Implementing the National Local Public Health System Performance Assessment: evaluation of a readiness process in Kentucky.

The objectives of the study described in this article were to test training and resource materials for preparing Kentucky public health agency staff to lead the National Local Public Health System Performance Assessment and to identify barriers encountered in implementation. Readiness supports provided to five Kentucky district and county health departments that led the system assessment process in 12 counties were evaluated using training pre- and posttests, performance assessment posttests, observations, and interviews. The training and materials provided in this study appeared to be the minimum needed for these Kentucky health departments. Training sequences need to allow time for independent study of assessment processes, and training in using and interpreting the assessment instrument should be included. Partner orientation materials targeted for nonpublic health partners would be useful. In Kentucky, barriers to completing the assessment included questions about its purpose and benefits and the lack of a self-identified local public health system. Formal training of health department staff, committed leadership, and adequate personnel resources can help overcome these barriers. The health departments that brought together system partners for the performance assessment considered it a valuable community-building educational event.     

The Antifungal Itraconazole Is a Potent Inhibitor of Chikungunya Virus Replication

Chikungunya virus (CHIKV) is the causative agent of chikungunya fever, a disabling disease that can cause long-term severe arthritis. Since the last large CHIKV outbreak in 2015, the reemergence of the virus represents a serious public health concern. The morbidity associated with viral infection emphasizes the need for the development of specific anti-CHIKV drugs. Herein, we describe the development and characterization of a CHIKV reporter replicon cell line and its use in replicon-based screenings. We tested 960 compounds from MMV/DNDi Open Box libraries and identified four candidates with interesting antiviral activities, which were confirmed in viral infection assays employing CHIKV-nanoluc and BHK-21 cells. The most noteworthy compound identified was itraconazole (ITZ), an orally available, safe, and cheap antifungal, that showed high selectivity indexes of >312 and >294 in both replicon-based and viral infection assays, respectively. The antiviral activity of this molecule has been described against positive-sense single stranded RNA viruses (+ssRNA) and was related to cholesterol metabolism that could affect the formation of the replication organelles. Although its precise mechanism of action against CHIKV still needs to be elucidated, our results demonstrate that ITZ is a potent inhibitor of the viral replication that could be repurposed as a broad-spectrum antiviral.     

THE DEMONSTRATION OF ONE-STEP GROWTH CURVES OF INFLUENZA VIRUSES THROUGH THE BLOCKING EFFECT OF IRRADIATED VIRUS ON FURTHER INFECTION

After allantoic injection of chick embryos with a known amount of influenza virus, the process of adsorption of the agent onto host cells and infection of them can be interrupted at a given time by the administration of large quantities of heterologous virus inactivated by irradiation. A sudden great increase in the amount of free virus in the allantoic fluid occurring after 6 hours in the case of the PR8 strain, and 9 hours in that of the Lee strain, indicates that the untreated virus associated with the host cells has multiplied. The length of the period preliminary to this increase remains the same even though the concentration of the original inoculum is varied over a wide range. Since administration of the irradiated virus leaves no susceptible host cells, because of the interference phenomenon, and further adsorption of active virus is minimized or entirely prevented, practically the entire new increment of virus can be found in the allantoic fluid and assayed; for every ID₅₀ adsorbed about 50 ID₅₀ are released. Homologous irradiated virus, on the other hand, when injected after infection of the allantoic sac, reduces the yield of virus to a more or less considerable extent. Some inhibitory effect can still be observed when the homologous irradiated virus is given several hours after infection. This effect is linked to the virus particle and destroyed by prolonged irradiation.     

ETIOLOGY OF OROYA FEVER : XVI. VERRUGA IN THE DOG AND THE DONKEY

In the experiments here reported, definite verruga lesions, in which the presence of Bartonella bacilliformis was established by culture or by passage to rhesus monkeys, were produced in a dog and in a donkey by inoculation of cultures or monkey passage strains. The reaction induced in these animals was entirely local, however; blood cultures were sterile. Histologically, the lesions produced were similar to those obtained in monkeys by inoculation of Bartonella bacilliformis, except for the presence of a marked polynuclear leucocytic exudate. In another donkey a lesion histologically suggestive of verruga was produced, while in one donkey and a horse the results of inoculation were negative or indefinite. The intravenous injection of a filtrate or of heat-killed cultures of Bartonella bacilliformis into two donkeys was followed by the appearance of large, soft, subcutaneous swellings, on various parts of the body, not resembling in any way verruga lesions.     

The Achilles’ heel of cancer survivors: fundamentals of accelerated cellular senescence

Recent improvements in cancer treatment have increased the lifespan of pediatric and adult cancer survivors. However, cancer treatments accelerate aging in survivors, which manifests clinically as the premature onset of chronic diseases, such as endocrinopathies, osteoporosis, cardiac dysfunction, subsequent cancers, and geriatric syndromes of frailty, among others. Therefore, cancer treatment–induced early aging accounts for significant morbidity, mortality, and health expenditures among cancer survivors. One major mechanism driving this accelerated aging is cellular senescence; cancer treatments induce cellular senescence in tumor cells and in normal, nontumor tissue, thereby helping mediate the onset of several chronic diseases. Studies on clinical monitoring and therapeutic targeting of cellular senescence have made considerable progress in recent years. Large-scale clinical trials are currently evaluating senotherapeutic drugs, which inhibit or eliminate senescent cells to ameliorate cancer treatment–related aging. In this article, we survey the recent literature on phenotypes and mechanisms of aging in cancer survivors and provide an up-to-date review of the major preclinical and translational evidence on cellular senescence as a mechanism of accelerated aging in cancer survivors, as well as insight into the potential of senotherapeutic drugs. However, only with time will the clinical effect of senotherapies on cancer survivors be visible.

Cancer survival times have increased annually owing to advances in early detection and treatment that prolong patient survival. However, increasing survivorship has underscored the observation that cancer survivors develop age-related diseases prematurely, which cause significant morbidity, health expenditures, and mortality. Many cancer survivors have been exposed to chemotherapy, radiotherapy, or both; despite eradicating cancer cells, these therapies also damage normal cells to accelerate biologic aging, such that a discrepancy exists between their biologic and chronologic age (1). Considerable data exist regarding the phenotypes of accelerated aging. However, mechanical and molecular uncertainties have limited the study of these manifestations in a clinical context. Our Review discusses accelerated aging phenotypes in cancer survivors and the cellular mechanisms underpinning these phenomena. We then discuss the translational evidence on how accelerated aging phenotypes, mainly related to senescence, are being targeted while highlighting areas of uncertainty for future research to address.