Covid-19 vaccine dissemination: A public health ethical evaluation of Pennsylvania's plan during Phase 1A.

Background: The novel COVID-19 pandemic afforded public health leaders an opportunity to expedite vaccine development and dissemination. The United States found itself faced with the arduous task of ensuring swift and equitable distribution of limited resources, in the midst of often-competing priorities, including public health ethics, medical ethics, economic demands, and societal strains. Methodology: Using the American Public Health Association's (APHA) newly revised public health code of ethics, which provides a decision-making framework and guidance for ethical analysis, we analyzed how Pennsylvania's COVID-19 vaccine dissemination plan aligned with the four core functions of public health ethics inquiry. Results/Discussion: Upon investigation, the state's plan evidenced use of public health ethics in goal setting and design. However, the core public health value given the highest priority, promoting health and safety, competed with the other core public health values of inclusivity and engagement, health justice and equity, and professionalism and trust. Despite known social disparities and risk factors, the state plan for COVID-19 vaccine dissemination aligned closely with federal guidance and prioritized all healthcare personnel and long-term care facility populations over high-risk individuals residing in the community. Conclusion/Perspectives: Should another pandemic necessitate allocation of scarce resources, especially preventative measures such as vaccines, decision-making agencies must consider disparate populations in planning and dissemination of material to the public. Any anticipated limitations in the ability to fulfill public health ethical principles should be clearly communicated to the public prior to implementation, thereby increasing trust.

Relative importance of bacteria and fungi in a tropical headwater stream: leaf decomposition and invertebrate feeding preference.

Bacteria and fungi provide critical links between leaf detritus and higher trophic levels in forested headwater food webs, but these links in tropical streams are not well understood. We compared the roles of bacteria and fungi in the leaf decomposition process and determining feeding preference for two species of freshwater shrimp found in the Luquillo Experimental Forest, Puerto Rico, using experimental microcosms. We first tested the effects of four treatments on decomposition rates for leaves from two common riparian species, Cecropia scheberiana (Moraceae) and Dacryodes excelsa (Burseraceae), in laboratory microcosms. Treatments were designed to alter the microbial community by minimizing the presence of bacteria or fungi. The fastest decay rate was the control treatment for D. excelsa where both bacteria and fungi were present (k = -0.0073 day(-1)) compared to the next fastest rate of k = -0.0063 day(-1) for the bacterial-conditioned D. excelsa leaves. The fastest decay rate for C. scheberiana was also the control treatment (k = -0.0035 day(-1)), while the next fastest rate was for fungal-conditioned leaves (k = -0.0029 day(-1)). The nonadditive effect for leaf decomposition rates observed in the control treatments where both fungi and bacteria were present indicate that bacteria and fungi perform different functions in processing leaf litter. Additionally, leaf types differed in microbial colonization patterns. We next tested feeding preference for leaf type and microbe treatment in microcosms using two species of freshwater shrimp: Xiphocaris elongata, a shredder, and Atya lanipes, a scraper/filterer. To estimate feeding preferences of individual shrimp, we measured change in leaf surface area and the amount of particles generated during 5-day trials in 16 different two-choice combinations. X. elongata preferred D. excelsa over C. scheberiana, and leaves with microbial conditioning over leaves without conditioning. There was no clear preference for fungal-conditioned leaves over bacterial-conditioned leaves. This lack of preference for which microbes were responsible for the conditioning demonstrates the importance of both bacterial and fungal resources in these tropical stream food web studies.

Modulation of C3 gene expression in HepG2 human hepatoma cells.

Inflammation elicits an acute phase response, which includes changes in plasma concentrations of a number of cytokines, reflecting changes in their gene transcription in the liver. In this study, the induction of complement factor 3 (C3) was investigated in HepG2 cells, a human hepatoma cell line often used as a model system for cytokine-dependent expression of acute phase proteins of the liver. By using a very sensitive RT-PCR assay, the amount of mRNA for C3 was measured after induction with lipopolysaccharide (LPS) and interleukin-6 (IL-6). Both substances were found to up-regulate C3 gene expression. C3 mRNA level was lower in LPS-treated cells compared to IL-6 induction and also reached maximum expression at an earlier time point. These findings suggest a coordinate stimulation of C3 expression in the hepatocytes, which then maintains the host response to infectious agents.

Attenuated endothelin- mRNA expression with endothelin- receptor blockade during hypoxaemia and reoxygenation in newborn piglets.

UNLABELLED: We investigated the cause of decreased plasma endothelin-1 (ET-1) during hypoxaemia and reoxygenation in newborn piglets subjected to simultaneous blocking of the ET-1 receptors. Changes in plasma ET-1 and prepro-ET-1 mRNA expression in the main pulmonary artery and the left lower lobe in the lung were studied in 1-2-d-old piglets. Ten minutes prior to hypoxaemia, the hypoxaemia group (n = 10) was given saline, two groups (both n = 9) were given 1 and 5 mg/kg i.v. SB 217242 (an ET-1 receptor antagonist). Two groups served as normoxic controls, with and without SB 217242 5 mg/kg i.v. Hypoxaemia was induced by ventilating with 8% O2 until base excess was <-20 mmol/l or mean arterial blood pressure was <20 mmHg. Reoxygenation was performed for 2 h with room air. During hypoxaemia, plasma ET-1 decreased in the hypoxaemia group, remained unchanged in the 1-mg group and increased in the 5-mg group. At the end of reoxygenation, plasma ET-1 was above baseline in the 1-mg and 5-mg groups. In the pulmonary artery, the hypoxaemia group showed 2- to 5-fold higher prepro-ET- 1 mRNA expression compared to all the other groups (p < 0.05). There were trends for higher prepro-ET-1 mRNA expression in pulmonary tissue in the hypoxaemia group compared to the two receptor-blocking groups (p < 0.07). CONCLUSIONS: We conclude that hypoxaemia and reoxygenation increase prepro-ET-1 mRNA expression in the pulmonary artery in newborn piglets. These observations suggest that the half-life of ET-1 is decreased during hypoxaemia and reoxygenation in newborn piglets.

Effects of volatile aldehydes from Aspergillus-resistant varieties of corn on Aspergillus parasiticus growth and aflatoxin biosynthesis.

The fungi Aspergillus flavus and Aspergillus parasiticus produce a potent class of hepatocarcinogens known as aflatoxins. Corn-derived volatile compounds have been previously found to affect growth and aflatoxin production in A. flavus. In this study, the effects on A. parasiticus of three corn-derived volatile compounds, n-decyl aldehyde, hexanal and octanal, were measured. These three compounds were previously found to be variably expressed in five Aspergillus-resistant maize strains and three susceptible strains. In this study, A. parasiticus radial growth was restricted least by n-decyl aldehyde and most by octanal. Treatments of 100 microl of both hexanal and octanal were found to completely inhibit radial growth of the fungus using an agar plate assay method. While the volatile compound n-decyl aldehyde had less of an effect on radial growth than the other volatiles, the n-decyl aldehyde treated colonies had a predominance of uniquely aerial hyphae. These colony structures were found to have more complex hyphae and significantly fewer conidiophores than the control and other aldehyde treatments. Furthermore, aflatoxin production by the fungus was reduced by n-decyl aldehyde and hexanal, but was stimulated by octanal. The results presented here indicate that all three volatile compounds reduce radial growth but only n-decyl aldehyde significantly inhibits aflatoxin biosynthesis in A. parasiticus.

Attenuated endothelin-1 mRNA expression with endothelin-1 receptor blockade during hypoxaemia and reoxygenation in newborn piglets.

We investigated the cause of decreased plasma endothelin-1 (ET-1) during hypoxaemia and reoxygenation in newborn piglets subjected to simultaneous blocking of the ET-1 receptors. Changes in plasma ET-1 and prepro-ET-1 mRNA expression in the main pulmonary artery and the left lower lobe in the lung were studied in 1-2-d-old piglets. Ten minutes prior to hypoxaemia, the hypoxaemia group (n = 10) was given saline, two groups (both n = 9) were given 1 and 5 mg/kg i.v. SB 217242 (an ET-1 receptor antagonist). Two groups served as normoxic controls, with and without SB 217242 5 mg/kg i.v. Hypoxaemia was induced by ventilating with 8% O2 until base excess was 20mmol/l or mean arterial blood pressure was < 20mmHg. Reoxygenation was performed for 2h with room air. During hypoxaemia, plasma ET-1 decreased in the hypoxaemia group, remained unchanged in the 1-mg group and increased in the 5-mg group. At the end of reoxygenation, plasma ET-1 was above baseline in the 1-mg and 5-mg groups. In the pulmonary artery, the hypoxaemia group showed 2- to 5-fold higher prepro-ET-1 mRNA expression compared to all the other groups (p < 0.05). There were trends for higher prepro-ET-1 mRNA expression in pulmonary tissue in the hypoxaemia group compared to the two receptor-blocking groups (p < 0.07). CONCLUSIONS: We conclude that hypoxaemia and reoxygenation increase prepro-ET-1 mRNA expression in the pulmonary artery in newborn piglets. These observations suggest that the half-life of ET-1 is decreased during hypoxaemia and reoxygenation in newborn piglets.

Drug-induced hemolytic anemias: increasing complications to therapeutic interventions.

There are recent reports of severe drug-induced immune hemolysis caused by several different classes of drugs. Second and third generation cephalosporins, diclofenac, fludarabine, carboplatin, and beta-lactamase inhibitors are among the drugs associated with severe or fatal hemolysis. Studies on patients who exhibit hemolysis after ingesting these drugs indicate that the four classical mechanisms of drug-induced hemolytic anemia may overlap. These studies appear to support the unified theory for induction of drug-induced immune hemolytic anemia.

Laboratory investigation of autoimmune hemolytic anemias.

The investigation of suspected autoimmune hemolytic anemias includes not only the laboratory investigation but also the patient's presenting symptoms and a complete medical history. A drug history is especially important if drug-induced hemolytic anemia is suspected. The patient's direct antiglobulin test results, both polyspecific and monospecific, guide the remainder of the workup. Serum and eluate testing may include untreated reagent red cells with and without the presence of unbound drug(s) and drug-treated reagent red cells. If autoantibodies are demonstrable in the serum, removal of those autoantibodies and subsequent testing for underlying alloantibodies is essential in the provision of safe blood for transfusion.

The effects of selected cotton-leaf volatiles on growth, development and aflatoxin production of Aspergillus parasiticus.

The fungi Aspergillus flavus and Aspergillus parasiticus produce the hepatocarcinogenic, secondary metabolites, aflatoxins, in cottonseed, corn, peanuts and treenuts. Results have shown that aflatoxigenic strains of A. flavus and A. parasiticus grown in the presence of specific cotton-leaf volatiles exhibit alterations in aflatoxin production accompanied by variations in growth of the fungi. In this study, two alcohols (3-methyl-1-butanol (3-MB) and nonanol) and two terpenes (camphene and limonene) were chosen as representative cotton-leaf volatiles based on the effects they had on fungal growth and/ or aflatoxin production in previous investigations. The morphological effects of volatile exposure were examined in correlation with fungal growth and aflatoxin production. 3-MB-treated samples exhibited a decrease in fungal radial growth which was directly proportional to the volatile dosage. Additionally, 3-MB treatment resulted in loss of mycelial pigmentation and a decrease in sporulation. Limonene and camphene-treated samples yielded negligible differences in radial growth and morphology when compared to unexposed controls. In addition to radial growth inhibition, samples grown in the presence of nonanol demonstrated uniquely aerial hyphae. In comparison to an unexposed control, aflatoxin production increased in cultures exposed to 3-MB but decreased when exposed to the other three volatiles studied.

Stable pediatric blunt trauma patients: is trauma team activation always necessary?

BACKGROUND: An increasing number of studies on adult trauma patients have questioned the need for trauma team activation for stable patients dictated only by mechanism of injury. This triage approach seems to burden the limited resources of the trauma center and may prove to be cost-ineffective. The objective of our study was to determine the predictive value and the sensitivity and specificity of blunt injury mechanism for major trauma in stable pediatric trauma patients. METHODS: Patients 0 to 14 years old injured by injury mechanisms modified from the American College of Surgeons trauma triage criteria and presenting to our American College of Surgeons-verified regional pediatric trauma center from the field between July 1, 1993, and July 31, 1994, were included. Physiologically and anatomically stable patients were identified and subgroup analysis was performed to determine the negative and positive predictive value and sensitivity, and the specificity of blunt injury mechanisms for major trauma [Injury Severity Score > 15] in this group. RESULTS: One hundred ninety-four patients met the study criteria. One hundred forty-three patients (73.6%) had trauma team activation only for mechanism of injury. Of these patients, four patients had Injury Severity Score > 15. The positive and negative predictive values of injury mechanisms modified from the American College of Surgeons trauma triage criteria were 2.8% and 90.2%, respectively, for major trauma in stable pediatric blunt trauma patients. The sensitivity and specificity were 44.4% and 24.9%, respectively. CONCLUSION: Mechanisms of injury seem to have limited value as predictors of injury severity in stable pediatric blunt trauma patients. A modified response level for these patients may prove to be a safe and practical alternative to current practice.

Isolation and immunocytochemical characterization of three tachykinin-related peptides from the mosquito, Culex salinarius.

Three myotropic peptides belonging to the Arg-amide insect tachykinin family were isolated from whole-body extracts of the mosquito, Culex salinarius. The peptides, APSGFMGMR-NH2, APYGFTGMR-NH2 and APSGFFGMR-NH2 (designated culetachykinin I, II, and III) were isolated and purified on the basis of their ability to stimulate muscle contractions of isolated Leucophaea maderae hindgut. Biologically inactive methionine sulfoxides of two of the three peptides were isolated using an ELISA system based upon antiserum raised against APYGFTGMR-NH2 and identified with mass spectrometry. Immunocytochemistry localized these peptides in cells in the brain, antennae, subesophageal, thoracic and abdominal ganglion, proventriculus and midgut. Nerve tracts containing these peptides were found in the median nerve of the brain, central body, nervi corpus cardiaci, cervical nerve, antennal lobe and on the surface of the midgut.

Injury prevention education in United States medical school curricula.

BACKGROUND: In 1993, representatives from the Centers for Disease Control and Prevention recommended that a national injury control training plan be developed that would encourage education about injuries and injury prevention in the required curricula of medical schools. METHODS: A mail survey of curriculum officers was conducted to identify the availability of, characteristics of, and support for educational opportunities in injury prevention at medical schools in the United States. RESULTS: Eighty-seven medical schools (70.2%) responded. Forty-one (47.1%) covered injury prevention in their required curricula. Twenty-six (29.9%) offered nonclinical elective opportunities on injury prevention subjects. In medical schools associated with trauma centers, injury prevention information was almost four times more likely to be included in the required curricula. CONCLUSION: Educational opportunities for medical students in injury prevention are limited. Trauma centers appear to support these efforts at their medical school affiliates.

Pediatric injury prevention. Preparing residents for patient counseling.

OBJECTIVES: To describe counseling practices on injury prevention and barriers to patient counseling by pediatric residents and determine whether education about injury prevention or use of educational aids promotes this activity in resident ambulatory practices. DESIGN: Cross-sectional mail survey. SETTING: Accredited US pediatric residency programs. PARTICIPANTS: Pediatric chief residents. MAIN OUTCOME MEASURE: Reported frequencies of patient counseling performed on various injury prevention topics. RESULTS: All residents reported that they were expected to educate patients and families about injury prevention in the continuity clinic setting. Almost all residents (98.5%) reported that they counseled on at least 1 injury prevention topic. On all topics except for poisoning prevention, residents were most likely to counsel patients and families on those topics about which they had received education. Additionally, those residents familiar with the American Academy of Pediatrics The Injury Prevention Program included more injury prevention topics in their counseling repertoire (P = .01). The most frequently identified barriers to counseling included lack of information about the topic and lack of time in the visit. CONCLUSIONS: Most pediatric residents counsel their patients and families on a variety of injury prevention topics. This activity is promoted by the education offered during residency training. Focused efforts should be made to educate residents about those injury topics not being taught and to address counseling barriers with educational interventions that promote prevention counseling during patient visits.

Waterborne transmission of Cryptosporidium, Cyclospora and Giardia.

Waterborne transmission of Cryptosporidium, Cyclospora, and Giardia has been associated with numerous recent outbreaks of diarrheal disease. Epidemiologic evidence shows that many community-acquired infections originate from public water sources. Drinking water, even when chlorinated and filtered, has been implicated in several outbreaks. Cryptosporidium and Cyclospora are resistant to chlorine. Giardia cysts are not killed immediately by chlorine and are less susceptible than most other organisms. Swimming pools and other recreational waters have also been implicated as transmission sources. All 3 organisms pose a challenge to the water industry, as they are difficult to detect in water when small numbers of cysts or oocysts are present. Small numbers of these organisms can cause disease; therefore, the clinical laboratory must be vigilant in screening, identifying, and reporting outbreaks of illness due to these protozoa.

Emerging intestinal protozoa: a diagnostic dilemma.

Increasing isolation of Cryptosporidium, Cyclospora, and microsporidia from immunocompromised patients with severe diarrhea has prompted study of these organisms. Only recently recognized as human pathogens, they have also been associated with several waterborne outbreaks of diarrhea in immunocompetent individuals. Cryptosporidium and Cyclospora have been shown to be transmitted through fecally contaminated food and water. The mode of transmission for microsporidia is still unclear. While the life cycle and pathogenesis of Cryptosporidium are beginning to be understood, the microsporidia and Cyclospora are less well elucidated. The laboratory diagnosis of these protozoa is difficult. The routine ova and parasites screen does not include screening for them. Many microscopic methods, including wet mounts, modified acid-fast and trichrome stains, and immunofluorescence methods have been shown to be effective screening methods in the hands of experienced microscopists. Enzyme immunoassay and polymerase chain reaction methods also show promise. The proper identification of these pathogens rests with well-trained laboratory personnel. As appropriate treatment differs for each genus, communication between the laboratory and the physician is vital to the recovery of the patient.

Immunologic responses to vaccinia vaccines administered by different parenteral routes.

To develop a less reactogenic but equally immunogenic vaccine, this study of 91 human volunteers compared the safety and immunogenic potency of a new, cell culture-derived vaccinia virus vaccine administered intradermally and intramuscularly with the licensed vaccinia vaccine administered by scarification. Cutaneous pox lesions developed in a higher proportion of scarification vaccinees. Scarification and intradermal vaccine recipients who developed cutaneous pox lesions had more local reactions but also achieved significantly higher cell-mediated and neutralizing antibody responses than those who did not develop pox lesions. Although less reactogenic, intradermal or intramuscular administration of vaccinia vaccine without the concomitant development of a cutaneous pox lesion induced lower immune responses.

Single dose cefazolin prophylaxis for postcesarean infections: before vs. after cord clamping.

The objective of this study was to test the hypothesis that 1 g of cefazolin administered preoperatively is no more effective than the same dose administered after cord clamping in preventing postcesarean infectious morbidity. Ninety consecutive laboring subjects undergoing cesarean delivery at > or = 37 weeks gestation were randomized by computer to receive 1 g of cefazolin intravenously preoperatively or after cord clamping in a double-blinded, placebo-controlled study. The 2 groups were compared for differences in maternal and neonatal demographics, and intrapartum and operative characteristics associated with postcesarean infection. Primary maternal outcome variables were endometritis or wound infection. Secondary outcomes included intra-abdominal abscess formation, septic pelvic thrombophlebitis, pneumonia, or urinary tract infection. Neonatal outcomes included sepsis screens, sepsis, pneumonia, and meningitis. Subjects were followed 6 weeks postoperatively for late complications. Subjects receiving cefazolin preoperatively or after cord clamping had similar maternal and neonatal demographics, and intrapartum and operative characteristics. One patient in the former group experienced both endometritis and wound infection. In the latter group, 2 wound infections and 1 case of endometritis occurred (P = 0.35). There were no secondary maternal infections. Two infants treated for pneumonia and 2 other infants readmitted with febrile illnesses were born to mothers receiving cefazolin preoperatively. Overall, 8 neonates were evaluated for suspected sepsis and all had negative studies. Six of these infants' mothers received cefazolin preoperatively (P = 0.28). In conclusion, 1 gram of cefazolin preoperatively is no more effective than the same dose administered after cord clamping in preventing postcesarean infectious morbidity, but is associated with a trend toward increased suspected sepsis in the newborn. However, this trend may be related to differences between the study groups' risk factors for infection.

Immunocytochemical localization of testis ecdysiotropin in the pupa of the gypsy moth, Lymantria dispar (L.) (Lepidoptera: Lymantriidae).

Antiserum against testis ecdysiotropin isolated from the gypsy moth, Lymantria dispar, reacted with neurons in the protocerebrum, optic and antennal lobes, subesophageal, thoracic and abdominal ganglia, as well as in nerve tracts extending through the optic lobes, tritocerebrum, and interganglionic connectives of the pupal stage of these insects. Testis ecdysiotropin is a peptide required by immature moths to initiate production of testes ecdysteroid, which is necessary for the development of the male reproductive system and initiation of spermatogenesis. Antiserum against testis ecdysiotropin also detected an accumulation of testis ecdysiotripic-like material between the inner and outer testis sheaths of pupae. The localization of this peptide in the imaginal disks of the last larval stage, cells and nerve fibers in the optic and antennal lobes of the pupa of both sexes, as well as in the testes during development of the adult reproductive system indicates that testis ecdysiotropin has a much larger impact on adult metamorphosis than development of the reproductive system and initiation of gametogenesis. Although this peptide may have a modulatory role in the central nervous system (CNS), it may also initiate a cascade of activity required for the development of the adult nervous system, in addition to its role in reproduction.