

Vogt Koyanagi Harada disease following a recent COVID-19 infection

A 23-year-old female presented with a 3-day history of bilateral (OU) diminution of vision 3 weeks after COVID-19 infection. Best corrected visual acuity (BCVA) was 20/30 in right eye and 20/40 in left eye. Anterior segment showed OU 1+ cells in anterior chamber and anterior vitreous face. Fundus OU showed disc hyperemia and multiple pockets of subretinal fluid (SRF), confirmed on optical coherence tomography. Fundus fluorescein angiography showed multiple pin point leaks suggestive of Vogt Koyanagi Harada disease. Oral corticosteroids 1 mg/kg/day were started. At 2-months’ follow-up, her BCVA improved to 20/25 OU with complete resolution of SRF.     

A brief review of mRNA therapeutics and delivery for bone tissue engineering

The therapeutics for bone tissue regeneration requires constant advancements owing to the steady increase in the number of patients suffering from bone-related disorders, and also to find efficient and cost-effective treatment modalities. One of the major advancements in the field of therapeutics is the development of mRNAs. mRNAs, which have been extensively tested for the vaccines, could be very well utilized as a potential inducer for bone regeneration. The ability of mRNAs to enter the cells and instruct the cellular machinery to produce the required native proteins such as BMP or VEGF is a great way to avoid the issues faced with growth factor deliveries such as the production cost, loss of biological function etc. However, there have been a few hurdles for using mRNAs as an effective therapeutic agent, such as proper dosing, tolerating the degradation by RNases, improving the half-life, controlling the spatio-temporal release and reducing the off-target effects. This brief review discusses the various developments in the field of mRNA therapeutics especially for bone tissue engineering, how nano-formulations are being developed to effectively deliver the mRNAs into the cells by evading the immune responses, how researchers have developed certain strategies to increase the half-life, to successfully deliver the mRNAs to specific bone defect area and bring about effective bone regeneration.

This review provides an update on the various mRNA preparations, carriers that can deliver these preparations and how they could potentially enhance the bone regeneration.