Initial impact of the COVID-19 pandemic on public health training: participatory action research to understand experiences in the East Midlands.

BACKGROUND: Specialty public health training consists of 48 months of practice across the domains of health protection, healthcare public health and health improvement.With the onset of the COVID-19 pandemic, activity pivoted towards pandemic management and the response became a significant element of registrar practice.This research aimed to understand the impact of this shift in focus on registrars' role and training. METHODS: Participatory action research comprising (i) a reflective survey sent to all specialty registrars in the East Midlands training region and (ii) Delphi rounds with survey respondents to generate consensus and define themes. RESULTS: Sixteen (44%) registrars completed the survey with 12 (75%) participating in the Delphi rounds. The early pandemic response stages both challenged and re-affirmed registrars' role and identity in public health and training while providing unique and diverse learning and development. Underpinning these themes is a variability in experience depending on prior experience, placement and training stage. CONCLUSIONS: The pandemic impacted the practice, training and home-life of registrars who were required to negotiate significant challenge and uncertainty. This original work adds to a growing body of correspondence and opinion pieces articulating the experiences and challenges of medical and public health education during a pandemic.

Limited antigenic variation in the Trypanosoma cruzi candidate vaccine antigen TSA-1.

Chagas disease (American trypanosomiasis caused by Trypanosoma cruzi) is one of the most important neglected tropical diseases in the Western Hemisphere. The toxicities and limited efficacies of current antitrypanosomal drugs have prompted a search for alternative technologies such as a therapeutic vaccine comprised of T. cruzi antigens, including a recombinant antigen encoding the N-terminal 65 kDa portion of Trypomastigote surface antigen-1 (TSA-1). With at least six known genetically distinct T. cruzi lineages, variability between the different lineages poses a unique challenge for the development of broadly effective therapeutic vaccine. The variability across the major lineages in the current vaccine candidate antigen TSA-1 has not previously been addressed. To assess the variation in TSA-1, we cloned and sequenced TSA-1 from several different T. cruzi strains representing three of the most clinically relevant lineages. Analysis of the different alleles showed limited variation in TSA-1 across the different strains and fit with the current theory for the evolution of the different lineages. Additionally, minimal variation in known antigenic epitopes for the HLA-A 02 allele suggests that interlineage variation in TSA-1 would not impair the range and efficacy of a vaccine containing TSA-1.

Fit for Duty: Lessons Learned from Outpatient and Homebound Hematopoietic Cell Transplantation to Prepare Family Caregivers for Home-Based Care.

In the past decade, the demand for home-based care has been amplified by the Coronavirus disease 2019 pandemic. Home-based care has significant benefits for patients, their families, and healthcare systems, but it relies on the often-invisible workforce of family and friend caregivers who shoulder essential health care responsibilities, frequently with inadequate training and support. Hematopoietic cell transplantation (HCT), a potentially curative but intensive treatment for many patients with blood disorders, is being increasingly offered in home-based care settings and necessitates the involvement of family caregivers for significant patient care responsibilities. However, guidelines for supporting and preparing HCT caregivers to effectively care for their loved ones at home have not yet been established. Here, informed by the literature and our collective experience as clinicians and researchers who care for diverse patients with hematologic malignancies undergoing HCT, we provide considerations and recommendations to better support and prepare family caregivers in home-based HCT and, by extension, family caregivers supporting patients with other serious illnesses at home. We suggest tangible ways to screen family caregivers for distress and care delivery challenges, educate and train them to prepare for their caregiving role, and create an infrastructure of support for family caregivers within this emerging care delivery model.

Pre-Transplant Marital Status and Hematopoietic Cell Transplantation Outcomes

Background: Evidence about the impact of marital status before hematopoietic cell transplantation (hct) on outcomes after hct is conflicting. Methods: We identified patients 40 years of age and older within the Center for International Blood and Marrow Transplant Research registry who underwent hct between January 2008 and December 2015. Marital status before hct was declared as one of: married or living with a partner, single (never married), separated or divorced, and widowed. We performed a multivariable analysis to determine the association of marital status with outcomes after hct. Results: We identified 10,226 allogeneic and 5714 autologous hct cases with, respectively, a median follow-up of 37 months (range: 1-102 months) and 40 months (range: 1-106 months). No association between marital status and overall survival was observed in either the allogeneic (p = 0.58) or autologous (p = 0.17) setting. However, marital status was associated with grades 2-4 acute graft-versus-host disease (gvhd), p < 0.001, and chronic gvhd, p = 0.04. The risk of grades 2-4 acute gvhd was increased in separated compared with married patients [hazard ratio (hr): 1.13; 95% confidence interval (ci): 1.03 to 1.24], and single patients had a reduced risk of grades 2-4 acute gvhd (hr: 0.87; 95% ci: 0.77 to 0.98). The risk of chronic gvhd was lower in widowed compared with married patients (hr: 0.82; 95% ci: 0.67 to 0.99). Conclusions: Overall survival after hct is not influenced by marital status, but associations were evident between marital status and grades 2-4 acute and chronic gvhd. To better appreciate the effects of marital status and social support, future research should consider using validated scales to measure social support and patient and caregiver reports of caregiver commitment, and to assess health-related quality of life together with health care utilization.

Properties of the initial reaction of bleomycin and several of its metal complexes with Ehrlich cells.

Characteristics of the reaction of bleomycin-A2 (BLM) and several of its metal complexes with Ehrlich cells in culture are described. Short incubation of BLM and Fe(III)-, Cu-, Zn-, and CdBLM with Ehrlich cells effectively inhibits cell proliferation. There is a sharp break at 30 min in the dependence of cytotoxicity upon time of exposure of cells to these forms of the drug. Qualitatively, the same curve can be generated by sequential additions of CoCl2 to cells during their first hour of incubation with BLM or Fe(III)BLM. The cobalt salt has less effect on CuBLM. The kinetics of initiation of the effect are directly correlated with the rapid kinetics of uptake of [3H]BLM by cells. Measurements of the initial rate of association of drug with cells as a function of extracellular BLM concentration suggest that a binding step is involved, for the rate of association approaches a maximal velocity at large concentrations of BLM. Uptake leads to both specific and nonspecific binding of tritium label; however, very little BLM gets into these cells. The internal concentration is estimated to be less than that in the external medium. BLM and its Fe(III) and copper complexes are taken up by Ehrlich cells to the same general extent after 60 min incubation; the cellular uptake of CoBLM is 25-50 times higher. Even the distributions of Fe(III)-, Cu-, and metal-free BLM within cytosol are comparable. A fraction binds to macromolecules; the rest appears unbound in low molecular weight fractions. The binding of [3H]BLM to cells cannot be reversed by incubation of labeled cells in drug-free medium or in media containing large concentrations of cold BLM.

Inhibition of tumor cell transplantability by iron and copper complexes of 5-substituted 2-formylpyridine thiosemicarbazones.

The cytotoxicity of copper and iron complexes of 5-substituted 2-formylpyridine thiosemicarbazones against Ehrlich ascites tumor cells has been measured. Brief in vitro incubation of cells and drugs is followed by implantation into host mice. Subsequent degree of tumor development is a measure of cytotoxicity. A spectrum of activities for the iron complexes is observed, starting with the least active as designated by its 5-substitution: OH less than OCOCH3 approximately N(CH3)2 less than H less than CH3 approximately Cl approximately CF3. The last three complexes can prevent completely tumor growth in the new host. Copper complexes of 5-H and 5-CH3 also prevent successful tumor cell transplantation.

Passive smoking in children. Racial differences in systemic exposure to cotinine by hair and urine analysis.

Passive smoking has been shown to adversely affect the health of infants and children. Black children and adults appear to be more susceptible to a variety of tobacco smoke health hazards for unknown reason. The objectives of this study were as follows: (1) to correlate the number of cigarettes reported to have been smoked by parents with urine and hair concentrations of cotinine in children; and (2) to identify race differences in systemic exposure to cotinine in children. This was an observational study in a consulting pediatric office on 169 nonsmoking children between 2 and 18 years of age, not actively smoking. The outcome measures of interest were urinary cotinine concentrations corrected for milligram of creatinine and hair concentration of cotinine (per milligram of hair). There were significant correlations between the number of cigarettes the child was exposed to and urinary cotinine (r = 0.68, p = 0.0001) or hair cotinine concentrations (r = 0.19, p = 0.02), and between urinary and hair cotinine (r = 0.3, p = 0.0005). In this cohort, parents of black children (n = 21) tended to smoke less (6.6 +/- 3/d, mean +/- SEM) than white parents (n = 97) (12 +/- 1.8, mean +/- SEM) (p = 0.2). Despite being exposed to less cigarettes, black children had higher hair concentrations of cotinine than white children (0.89 +/- 0.25 ng/mg vs 0.48 +/- 0.05 ng/mg; p = 0.05). The ratio hair/urine concentrations of cotinine was twofold higher in black children (0.035 +/- 0.01 vs 0.019 +/- 0.002; p = 0.004). White children with dark hair did not differ significantly from white children with fair hair in any of these indexes. The amount of urinary cotinine per milligram of creatinine caused by 1 cigarette per day was twofold higher in black children (14.7 +/- 5.2 ng/mg of creatinine) than in white children (6.3 +/- 1.2 ng/mg of creatinine) (p = 0.02). These data suggest that black children handle cigarette smoke differently from white children and that black children have higher systemic exposure to this constituent of cigarette smoke.

Identification of brain metabolites by magnetic resonance spectroscopy in MND/ALS.

Magnetic resonance spectroscopy (MRS) has provided a novel means of studying the brain biochemistry of motor neurone disease/amyotrophic lateral sclerosis (MND/ALS) patients in vivo in situ. Previous studies have demonstrated changes in the ratios of areas under specific spectral peaks in MND/ALS patients (Jones et al., 1995). However, the significance of such findings cannot be fully elucidated without first ascertaining the biochemical identity of each peak. Each peak in a MRS spectrum corresponds to the resonance of specific protons in a particular chemical environment. Many biochemicals contain similar protons in similar environments so it is possible that a single spectral peak could represent protons from more than one biochemical. In this study of major brain MRS peaks we have demonstrated that peaks are potentially composed of a number of protons from different chemicals. For example, the peak at chemical shift 2.01 ppm, conventionally recognised as the neurotransmitter N-acetyl aspartate, may actually be a result of the protons of the N-acetyl moiety (Frahm et al., 1991). We have consequently shown that other N-acetylated compounds such as N-acetyl glutamate are also capable of producing a peak here, whereas their non-acetylated derivatives are not. We have also shown GABA is capable of producing a peak at chemical shift 3.00 ppm, a peak which is generally assigned to creatine/phosphocreatine. These findings have important implications in the identification of spectral peaks in MRS studies and in the interpretation of spectral differences between MND patients and controls.

A comparison of the genotoxic effects of carboplatin and cisplatin in Escherichia coli.

cis-Diammine(1,1,-cyclobutanedicarboxylato)platinum(II) (carboplatin) is a second generation platinum anticancer agent with antineoplastic properties like that of its parent compound, cis-diamminedichloroplatinum(II) (cisplatin) but with substantially less deleterious side effects in treated patients with cisplatin. We compared their genotoxic effects in Escherichia coli and found carboplatin to be less cytotoxic (measured as loss of colony forming ability) that cisplatin in that equitoxic doses required greater than 60 time more carboplatin. However, solutions of carboplatin containing chloride ion became more cytotoxic to E. coli after a 24 h incubation period than similar freshly made solutions. Two platinum conversion products which were neither present in freshly made solutions nor in solutions lacking chloride were resolved by thin-layer chromatography (TLC). One of the conversion products migrated like cisplatin and its occurrence in carboplatin solutions was associated with cisplatin-like properties, enhanced cytotoxicity and ability to induce the SOS responses in E. coli. The SOS-inducing abilities were determined by induction of a sulA::lacZ fusion. Likewise, adducts formed in end-labeled oligonucleotides treated with carboplatin appeared identical to those caused by cisplatin when carboplatin was preincubated in chloride-containing solutions but not by carboplatin in freshly made solutions. It is likely that responses evoked by carboplatin in biological systems are partly due to activation of carboplatin by its conversion of cisplatin.

Composite hooks enhance rotational control.

We find hooks placed in positions of convenience useful in correcting rotations, especially with lingual appliances. The steps involved in building them are straightforward. Following acid etching of the spot where the hook is to be placed, a small amount of bonding material is carried onto the enamel surface and a base established by a series of circular motions with the tip of an explorer. The bonding material is then extruded with the tip of the explorer. As soon as the material is extruded to the desired length and curvature, the UV light is applied. Of course, if needed, bigger hooks can be constructed and then trimmed to shape with a bur. A short-beak band remover works best (in a scraping motion) for the removal of these hooks. The following figures illustrate the point (Figs. 1-7).

Tongue pressures and tooth stability after anterior maxillary osteotomy.

Tongue pressures against the maxillary dentition during swallowing were measured in a series of ten patients who underwent anterior maxillary osteotomy for correction of protrusion. In these patients, tongue pressures were low initially, especially pressures by the sides of the tongue in the molar region. After surgical retraction of the incisors, tongue pressures increased, but the increases brought pressures up to normal levels from the previous abnormally low values. The data are consistent with the view that function (swallowing) adapts to oral form, rather than the other way around.

Treatment of septic olecranon and prepatellar bursitis with percutaneous placement of a suction-irrigation system. A report of 12 cases.

Ten cases of septic olecranon bursitis and two cases of septic prepatellar bursitis were treated in the period from 1975 to 1980 with antibiotics and percutaneous tube placement for suction-drainage and local antibiotic irrigation. All patients had positive bacterial cultures: Staphylococcus aureus in nine, beta-hemolytic Streptococcus in two, and Staphylococcus epidermidis in one. Intravenous antibiotics, local suction-drainage, and irrigation with a solution of 1% kanamycin and 0.1% polymyxin controlled the infection in each case. The antibiotic treatment averaged 19 days, compared with 24 days in a series in which suction-irrigation was not used. In contrast with studies in which aspiration or incision and drainage were performed, there were no complications or recurrences. Percutaneous suction-irrigation appears to be a safe, effective method of treatment that is particularly beneficial in severe cases of septic bursitis in which continuous drainage is desirable.

An extrapolation of the physical attractiveness and sex variables within the Byrne attraction paradigm.

Twenty male and 20 female volunteer general psychology students were assigned to one of four treatment conditions in a totally randomized 2 by 2 ANOVA to test the hypothesis that subjects would perceive attractive strangers of the opposite sex as possessing attitudes similar to their own. Physical attractiveness was defined in terms of independent ratings via a Q sort of 74 male and 74 female yearbook pictures. The ANOVA yielded a significant main effect for attractiveness. These results were interpreted as supporting both the Byrne attraction paradigm and Newcomb's cognitive symmetry hypothesis. A follow-up experiment, using a population of adult apartment residents who were allowed to choose the stimulus photograph they felt to be most or least attractive, replicated the results obtained in Experiment I and revealed an even more pronounced attractiveness effect.

Steps in the negative-differential-conductivity regime of a superconductor.

Current-voltage characteristics were measured in the mixed state of Y(1)Ba(2)Cu(3)O(7-delta) superconducting films in the regime where flux flow becomes unstable and the differential conductivity dj/dE becomes negative. Under conditions where its negative slope is steep, the j(E) curve develops a pronounced staircase-like pattern. We attribute the steps in j(E) to the formation of a dynamical phase consisting of the successive nucleation of quantized distortions in the local vortex velocity and flux distribution within the moving flux matter.

Pharmacokinetic predisposition to nicotine from environmental tobacco smoke: a risk factor for pediatric asthma.

During the last decade several studies have shown that children whose parents smoke have higher rates of asthma. Recently, hair concentrations of cotinine have been shown to reflect systemic exposure to this constituent of smoke in both children and adults. At the present time it is not known, however, why some children exposed to passive smoking have asthma while others, similarly exposed, do not. The present study aimed at verifying whether asthmatic children are different from nonasthmatic children exposed to similar degrees of passive smoking in the way their bodies handle nicotine, a constituent of cigarette smoke. Seventy-eight asthmatic children were compared to 86 control children, all attending a consulting pediatric clinic in Toronto. A questionnaire completed by the parents and children detailed the daily number of cigarettes the child was exposed to and the identity of the smokers. Clinical data were extracted from the patients' charts. Urinary (corrected for creatinine) and hair concentrations of cotinine were measured by radioimmunoassays. The asthmatic and control children were of similar age, gender, and ethnic distribution, parental education, and socioeconomic status. Parents of asthmatic children tended to report a lower daily number of cigarettes (7.4 +/- 1.3/day vs. 11.2 +/- 2.3/day, p = 0.14), and this report agreed with the trend of urinary cotinine (47.1 +/- 9.1 ng/mg vs. 62.6 +/- 11.5 ng/mg, respectively). Conversely, children with asthma had on average twofold higher concentrations of cotinine in their hair (0.696 +/- 0.742 ng/mg) than control children (0.386 +/- 0.383) (p = 0.0001). In a similar manner, the hair:urine concentration ratio was significantly higher in children with asthma (0.028 +/- 0.002) than in their controls (0.18 +/- 0.003) (p = 0.0001). These results suggest that under exposure to similar amounts of nicotine, children with asthma have on average twofold higher systemic exposure to this constituent of cigarette smoke. These data suggest that out of all children passively exposed to environmental tobacco smoke, those who exhibit asthma have a higher systemic exposure to nicotine, possibly due to lower clearance rate. This is the first evidence of pharmacokinetic predisposition to environmental tobacco smoke as an etiological factor in pediatric asthma.

Hypoxia inhibits nitric oxide synthesis in isolated rabbit lung.

Nitric oxide (NO.) has been proposed to modulate hypoxic vasoconstriction in the lung. The activity of nitric oxide synthase (NOS) can be inhibited by hypoxia because molecular oxygen is a necessary substrate for the enzyme. On the basis of this mechanism, we hypothesized that NOS activity has a key role in regulation of pulmonary vascular tone during hypoxia. We measured oxidation products of NO. released into the vasculature of isolated buffer-perfused rabbit lung ventilated with normoxic (21% O2), moderately hypoxic (5% O2), or anoxic (0% O2) gas using two methods. Mean PO2 in perfusate exiting the lung was 25 Torr during anoxic ventilation and 47 Torr during moderately hypoxic ventilation. We found that the amount of the NO. oxidation product nitrite released into the perfusate was suppressed significantly during ventilation with anoxic but not moderately hypoxic gas. During normoxic ventilation, nitrite release was inhibited by pretreatment with NG-monomethyl-L-arginine, a competitive inhibitor of NOS. To confirm that changes in nitrite concentration reflected changes in NO. release into the perfusate, major oxidation products of NO. (NOx) were assayed using a method for reduction of these products to NO. by vanadium(III) Cl. Release of NOx into the perfusate was suppressed by severe hypoxia (anoxic ventilation), and this effect was reversed by normoxia. Pulmonary vasoconstriction was observed during severe but not moderate hypoxia and was related inversely to the rate of nitrite release. These observations provide evidence that decreased NO. production contributes to the pulmonary vasoconstrictor response during severe hypoxia.