Perceived Susceptibility and Severity of COVID-19 on Prevention Practices, Early in the Pandemic in the State of Florida.

Early in the pandemic and prior to the development of the COVID-19 vaccine, prevention measures were promoted to help inhibit the spread of the virus. To optimize adherence to prevention practices, it's important to understand factors that may influence adherence. A study was conducted in the month of April, 2020, to explore the influence of perceptions of COVID-19 on prevention practices. The sample included members of a public social-media group focused on providing updates and information on COVID-19. A total of 719 individuals completed an online survey that assessed various aspects of COVID-19 which included experience, perceptions, and prevention practices. The perceptions of COVID-19 included perceived susceptibility of contracting the virus, and perceived potential severity if contracted COVID-19. To assess prevention practices, the survey included a 10-item prevention practices questionnaire that included items such as wearing a mask, and social distancing. Results revealed that perceived susceptibility of contracting COVID-19, and potential severity of COVID-19 were significant in predicting prevention practices. Further, results suggest that perceived potential severity predicts a greater proportion of the variance in prevention practices than susceptibility of contracting COVID-19. In addition, a moderation analysis revealed no interaction between perceived susceptibility and severity, which provides evidence that the variables do not influence one another. Theoretical and practical implications are discussed.

Genetic variation in the nuclear factor kappaB pathway in relation to susceptibility to rheumatoid arthritis.

OBJECTIVE: To examine genetic association between rheumatoid arthritis (RA) and known polymorphisms in core genes of the nuclear factor (NF)kappaB pathway, the major intracellular pathway in RA pathogenesis. METHODS: Discovery and replication sample sets of Spanish patients with RA and controls were studied. A total of 181 single nucleotide polymorphisms (SNPs) uniformly spaced along the genomic sequences of 17 core genes of the NFkappaB pathway (REL, RELA, RELB, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, IKBKA, IKBKB, IKBKE, IKBKAP, KBRAS1, KBRAS2, MAP3K1, MAP3K14, TAX1BP1) were studied by mass spectrometry analysis complemented with 5'-nuclease fluorescence assays in the discovery set, 458 patients with RA and 657 controls. SNPs showing nominal significant differences were further investigated in the replication set of 1189 patients with RA and 1092 controls. RESULTS: No clear reproducible association was found, although 12 SNPs in IKBKB, IKBKE and REL genes showed significant association in the discovery set. Interestingly, two of the SNPs in the IKBKE gene, weakly associated in the discovery phase, showed a trend to significant association in the replication phase. Pooling both sample sets together, the association with these two SNPs was significant. CONCLUSION: We did not find any major effect among the explored members of the NFkappaB pathway in RA susceptibility. However, it is possible that variation in the IKBKE gene could have a small effect that requires replication in additional studies.

Cognitive dysfunction in systemic lupus erythematosus: prevalence and correlates.

Little is known about the mechanisms and relevance of cognitive dysfunction in systemic lupus erythematosus (SLE) patients who never displayed major neuropsychiatric manifestations (nSLE). Thirty-one nSLE female patients and 31 cognitively healthy control women were recruited. Sociodemographic, clinical, neuropsychological and SLE-related markers were collected including cerebral perfusion by single-photon emission computed tomography. Prevalences of cognitive complaints were 22.6% in nSLE versus 6.5% in the control group (p = 0.147); respective prevalences of cognitive dysfunction were 32.3 versus 6.5% (p = 0.01). Within the nSLE group, all cognitive domains appeared similarly affected, and correlations were found between cognitive dysfunction and less skilled occupation (r = -0.41, p = 0.02) and between cognitive complaints and depressive symptoms (r = 0.35, p = 0.05). Cognitive dysfunction is rather frequent in nSLE and seems to negatively impinge on social functioning.

The attrition rate of patients in the antiretroviral therapy program in two outpatient treatment centers in Bangui.

To determine the rate of attrition of patients in the antiretroviral treatment program in Bangui and factors associated with this loss to follow-up. This was a retrospective descriptive, analytical cohort study from January 1, 2014 to March 31, 2017 in two large outpatient treatment centers in Bangui. Data were entered in and analyzed with Epi info version 3.5.4 software. Survival probability was calculated by a Kaplan Meier curve. The Cox model and logistic regression were used to determine the association between attrition and risk factors. A total of 292 patients were registered. Attrition rates at 6, 12, and 24 months were 14%, 20% and 31%, respectively. Factors associated with attrition were patients' age (young), living alone (compared to living with a partner), distance between place of residence and treatment center, presence of opportunistic infections, low hemoglobin levels, and lack of therapeutic education. This study identified the main risk factors for patients leaving the care system. Innovative strategies including differentiated approaches must be implemented to improve quality of screening, early start of treatment, and geographical access to care. Particular emphasis should be placed on therapeutic education to train and educate patients about their illness and how to manage it.

A double-blind placebo controlled trial of etanercept in patients with giant cell arteritis and corticosteroid side effects.

OBJECTIVE: Open label studies have suggested that tumour necrosis factor (TNF) antagonists led to sustained improvement and corticosteroid sparing effect in patients with giant cell arteritis (GCA). To confirm these observations, we conducted a randomised, double-blind, placebo controlled trial with etanercept in patients with biopsy-proven GCA with side effects secondary to corticosteroids. METHODS: We randomly assigned patients with GCA to receive etanercept (n = 8) or placebo (n = 9) over 1 year together with corticosteroids that were reduced according to a predefined schedule. The primary outcome was the ability to withdraw the corticosteroid therapy and control the disease activity at 12 months. RESULTS: Baseline characteristics were similar in the two groups, although patients in the etanercept group showed higher levels of basal glycaemia (p = 0.02) and a higher erythrocyte sedimentation rate (ESR) (p = 0.01). After 12 months, 50% of the patients in the etanercept group and 22.2% in the placebo group were able to control the disease without corticosteroid therapy (p value not significant). Patients in the etanercept group had a significant lower dose of accumulated prednisone during the first year of treatment (p = 0.03). There were no differences in the number and type of adverse events. CONCLUSION: The limited number of patients included in this study does not allow us to draw definitive conclusions. Etanercept therapy was well tolerated in this aged population. The therapeutic role of etanercept in patients with GCA should be evaluated in studies with a larger number of patients.

Attitude of men who have sex with men toward condom use in Bangui, Central African Republic (CAR).

to understand the attitude of men who have sex with men (MSM) towards the use of condoms, to identify potential barriers to their use, environmental factors that facilitate or on the contrary, prevent this use, beliefs about contracting HIV, and priority needs of MSM for general prevention of sexually transmitted infections (STI). Individual interviews conducted in private with 20 MSM. In general, MSM recognize that condoms protect against STI as well as preventing unwanted pregnancies (although this is not our purpose here). The disadvantages of condom use that they reported included the potential for them to break and their reduction of pleasure. Barriers to their use include the belief that the partner is not HIV-positive, the shame of buying condoms, inability to wear them, and lack of financial resources, as well as social norms and false beliefs. MSM are aware of the positive role of condoms against STIs, including HIV. They perceive the dangerousness of the HIV, but do not feel vulnerable to this disease. They have identified obstacles to condom use, and their lists of perceived needs suggest solutions to them. Implementing these solutions in interventions should improve the frequency of condom use.

Molecular structure and evolution of double-minute chromosomes in methotrexate-resistant cultured mouse cells.

To determine whether microscopically visible double-minute chromosomes (DMs) are derived from submicroscopic precursors, we monitored the amplification of the dihydrofolate reductase (DHFR) gene in 10 independent isolates of methotrexate (MTX)-resistant mouse cells. At every other doubling in MTX concentration, the cells were examined both microscopically, to detect the presence of microscopically visible DMs, and by pulsed-field gel electrophoresis and hybridization to a DHFR-specific probe, to detect submicroscopic DMs. One of the cloned MTX-resistant isolates was examined in detail and was shown to originally contain amplified DHFR genes on circular DMs measuring 1 and 3 Mb in size; additionally, metaphase chromosome preparations from this cloned isolate were examined and were shown to contain microscopically visible DMs too large to enter a pulsed-field gel. During stepwise selection for increasing levels of MTX, the smaller DMs (not microscopically visible) were shown to be preferentially amplified, whereas the larger (microscopically visible) ones decreased in relative numbers. Rare-cutting NotI digestion patterns of total genomic DNA that includes the DMs containing the DHFR gene suggest that the DMs increase in copy number without any further significant rearrangements. We saw no evidence from any of the 10 isolates to suggest that microscopically visible DMs are formed from smaller submicroscopic precursors.

CpG island mapping of a mouse double-minute chromosome.

The development of double-minute chromosomes (DMs) and subsequent gene amplification are important genomic alterations resulting in increased oncogene expression in a variety of tumors. The molecular mechanisms mediating the development of these acentric extrachromosomal elements have not been completely defined. To elucidate the mechanisms involved in DM formation, we have developed strategies to map amplified circular DM DNA. In this study, we present a long-range restriction map of a 980-kb DM. A cell line cloned from mouse EMT-6 cells was developed by stepwise selection for resistance to methotrexate. This cloned cell line contains multiple copies of the 980-kb DM carrying the dihydrofolate reductase (DHFR) gene. A long-range restriction map was developed in which a hypomethylated CpG-rich region near the DHFR gene served as a landmark. This strategy was combined with plasmid-like analysis of ethidium bromide-stained pulsed-field gels and indicated that a single copy of the DHFR gene was located near a hypomethylated region containing SsII and NotI sites. At least 490 kb of this DM appears to be composed of unrearranged chromosomal DNA.

Risk factors for transmission of HIV from mother to child in Bangui.

the prevalence of human immunodeficiency virus infection (HIV) in pregnant women in Central Africa is 4.5%. Although a program to prevent mother-child transmission of HIV has been implemented throughout the country, the number of infected infants continues to increase. In this context, our study sought to determine the rate of mother-child transmission of HIV and to identify the main risk factors. this prospective cross-sectional study took place from November 1, 2014, to November 1, 2015, in all 16 maternal and child health centers in Bangui. The study population comprised the infants born to HIV-positive mothers and seen at these centers for HIV testing 6 weeks after birth. The mothers were interviewed and their files examined to identify the risk factors of HIV transmission to their babies. the study included 656 infants. The maternal-fetal transmission rate of HIV was 7%. The main risk factors were the absence of antiretroviral prophylaxis for mothers or children and rupture of the membranes more than 24 hours before labor. HIV transmission from mother to child is a public health problem in Bangui. Vigorous action, such as interventions with antiretroviral medication, good obstetric practices, and especially the implementation of the 2013 WHO recommendations, should certainly reduce the number of new infections among newborns in Bangui.

Comparing organ-at-risk doses for high-dose-rate vaginal brachytherapy between three different planning workflows.

PURPOSE: The aim of this study was to compare the organ-at-risk doses to the rectum and the bladder in postoperative endometrial cancer patients who receive high-dose-rate vaginal brachytherapy (HDR-VB), when using three different methods of treatment planning: (Workflow A) individualized treatment planning before every fraction, (Workflow B) individualized treatment planning for first fraction only), and (Workflow C) using a template plan based on applicator choice and prescription specifics without patient-specific imaging or planning (standardized template approach). METHODS AND MATERIALS: Alternative plans were retrospectively created using workflows B and C for 22 patients who previously received postoperative HDR-VB using a vaginal cylinder and planned using Workflow A for endometrial cancer. The rectum and bladder were contoured on the CTs used for each fraction for dose comparison between the three methods. D50, D2cc, D1cc, D0.1cc, and V100 of the bladder and the rectum were compared using the two-sided Wilcoxon signed-rank test. RESULTS: A total of 123 fractions were available for comparison. For Workflow A vs. Workflow B, there was no significant difference for any rectal or bladder dosimetric parameter. For Workflow A vs. Workflow C, Workflow A delivered a significantly higher median dose to the rectum than Workflow C for D50, D2cc, D1cc, and V100. Workflow C delivered a significantly higher dose to the bladder than Workflow A: D2cc, D1cc, D0.1cc, and V100. However, the magnitudes of the differences were small; the dose index difference was >75 cGy for only two fractions. CONCLUSION: Plan standardization in HDR-VB may result in considerable time and cost savings with minimal organ-at-risk dose differences.

Mobilising Expertise and Resources to Close the Radiotherapy Gap in Cancer Care.

Closing the gap in cancer care within low- and middle-income countries and in indigenous and geographically isolated populations in high-income countries requires investment and innovation. This is particularly true for radiotherapy, for which the global disparity is one of the largest in healthcare today. New models and paradigms and non-traditional collaborations have been proposed to improve global equity in cancer control. We describe recent initiatives from within the radiation oncology community to increase access to treatment, build the low- and middle-income countries' radiation oncology workforce, mobilise more professionals from within high-income countries and raise awareness of the global need for equitable cancer care.

SERS Investigation of Cancer Cells Treated with PDT: Quantification of Cell Survival and Follow-up.

In this study Surface Enhanced Raman Spectroscopy (SERS) data recorded from mouse mammary glands cancer cells (4T1 cell line) was used to assess information regarding differences between control, death and viable cells after Photodynamic Therapy (PDT) treatment. The treatment used nanoemulsions (NE/PS) loaded with different chloroaluminumphthalocyanine (ClAlP) photosensitizer (PS) contents (5 and 10 µmol × L-1) and illumination (660 nm wavelength) at 10 J × cm-2 (10 minutes). The SERS data revealed significant molecular alterations in proteins and lipids due to the PDT treatment. Principal Component Analysis (PCA) was applied to analyze the data recorded. Three-dimensional and well reproductive PCA scatter plots were obtained, revealing that two clusters of dead cells were well separated from one another and from control cluster. Overlap between two clusters of viable cells was observed, though well separated from control cluster. Moreover, the data analysis also pointed out necrosis as the main cell death mechanism induced by the PDT, in agreement with the literature. Finally, Raman modes peaking at 608 cm-1 (proteins) and 1231 cm-1 (lipids) can be selected for follow up of survival rate of neoplastic cells after PDT. We envisage that this finding is key to contribute to a quick development of quantitative infrared thermography imaging.

The scid defect results in much slower repair of DNA double-strand breaks but not high levels of residual breaks.

Severe combined immune deficiency (scid) mice fail to produce mature B and T cells and are sensitive to ionizing radiation. They contain a mutation in the 460-kDa catalytic subunit of the DNA-dependent protein kinase that is involved in both V(D)J rejoining and DNA double-strand break (DSB) repair. The kinetics of DSB rejoining was quantified in both scid cells and the parental C.B-17 cells after three different doses of X irradiation: 3, 7.5 and 10 Gy. Repair of DNA DSBs was determined using pulsed-field gel electrophoresis, Southern hybridization and phosphor image analysis. After X irradiation, the cells were allowed to repair at 37 degrees C for up to 1 h or up to 24 h. The most profound difference between the two cell lines was the greatly reduced rate of the slow component of DSB repair in scid cells. C.B-17 cells repaired most of the damage within 1 h, whereas scid cells required 4 to 6 h to reach a similar level after the same dose. No residual or unrepairable DSBs were detected in either cell line 24 h after doses as high as 10 Gy. The scid cells subjected to two doses of 1.5 Gy separated by increasing amounts of time showed no ability to repair sublethal damage between doses, whereas C.B-17 cells receiving two doses of 3.75 Gy separated by increasing periods did show increased levels of survival. These results indicate that scid cells can repair radiation-induced DNA DSBs, although at a reduced rate, but they lack the ability to undergo repair of sublethal damage.

An assay for quantifying DNA double-strand break repair that is suitable for small numbers of unlabeled cells.

A system based on pulsed-field gel electrophoresis (PFGE) is described which measures the induction and repair of DNA double-strand breaks (DSBs) in a biologically relevant X-ray dose range (below 10 Gy) using as few as 125 cells per time. This system was used to measure repair in cells of a freshly obtained human glioblastoma multiforme tumor. No prelabeling of the cells is required, and many different cell types can be studied using this system. Under the pulsed-field conditions used, DNA in the range of 2 to 6 Mb enters the PFGE gel and forms an upper compression zone directly under each well. To quantify the DSBs after electrophoresis, the DNA was transferred to nylon membranes and hybridized with 32P-labeled chromosomal DNA. Phosphor screens were exposed to the membranes and scanned on a phosphor imager. The kinetics of induction and repair was determine by measuring the amount of DNA in the compression zones compared to the amount in the wells. EMT-6 cells were used to demonstrate this method. Induction of DSBs by doses of 0-7.5 Gy X rays was assayed using approximately 12,500 cells per dose and was shown to be linear. Double-strand breaks from 1 Gy were detected above background. To determine a lower limit of the number of cells that could be used to measure DSB repair, cells were embedded in agarose at decreasing concentrations per plug, exposed to 7.5 Gy X irradiation and allowed to repair at 37 degrees C for up to 60 min. DNA from approximately 12,500, 1,250 and 125 cells per time was loaded and subjected to PFGE. The average fast-repair half-time was 3 min and the slow-repair half-time was 35 min. The kinetics of DSB repair in glioblastoma multiforme cells was also determined using this system. Agarose plugs were prepared from a cell suspension, irradiated with 7.5 Gy X rays and allowed to repair for up to 90 min. DNA from approximately 1,250 tumor cells was electrophoresed and analyzed as described above for EMT-6 cells. For this particular tumor, approximately 75% of the induced DSBs were repaired after 90 min. Data presented show that this PFGE-based system is an extremely sensitive method for measuring DSB induction and repair after low doses of X rays using very few cells.

Induction and repair of DNA double-strand breaks in the same dose range as the shoulder of the survival curve.

We have used pulsed-field gel electrophoresis (PFGE) to test two hypotheses that have been proposed to explain the survival curves with shoulders which are characteristic of low-LET ionizing radiation: (1) Neutral elution studies of the induction of double-strand breaks (DSBs) have suggested that ionizing radiation might induce DSBs in a nonlinear fashion at low doses. (2) Based on analogies to enzyme kinetics, DSB repair might be saturating in the shoulder region. We quantified DSB induction and survival resulting from doses between 0 and 5 Gy spanning the shoulder region of the survival curve. We found that DSB induction was linear at all doses tested down to 0.5 Gy, the limits of sensitivity. Therefore, nonlinear DSB induction cannot account for the shape of the survival curve. To determine whether the DSB repair system was saturated in the shoulder region, we quantified the rate of DSB repair as a function of dose of X rays between 1.25 and 20 Gy. The repair of DSBs was exponential with half-times of repair constant for doses below 10 Gy, and averaged 28 min. We determined the initial rate of repair from the exponential repair kinetics for each dose. The initial rate of repair after radiation treatment increased linearly with dose up to at least 10 Gy. Therefore, saturating DSB repair cannot explain the shoulder of the survival curve.

Induction and repair of DNA double-strand breaks.

Induction and repair of DNA double-strand breaks (DSBs) was measured using a pulsed-field gel electrophoresis system. A cell line of methotrexate-resistant EMT-6 cells that contain numerous double-minutes (DMs) 3 million base pairs in size was employed. The electrophoretic mobility of these DMs depends on whether they have zero, one, or more than one DSB. With no DSBs the DMs remain as circles and are trapped in the origin of electrophoresis, but with one DSB the DMs migrate as a discrete band and can be detected easily through hybridization with a gene-specific probe. Using a clamped homogeneous electrical field apparatus, the induction of DSBs in the 1.5 to 12 Gy X-ray dose range is studied and is shown to be linear. Double-strand break repair following 7.5 Gy is studied, and is shown to be exponential. The kinetics of both induction and repair of DSBs induced in DM DNA was compared to the induction and repair of DSBs in chromosomal DNA and is shown to be similar. The kinetics of repair of DSBs following 7.5 Gy for cells embedded in agarose and cells in suspension is shown to be similar.

The reliability and predictive value of an amniotic fluid scoring system in severe second-trimester oligohydramnios.

Sixty-two cases of oligohydramnios diagnosed by ultrasound between 13-28 weeks' gestation were reviewed. Three experienced ultrasonographers used a subjective scale to rate the oligohydramnios as mild, moderate, severe, or anhydramniotic. Interobserver reliability was excellent (intraclass correlation coefficient 0.81). The overall perinatal mortality rate was 43%, and the incidence of pulmonary hypoplasia was 33%. One-third had lethal congenital anomalies. The frequency of adverse outcome correlated strongly with the most severe degrees of oligohydramnios; 88% of the fetuses with severe oligohydramnios or anhydramnios had lethal outcomes, compared with 11% in the mild/moderate group. The presence of an anuric urinary tract anomaly was associated with the most severe grades of oligohydramnios and was uniformly fatal. Pulmonary hypoplasia was diagnosed in 60% of the severe group versus 6% in the moderate group. We conclude that subjective grading of oligohydramnios by experienced observers is both reliable and predictive of outcome. The finding of severe oligohydramnios in the second trimester is highly predictive of poor fetal outcome and should stimulate a thorough search for etiology and consideration of intervention. Moderate grades of reduced amniotic fluid may be managed with relative optimism.

Blunt traumatic rupture of the right hemidiaphragm and Budd-Chiari syndrome.

We present 2 cases of delayed diagnosis of rupture of the right hemidiaphragm caused by blunt thoracic trauma, in which herniation of the liver toward the thoracic cavity had occurred. Both patients showed signs of noncardiogenic hepatic venous outflow obstruction. Venous outflow returned to normal on reintroduction of the liver into the abdominal cavity and closure of the defect in the diaphragm. The pathogenesis, diagnosis, and treatment of this problem are discussed.

Extracorporeal shock-wave lithotripsy in children.

OBJECTIVES: To analyze the efficacy and complication rates of extracorporeal shock-wave lithotripsy in children. METHODS: Between 1987 and 1994, 8760 patients with urinary calculi were treated at our institution. A total of 70 (0.8%) children 3 to 14 years old underwent lithotripsy using the Siemens Lithostar or the Lithostar Plus. A total of 100 calculi in 74 urinary tracts were treated, requiring 129 extracorporeal shock-wave lithotripsy sessions. There were 47 caliceal stones, 31 in the renal pelvis, 16 in the ureter, and 6 staghorn stones. The Lithostar Plus was used in 8 patients, for 3 caliceal, 3 pelvic, and 2 staghorn stones. Follow-up consisted of nephrotomogram or ultrasound 1 day and 1 to 3 months postoperatively. RESULTS: Complete removal of all stone fragments was achieved in 98.5% of the patients after 3 months. Re-treatment was necessary in 20 patients (29.4%). All patients were treated as outpatients, 51 (72.9%) with intravenous sedation and 19 (27.1%) without anesthesia. Complications were present in 7 patients (10%) who had colic and received medical treatment, and convalescence was uneventful. CONCLUSIONS: Extracorporeal shock-wave lithotripsy using the Lithostar and the Lithostar Plus has been demonstrated to be an effective noninvasive procedure to treat radiopaque and even radiolucent or slightly opaque urinary calculi in children.

G proteins in aortic endothelial cells and bradykinin-induced formation of nitric oxide.

In bovine aortic endothelial cells (BAEC), pertussis toxin (PTx) ADP-ribosylated two major substrates with apparent molecular masses of 40 and 41 kDa, whereas cholera toxin (CTx) ADP-ribosylated two other substrates of 44 and 50 kDa. [alpha-32P]GTP bound to three bands in the 22-27 kDa range. Immunoblot analysis revealed the simultaneous presence of G alpha i1, G alpha i2, G alpha i3, G alpha q or G alpha 11 and of different forms of G alpha s but did not detect significant levels of G alpha 0. Bradykinin caused a 9-fold increase in intracellular cyclic GMP level in BAEC (measured as an index of NO production). Preincubation of BAEC with CTx, but not with PTx, inhibited bradykinin-dependent production of cyclic GMP. These results show that G alpha s, G alpha q or alpha 11, Gi and small GTP-binding proteins are present in BAEC and suggest that a CTx-sensitive G-protein (possibly either small G-protein, G alpha q or G alpha 11) could be associated with the bradykinin-mediated NO formation.