What is already known on this topic? In June 2022, COVID-19 vaccines were authorized for use in children aged 6 months–5 years. Intent to vaccinate and vaccination rates in children have been low. ...What is added by this report? During July 2021–May 2022, in a longitudinal cohort of 393 children aged <5 years in four states, parental intent to vaccinate children against COVID-19 and perception of COVID-19 vaccine safety and effectiveness declined over a 3-month period, but intent to vaccinate and perceptions of vaccine safety returned to baseline after 6 months. What are the implications for public health practice? Identifying and addressing barriers to COVID-19 vaccination in children aged <5 years and educating parents about COVID-19 vaccine effectiveness and safety in young children are critical to increasing pediatric COVID-19 vaccination coverage.
Coagulopathies are commonly encountered in victims of pit viper envenomation. In the majority of patients these defects improve with administration of antivenin. However, blood products are often ...transfused based on arbitrary criteria and with significant risk to the patient. This article documents the effectiveness and risks of antivenin administration and the risks of blood product transfusion. We recommend that blood products not be used except for clearly defined clinical indications.
Although the full mechanisms are not yet elucidated, research into the mechanism of toxicity of aluminum (Al) on bone formation and remodeling and on hematopoietic tissue is ongoing. In contrast, ...little information exists on the interactive effects of systemic Al and the kidney. In bone, both clinically and experimentally, high doses of Al inhibit remodeling, slowing both osteoblast and osteoclast activities and producing osteomalacia and adynamic bone disease. In contrast, while very low levels of Al are mitogenic in bones of experimental animals, the effect of low levels of Al in humans is unknown. Aluminum has been shown to have its mitogenic action at the osteoblast, but whether the effect on resorption is via osteoblast-directed changes in osteoclast activity has not yet been determined. Parathyroid hormone (PTH) levels are disrupted by Al in humans and animals. Whether altered PTH levels play a major or even a minor role in Al-dependent osteotoxicity requires clarification. In hematopoietic tissue, Al causes a microcytic anemia, not reversible by iron. Friend leukemia cells treated with Al have been reported to accumulate excess iron, without incorporating it into ferritin or heme. It is not yet known which steps in iron metabolism are disrupted by Al, if they involve a single mechanism of action, or even if this disruption in iron metabolism accounts for the anemia seen in Al toxicosis. In kidney, research is needed to evaluate Al nephrotoxicity; there are almost no studies in this area. Furthermore, research is needed to evaluate mechanisms of renal Al excretion, presently shown by one study to occur at the distal tubule. Such studies might well throw light on whether Al plays a role in aggravating renal insufficiency, or whether the role of the kidney in Al toxicosis is limited to the causative effect of renal compromise on Al accumulation. In summary, while a number of mechanisms have been proposed for the toxic action of Al, no single mechanism emerges to explain these diverse effects of systemic Al. Recommendations for future research are presented and summarized in Table 1.
These studies investigated the effects of retinoic acids on endothelial cell proliferation. Three human neoplastic cell lines, U-373 MG glioblastoma, DU-145 prostate carcinoma, and TCCSUP bladder ...transitional cell carcinoma, were treated with all-
trans, 9-
cis, or 13-
cis retinoic acids at 0.0001 to 10 μM. Hypoxia was used to ensure the expression of the angiogenic phenotype. Conditioned media (CM) were prepared by hypoxic culturing of the tumor cells with retinoic acids for 24 hours. Then CM were transferred to bovine capillary endothelial cells for 48 hours of normoxic culturing, counted and compared to controls. CM from U-373 MG and DU-145 cells, but not TCCSUP cells, treated with all-
trans or 9-
cis retinoic acids at several concentrations below 1 μM, caused significant (P<0.05) increases in endothelial cell proliferation of between 13 to 18%. Both nonconditioned and conditioned media, for retinoic acid concentrations above 1 μM, inhibited endothelial cell proliferation. All CM for 13-
cis retinoic acid decreased endothelial cell proliferation. These results show that the cytotoxicity of retinoic acids and the growth promoting/inhibiting ability of the conditioned media is retinoic acid isoform, time, concentration, and cell type dependent. Most importantly, the conditioned media from tumor cells treated with low concentrations of all-
trans or 9-
cis retinoic acids significantly increased endothelial cell proliferation.
: This paper provides specific guidelines on the management of tuberculosis infection and disease, covering general principles, recommended drug regimens and discuss the evidence to support these. It ...also covers use of corticosteroids, intermittent therapy, directly observed therapy and an approach to the management of a patient with drug‐resistant tuberculosis.
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