COVID-19 vaccination and breakthrough infections in patients with cancer.

BACKGROUND: Vaccination is an important preventive health measure to protect against symptomatic and severe COVID-19. Impaired immunity secondary to an underlying malignancy or recent receipt of antineoplastic systemic therapies can result in less robust antibody titers following vaccination and possible risk of breakthrough infection. As clinical trials evaluating COVID-19 vaccines largely excluded patients with a history of cancer and those on active immunosuppression (including chemotherapy), limited evidence is available to inform the clinical efficacy of COVID-19 vaccination across the spectrum of patients with cancer. PATIENTS AND METHODS: We describe the clinical features of patients with cancer who developed symptomatic COVID-19 following vaccination and compare weighted outcomes with those of contemporary unvaccinated patients, after adjustment for confounders, using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19). RESULTS: Patients with cancer who develop COVID-19 following vaccination have substantial comorbidities and can present with severe and even lethal infection. Patients harboring hematologic malignancies are over-represented among vaccinated patients with cancer who develop symptomatic COVID-19. CONCLUSIONS: Vaccination against COVID-19 remains an essential strategy in protecting vulnerable populations, including patients with cancer. Patients with cancer who develop breakthrough infection despite full vaccination, however, remain at risk of severe outcomes. A multilayered public health mitigation approach that includes vaccination of close contacts, boosters, social distancing, and mask-wearing should be continued for the foreseeable future.

Analysis of specific mRNA gene expression profiles as markers of egg and embryo quality for hybrid catfish aquaculture.

Despite best efforts to optimize reproduction, egg incubation, and larval performance in captivity, inconsistencies in hatchery fish production are still created by high variations in egg quality from individual females. In some hatchery species, egg quality and generation of viable embryos are correlated to abundances of specific mRNAs. Channel catfish females show considerable extremes in egg quality, causing inconsistencies in channel catfish, Ictalurus punctatus, female × blue catfish, Ictalurus furcatus, male hybrid fry production. The objectives of this study were to examine relative transcripts linked to egg and embryo quality and determine expression between low-hatch and high-hatch egg batches through early development (0, 24, 48, and 96 h post-fertilization; HPF). RNA was extracted from eggs/embryos of nine females (n = 4 high-quality, n = 5 low-quality) and Real-Time PCR was used to quantify relative gene expression. The transcripts assessed in this study perform critical cellular functions, including tubulin ß (tubb), cathepsin D (ctsd), cathepsin Z (ctsz), cathepsin B (ctsb), cyclin B (ccnb1), exportin-1 (xpo1), ring finger protein 213 (rnf213), glucocorticoid receptor-1 (GR-1), and heat shock protein 70 (hsp70). Relative gene expression of all transcripts except GR-1 and hsp70 were up-regulated in the high-hatch group and peaked at 48 HPF (neurulation stage), indicating the importance of these gene products at this threshold to normally progress until hatch. Due to lack of expression during earlier stages, maternally derived mRNAs for these genes do not seem to impact early embryonic development. Using mRNA markers as a selection mechanism for hatchery broodstock may lead to more high-hatch egg batches by reducing problems associated with poor egg quality.

Ontogeny of the cortisol stress response and glucocorticoid receptor expression during early development in channel catfish, Ictalurus punctatus.

Cortisol is a glucocorticoid hormone which is an endocrine signaling molecule in all vertebrates and acts through intracellular glucocorticoid receptors (GRs). Cortisol affects many biological functions including immunity, stress, growth, and reproduction. The objective of this study was to investigate the ontogeny of the cortisol and GR stress response in channel catfish (Ictalurus punctatus) at several early life stages. To accomplish this, resting and stress-induced levels of tissue cortisol and the two catfish GRs (GR-1 and GR-2) expression were measured. Resting cortisol levels in newly fertilized eggs averaged 2.4 ±â€¯0.2 ng/egg and decreased to 0.4 ±â€¯0.01 ng/egg by day 5. Cortisol levels in newly fertilized eggs subjected to an acute stress (lowered dissolved oxygen from 6.5 mg/L to 1.8 mg/L) averaged 2.3 ±â€¯0.1 ng/egg and decreased to 0.3 ±â€¯0.03 ng/egg by day 5. At hatching, resting cortisol levels were 24 ±â€¯1.0 ng/0.1 g tissue while levels increased to 83 ±â€¯2.0 ng/0.1 g tissue in fry subjected to an acute stress (P < .05). Four days post-hatch, resting cortisol levels were 83 ±â€¯1.0 ng/0.1 g tissue while levels increased to 149 ±â€¯4.0 ng/0.1 g tissue in fry subjected to an acute stress (P < .01). There was no significant difference between GR-1 and GR-2 mRNA in stressed and unstressed newly hatched fry. Four days post-hatch, GR-1 mRNA increased 3-fold while GR-2 mRNA increased 2-fold in fry that were subjected to low dissolved oxygen conditions (P < .05). These results indicate that cortisol biosynthesis, integration and maturation of the hypothalamic-pituitary-interrenal (HPI) axis can be observed in channel catfish at hatching. The upregulation of GR-1 and -2 mRNA in stressed fry supports roles for both transcripts in integrating the channel catfish stress response.

No apparent cost of evolved immune response in Drosophila melanogaster.

Maintenance and deployment of the immune system are costly and are hence predicted to trade-off with other resource-demanding traits, such as reproduction. We subjected this longstanding idea to test using laboratory experimental evolution approach. In the present study, replicate populations of Drosophila melanogaster were subjected to three selection regimes-I (Infection with Pseudomonas entomophila), S (Sham-infection with MgSO4 ), and U (Unhandled Control). After 30 generations of selection flies from the I regime had evolved better survivorship upon infection with P. entomophila compared to flies from U and S regimes. However, contrary to expectations and previous reports, we did not find any evidence of trade-offs between immunity and other life history related traits, such as longevity, fecundity, egg hatchability, or development time. After 45 generations of selection, the selection was relaxed for a set of populations. Even after 15 generations, the postinfection survivorship of populations under relaxed selection regime did not decline. We speculate that either there is a negligible cost to the evolved immune response or that trade-offs occur on traits such as reproductive behavior or other immune mechanisms that we have not investigated in this study. Our research suggests that at least under certain conditions, life-history trade-offs might play little role in maintaining variation in immunity.

Serosurveillance of foot and mouth disease in Karnataka state, India: a 3 years study.

A prospective serological investigation was conducted to determine the prevalence and distribution of foot-and-mouth disease (FMD), as well as to monitor the effectiveness of the FMD control programme (FMD-CP) through vaccination in Karnataka, India. Random serum samples were collected every year between May and August before the start of vaccination in 2011, and subsequently following two phases of vaccination in 2012 and 2013. Infection status (seroprevalence) was inferred by subjecting the sera to indirect r3AB3 non-structural protein-ELISA, using kits developed by the Project Directorate on FMD, India. The seromonitoring of FMD-CP was carried out by detecting antibodies deemed to be protective in the pre- and post-vaccinal sera, using liquid-phase blocking-ELISA for structural proteins. The results revealed significant decrease in seroprevalence from 58 to 21 %, providing more definitive data supporting our earlier findings obtained through clinical observations (Hegde et al. in Virusdisease 25:504-509, 2014), and detecting active infection in some of the populations which were considered to be free based on passive surveillance. On the other hand, after four rounds of vaccination, a gradual and significant increase from 4.5 to 59 % of animals carrying antibody levels deemed to be protective was observed against all the three serotypes. The findings of this study could be useful for further strategizing to strengthen the ongoing FMD-CP in Karnataka State, India.

Epidemiology of foot and mouth disease in Karnataka state, India: a retrospective study.

A retrospective study on the epidemiology of foot and- mouth disease (FMD) in Karnataka, India between the years 1977 and 2012-13 based on the data collected through passive and active surveillance was undertaken. A total of 11,159 outbreaks with 0.271 million cases of FMD were recorded from 30 different revenue districts of Karnataka. There was a significant difference between the years for the annual incidence of FMD (P = <0.001, F = 19.10) and also between the months (P = <0.001, F = 4.22). Cattle and buffaloes were the predominant species affected being involved in all of the outbreaks reported. A significant correlation was observed between livestock density and the number of outbreaks reported (r = 0.70, p < 0.02), and number of cases (r = 0.76, p < 0.01) for all the agro-climatic zones. The Central dry zone (n = 2257, 19.89 %) reported the highest number of outbreaks followed by the Northern dry zone (n = 1881, 16.58 %) and the Southern transition zone (n = 1761, 15.52 %), and attack rates were concentrated in the North/Northeastern/Central dry and transition zones. A large majority of the outbreaks were caused by serotype O (64.04 %), followed by Asia 1 (19.87 %) and A (12.27 %). Serotype C was not reported since 1993 in the state. In recent years, serotype O has dominated (82.59 %), with the rest of the outbreaks being almost equally caused by A (9.01 %) and Asia 1 (8.40 %). The study highlights the significance of the O serotype and cattle as the main indicator species in the epidemiology of FMD in Karnataka, India. The findings from this study can be used as baseline epidemiological data for further research to identify endemic and epidemic areas for the development of a sustainable programme for the progressive control of FMD in the state of Karnataka as well as other endemic settings.

Sexual activity increases resistance against Pseudomonas entomophila in male Drosophila melanogaster.

BACKGROUND: Maintenance and deployment cost of immunity is high, therefore, it is expected to trade-off with other high cost traits like sexual activity. Previous studies with Drosophila melanogaster show that male's ability to clear bacteria decreases with increase in sexual activity. We subjected this idea to test using two pathogens (Pseudomonas entomophila and Staphylococcus succinus) and three different populations of Drosophila melanogaster. RESULTS: We found that sexual activity enhanced male survivorship in a pathogen specific manner. Sexually active males show higher resistance than virgins upon infection with Pseudomonas entomophila. Interestingly, the beneficial effects of sexual activity increased with time of co-habitation with females and declined when access to females was restricted. We observed no change in male survivorship upon experimentally varying the number of sexual interactions. CONCLUSION: Our results show that the sexual activity-immunity trade-off in males cannot be generalised. The trade-off is potentially mediated through complex interactions between the host, pathogen and the environment experienced by the host.

dSir2 in the adult fat body, but not in muscles, regulates life span in a diet-dependent manner.

Sir2, an evolutionarily conserved NAD(+)-dependent deacetylase, has been implicated as a key factor in mediating organismal life span. However, recent contradictory findings have brought into question the role of Sir2 and its orthologs in regulating organismal longevity. In this study, we report that Drosophila Sir2 (dSir2) in the adult fat body regulates longevity in a diet-dependent manner. We used inducible Gal4 drivers to knock down and overexpress dSir2 in a tissue-specific manner. A diet-dependent life span phenotype of dSir2 perturbations (both knockdown and overexpression) in the fat body, but not muscles, negates the effects of background genetic mutations. In addition to providing clarity to the field, our study contrasts the ability of dSir2 in two metabolic tissues to affect longevity. We also show that dSir2 knockdown abrogates fat-body dFOXO-dependent life span extension. This report highlights the importance of the interplay between genetic factors and dietary inputs in determining organismal life spans.

Tooth element levels indicating exposure profiles in diabetic and hypertensive subjects from Mysore, India.

Element contents of teeth elucidate exposure nature, but less is known about association of tooth element concentrations of diabetics and hypertensives with exposure profile. Present study aims to estimate copper, chromium, iron, zinc, nickel, and lead concentrations in the permanent teeth of control, diabetic, and hypertensive subjects from Mysore. The results show that lead levels of teeth (Pb-T) are higher in the hypertensives and diabetics, whereas copper levels of teeth (Cu-T) are lower in the hypertensives and users of stainless steel utensils than that of controls and users of mixed utensils. The elevated Cu-T levels found in the users of mixed utensils that being made of several metals are ascribed to leaching effect of sour and spicy food of Indian cuisine. The element levels were influenced by diet (Zn-T), place of living, sex and income (Pb-T) of the subjects, but not by age, drinking water from different sources, and certain habits viz., smoking, alcohol consumption, chewing betel, and nut. Thus, it is evident that high Pb-T and low Cu-T levels may be related with diabetes and hypertension and high Pb-T and Cu-T levels, respectively, in the urbanites, and the users of mixed utensils may show different exposure profiles from environment and utensils.

Reproductive behaviour evolves rapidly when intralocus sexual conflict is removed.

BACKGROUND: Intralocus sexual conflict can inhibit the evolution of each sex towards its own fitness optimum. In a previous study, we confirmed this prediction through the experimental removal of female selection pressures in Drosophila melanogaster, achieved by limiting the expression of all major chromosomes to males. Compared to the control populations (C(1-4)) where the genomes are exposed to selection in both sexes, the populations with male-limited genomes (ML(1-4)) showed rapid increases in male fitness, whereas the fitness of females expressing ML-evolved chromosomes decreased. METHODOLOGY/PRINCIPAL FINDINGS: Here we examine the behavioural phenotype underlying this sexual antagonism. We show that males expressing the ML genomes have a reduced courtship level but acquire the same number of matings. On the other hand, our data suggest that females expressing the ML genomes had reduced attractiveness, stimulating a lower rate of courtship from males. Moreover, females expressing ML genomes tend to display reduced yeast-feeding behaviour, which is probably linked to the reduction of their fecundity. CONCLUSION/SIGNIFICANCE: These results suggest that reproductive behaviour is shaped by opposing selection on males and females, and that loci influencing attractiveness and foraging were polymorphic for alleles with sexually antagonistic expression patterns prior to ML selection. Hence, intralocus sexual conflict appears to play a role in the evolution of a wide range of fitness-related traits and may be a powerful mechanism for the maintenance of genetic variation in fitness.

Adamantinoma of the tibia with late skeletal metastasis: an unusual presentation.

Adamantinoma is a rare tumour of long bones that occurs most commonly in the tibia. Its pathogenesis is unknown. It is locally aggressive and recurrences are common after resection. Metastases have been reported in 10% to 20% of cases, most commonly in the lungs and rarely in the lymph nodes. We report a patient who developed a skeletal metastasis four years after resection of the primary tumour. There was no evidence of recurrence at the primary site or of secondary deposits in the lungs.

Inhibition of gamma-radiation induced DNA damage in plasmid pBR322 by TMG, a water-soluble derivative of vitamin E.

Alpha-tocopherol monoglucoside (TMG), a water-soluble derivative of alpha-tocopherol, has been examined for its ability to protect DNA against radiation-induced strand breaks. Gamma radiation, up to a dose of 6 Gy (dose rate, 0.7 Gy/minute), induced a dose-dependent increase in single strand breaks (SSBs) in plasmid pBR322 DNA. TMG inhibited the formation of gamma-radiation induced DNA single strand breaks (SSBs) in a concentration-dependent manner; 500 microM of TMG protected the single strand breaks completely. It also protected thymine glycol formation induced by gamma-radiation in a dose-dependent manner, based on an estimation of thymine glycol by HPLC.

Subunit interface mutation disrupting an aromatic cluster in Plasmodium falciparum triosephosphate isomerase: effect on dimer stability.

A mutation at the dimer interface of Plasmodium falciparum triosephosphate isomerase (PfTIM) was created by mutating a tyrosine residue at position 74, at the subunit interface, to glycine. Tyr74 is a critical residue, forming a part of an aromatic cluster at the interface. The resultant mutant, Y74G, was found to have considerably reduced stability compared with the wild-type protein (TIMWT). The mutant was found to be much less stable to denaturing agents such as urea and guanidinium chloride. Fluorescence and circular dichroism studies revealed that the Y74G mutant and TIMWT have similar spectroscopic properties, suggestive of similar folded structures. Further, the Y74G mutant also exhibited a concentration-dependent loss of enzymatic activity over the range 0.1-10 microM. In contrast, the wild-type enzyme did not show a concentration dependence of activity in this range. Fluorescence quenching of intrinsic tryptophan emission was much more efficient in case of Y74G than TIMWT, suggestive of greater exposure of Trp11, which lies adjacent to the dimer interface. Analytical gel filtration studies revealed that in Y74G, monomeric and dimeric species are in dynamic equilibrium, with the former predominating at low protein concentration. Spectroscopic studies established that the monomeric form of the mutant is largely folded. Low concentrations of urea also drive the equilibrium towards the monomeric form. These studies suggest that the replacement of tyrosine with a small residue at the interface of triosephosphate isomerase weakens the subunit-subunit interactions, giving rise to structured, but enzymatically inactive, monomers at low protein concentration.

Antimalarial activities of peptide antibiotics isolated from fungi.

Malaria caused by Plasmodium falciparum is a major public health problem in the developing countries of the world. Clinical treatment of malaria has become complicated due to the occurrence of infections caused by drug resistant parasites. Secondary metabolites from fungi are an attractive source of chemotherapeutic agents. This work reports the isolation and in vitro antiplasmodial activities of peptide antibiotics of fungal origin. The three peptide antibiotics used in this study were efrapeptins, zervamicins, and antiamoebin. The high-performance liquid chromatography-purified peptides were characterized by nuclear magnetic resonance and mass spectral analysis. All three fungal peptides kill P. falciparum in culture with 50% inhibitory concentrations in the micromolar range. A possible mode of action of these peptide antibiotics on P. falciparum is presented.

Safflower petals: a source of gamma linolenic acid.

Safflower petals have been shown to have a lot of medicinal and therapeutic values. Indian safflower petal samples were analyzed for the red pigment carthamin, protein and oil contents. The petal oil (4.0-5.8%) was further analyzed for its fatty acids followed by alpha linolenic acid (15-19%) and palmitic acids (14-16%). Gamma linolenic acid, which has a lot of therapeutic value was present to an extent of 2-3%; decanoic and dodecanoic acids (2-5%) were also present.

Screening for resistance to Aspergillus flavus and aflatoxin production in groundnut.

All the varieties, advanced breeding lines, germplasm lines, and wild species used in the experiments differed significantly for their ability to allow invasion and aflatoxin production by an aflatoxigenicAspergillus flavus strain. Infection and colonisation were strongly correlated (r = 0.82), while there was no relation between infection and aflatoxin content or colonisation and aflatoxin content (r = 0.15). The varieties ICGS11 and S 206 supported less infection and colonisation (range 35 to 40%). Lowest aflatoxin content was recorded in Chitra (3,200 ppb), while it was highest in Kaushal (38,250 ppb). A cross derivative of GAUG1 × NC Ac 17133 R F showed lowest infection and colonisation (86,3 and 25,28%, respectively), and also supported moderate aflatoxin production (4,000 ppb). Among germplasm lines spancross supported lowest aflatoxin production (2,026 ppb) while both the wild species vz. ICG 8127 and ICG 8128 were highly susceptible to infection, colonisation, and aflatoxin production.

Prevention of Aflatoxin contamination through some commercial chemical products and plant extracts in groundnut.

The effect of rock salts, NaCI, propionic acid, NCP.75, plant products - asafoetida, turmeric powder and aqueous leaf extracts ofAzadirachta indica, Lawsonia alba, Pongamia glabra andTridax procumbens on seed colonization and aflatoxin production byAspergillus flavus (NRRL-3000) was studied in two Spanish bunch groundnut varieties (J-11 and JL-24). All these treatments inhibited seed colonization and aflatoxin production to varying degrees. Inhibition of seed colonization with chemicals, plant products and aqueous leaf extracts was observed to range between 17 to 96%, 27 to 100%, and 8 to 75% while inhibition of aflatoxin production ranged from 14 to 74%, 42 to 71%, and 6 to 64%, respectively. In general, salts (20g/L), propionic acid (10mL/L), asafoetida (pure Ig/L and impure 20g/L), andAzadirachta indica aqueous leaf extract (20 g/L) are better in preventing aflatoxin contamination in both the groundnut varieties.