Association Between Atherosclerotic Cardiovascular Disease (ASCVD) Risk Score and Arteriovenous Fistula Failure in Patients on Maintenance Hemodialysis.

BACKGROUND: Arteriovenous fistula (AVF) is the vascular access of choice for hemodialysis in end-stage renal disease (ESRD) patients but has a significant failure rate. Atherosclerotic cardiovascular disease (ASCVD) is a major cause of mortality in ESRD patients. Atherosclerosis of the peripheral vessels may contribute to poor maturation of AVF leading to the exploration of the ASCVD score as a prognostic tool for AVF failure. METHODS: This study included 110 hemodialysis patients with AVFs and aimed to examine the association between ASCVD score and AVF failure. Participants were categorized into the presence of vascular access failure (N=12) and absence of vascular access failure (N=98), and demographic and clinical data were collected.  Results: The study comprised predominantly male patients (63.6%), with a notable prevalence of hypertension and diabetes. Twelve patients experienced AVF failure, with pseudoaneurysms and thrombosis being the predominant causes. The ASCVD risk group at intermediate and high stages exhibited a statistically significant risk (relative risk (RR)=1.403; 95% CI, 1.041-1.904) of AVF failure in comparison to the low and borderline ASCVD risk groups. There was no association of age, gender (male and female), body mass index (BMI), serum calcium, serum phosphorus, intact parathyroid hormone (iPTH), and serum albumin with AVF failure. CONCLUSION: The ASCVD score emerges as a potential prognostic tool to identify dialysis patients at high risk of AVF failure, suggesting avenues for targeted interventions and improved patient care. However, limitations of the ASCVD risk estimator and study limitations, such as small sample size and absence of mortality data, warrant cautious interpretation and necessitate further exploration in larger patient populations.

The clinical management of hepatic sarcoidosis: A systematic review.

Background: Hepatic sarcoidosis is an uncommon clinical condition in which clear recommendations are lacking in its treatment. We aimed to review systematically the literature on hepatic sarcoidosis treatment to guide clinicians. Methods: Using MEDLINE, PubMed, CINAHL, Cochrane Library, and Google Scholar databases, we searched original articles on clinical studies reporting the outcome of adult hepatic sarcoidosis patients following treatment with various pharmacological agents. The primary end point was focused on assessing symptomatic relief and biochemical improvement posttreatment. Results: Out of 614 retrieved references, 34 published studies were eligible, providing data for a total of 268 patients with hepatic sarcoidosis. First-line therapy with corticosteroids alone was reported in 187 patients, whilst ursodeoxycholic acid (UDCA) was used in 40 patients. Symptomatic and biochemical responses were reported among 113(60.4%) and 80(42.8%) cases of corticosteroids respectively, whereas UDCA showed a complete response in 23(57.5%) patients. Second-line therapy was used in steroid-refractory cases, with most cases being reported for azathioprine (n = 32) and methotrexate (n = 28). Notably, 15(46.9%) and 11(39.2%) patients showed both clinical and biochemical responses respectively. Biological therapy including anti-tumor necrosis factor (anti-TNF) was used as third line therapy in twelve cases with a 72.7% symptomatic and biochemical response rate each. Conclusion: The quality of evidence for the treatment of hepatic sarcoidosis was poor. Nevertheless, it appears that corticosteroid or UDCA may be utilized as first-line therapy. For cases that are refractory to corticosteroids, steroid-sparing immunosuppressive agents and anti-TNF have shown some promising results, but further high-quality studies are required.

Tyrosine Sulfation Modulates the Binding Affinity of Chemokine-Targeting Nanobodies.

Chemokines are an important family of small proteins integral to leukocyte recruitment during inflammation. Dysregulation of the chemokine-chemokine receptor axis is implicated in many diseases, and both chemokines and their cognate receptors have been the targets of therapeutic development. Analysis of the antigen-binding regions of chemokine-binding nanobodies revealed a sequence motif suggestive of tyrosine sulfation. Given the well-established importance of post-translational tyrosine sulfation of receptors for chemokine affinity, it was hypothesized that the sulfation of these nanobodies may contribute to chemokine binding and selectivity. Four nanobodies (16C1, 9F1, 11B1, and 11F2) were expressed using amber codon suppression to incorporate tyrosine sulfation. The sulfated variant of 16C1 demonstrated significantly improved chemokine binding compared to the non-sulfated counterpart, while the other nanobodies displayed equipotent or reduced affinity upon sulfation. The ability of tyrosine sulfation to modulate chemokine binding, both positively and negatively, could be leveraged for chemokine-targeted sulfo-nanobody therapeutics in the future.

Structural basis of chemokine recognition by the class A3 tick evasin EVA-ACA1001.

Ticks produce chemokine-binding proteins, known as evasins, in their saliva to subvert the host's immune response. Evasins bind to chemokines and thereby inhibit the activation of their cognate chemokine receptors, thus suppressing leukocyte recruitment and inflammation. We recently described subclass A3 evasins, which, like other class A evasins, exclusively target CC chemokines but appear to use a different binding site architecture to control target selectivity among CC chemokines. We now describe the structural basis of chemokine recognition by the class A3 evasin EVA-ACA1001. EVA-ACA1001 binds to almost all human CC chemokines and inhibits receptor activation. Truncation mutants of EVA-ACA1001 showed that, unlike class A1 evasins, both the N- and C-termini of EVA-ACA1001 play minimal roles in chemokine binding. To understand the structural basis of its broad chemokine recognition, we determined the crystal structure of EVA-ACA1001 in complex with the human chemokine CCL16. EVA-ACA1001 forms backbone-backbone interactions with the CC motif of CCL16, a conserved feature of all class A evasin-chemokine complexes. A hydrophobic pocket in EVA-ACA1001, formed by several aromatic side chains and the unique disulfide bond of class A3 evasins, accommodates the residue immediately following the CC motif (the "CC + 1 residue") of CCL16. This interaction is shared with EVA-AAM1001, the only other class A3 evasins characterized to date, suggesting it may represent a common mechanism that accounts for the broad recognition of CC chemokines by class A3 evasins.

Assessment of Postoperative Swelling and Pain Following Alveolar Ridge Preservation with Different Biomaterials: A Randomized Controlled Trial.

Background: This randomized controlled trial aimed to assess and compare postoperative swelling and pain in patients undergoing alveolar ridge preservation using RidgeMax Pro and AlveoGraft Plus. Methods: A total of 20 patients requiring tooth extraction were enrolled in this study and randomly assigned to two groups: Group A received alveolar ridge preservation with RidgeMax Pro and Group B with AlveoGraft Plus. Postoperative swelling was evaluated by measuring facial dimensions using standardized facial photographs at baseline and at 24, 48, and 72 hours postoperatively. Pain was assessed using a visual analog scale (VAS) at the same time points. Statistical analysis was performed using t-tests and repeated measures ANOVA. Results: Both RidgeMax Pro and AlveoGraft Plus demonstrated effective alveolar ridge preservation without any reported complications. In terms of postoperative swelling, Group A (RidgeMax Pro) exhibited significantly lower facial swelling compared to Group B (AlveoGraft Plus) at all time points (P < 0.05). The mean pain scores on the VAS were consistently lower in Group A than in Group B across the assessment time points (P < 0.05). The trend of reduced swelling and pain in Group A persisted throughout the 72-hour follow-up period. Conclusion: Alveolar ridge preservation with RidgeMax Pro (Trade Name: RidgeMax Pro) resulted in significantly reduced postoperative swelling and pain compared to AlveoGraft Plus (Trade Name: AlveoGraft Plus).

Aesthetic Outcome and Patient Perception of Immediate vs. Delayed Loading of Implant-Supported Single Crowns: A Randomized Controlled Trial.

Background: This randomized controlled trial aimed to compare the aesthetic outcome and patient perception of immediate versus DL of implant-supported single crowns. Methods: A total of 60 patients with a single missing tooth were enrolled and randomly assigned to two groups: immediate loading (IL) and delayed loading (DL). Each group consisted of 30 patients with a total of 30 implants. In the IL group, crowns were loaded onto implants immediately after placement, while in the DL group, a healing period of 3 months was observed before crown placement. Aesthetic outcome was assessed using the Pink Esthetic Score (PES) for soft tissue and the White Esthetic Score (WES) for the crown. Patient perception was evaluated through a visual analog scale (VAS) for satisfaction, comfort, and overall experience. Results: The IL group demonstrated comparable aesthetic outcomes to the DL group, with mean PES and WES scores of 10.2 ± 1.5 and 8.7 ± 1.2, respectively, in the IL group, and 10.5 ± 1.3 and 8.5 ± 1.4 in the DL group. Patient perception in terms of satisfaction, comfort, and overall experience was similarly high in both groups, with VAS scores above 8 for each parameter. Conclusion: This randomized controlled trial suggests that both IL and DL of implant-supported single crowns result in favorable aesthetic outcomes and high levels of patient satisfaction.

Enhanced TNT vapor sensing through a PMMA-mediated AIPE-active monocyclometalated iridium(III) complex: a leap towards real-time monitoring.

Based on the explosive nature and harmful effects of nitro-based explosive materials on living beings and the environment, it is extremely important to develop luminescence-based probe molecules for their detection with excellent selectivity and sensitivity. Two AIPE (aggregation-induced phosphorescence emission)-active iridium(III) complexes (M1 and M2) were developed for the sensitive detection of TNT in both contact and non-contact modes. The aggregate solutions of both complexes (M1 and M2 in THF/H2O, 1/9 by volume) detected TNT at the pico-molar (pM) level. These complexes showed greatly enhanced emission intensity while embedded in a PMMA(polymethyl methacrylate) matrix film. The amplified quantum efficiency, improved phosphorescence lifetime, and enhanced porous network of M2-PMMA composite helps to improve the sesitivity of TNT vapor detection. Interestingly, the sensitivity of the detection of TNT by the M2 complex was significantly improved (5-fold) in a PMMA-incorporated complex (CP) with an observed limit of detection (LOD) of 12.8 ppb. From the BET analysis of CP, it was observed that the mesoporous network of CP has an average pore diameter of 8.52 nm and a surface area of 2.03 m2 g-1. The porous network of CP assists in trapping TNT vapor in a polymeric network containing an electron-rich probe (iridium(III) complex, M2), which helps to effectively trap TNT, thus enhancing electronic communication. As a result, significant emission quenching was observed.

Assessment of radioactivity and radiological hazards associated with bricks in eastern Nepal.

This comprehensive study examines the concentration of natural radionuclides in bricks from the Terai region of the Koshi province, aiming to assess the radioactivity levels and associated radiological hazards, ultimately quantifying the dose limit. The average concentrations of 226Ra, 232Th, and 40K were 27.1 ± 5.7, 42.6 ± 9.8, and 601.5 ± 93.8 Bq/kg, with their respective contributions to total activity being 20.18 %, 45.35 %, 34.48 %,. Despite this, their concentration distribution followed the pattern 40K > 232Th > 226Ra. The elevated presence of 40K in the bricks is attributed to the use of phosphate fertilizers in the soil to enhance crop productivity. Notably, the calculated values of radiological hazard parameters, including radium equivalent activity, absorbed gamma dose, and effective dose, are well below the recommended safety thresholds. Consequently, this study suggests that bricks, when used in substantial quantities, pose no significant radiological risks and are considered safe for use as a building material. The extension of such investigations nationwide is recommended to assess the overall radioactivity levels and establish dose limits.

Assessment of radioactivity in sand samples from eastern Nepal in perspective of radiological hazards.

This study was conducted to investigate the activity concentrations of 226Ra, 232Th and 40K in the sand samples and the health hazards associated with them utilizing a NaI (Tl) gamma spectrometer. The average activity concentrations of 226Ra, 232Th and 40K were found to be 24.8 ± 10.1, 39.8 ± 16.4 and 531.3 ± 52.8 Bq kg-1, respectively. The calculated radiological hazard parameters, including radium equivalent activity, absorbed gamma dose and effective dose rate, were found to be 122.7 ± 34.0 Bq kg-1, 57.7 ± 14.9 nGy h-1 and 0.3 ± 0.1 mSv y-1, respectively. Notably, these results were observed to be below the recommended thresholds. Other measured hazard indices were also lower than the prescribed values. From a radiological perspective, the present study concludes that the sand samples do not pose any threat to human health when utilized as a building material.

Prokaryotic and eukaryotic dual-expression plasmid-mediated delivery of Campylobacter jejuni antigens by live-attenuated Salmonella: A strategy for concurrent Th1 and Th2 immune activation and protection in chickens.

Salmonella and Campylobacter are food-borne pathogens that significantly affect poultry production and are transmitted to humans. Long-term protection against these pathogens in chicken relies on a balanced Th1 and Th2 response. C. jejuni antigens were screened and a fusion antigen, including CadF + FlaA adhesin and flagellin antigenic fragments was developed and safely delivered by low-endotoxicity S. Typhimurium through pJHL270, a dual-expression plasmid featuring prokaryotic (Ptrc) and eukaryotic (CMV) promoters. Antigen expression in Salmonella and host cells was confirmed by western blotting and IFA. The vaccine construct JOL2999, triggered significant increases in IgY, IgA antibodies, CD4+ and CD8+ T cells, indicating humoral, mucosal, and cell-mediated responses against both pathogens. Elevations in pro-inflammatory cytokines TNFα, INF-γ, IL-2, and IL-4 and MHC I and II cell populations further suggest simultaneous Th1 and Th2 immune activation. Reduced pathogen load and histopathological inflammatory signs in vital organs upon challenge confirmed the protective efficacy in chickens.

Risk factors for corneal abrasions in Nepal: a community-based study.

BACKGROUND: South Asia is experiencing rapid urbanization, which may be changing the risk factor profile for ocular trauma. The objective of this study was to compare risk factors for traumatic corneal abrasions in rural versus urban Nepal, and to assess if any risk factors were associated with a poor outcome. METHODS: In a prospective, cross-sectional, community-based study performed as part of a cluster-randomized trial, community health workers from Nepal were trained to diagnose and treat traumatic corneal abrasions. Participants with an abrasion were invited to complete a risk factor survey. The main exposure variable was the object of eye injury, stratified by rural-urban residence. The main outcome measure was a lack of corneal healing after a three-day course of antimicrobials. RESULTS: Of 3657 participants diagnosed with a corneal abrasion, 2265 completed a survey. Eye trauma occurred most frequently during agricultural activities. The most common object of injury was vegetative matter, accounting for approximately 40% of injuries in rural, peri-urban, and urban communities. Wood injuries were more common in rural communities (24%) compared with urban or peri-urban communities (13%). Eye injury from an animal was more likely to result in a non-healing corneal abrasion after 3 days of treatment compared with other types of trauma (prevalence ratio 2.59, 95%CI 1.16-5.76). CONCLUSIONS: Health promotion activities for prevention of corneal ulcers in Nepal should focus on agricultural trauma in both rural and urban areas. Community members experiencing eye trauma from an animal may benefit from early referral to an eye clinic.

Diagnostic accuracy of smartphone corneal photography for detection of corneal opacities in a resource-limited setting: a community-based study.

Purpose: To evaluate the diagnostic accuracy of smartphone corneal photography in detecting corneal opacities in a community-based setting. Methods: A case-control, diagnostic accuracy study was nested in a cluster-randomized trial of a corneal ulcer prevention intervention in Nepal. Smartphone corneal photography was performed annually on community members self-reporting a potential risk factor for a corneal infection. Corneal photographs were graded for the presence or absence of an opacity. All cases with an opacity on smartphone photography and an equal number of controls were invited for a comprehensive eye examination with a slit lamp biomicroscope at an eye hospital. A mobile team visited participants unable to come to the hospital, conducting a limited examination with a penlight. Results: Of 1332 study participants (666 cases and 666 controls), 1097 had a penlight examination (535 cases and 562 controls) and 191 had a slit lamp examination (120 cases and 71 controls). When penlight examination was considered the reference standard, smartphone diagnosis of a corneal opacity had a positive predictive value (PPV) of 47% (95% confidence interval 43-52%) and negative predictive value (NPV) of 95% (93-97%). When slit lamp examination was considered the reference standard, the overall PPV and NPV were 71% (62-78%) and 80% (70-88%), respectively. The NPV was greater for detection of opacities > 1mm, estimated at 95% (90-98%). Conclusions: Corneal photography performed in a resource-limited community-based setting using a smartphone coupled to an external attachment had acceptable diagnostic accuracy for detection of corneal opacities large enough to be clinically meaningful.

Robust Optical Detection of Ga3+ by a Rhodamine- and Coumarin-Based Proficient Probe: Theoretical Investigations and Biological Applications.

The present investigation highlights a rhodamine-B- and coumarin-based efficient probe that selectively detects Ga3+ over other metal ions. The active pocket of the ligand for trapping the metal ions and the binding stoichiometry of its Ga3+ complex were discovered by single-crystal X-ray diffraction (SC-XRD) analysis. This binding stoichiometry was further confirmed in the solution state by mass spectrometry and Job's plot. The detection limit was found to be at the nanomolar level. Pyrophosphate being a well-known quencher could easily quench the fluorescence intensity of the RC in the presence of Ga3+ and reversibly recognize Ga3+ in the solution. The spiro ring opening of the ligand after Ga3+ insertion is proposed to be the principal mechanism for the turn-on fluorescence response. This ring opening was confirmed by SC-XRD data and nuclear magnetic resonance (NMR) titration experiments. Both ground- and excited-state calculations of the ligand and complex have been carried out to obtain information about their energy levels and to obtain the theoretical electronic spectra. Furthermore, the live-cell imaging of the probe only and the probe after the addition of Ga3+ have been carried out in HaCaT cells and satisfactory responses were observed. Interestingly, with the help of this probe, Ga3+ can be tracked inside the intracellular organelle such as lysosomes along with other regions of the cell. The article highlights a rhodamine-coumarin-based probe for the detection of Ga3+ over other metal ions with a nanomolar level detection limit. Structural characterization of the ligand and its Ga3+ complex was investigated by SC-XRD. Density functional theory (DFT) and time-dependent DFT (TD-DFT) studies were carried out to explore the excited-state energies and electronic spectra. The application of the probe for the detection of Ga3+ in live cells has been explored, and positive responses were observed.

Most common health problems in general practice among adolescents, and young adults' survivors of lymphoma: a register-based cohort study in Norway.

BACKGROUND: The aim was to investigate the distribution of health problems in general practice (GP) among adolescent and young adult (AYA) survivors of lymphoma and to compare problem rates with the general population. METHODS: All GP consultations between 2006 and 2020 were identified from the national GP claims register. Diseases and complaints presented 3-10 years after the cancer diagnosis were identified using the International Classification of Primary Care codes (ICPC-2) and compared by applying logistic regression models, presented with odds ratio (OR) and 95%CI. RESULTS: A total of 2,500,557 AYAs, of whom 1105 were diagnosed with lymphoma, and over 50 million GP consultations were included. The most common causes of consultation among AYA survivors of lymphoma were related to Hodgkin's disease (13%), pregnancy (11%), respiratory diseases (9%), psychological problems (8%), musculoskeletal system (6%) and fatigue (4%). Almost all these problems were significantly higher among AYA lymphoma survivors compared to the general population (OR ranging from 1.1 to 1.5). CONCLUSION: Compared to the general population, young lymphoma survivors have increased contact with the GP for a considerable number of health problems for up to 10 years post-diagnosis. This emphasizes the importance of robust follow-up and a good flow of information between hospital and primary care.

Experimental analysis of diverse actin-like proteins from various magnetotactic bacteria by functional expression in Magnetospirillum gryphiswaldense.

IMPORTANCE: To efficiently navigate within the geomagnetic field, magnetotactic bacteria (MTB) align their magnetosome organelles into chains, which are organized by the actin-like MamK protein. Although MamK is the most highly conserved magnetosome protein common to all MTB, its analysis has been confined to a small subgroup owing to the inaccessibility of most MTB. Our study takes advantage of a genetically tractable host where expression of diverse MamK orthologs together with a resurrected MamK LUCA and uncharacterized actin-like Mad28 proteins from deep-branching MTB resulted in gradual restoration of magnetosome chains in various mutants. Our results further indicate the existence of species-specific MamK interactors and shed light on the evolutionary relationships of one of the key proteins associated with bacterial magnetotaxis.

Inflammation-Related Immune-Modulatory SLURP1 Prevents the Proliferation of Human Colon Cancer Cells, and Its Delivery by Salmonella Demonstrates Cross-Species Efficacy against Murine Colon Cancer.

This study investigates the anticancer properties of the α7-nAChR antagonist SLURP1 with a specific focus on its effect as an inflammation modulator on human colorectal cancer cell lines Caco2, Colo320DM, and H508 cells. The investigation includes the evaluation of cell cycle arrest, cell migration arrest, endogenous expression of SLURP1 and related proteins, calcium influx, and inflammatory responses. The results demonstrate that SLURP1 not only inhibits cell proliferation but also has the potential to arrest the cell cycle at the G1/S interface. The impact of SLURP1 on cell cycle regulation varied among cell lines, with H508 cells displaying the strongest response to exogenous SLURP1. Additionally, SLURP1 affects the nuclear factor kappa B expression and effectively reverses inflammatory responses elicited by purified lipopolysaccharides in H508 and Caco2 cells. This study further confirmed the expression of human SLURP1 by Salmonella, under Ptrc promoter, through Western blot analysis. Moreover, Salmonella secreting SLURP1 revealed a significant tumor regression in a mouse CT26 tumor model, suggesting the cross-species anticancer potential of human SLURP1. However, further investigations are required to fully understand the mechanisms underlying SLURP1's ability to prevent cancer proliferation and its protective function in humans.

Relationship Between Intraocular Pressure and Age: A Population-Based Study in Nepal.

PRCIS: Intraocular pressure (IOP) decreased with age in a population-based study in Nepal, from a mean of 14.1 mm Hg among those 60-64 years old to 13.0 mm Hg among those 80 years old or older. PURPOSE: Few studies have assessed the distribution of IOP from the Indian subcontinent, despite its large population and high burden of glaucoma. The objective of this study was to assess the distribution of IOP measurements from adults living in a lowland region of Nepal. METHODS: In a population-based cross-sectional study, all individuals aged 60 years and older from an area of lowland Nepal were invited for an IOP assessment with a rebound tonometer. RESULTS: Of 160 communities (28,672 people aged ≥60 y) enrolled, 79 (13,808 people aged ≥60 y) were randomly selected for IOP testing. Of those eligible, 10,017 (72.5%) individuals underwent tonometry. Mean IOP decreased monotonically over 5-year age groups, from 14.1 mm Hg (SD: 3.6) among those aged 60-64 years to 13.0 mm Hg (SD: 4.2) among those 80 years or older. The 97.5th percentile IOP measurement was 21.0 mm Hg for all age groups. In adjusted analyses, younger age, self-reported diabetes, and higher population density were each associated with higher IOP, and self-reported cataract surgery was associated with lower IOP. CONCLUSIONS: Mean IOP was lower among older individuals in Nepal, consistent with many studies from East Asia and in contrast to many studies from western populations. These results suggest that ethnic background might be a consideration when diagnosing ocular hypertension.

AI-2 quorum sensing controlled delivery of cytolysin-A by tryptophan auxotrophic low-endotoxic Salmonella and its anticancer effects in CT26 mice with colon cancer.

INTRODUCTION: The limitations of conventional cancer therapies necessitate target-oriented, highly invasive, and safe treatment approaches. Hence, the intrinsic anti-tumor activity of Salmonella can offer better options to combat cancers. OBJECTIVES: This study aims to utilize attenuated Salmonella and deliver cytolytic protein cytolysin A (ClyA) under quorum sensing (QS) signaling for precise localized expression in tumors but not in healthy organs. METHODS: The therapeutic delivery strain was imposed with tryptophan auxotroph for selective colonization in tumors by trpA and trpE deletion, and lipid-A and O-antigen were altered by pagL and rfaL deletions using lambda red recombination method. The strain was transformed with the designed QS-controlled ClyA expression vector which was validated by western blot. The in vivo passaged therapeutic strain was used for treatment four times at a weekly interval, with a dose of 5 × 106 CFU/mouse for cancer therapy. RESULTS: The attenuated strain induced minimal endotoxicity-related cytokines TNF-α, IL-1ß, and IFN-γ and exhibited adequate colonization despite earlier exposure in mice. The QS-controlled ClyA expression was confirmed by western blot from bacterial cultures grown at different cell densities. The results demonstrated that the in vivo passaged strain preferentially colonized the tumor after vacating the spleen, liver, and lung, leaving no outward histological scars. The anti-cancer effect of the designed construct was evaluated in the murine CT26 colon cancer model. The expression of ClyA increased tumoricidal activity by 67 % compared to vector control. CONCLUSION: Hence, the anti-tumor effect of the engineered Salmonella strain was improved by ClyA expression via QS activation after achieving the threshold bacterial cell density. Further, immunohistochemical staining of the tumor and other organs corroborated the QS-controlled tumor-specific expression of ClyA. Overall, the results imply that the developed anti-cancer Salmonella has low endotoxicity and QS-controlled expression of ClyA as beneficial safety elements and supports recurrent Salmonella inoculation by O-antigen deficiency.

Immunogenicity and safety of HavisureTM vaccine developed by Human Biologicals Institute in healthy subjects of 12 months to 49 years of age: A phase II/III, randomized, single blind, non-inferiority study.

BACKGROUND: Hepatitis A is an inflammation of the liver caused by the hepatitis A virus (HAV). It is transmitted mainly because of poor personal hygiene via the faecal/oral route through ingestion of contaminated food or water or through the direct contact with an infectious person. Though most of the infected individuals recover from the infection, a few may develop fatal fulminant hepatitis. In this randomized, multicenter study, immunogenicity and safety of Havisure™ vaccine of Human Biologicals Institute was compared with Havrix® vaccine. METHODS: The study was carried out in 528 eligible healthy subjects, in two age groups across eight centres in India. Group A included subjects of 19-49 years and Group B subjects of 12 months to below 19 years of age. All subjects received two doses of either Havisure™ vaccine or Havrix® vaccine as per randomization at six months interval. Blood samples for antibody titre estimation were collected before vaccination and 4-6 weeks after 2nd dose of vaccination. Immunogenicity was assessed by estimating seroconversion rate, seroprotection rate, and geometric mean titres of antibodies. Safety was evaluated by collection and analysis of data on solicited and unsolicited adverse events. RESULTS: Of 528 enrolled subjects, 493 subjects completed the study. There was 100% seroconversion and seroprotection in both the vaccine arms. There was no statistical difference in the geometric mean titres between the two vaccine arms. Pain and swelling at the site of injection were the most common local adverse events whereas fever and headache were the most common systemic adverse events observed in both vaccine arms. No serious adverse event was reported in the study. CONCLUSION: The study results indicate that the Havisure™ vaccine is immunogenic and safe when administered to healthy subjects of 12 months to 49 years of age, and is non-inferior to Havrix® Vaccine.