Retrospective analysis of respiratory virus infections in adults with hematologic malignancies.

OBJECTIVE: The study aimed to evaluate respiratory virus infections in adult patients with hematological malignancies (HM). PATIENTS AND METHODS: The medical records of patients who were followed up by the hematology clinic at Basaksehir Çam and Sakura City Hospital between March 2021 and March 2023 with a diagnosis of HM and who underwent real-time polymerase chain reaction (RT-PCR) testing for nasopharyngeal/oropharyngeal specimens taken with suspected respiratory tract infection constituted the study data. RESULTS: Infections were symptomatic in 64.56% of patients, and the most common symptoms were fever (48.10%) and cough (18.99%). The mortality rate was 25.32% over a two-year period. When the samples were examined, positive test frequency was 43.04%, and the three most common pathogens were Influenza A (10.13%), SARS-CoV-2 (8.86%), and rhinovirus/enterovirus (7.59%). The frequency of positive tests from HMs was highest in patients with AML (p=0.042). Respiratory PCR kit positivity was higher in patients who had any symptoms (p=0.002) and cough (p=0.003). Test positivity was higher in patients with any pathological radiological finding (p=0.039) and ground glass appearance (p=0.010). The risk of death was found to be 5.848 times higher in patients with dyspnea compared to those without (OR: 5.848, 95% CI: 1.143-29.915, p=0.034). CONCLUSIONS: Respiratory tract virus panel PCR test positivity is more common in patients with HM presenting with respiratory tract infection symptoms in the presence of AML diagnosis, symptomatic infection, cough, radiological findings, and ground glass appearance. Mortality risk is high in HM patients with respiratory tract virus infection who have shortness of breath.

An amyloid beta vaccine that safely drives immunity to a key pathological species in Alzheimer's disease: pyroglutamate amyloid beta.

Pyroglutamate amyloid beta3-42 (pGlu-Abeta3-42), a highly amyloidogenic and neurotoxic form of Abeta, is N-terminally truncated to form a pyroglutamate and has recently been proposed as a key target for immunotherapy. Optimized ACI-24, a vaccine in development for the treatment and prevention of Alzheimer's disease, focuses the antibody response on the first 15 N-terminal amino acids of Abeta (Abeta1-15). Importantly, clinical data with an initial version of ACI-24 incorporating Abeta1-15, established the vaccine's safety and tolerability with evidence of immunogenicity. To explore optimized ACI-24's capacity to generate antibodies to pGlu-Abeta3-42, pre-clinical studies were carried out. Vaccinating mice and non-human primates demonstrated that optimized ACI-24 was well-tolerated and induced an antibody response against Abeta1-42 as expected, as well as high titres of IgG reactive with pyroGlu-Abeta. Epitope mapping of the polyclonal response confirmed these findings revealing broad coverage of epitopes particularly for Abeta peptides mimicking where cleavage occurs to form pGlu-Abeta3-42. These data are in striking contrast to results obtained with other clinically tested Abeta targeting vaccines which generated restricted and limited antibody diversity. Taken together, our findings demonstrate that optimized ACI-24 vaccination represents a breakthrough to provide a safe immune response with a broader Abeta sequence recognition compared to previously tested vaccines, creating binders to pathogenic forms of Abeta important in pathogenesis including pGlu-Abeta3-42.

Light-responsive azo-containing organogels.

While azo compounds are widely employed as radical initiators, they have rarely been used as stimuli-responsive motifs in macromolecular constructs. In this study, an azo-based cross-linker was prepared and reacted with poly(vinyl alcohol) to afford a series of stimuli-responsive organogels. Irradiation of these materials with UV light causes de-cross-linking and triggers a solid-to-liquid phase transition. Model adhesives with de-bonding-on-demand capability based on this design were explored.

High-dose exposure to valsartan with suicidal intention.

Valsartan is a strong angiotensin receptor inhibitor specific for the angiotensin I receptor, which has been proven safe and well-tolerated in clinical trials. We were able to confirm its safety and tolerability in a case of high-dose exposure to valsartan with suicidal intention. A 25-year-old, fully conscious, female patient was brought to our hospital by relatives on July 24, 2001, at 9:15 p.m. following intake of a high dose of valsartan. It was established that she had taken 28 Diovan 80 mg tablets (2.24 g) 5 hours before admission to the hospital. Her clinical condition at the time of admission was good and did not deteriorate after admission. During the follow-up, her blood pressure never fell below 90/60 mmHg. The only complaint she had were painful muscle cramps which, with only supportive therapy, disappeared spontaneously over 2 days, and her blood pressure also returned to normal during this period. This report demonstrates the effect/side effect profile of valsartan when taken at a high dose, not achievable in a clinical trial.

Broad spectrum antiprotozoal agents that inhibit histone deacetylase: structure-activity relationships of apicidin. Part 1.

Apicidin, a natural product recently isolated at Merck, inhibits both mammalian and protozoan histone deacetylases (HDACs). The conversion of apicidin, a nanomolar inhibitor of HDACs, into a series of side-chain analogues that display picomolar enzyme affinity is described within this structure-activity study.

Broad spectrum antiprotozoal agents that inhibit histone deacetylase: structure-activity relationships of apicidin. Part 2.

Recently isolated at Merck, apicidin inhibits both mammalian and protozoan histone deacetylases (HDACs). The conversion of apicidin, a nonselective nanomolar inhibitor of HDACs, into a series of picomolar indole-modified and parasite-selective tryptophan-replacement analogues is described within this structure-activity study.

Chemical modification of nodulisporic acid A: preliminary structure-activity relationships.

Medicinal chemistry efforts were initiated to identify the key constituents of the nodulisporic acid A (1) pharmacophore that are integral to its potent insecticidal activity. New semisynthetic derivatives delineated 1 into 'permissive' and 'nonpermissive' regions and led to the discovery of new nodulisporamides with significantly improved flea efficacy.

Chemical enhancement of viral transformation in Syrian hamster embryo cells by gaseous and volatile chlorinated methanes and ethanes.

Methods were developed for exposing cells in vitro to gases or vapors of volatilized organic liquids. Compounds were selected for their industrial importance, environmental impact, and suspected role in the etiology of some human cancers. Exposure chambers were designed for easy insertion of dishes of cultured cells and were equipped with inlet and outlet ports for introduction and purging of test gases. A gas delivery system utilizing a mass flow meter was used for the quantitative distribution of test gases into exposure chambers. For volatile compounds, appropriate volumes of cold (4 degrees) liquids in glass Petri dishes were quickly placed into chambers, the system sealed, and the compounds rapidly volatilized at 37 degrees. For exposure, the cells and chambers were placed in an incubator and rocked at a constant rate so that a portion of the cells was always in direct contact with the test gases or vapors. Known sample volumes were removed after various treatment times and test gas concentrations determined by standard gas chromatographic techniques. After exposure, the cells were removed and assayed for viability and increased sensitivity to viral transformation. Under these experimental conditions, the volatile liquids 1,1,1-trichloroethane, dichloromethane, chloroform, 1,2-dichloroethane, and 1,1-dichloroethane significantly enhanced transformation of Syrian hamster embryo cells by SA7 adenovirus, while acetone exerted no effect. The gases chloromethane and vinyl chloride were also active in this test system, while bromomethane, methane, and ethane were inactive. Incorporation of some of these compounds into liquid cell culture medium for cell treatment was either unsuccessful or produced only a weak enhancement response. Methodology is now available to evaluate volatile and gaseous carcinogens or mutagens and can be used to identify their mechanisms of action and the relative hazards of these agents to human health.

Aggressive behaviour of female prairie deer mice in laboratory populations.

Prairie deer mice (Peromyscus maniculatus bairdii), living in asymptotic laboratory populations established two years earlier, were observed for agonistic responses to conspecific intruders. In the first experiment, intruders of six age-sex classes were placed into 10 of the populations for 10 min. The sex of the intruder did not influence the behaviour of the residents, but juveniles elicited more regression than did adults. A second experiment revealed that female residents were responsible for almost all of the attacks upon juveniles. Experiment 3, in which the responses of pairs of deer mice to juvenile intruders were recorded, demonstrated that the aggressiveness of a female was enhanced by the presence of a male. In the final experiment, females were observed to be highly aggressive during the first few days after giving birth. The aggressive behaviour of the female deer mouse may have greater significance for population dynamics than that of the male.