Utility and Evaluation of Applied Project Management Processes Within a Large Multicountry Health Systems Development Project Conducted During the Coronavirus Disease 2019 (COVID-19) Pandemic.

The increasing trends in antimicrobial resistance (AMR) continue to pose a significant threat to human health, with grave consequences in low- and middle-income countries. In collaboration with local governments and microbiology laboratories in South Asian and Southeast Asian countries, the Capturing Data on Antimicrobial Resistance Patterns and Trends in Use in Regions of Asia (CAPTURA) project worked to identify gaps and expand the volume of existing AMR data to inform decision-makers on how to best strengthen their national AMR surveillance capacity. This article describes overall project management processes and the strategies implemented to address the disruptive impact of the coronavirus disease 2019 (COVID-19) pandemic on the project activities across diverse contexts in different countries. Also, it assesses in-country team's feedback on the conduct of activities and their overall impact on project completion. The strategies employed were tailored to the specific context of each country and included increased communication and collaboration among consortium partners and in-country teams, as well as hiring of additional in-country team members. This paper highlights the importance of local representation and capacities as well as real-time (virtual) engagement with stakeholders, ensuring close monitoring of the local situation and ability to tailor context-specific mitigation strategies to continue project implementation during disruptive external circumstances.

Recording and Reporting of Antimicrobial Resistance (AMR) Priority Variables and Its Implication on Expanding Surveillance Sites in Nepal: A CAPTURA Experience.

Data on antimicrobial resistance (AMR) from sites not participating in the National AMR surveillance network, conducted by National Public Health Laboratory (NPHL), remain largely unknown in Nepal. The "Capturing Data on Antimicrobial Resistance Patterns and Trends in Use in Regions of Asia" (CAPTURA) assessed AMR data from previously untapped data sources in Nepal. A retrospective cross-sectional data review was carried out for the AMR data recorded between January 2017 and December 2019 to analyze AMR data from 26 hospital-based laboratories and 2 diagnostic laboratories in Nepal. Of the 56 health facilities initially contacted to participate in this project activity, 50.0% (28/56) signed a data-sharing agreement with CAPTURA. Eleven of the 28 hospitals were AMR surveillance sites, whereas the other 17, although not part of the National AMR surveillance network, recorded AMR-related data. Data for 663 602 isolates obtained from 580 038 patients were analyzed. A complete record of the 11 CAPTURA priority variables was obtained from 45.5% (5/11) of government hospitals, 63.6% (7/11) of private hospitals, and 54.6% (6/11) of public-private hospitals networked with NPHL for AMR surveillance. Similarly, 80% (8/10) of clinics and 54.6% (6/11) of laboratories outside the NPHL network recorded complete data for the 10 Global Antimicrobial Resistance and Use Surveillance System (GLASS) priority variables and 11/14 CAPTURA priority variables. Retrospective review of the data identified areas requiring additional resources and interventions to improve the quality of data on AMR in Nepal. Furthermore, we observed no difference in the priority variables reported by sites within or outside the NPHL network, thus suggesting that policies could be made to expand the surveillance system to include these sites without substantially affecting the government's budget.

Equity in Transplantation Access in Nepal: An Analysis of Gender, Geographic, and Caste-Based Disparities in Transplants.

Transplantation is a lifesaving modality for addressing various organ failures. While kidney transplant services became available in Nepal in 2008, the introduction of liver transplantation is more recent. The government provides financial assistance to support lifelong dialysis and kidney transplantation. The importance of equitable access to transplantation cannot be overemphasized. This study aims to examine the equity in accessing transplantation services. This retrospective observational study encompasses patients who underwent kidney transplantation up until December 2022 across five major hospitals. Through standardized data collection and analysis, we evaluated the distribution of recipients based on gender, caste/ethnicity, and geographic location. A total of 2040 kidney transplantations were performed during the period. Notably, 79% of the recipients were men and, interestingly, 70% of the donors were women. Geographically, the highest proportion (31.8%) of recipients were from Bagmati, while the lowest (l2.8%) were from Karnali. Regarding caste and ethnicity, Janajatis accounted for 31% and Chhetris for 22.9%; Madhesis were lowest at 8.12%. Only 17 liver transplantations were conducted during the same period. Although access to kidney transplantation exists in Nepal, this study highlights persistent disparities. Women, rural and remote populations, as well as specific ethnic and caste groups encounter barriers to accessing transplantation services.

Development and validation of a spectrophotometric method for quantification of residual cyclodextrin (DIMEB; Heptakis) in pertussis antigens.

Methylated derivatives of cyclodextrins such as DIMEB (2,6-di-O-methyl)-ß-cyclodextrin or Heptakis is commonly used as culture medium modifier in manufacturing of pertussis antigens for promoting the growth of bacteria. We report here development and validation of a spectrophotometric method for estimation of DIMEB in different product matrices of pertussis vaccine antigens i.e. Filamentous haemagglutinin (FHA), Pertactin (PRN) and Pertussis toxin (PT). The detection is based on characteristic reaction of hydrolyzed sugars derivatives from DIMEB i.e., furfural derivatives with anthrone reagent to form colored complexes which could be quantified at 625 nm. Method showed excellent linearity with correlation coefficient (R2) > 0.995 over the concentration of 5.0-80.0 µg. LOD and LOQ of 1.47 µg and 4.46 µg respectively was reported. The overall precision (repeatability and intermediate precision) showed % RSD for DIMEB content <10.0% for all the matrices. % Recoveries for DIMEB after three different spike levels (low, middle and high) were within 90%-113%. The method was successfully applied for determination of residual DIMEB in different product matrices of FHA, PRN and PT protein antigens. This can be used to monitor residual DIMEB levels during manufacturing of acellular pertussis antigens.

Human Infection Challenge with Serotype 3 Pneumococcus.

Rationale: Streptococcus pneumoniae serotype 3 (SPN3) is a cause of invasive pneumococcal disease and associated with low carriage rates. Following the introduction of pediatric 13-valent pneumococcal conjugate vaccine (PCV13) programs, SPN3 declines are less than other vaccine serotypes and incidence has increased in some populations coincident with a shift in predominant circulating SPN3 clade, from I to II. A human challenge model provides an effective means for assessing the impact of PCV13 on SPN3 in the upper airway. Objectives: To establish SPN3's ability to colonize the nasopharynx using different inoculum clades and doses, and the safety of an SPN3 challenge model. Methods: In a human challenge study involving three well-characterized and antibiotic-sensitive SPN3 isolates (PFESP306 [clade Ia], PFESP231 [no clade], and PFESP505 [clade II]), inoculum doses (10,000, 20,000, 80,000, and 160,000 cfu/100 µl) were escalated until maximal colonization rates were achieved, with concurrent acceptable safety. Measurement and Main Results: Presence and density of experimental SPN3 nasopharyngeal colonization in nasal wash samples, assessed using microbiological culture and molecular methods, on Days 2, 7, and 14 postinoculation. A total of 96 healthy participants (median age 21, interquartile range 19-25) were inoculated (n = 6-10 per dose group, 10 groups). Colonization rates ranged from 30.0-70.0% varying with dose and isolate. 30.0% (29/96) reported mild symptoms (82.8% [24/29] developed a sore throat); one developed otitis media requiring antibiotics. No serious adverse events occurred. Conclusions: An SPN3 human challenge model is feasible and safe with comparable carriage rates to an established Serotype 6B human challenge model. SPN3 carriage may cause mild upper respiratory symptoms.

A randomised controlled trial of intrapleural balloon intercostal chest drains to prevent drain displacement.

BACKGROUND: Chest drain displacement is a common clinical problem that occurs in 9-42% of cases and results in treatment failure or additional pleural procedures conferring unnecessary risk. A novel chest drain with an integrated intrapleural balloon may reduce the risk of displacement. METHODS: A prospective randomised controlled trial comparing the balloon drain to standard care (12 F chest drain with no balloon) with the primary outcome of objectively defined unintentional or accidental chest drain displacement. RESULTS: 267 patients were randomised (primary outcome data available in 257, 96.2%). Displacement occurred less frequently using the balloon drain (displacement 5 of 128, 3.9%; standard care displacement 13 of 129, 10.1%) but this was not statistically significant (OR for drain displacement 0.36, 95% CI 0.13-1.0, Chi-squared 1 degree of freedom (df)=2.87, p=0.09). Adjusted analysis to account for minimisation factors and use of drain sutures demonstrated balloon drains were independently associated with reduced drain fall-out rate (adjusted OR 0.27, 95% CI 0.08-0.87, p=0.028). Adverse events were higher in the balloon arm than the standard care arm (balloon drain 59 of 131, 45.0%; standard care 18 of 132, 13.6%; Chi-squared 1 df=31.3, p<0.0001). CONCLUSION: Balloon drains reduce displacement compared with standard drains independent of the use of sutures but are associated with increased adverse events specifically during drain removal. The potential benefits of the novel drain should be weighed against the risks, but may be considered in practices where sutures are not routinely used.

Comparative genomics of whole-cell pertussis vaccine strains from India.

BACKGROUND: Despite high vaccination coverage using acellular (ACV) and whole-cell pertussis (WCV) vaccines, the resurgence of pertussis is observed globally. Genetic divergence in circulating strains of Bordetella pertussis has been reported as one of the contributing factors for the resurgence of the disease. Our current knowledge of B. pertussis genetic evolution in circulating strains is mostly based on studies conducted in countries using ACVs targeting only a few antigens used in the production of ACVs. To better understand the adaptation to vaccine-induced selection pressure, it will be essential to study B. pertussis populations in developing countries which are using WCVs. India is a significant user and global supplier of WCVs. We report here comparative genome analyses of vaccine and clinical isolates reported from India. Whole-genome sequences obtained from vaccine strains: WCV (J445, J446, J447 and J448), ACV (BP165) were compared with Tohama-I reference strain and recently reported clinical isolates from India (BPD1, BPD2). Core genome-based phylogenetic analysis was also performed using 166 isolates reported from countries using ACV. RESULTS: Whole-genome analysis of vaccine and clinical isolates reported from India revealed high genetic similarity and conserved genome among strains. Phylogenetic analysis showed that clinical and vaccine strains share genetic closeness with reference strain Tohama-I. The allelic profile of vaccine strains (J445:ptxP1/ptxA2/prn1/fim2-1/fim3-1; J446: ptxP2/ptxA4/prn7/fim2-2/fim3-1; J447 and J448: ptxP1/ptxA1/ prn1/fim2-1/fim3-1), which matched entirely with clinical isolates (BPD1:ptxP1/ptxA1/prn1/fim2-1 and BPD2: ptxP1/ptxA1/prn1/fim2-1) reported from India. Multi-locus sequence typing (MLST) demonstrated the presence of dominant sequence types ST2 and primitive ST1 in vaccine strains which will allow better coverage against circulating strains of B. pertussis. CONCLUSIONS: The study provides a detailed characterization of vaccine and clinical strains reported from India, which will further facilitate epidemiological studies on genetic shifts in countries which are using WCVs in their immunization programs.

Development and validation of magnetic bead pentaplex immunoassay for simultaneous quantification of murine serum IgG antibodies to acellular pertussis, diphtheria and tetanus antigens used in combination vaccines.

We describe here a magnetic bead-based multiplex (pentaplex) immunoassay (MIA) platform developed as an alternative to enzyme-linked immunosorbent assays (ELISA) used in immunogenicity testing of DTaP/TdaP vaccine in animals. MIA simultaneously measures the concentration of serum (IgG) antibodies against B. Pertussis antigens; pertussis toxin, filamentous hemagglutinin (FHA), pertactin (PRN) and tetanus (T) and diphtheria (D) toxoid in the Tdap vaccine immunized animals. Assay validation experiments were done using a panel of serum samples. The results are expressed in IU/ml using WHO reference mice serum. The standard curve was linear with 4PL logistic fit over an eight 2-fold dilution range with LOQ of 0.003, 0.022, 0.005 IU/ml for PT, FHA and PRN and 0.016 U/ml for T and D antigens indicating sensitivity. No interference was observed in monoplex versus multiplex measurements. Specificity was demonstrated by ≥90% homologous and ≤15% heterologous inhibition for all the antigens. The assay was reproducible, with a mean coefficient of variation (CV) of ≤10% for intra-assay duplicates and ≤25% for interassays using different lots of beads and analyst. Accuracy was demonstrated wherein the ratio of observed vs. assigned unitages were within 80-120%. The study suggests that the Pentaplex (MIA) platform meets all the criteria for the serological assay combination vaccines with additional advantages of high throughput, reduced sample volumes, faster analysis with reduced manpower in contrast to conventional monoplex ELISA.

Development and application of HPLC-RI and HPLC-MS/MS based methods for quantification of residual deoxycholate levels in pneumococcal polysaccharides.

The analysis of residual sodium deoxycholate (DOC); a detergent of biological origin used in manufacturing of polysaccharide vaccines is challenging due to complex sample matrices and the lack of suitable methods. Here we report, rapid and sensitive high-performance liquid chromatography-refractive index (HPLC-RI) and tandem mass spectrometry (HPLC-MS/MS) methods for estimation of residual DOC in pneumococcal polysaccharides. For HPLC-RI method, separation was achieved using Luna C18 column and mobile phase compositions of acetonitrile: methanol: 20 mM sodium acetate (60:05:35% v/v). For HPLC-MS/MS method, separation was achieved using a Hypersil BDS C18 column with gradient elution of methanol and water (0.1% formic acid). MS/MS method showed linearity (r2 = 0.997) over the range of 10-320 ng/mL with limits of detection (LOD) and lower limit of quantitation (LOQ) of 3 and 10 ng/mL respectively. Precision (% RSD) and accuracy (% recovery) for both methods were in the range of 0.74-8.29% and 82.33-117.86% respectively. Sample matrices interferences were addressed following novel sample clean-up method based on liquid-liquid extraction. Both methods enabled traceable quantitation of DOC in intermediate and purified pneumococcal polysaccharides of serotypes: 1, 5, 6A, 6B, 7F, 9V, 14, 19A, 19F and 23F.

Effects of Azardirachta indica on Vascular Endothelial Growth Factor and Cytokines in Diabetic Deep Wound.

A chronic, unhealed diabetic wound is one of the severe complications of diabetes mellitus. Azadirachta indica has been reported to have antidiabetic and antiapoptotic properties. The present work incorporates the healing potential of 50 % ethanol A. indica leaves extract against deep surgical wounds in streptozotocin-induced mild diabetic rats. A. indica leaves extract (500 mg/kg) was administered orally, once daily for ten days. Serum glucose, cholesterol, and triglycerides as well as body weight, food, and water intake, and tissue antioxidants (catalase, superoxide dismutase and reduced glutathione), free radicals (lipid peroxidation and nitric oxide), myeloperoxidase, total collagens (hydroxyproline, hexuronic acid and hexosamine), protein, vascular endothelial growth factor, and cytokines (tumor necrotic factor-α and interleukin-1ß) were estimated. Histology was done for connective tissue formation and inflammatory and healing in deep granulation tissue after A. indica leaves extract treatment. Diabetic rats showed an increase in serum glucose, cholesterol, and triglycerides levels, food and water intake, and granular tissue free radicals, myeloperoxidase, and cytokines, but a decrease in body weight, total collagen, and vascular endothelial growth factor levels. A. indica leaves extract reversed the increased serum glucose, cholesterol, and triglycerides, food and water intake, and tissue free radicals, myeloperoxidase and, cytokines, but increased body weight, tissue antioxidants, total collagen, and vascular endothelial growth factor contents. The results thus indicated an improvement in wound healing by A. indica leaves extract in diabetic rats through enhanced angiogenesis mediated through the inhibition of hyperglycemia, oxidative stress, and down- and upregulation of inflammatory mediators and growth factor expression.

Mallotus philippinensis Muell. Arg fruit glandular hairs extract promotes wound healing on different wound model in rats.

BACKGROUND: Mallotus philippinensis Muell. Arg (MP, Euphorbiaceae) are widely distributed perennial shrub or small tree in tropical and subtropical region in outer Himalayas regions. Since, Mallotus philippinensis have been shown to have a number of medicinal values. Hence our present study was to investigate the healing potential of fruit extract in rat wound models. METHODS: The study includes acute toxicity and wound healing potential of 50% ethanol extract of MP fruit glandular hair (MPE). MPE (200 mg/kg) was administered orally, once daily for 10 days (incision and dead space wound) and 22 days (excision wound). MPE was found safe when given to rats upto 10 times of optimal effective dose. Wound breaking strength (WBS) in Incision wound and rate of contraction, period of epithelization and scar area in Excision wound were evaluated. Granulation tissue free radicals (nitric oxide and lipid peroxidation), antioxidants (catalase, superoxide dismutase, and reduced glutathione), acute inflammatory marker (myeloperoxidase), connective tissue markers (hydroxyproline, hexosamine, and hexuronic acid), and deep connective tissue histology were studied in Dead space wound. RESULTS: MPE significantly increased WBS and enhanced wound contraction, and decreased both epithelization period and scar area compared with control group. MPE was found to decrease free radicals (50.8 to 55.2%, P<0.001) and myeloperoxidase (44.0%, P<0.001) but enhanced antioxidants (41.1 to 54.5%, P<0.05 to P<0.001) and connective tissue markers (39.5 to 67.3%, P<0.05 to P<0.01). Histopathological evaluation revealed more density of collagen formation with minimal inflammatory cells in deeper tissues. CONCLUSION: Thus, the study revealed Mallotus philippinensis fruit hair extract, safe and effective in wound healing and the healing effects seemed to be due to decrease in free radical generated tissue damage, promoting effects on antioxidant status and faster collagen deposition as evidenced biochemically and histology.

HPLC/tandem mass spectrometric studies on steroidal saponins: an example of quantitative determination of Shatavarin IV from dietary supplements containing Asparagus racemosus.

Asparagus racemosus (AR) is a popular botanical present in several Ayurvedic medicines and nutritional and dietary supplements with immunomodulatory, galactogogue, and anticancer activity. A steroidal saponin known as shatavarin IV is one of the active constituents of AR. A new, selective, and rapid HPLC/MSIMS method has been developed and validated for quantitative estimation of shatavarin IV in crude, processed, and marketed samples of AR. The analytes were separated on a Luna C18 column using simple isocratic elution with water (0.1% acetic acid)-acetonitrie;(0.1% acetic acid; 70 + 30, vIv) at a flow rate of 0.8 mLlmin. The analytes were detected by electrospray ionization (ESI)-MS/MS and quantified using multiple reaction monitoring techniques in the positive ion mode. The method showed excellent linearity (r2 > 0.998) over the concentration range of 7.5 to 254 ng/mL with LOD of 2.5 ng/mL. Precision (RSD) and accuracy (recovery) were found in the ranges of 2.00 to 5.15 and 102 to 110%, respectively. The validated HPLC/ESI-MS/MS method was successfully applied to the quantification of shatavarin IV in crude, processed, and marketed (single or multiherb) AR samples. Therefore, this method could be used for QC and standardization of pharmaceutical or nutritional products containing AR.

Antioxidant capacity and radical scavenging effect of polyphenol rich Mallotus philippenensis fruit extract on human erythrocytes: an in vitro study.

Mallotus philippinensis is an important source of molecules with strong antioxidant activity widely used medicinal plant. Previous studies have highlighted their anticestodal, antibacterial, wound healing activities, and so forth. So, present investigation was designed to evaluate the total antioxidant activity and radical scavenging effect of 50% ethanol fruit glandular hair extract (MPE) and its role on Human Erythrocytes. MPE was tested for phytochemical test followed by its HPLC analysis. Standard antioxidant assays like DPPH, ABTS, hydroxyl, superoxide radical, nitric oxide, and lipid peroxidation assay were determined along with total phenolic and flavonoids content. Results showed that MPE contains the presence of various phytochemicals, with high total phenolic and flavonoid content. HPLC analysis showed the presence of rottlerin, a polyphenolic compound in a very rich quantity. MPE exhibits significant strong scavenging activity on DPPH and ABTS assay. Reducing power showed dose dependent increase in concentration absorption compared to standard, Quercetin. Superoxide, hydroxyl radical, lipid peroxidation, nitric oxide assay showed a comparable scavenging activity compared to its standard. Our finding further provides evidence that Mallotus fruit extract is a potential natural source of antioxidants which have a protective role on human Erythrocytes exhibiting minimum hemolytic activity and this justified its uses in folklore medicines.

Validation and Suitability Assessment of Multiplex Mesoscale Discovery Immunogenicity Assay for Establishing Serological Signatures Using Vaccinated, Non-Vaccinated and Breakthrough SARS-CoV-2 Infected Cases.

Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are multi-targeted and variable over time. Multiplex quantitative serological assays are needed to provide accurate and robust seropositivity data for the establishment of serological signatures during vaccination and or infection. We describe here the validation and evaluation of an electro-chemiluminescence (ECL)-based Mesoscale Discovery assay (MSD) for estimation of total and functional IgG relative to SARS-CoV-2 spike, nucleocapsid and receptor binding (RBD) proteins in human serum samples to establish serological signatures of SARS-CoV-2 natural infection and breakthrough cases. The 9-PLEX assay was validated as per ICH, EMA, and US FDA guidelines using a panel of sera samples, including the NIBSC/WHO reference panel (20/268). The assay demonstrated high specificity and selectivity in inhibition assays, wherein the homologous inhibition was more than 85% and heterologous inhibition was below 10%. The assay also met predetermined acceptance criteria for precision (CV < 20%), accuracy (70-130%) and dilutional linearity. The method's applicability to serological signatures was demonstrated using sera samples (n = 45) representing vaccinated, infected and breakthrough cases. The method was able to establish distinct serological signatures and thus provide a potential tool for seroprevalence of SARS-CoV-2 during vaccination or infection.

A phase III randomized-controlled study of safety and immunogenicity of DTwP-HepB-IPV-Hib vaccine (HEXASIIL®) in infants.

A fully liquid hexavalent containing Diphtheria (D), Tetanus (T) toxoids, whole cell Pertussis (wP), Hepatitis B (Hep B), type 1, 2, 3 of inactivated poliovirus (IPV) and Haemophilus influenzae type b (Hib) conjugate vaccine (DTwP-HepB-IPV-Hib vaccine, HEXASIIL®) was tested for lot-to-lot consistency and non-inferiority against licensed DTwP-HepB-Hib + IPV in an open label, randomized Phase II/III study. In Phase III part, healthy infants received DTwP-HepB-IPV-Hib or DTwP-HepB-Hib + IPV vaccines at 6, 10 and 14 weeks of age. Blood samples were collected prior to the first dose and 28 days, post dose 3. Non inferiority versus DTwP-HepB-Hib + IPV was demonstrated with 95% CIs for the treatment difference for seroprotection/seroconversion rates. For DTwP-HepB-IPV-Hib lots, limits of 95% CI for post-vaccination geometric mean concentration ratios were within equivalence limits (0.5 and 2). Vaccine was well-tolerated and no safety concerns observed.Clinical Trial Registration - CTRI/2019/11/022052.

Seropersistence of SII-ChAdOx1 nCoV-19 (COVID-19 vaccine): 6-month follow-up of a randomized, controlled, observer-blind, phase 2/3 immuno-bridging study in Indian adults.

AZD1222 (ChAdOx1 nCoV-19) is a replication-deficient adenoviral vectored coronavirus disease-19 (COVID-19) vaccine that is manufactured as SII-ChAdOx1 nCoV-19 by the Serum Institute of India Pvt Ltd following technology transfer from Oxford University/AstraZeneca. The non-inferiority of SII-ChAdOx1 nCoV-19 with AZD1222 was previously demonstrated in an observer-blind, phase 2/3 immuno-bridging study (trial registration: CTRI/2020/08/027170). In this analysis of immunogenicity and safety data 6 months post first vaccination (Day 180), 1,601 participants were randomized 3:1 to SII-ChAdOx1 nCoV-19 or AZD1222 (immunogenicity/reactogenicity cohort n = 401) and 3:1 to SII-ChAdOx1 nCoV-19 or placebo (safety cohort n = 1,200). Immunogenicity was measured by anti-severe acute respiratory syndrome coronavirus 2 spike (anti-S) binding immunoglobulin G and neutralizing antibody (nAb) titers. A decline in anti-S titers was observed in both vaccine groups, albeit with a greater decline in SII-ChAdOx1 nCoV-19 vaccinees (geometric mean titer [GMT] ratio [95% confidence interval (CI) of SII-ChAdOx1 nCoV-19 to AZD1222]: 0.60 [0.41-0.87]). Consistent similar decreases in nAb titers were observed between vaccine groups (GMT ratio [95% CI]: 0.88 [0.44-1.73]). No cases of severe COVID-19 were reported following vaccination, while one case was observed in the placebo group. No causally related serious adverse events were reported through 180 days. No thromboembolic or autoimmune adverse events of special interest were reported. Collectively, these data illustrate that SII-ChAdOx1 nCoV-19 maintained a high level of immunogenicity 6 months post-vaccination. SII-ChAdOx1 nCoV-19 was safe and well tolerated.

Healing effects of Musa sapientum var. paradisiaca in diabetic rats with co-occurring gastric ulcer: cytokines and growth factor by PCR amplification.

BACKGROUND: The present study evaluates the effects of extract of Musa sapientum fruit (MSE) on ulcer index, blood glucose level and gastric mucosal cytokines, TNF-α and IL-1ß and growth factor, TGF-α (affected in diabetes and chronic ulcer) in acetic acid (AA)-induced gastric ulcer (GU) in diabetic (DR) rat. METHODS: MSE (100 mg/kg, oral), omeprazole (OMZ, 2.0 mg/kg, oral), insulin (INS, 4 U/kg, sc) or pentoxyphylline (PTX, 10 mg/kg, oral) were given once daily for 10 days in 14 days post-streptozotocin (60 mg/kg, intraperitoneal)-induced diabetic rats while, the normal/diabetic rats received CMC for the same period after induction of GU with AA. Ulcer index was calculated based upon the product of length and width (mm2/rat) of ulcers while, TNF-α, IL-1ß and TGF-α were estimated in the gastric mucosal homogenate from the intact/ulcer region. Phytochemical screening and HPTLC analysis of MSE was done following standard procedures. RESULTS: An increase in ulcer index, TNF-α and IL-1ß were observed in normal (NR)-AA rat compared to NR-normal saline rat, which were further increased in DR-AA rat while, treatments of DR-AA rat with MSE, OMZ, INS and PTX reversed them, more so with MSE and PTX. Significant increase in TGF-α was found in NR-AA rat which did not increase further in DR-AA rat. MSE and PTX tended to increase while, OMZ and INS showed little or no effect on TGF-α in AA-DR rat. Phytochemical screening of MSE showed the presence of saponins, flavonoids, glycosides, steroids and alkaloids and HPTLC analysis indicated the presence of eight active compounds. CONCLUSION: MSE showed antidiabetic and better ulcer healing effects compared with OMZ (antiulcer) or INS (antidiabetic) in diabetic rat and could be more effective in diabetes with concurrent gastric ulcer.

Successful Management of Severe Recalcitrant Pemphigus Vulgaris with Lenalidomide.

Pemphigus variants are treated with immunosuppressives and immunomodulators, but often, clinical remission is challenging. We report a case of pemphigus vulgaris (PV) with involvement of skin, oral mucosa, and esophagus, which failed to respond to commonly used drugs but showed a good response to lenalidomide.