The ongoing COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global threat. Although non-pharmaceutical interventions have been rigorously and widely implemented, living conditions caused by the pandemic will last until highly effective vaccines are successfully improved and globally administered. Several first-generation COVID-19 vaccines were approved at the end of 2020. However, the COVID-19 pandemic is persisting worldwide. To be clear, the efficiency and the coverage of current vaccines are insufficient, but newly emerging and rapidly spreading variants are the most pressing concern. A second-generation COVID-19 vaccine worth mentioning, NVX-CoV2373, has demonstrated 90% overall efficacy as well as a high level of efficacy against circulating variants in Phase 3 clinical trials. Currently, NVX-CoV2373 is the only vaccine that has proven successful against variants during Phase 3/4 trials. Therefore, developing the next generation of vaccines is a promising strategy to ultimately prevail against SARS-CoV-2. This review provides up-to-date information on COVID-19 vaccines in terms of their efficacy and new platforms and the progression of COVID-19 vaccination. Moreover, this review also summarizes the efficacy of approved COVID-19 vaccines against variants. Lastly, this review highlights the global challenges for COVID-19 vaccines in development and vaccination, and it discusses opportunities for development of future COVID-19 vaccines and vaccination coverage.

The COVID -19 pandemic has had a catastrophic impact on the global economy and the healthcare industry. Unfortunately, the scientific community still hasn't discovered a definite cure for this virus. Also, owing to the unscrupulous use of antibiotics in wake of the current situation, another ongoing pandemic of antimicrobial resistance (AMR) has been entirely eclipsed. However, increased compliance to infection control measures like hand hygiene (both at hospital and community level), and restricted travel might be favorable. It is evident that the AMR strategies will be impacted disproportionately varying with the respective policies followed by the countries and hospitals to deal with the pandemic. The vaccination drive initiated globally has provided a glimmer of hope. In this article, the possible reciprocity between the two contemporaneous pandemics has been addressed. The world needs to be vigilant to punctuate the symphony between these lethal threats to global health. The restraint to combat against AMR will be boosted as our discernment of the problem also changes with the epidemiological interplay becoming more apparent in near future.

Dengue is a life-threatening mosquito borne viral disease. We are still in the era of supportive treatment where morbidity and mortality are a major concern. Dengue infection in presence of other co-infections makes this scenario rather worse. Timely recognition and raising alarm to be intensive is the need of the hour for primary care physicians practicing in the community and indoors. This review provides a comprehensive knowledge about the recent trends of coinfection in dengue as well as their management consideration which will be particularly helpful for physicians practicing in rural and remote areas of India.

Various stresses (high temperature, starvation, or sublethal Cryptococcal infection) increased the susceptibility of silkworms to bacterial infection by up to 100-fold, confirming the stress-induced immunosuppression reported in a range of species. When the silkworm was injected with a steroidal drug, betamethasone (1 mg/larva), the susceptibility of the silkworm to bacterial infection increased about 100-fold. This indicates that the immune function of the silkworm can be suppressed by a known compound that shows immunosuppressive effects in humans. We further tested the immunosuppressive effect of the culture supernatants (acetone extracts) of soil bacteria, and 24 out of 193 isolates showed the immunosuppressive activity. These results suggest that it is possible to search for immunosuppressive agents targeting innate immunity by using a silkworm bacterial infection model as a screening system, and that there may be candidate compounds for immunosuppressive agents among the substances produced by soil bacteria.

An electrophysiological bioassay was used to isolate the active compound from Hochuekkito (HET), which the current authors previously described as having potent agonist action against serotonin 2C receptors (5-HT2CR). Synthetic 5-HT2CR mRNA was injected into Xenopus oocytes to specifically express these receptors. Crude extracts and purified products were subjected to an electrophysiological bioassay using the voltage clamp method. HET stimulated a 5-HT2CR-induced current response, whereas Juzentaohoto (JTT), which has anti-depressive action similar to that of HET, did not. Current responses were not observed with an extract mixed with five types of herbal medicines common to HET and JTT but were detected with an extract with the five types of herbal medicines found in HET alone (Hoc5). When the responses to each of the five types of Hoc5 were examined, current responses were noted with Cimicifugae rhizoma (CR) and Citrus unshiu Markovich extracts. Since efficacy and the EC₅₀ value were higher for CR, its constituents were separated using three-dimensional high-performance liquid chromatography and the current response at each of the isolated peaks was examined. One constituent displayed a strong response and was identified as a single substance with a molecular weight of 283.1393 based on liquid chromatography/mass spectrometry. These results will contribute to the isolation of 5-HT2CR-stimulating constituents in HET and the identification of trace constituents with agonist action.

We aimed to investigate the association between anaphylaxis and anti-influenza drug use using the Japanese Adverse Drug Event Report (JADER) database, a national spontaneous reporting database in Japan. We surveyed registered cases from the JADER database between April 2004 and November 2019. The target drugs were five anti-influenza drugs, namely oseltamivir, zanamivir, peramivir, laninamivir, and baloxavir. Adverse events associated with anaphylaxis, "anaphylactic reaction," "anaphylactic shock," "anaphylactoid reaction," and "anaphylactoid shock," were evaluated. The association between anaphylaxis and anti-influenza drug use was assessed by calculating the reporting odds ratio (ROR) and information component (IC) as a measure of disproportionality. Signals were considered positive if the lower limit of the 95% confidence interval (CI) of ROR was > 1, and that of IC was > 0. The number of anaphylaxis cases associated with anti-influenza drug use was 199 (0.9%). Signals were detected for inhaled laninamivir (ROR: 4.24 [95% CI: 3.06-5.88], IC: 1.83 [1.35-2.30]), intravenous peramivir (ROR: 2.97 [2.11-4.17], IC: 1.40 [0.90-1.89]), and oral baloxavir (ROR: 3.05 [2.22-4.18], IC: 1.44 [0.98-1.90]). Conversely, signals were not detected for oral oseltamivir or inhaled zanamivir. Although zanamivir and laninamivir were used as dry powder inhalers containing lactose as an additive, they differed in terms of signal detection. Our analysis indicated that the signal of anaphylaxis may varies based on the main component or dosage form of each anti-influenza drug. Appropriate use of these drugs is essential to prevent anaphylaxis and improve health status.

A variable proportion of patients develop persistent/prolonged symptoms of Coronavirus Disease 2019 (COVID-19) infection (long COVID). We aimed to study the clinical predictors of persistent symptoms in patients with mild COVID-19 at 30 days post discharge (long COVID-19). We also tried to identify symptom clusters among mild COVID-19 patients. Fifty-seven patients admitted at a tertiary care centre after a positive RT-PCR report over a period of 2 months, were enrolled in the study. Details of presentation, history of illness, laboratory investigations and disease outcomes were recorded from documented medical records and discharge slip. The patients were contacted (telephonically) at 30 days after discharge and enquired regarding persistent symptoms, if any. Follow up data at 30 days post-discharge was available for 53 patients. Among them, the most common persistent symptom was fatigue (22.6%), followed by cough (9.4%) and myalgias (7.5%). There was a significant association of persistent symptoms with diarrhoea at presentation [OR 14.26 (95% CI 2.30-142.47; p = 0.009] and gap between symptom onset and admission [OR 1.40 (95% CI 1.08-1.93; p = 0.020] on multivariate logistic regression analysis. On cluster analysis, three phenotypes of mild COVID-19 were identified, which may have implications on monitoring and management. There appears to be a positive association of diarrhoea as a presenting manifestation and gap between symptom onset and admission with the persistence of symptoms classified as long COVID-19, even in mild illness. We also identified multiple phenotypes of mild COVID-19 illness, which warrant further exploration.

In the present study, to identify the clinical significance of the cytokeratin (CK) 20 staining pattern in Merkel cell carcinoma (MCC), we retrospectively analyzed the major clinicopathological and immunohistochemical characteristics of 12 cases of MCC. Typical dot-like pattern was seen in eight of our patients, while four patients showed peripheral staining pattern. Interestingly, all cases of MCC with dot-like CK20 tumor cells occurred in the head and neck region, while those with peripheral CK20 pattern tended to be located in other lesions (forearm, knee, or buttock): The difference of frequency in the head and neck regions was statistically significant. Dot-like CK20 staining pattern may therefore be resulted from ultraviolet exposure. Additionally, although without significance, metastasis was more frequent in those with dot-like CK20 than in peripheral CK20 staining: All patients with peripheral CK20 pattern had complete remission by surgical excision with or without radiation therapy. CK20 staining pattern may be a novel predictor of prognosis.

Alzheimer's disease (AD) is an irreversible brain disorder associated with severe progressive dementia and is characterized by deposits of amyloid plaques in the brain. Over the past 20 years, the mortality of strokes and heart disease has decreased, but deaths from AD have increased. The four drugs used clinically to treat AD can only relieve symptoms but cannot slow the progression of the disease. Aducanumab, a human monoclonal antibody that preferentially binds to aggregated amyloid-β to reduce the number of amyloid plaques and slow disease progression, was approved to treat AD by the US Food and Drug Administration on June 7, 2021. It is the first disease-modifying therapy for AD, but there is considerable controversy regarding the drug's approval. Aducanumab offers hope for millions of patients.

The principal concept of the percutaneous tandem drainage procedure for an intractable hepaticojejunostomy (HJ) leakage is to decrease the amount of fluid and divide the fluid-filled cavity into several small cavities, which can then be drained individually. Percutaneous abscess drainage (PAD) has a role in drainage of the fluid cavity, whereas percutaneous trans-anastomotic jejunum drainage (PTAJD) has a role in drainage to reduce the bile fluid and digestive juices. A decrease in fluid induces effective drainage of the fluid cavity by PAD. A negative pressure suction drain accelerates reduction of the fluid cavity. PAD is removed when the localized fluid cavity has collapsed. PTAJD is finally removed after a clamping test is performed. Since 2020, we performed the percutaneous tandem drainage for two patients, and an intractable HJ leakage was gently resolved within 3 months without any adverse event. The percutaneous tandem drainage technique is safe for steady drain management of an intractable HJ leakage.