An acute, ulcerative, sarcoidal tattoo reaction following SARS-CoV-2 mRNA-1273 vaccination.

Two weeks after her first dose of the SARS-CoV-2 mRNA-1273 (Moderna) vaccine, a 38-year-old woman developed acute-onset pain and ulceration within a tattoo on the distal left leg. Progressive ulceration was noted approximately one week following her second dose of the vaccine. A biopsy revealed sarcoidal granulomas and a dense neutrophilic infiltrate. Ultimately, the final diagnosis of what we have termed a "sarcoidal reaction with a Sweet-like phenomenon" was made; the patient experienced a reduction in pain and re-epithelialization of the ulcers with two weeks of the use of topical clobetasol 0.05% cream twice daily.

Predator odor produces anxiety-like behavioral phenotype in planarians that is counteracted by fluoxetine.

Avoidant behavior is a characteristic feature post-traumatic stress disorder (PTSD) and is modeled in mammals with predator odor. Light avoidance is a hallmark behavioral reaction in planarians. We hypothesized that planarians exposed to frog extract would display enhanced light avoidance that is prevented by fluoxetine. Enhanced light avoidance (i.e., less time spent in light compartment of a dish split into light and dark sides) after a 30-min frog extract exposure (0.0001-0.01%) manifested 15 min post-exposure, persisted for at least 24 h, and was counteracted by fluoxetine (10 µM). These results suggest conservation of an anxiety-like behavioral phenotype.

The influence of maternal nutrition on expression of genes responsible for adipogenesis and myogenesis in the bovine fetus.

The objective of this study was to determine whether altered maternal energy supply during mid-gestation results in differences in muscle histology or genes regulating fetal adipose and muscle development. In total, 22 Angus cross-bred heifers (BW=527.73±8.3 kg) were assigned randomly to the three dietary treatments providing 146% (HIGH; n=7), 87% (INT; n=7) or 72% (LOW; n=8) of the energy requirements for heifers from day 85 to day 180 of gestation. Fetuses were removed via cesarean section at day 180 of gestation and longissimus muscle (LM) and subcutaneous fat were collected and prepared for analysis of gene expression. Samples from the LM and semitendinosus (ST) were evaluated for muscle fiber diameter, area and number. The right hind limb was dissected and analyzed to determine compositional analysis. Fetal growth and muscle histology characteristics of the LM and ST were similar among treatments. Preadipocyte factor-1 expression was up-regulated in fetal LM (P<0.05) of HIGH fetuses as compared with INT, whereas LOW fetuses showed increased CCAAT/enhancer-binding protein-ß (C/EBP-ß) expression in LM as compared with INT (P<0.05). Peroxisome proliferator-activated receptor γand C/EBP-α did not differ as a result of dietary treatment in LM or subcutaneous fat samples. There was a tendency for increased expression of fatty acid synthase in LM of LOW fetuses as compared with INT (P<0.10). Myogenin was more highly expressed (P<0.05) in LM of the LOW fetuses, whereas µ-calpain expression was increased in the HIGH treatment compared with INT. A tendency for increased expression of IGF-II was observed for both LOW and HIGH fetuses compared with INT (P<0.10). Expression of stearoyl-CoA desaturase, myoblast determination protein 1, myogenic factor 5, myogenic regulatory factor-4, m-calpain, calpastatin, IGF-I and myostatin was similar between treatments. Collectively, these results suggest that fetal growth characteristics are not affected by the level of maternal nutritional manipulation imposed in this study during mid-gestation. However, differences in expression of fetal genes regulating adipose and muscle tissue growth and development could lead to differences in postnatal composition and warrants further investigation.

Isoniazid preventive therapy in HIV-infected children on antiretroviral therapy: a pilot study.

SETTING: Tuberculosis (TB) is a common cause of mortality and morbidity in children infected with the human immunodeficiency virus (HIV). Data on isoniazid preventive therapy (IPT) efficacy in HIV-infected children receiving antiretroviral therapy (ART) are inconclusive. OBJECTIVE: To assess the efficacy, tolerability and safety of isoniazid (INH) in HIV-infected children on ART. DESIGN: A pilot randomised controlled study of INH was undertaken in HIV-infected children on ART. The primary outcome measure was TB disease or death. RESULTS: A total of 167 children were randomised to receive INH (n = 85) or placebo (n = 82), and followed for a median of 34 months (interquartile range [IQR] 24-52). The median age was 35 months (IQR 15-65). There was one death in a child on INH and none in the placebo group. Eleven (6.6%) cases of TB occurred, 4 (5%) in the INH and 7 (9%) in the placebo group. Among the TB cases, 5 were culture confirmed-2 in the INH group and 3 in the placebo group, all susceptible to INH. Severe adverse events occurred rarely (n = 6; 2%). CONCLUSION: IPT is safe and well tolerated in HIV-infected children on concomitant ART. This study supports the need for a larger study to assess efficacy in HIV-infected children living in TB-endemic areas.

Multiplexed microsatellite recovery using massively parallel sequencing.

Conservation and management of natural populations requires accurate and inexpensive genotyping methods. Traditional microsatellite, or simple sequence repeat (SSR), marker analysis remains a popular genotyping method because of the comparatively low cost of marker development, ease of analysis and high power of genotype discrimination. With the availability of massively parallel sequencing (MPS), it is now possible to sequence microsatellite-enriched genomic libraries in multiplex pools. To test this approach, we prepared seven microsatellite-enriched, barcoded genomic libraries from diverse taxa (two conifer trees, five birds) and sequenced these on one lane of the Illumina Genome Analyzer using paired-end 80-bp reads. In this experiment, we screened 6.1 million sequences and identified 356,958 unique microreads that contained di- or trinucleotide microsatellites. Examination of four species shows that our conversion rate from raw sequences to polymorphic markers compares favourably to Sanger- and 454-based methods. The advantage of multiplexed MPS is that the staggering capacity of modern microread sequencing is spread across many libraries; this reduces sample preparation and sequencing costs to less than $400 (USD) per species. This price is sufficiently low that microsatellite libraries could be prepared and sequenced for all 1373 organisms listed as 'threatened' and 'endangered' in the United States for under $0.5 M (USD).

Bacteriologically confirmed tuberculosis in HIV-infected infants: disease spectrum and survival.

BACKGROUND: The human immunodeficiency virus (HIV) has resulted in epidemiological shifts with an emergence of tuberculosis (TB) amongst HIV-infected women and infants. There are limited data on the TB disease spectrum and outcome amongst HIV-infected infants. OBJECTIVES: We describe the clinical characteristics, treatment and survival of HIV-infected infants with culture-confirmed TB. METHODS: This retrospective hospital-based study from Cape Town, South Africa, used routine laboratory-based surveillance among infants diagnosed with culture-confirmed TB from 1 January 2004 to 31 December 2006. Folder and chest radiographic review were completed and vitality status established. TB was classified as pulmonary, extra-pulmonary or disseminated disease. RESULTS: Of 52 infants, 37 (71.1%) had pulmonary, 2 (3.9%) extra-pulmonary only, 7 (13.5%) pulmonary and extra-pulmonary and 6 (11.5%) disseminated TB. Forty-six (88.5%) were started anti-tuberculosis therapy; 37 (71.2%) received antiretroviral therapy (ART) and 17 (32.7%) died, 10 (19.2%) of whom never started ART. HIV stage 4 disease was associated with death. TB treatment outcome was poorly documented. CONCLUSIONS: TB is associated with advanced HIV disease and high mortality in HIV-infected infants. Missed opportunities for initiation of ART were frequent. Although the effects of young age, TB disease spectrum and HIV co-infection are difficult to distinguish, our findings support the initiation of early ART in HIV-infected infants with TB.

Quality characteristics of chunked and formed hams from pale, average and dark muscles were improved using an ammonium hydroxide curing solution.

Cooking yield, cooked pH, purge loss, moisture, lipid oxidation, external and internal color, break strength and elongation distance were assessed for pale (PALE), average (AVG) and dark (DARK) inside hams injected with either a control cure solution (CON) or BPI-processing technology cure solution (BPT). Following enhancement, muscles were chunked, vacuum tumbled, smoked and cooked to 66 degrees C. Cooked ham pH was 6.49 for DARK, 6.40 for AVG, and 6.30 for PALE, respectively (P<0.0001). Cooked pH was higher (P<.0001) for BPT than CON. Cooked ham moisture content was higher (P<0.0001) for BPT hams than CON hams (74.83 vs. 74.11%) but BPT did not significantly influence cooking yield or lipid oxidation. Consumers (n=150) of diverse demographics rated hams for appearance and taste. Results indicated that BPI-processing technology improved visual appearance of hams made from pale, average, and dark muscles and improved the eating quality of hams made from pale muscles.

High incidence of tuberculosis among HIV-infected infants: evidence from a South African population-based study highlights the need for improved tuberculosis control strategies.

BACKGROUND: There are limited population-based estimates of tuberculosis incidence among human immunodeficiency virus (HIV)-infected and HIV-uninfected infants aged < or =12 months. We aimed to estimate the population-based incidence of culture-confirmed tuberculosis among HIV-infected and HIV-uninfected infants in the Western Cape Province, South Africa. METHODS: The incidences of pulmonary, extrapulmonary, and disseminated tuberculosis were estimated over a 3-year period (2004-2006) with use of prospective representative hospital surveillance data of the annual number of culture-confirmed tuberculosis cases among infants. The total number of HIV-infected and HIV-uninfected infants was calculated using population-based estimates of the total number of live infants and the annual maternal HIV prevalence and vertical HIV transmission rates. RESULTS: There were 245 infants with culture-confirmed tuberculosis. The overall incidences of tuberculosis were 1596 cases per 100,000 population among HIV-infected infants (95% confidence interval [CI], 1151-2132 cases per 100,000 population) and 65.9 cases per 100,000 population among HIV-uninfected infants (95% CI, 56-75 cases per 100,000 population). The relative risk of culture-confirmed tuberculosis among HIV-infected infants was 24.2 (95% CI, 17-34). The incidences of disseminated tuberculosis were 240.9 cases per 100,000 population (95% CI, 89-433 cases per 100,000 population) among HIV-infected infants and 14.1 cases per 100,000 population (95% CI, 10-18 cases per 100,000 population) among HIV-uninfected infants (relative risk, 17.1; 95% CI, 6-34). CONCLUSIONS: This study indicates the magnitude of the tuberculosis disease burden among HIV-infected infants and provides population-based comparative incidence rates of tuberculosis among HIV-infected infants. This high risk of tuberculosis among HIV-infected infants is of great concern and may be attributable to an increased risk of tuberculosis exposure, increased immune-mediated tuberculosis susceptibility, and/or possible limited protective effect of bacille Calmette-Guérin vaccination. Improved tuberculosis control strategies, including maternal tuberculosis screening, contact tracing of tuberculosis-exposed infants coupled with preventive chemotherapy, and effective vaccine strategies, are needed for infants in settings where HIV infection and tuberculosis are highly endemic.

Effects of microbead surface chemistry on DNA loading and hybridization efficiency.

Polymer microbeads are witnessing renewed interest for performing biomolecule recognition assays with distinct advantages over planar microarray technology. In this study, DNA hybridization assays are performed on the surfaces of 1-microm-diameter, synthetically modified polystyrene microbeads. The microbead surfaces contain varying amounts of poly(acrylic acid) as a source of carboxylate groups to which a DNA capture strand may bind. Through a series of controlled experiments in which the microbead carboxylate density and DNA:surface area ratios are systematically altered, we find that the density of carboxylate groups on the microbead surface may be the most important parameter affecting not only the total number of DNA strands that may bind to the microbead surface but, surprisingly, also the efficiency of DNA hybridization with complementary strands. These studies are aimed directly at understanding the physical interactions between DNA strands and an anionic microbead surface.

NSET molecular beacon analysis of hammerhead RNA substrate binding and catalysis.

Nanometal surface energy transfer (NSET), which describes an energy transfer event from optically excited organic fluorophores to small metal nanoparticles, may be used as a molecular beacon/ruler similar to FRET, but with advantages over this classical technique. Here we use NSET to measure Mg(2+)-induced conformational changes for a hammerhead ribozyme and confirm these measurements using FRET. These optical experiments enhance our understanding of the different kinetic pathways for this ribozyme.

Fluorescent lifetime quenching near d = 1.5 nm gold nanoparticles: probing NSET validity.

The fluorescence behavior of molecular dyes at discrete distances from 1.5 nm diameter gold nanoparticles as a function of distance and energy is investigated. Photoluminescence and luminescence lifetime measurements both demonstrate quenching behavior consistent with 1/d(4) separation distance from dye to the surface of the nanoparticle. In agreement with the model of Persson and Lang, all experimental data show that energy transfer to the metal surface is the dominant quenching mechanism, and the radiative rate is unchanged throughout the experiment.

Nanometal surface energy transfer in optical rulers, breaking the FRET barrier.

Optical-based distance measurements are essential for tracking biomolecular conformational changes, drug discovery, and cell biology. Traditional Forster resonance energy transfer (FRET) is efficient for separation distances up to 100 A. We report the first successful application of a dipole-surface type energy transfer from a molecular dipole to a nanometal surface that more than doubles the traditional Forster range (220 A) and follows a 1/R(4) distance dependence. We appended a 1.4 nm Au cluster to the 5' end of one DNA strand as the energy acceptor and a fluorescein (FAM) to the 5' end of the complementary strand as the energy donor. Analysis of the energy transfer on DNA lengths (15, 20, 30, 60bp), complemented by protein-induced DNA bending, provides the basis for fully mapping the extent of this dipole surface type mechanism over its entire usable range (50-250 A). Further, protein function is fully compatible with these nanometal-DNA constructs. Significantly extending the range of optical based methods in molecular rulers is an important leap forward for biophysics.

The second-look operation improves survival in suboptimally debulked stage III ovarian cancer patients.

In a single-institution retrospective cohort study, 230 patients were treated for stage III primary ovarian cancer and 175 became eligible for second-look operations by virtue of a complete clinical response after primary surgical cytoreduction and platinum-based combination chemotherapy. Of these, 109 underwent a second-look operation. Optimal primary cytoreduction was defined as residual disease < or =1 cm. Median follow-up was 68.3 months. Five-year survival for all the 230 stage III ovarian cancers was 43.4%. Among all eligible patients (n = 175), there was no survival difference (P = 0.67) in those having second look (57.3%, 5-year survival) versus no second look (48.7%). In those patients with optimal primary cytoreduction (n = 118), there was no survival advantage to second look (69% versus 61%, P = 0.7). However, in those with suboptimal primary cytoreduction (n = 47), 5-year survival was 36% in those having second look versus only 13% in those refusing second look (P < 0.05). Multivariate analysis identified second-look surgery as the only significant independent prognostic variable affecting survival (RR = 0.321, P < 0.04). Patients with suboptimal debulking at primary surgery for stage III ovarian cancer appear to achieve a survival benefit from second-look surgical procedures, presumably from the early identification and treatment of residual disease.

Predicting protected sexual behaviour using the Information-Motivation-Behaviour skills model among adolescent substance abusers in court-ordered treatment.

The Information-Motivation-Behavioural skills model (Fisher & Fisher, 1992) was used to predict condom use among adolescents residing in a court-ordered inpatient substance abuse treatment programme (N = 271; 181 male and 90 female, primarily of minority ethnicity). In a predictive structural equation model, demographic variables, HIV transmission knowledge, and motivational variables of pro-condom norms and attitudes, and perceived susceptibility predicted condom use skills and condom use self-efficacy. Along with the other variables in the model, condom skills and condom self-efficacy were hypothesized to predict condom use over a three-month period. It was found that condom skills were predicted by greater age, pro-condom attitudes and greater perceived susceptibility. Condom self-efficacy was predicted by gender, pro-condom norms and condom attitudes. Condom use was significantly predicted by pro-condom norms and stronger condom self-efficacy. Both condom skills and knowledge did not significantly predict condom use. Significant demographic predictors of condom use included greater age and gender. Results suggest that changing personal attitudes about condoms and reinforcing the power of pro-condom beliefs among significant others will encourage condom use among adolescents who are at high risk for HIV and other STDs.

Redo carotid endarterectomy versus primary carotid endarterectomy.

BACKGROUND AND PURPOSE: Several authorities have recently advocated carotid stenting for recurrent carotid stenosis because of the perception that redo surgery has a higher complication rate than primary carotid endarterectomy (CEA). This study compares the early and late results of reoperations versus primary CEA. METHODS: All reoperations for recurrent carotid stenosis performed during a recent 7-year period by a single vascular surgeon were compared with primary CEA. Because all redo CEAs were done with polytetrafluoroethylene (PTFE) or vein patch closure, we only analyzed those primary CEAs that used the same patch closures. A Kaplan-Meier life-table analysis was used to estimate stroke-free survival rates and freedom from >/=50% recurrent stenosis. RESULTS: Of 547 primary CEAs, 265 had PTFE or saphenous vein patch closure, and 124 reoperations had PTFE or vein patch closure during the same period. Both groups had similar demographic characteristics. The indications for reoperation and primary CEA were symptomatic stenosis in 78% and 58% of cases and asymptomatic >/=80% stenosis in 22% and 42% of cases, respectively (P<0.001). The 30-day perioperative stroke and transient ischemic attack rates for reoperation and primary CEA were 4.8% versus 0.8% (P=0.015) and 4% versus 1.1%, respectively, with no perioperative deaths in either group. Cranial nerve injury was noted in 17% of reoperation patients versus 5.3% of primary CEA patients; however, most of these injuries were transient (P<0.001). Mean hospital stay was 1.8 days for reoperation versus 1.6 days for primary CEA. Cumulative rates of stroke-free survival and freedom from >/=50% recurrent stenosis for reoperation and primary CEA at 1, 3, and 5 years were 96%, 91%, and 82% and 98%, 96%, and 95% versus 94%, 92%, and 91% and 98%, 96%, and 96%, respectively (no significant differences). CONCLUSIONS: Reoperation carries higher perioperative stroke and cranial nerve injury rates than primary CEA. However, reoperations are durable and have stroke-free survival rates that are similar to primary CEA. These considerations should be kept in mind when carotid stenting is recommended instead of reoperation.

Unusual paranasal sinus tumors in two patients with common nasal complaints.

Common nasal complaints are managed by both the otolaryngologist and the primary care physician. We describe the cases of two patients with nasal obstruction who were referred to us for evaluation--one with severe headache and the other with profuse epistaxis. Their histories prior to referral included long-term, common rhinologic complaints of low-grade headache and mild epistaxis. Neither patient had been referred to us until their symptoms had become severe. Our examination revealed that both patients had rare paranasal sinus pathology. One patient had a fibroxanthoma of the frontal sinus, and the other had extramedullary hematopoiesis of the maxillary sinus. Fibroxanthoma of the frontal sinus is rare, and extramedullary hematopoiesis of the maxillary sinus has not been previously reported. These two unique cases serve as a reminder that long-term common rhinologic complaints can occasionally be a sign of life-threatening pathology and require a full evaluation by an otolaryngologist.

Substance-abusing adolescents at varying levels of HIV risk: psychosocial characteristics, drug use, and sexual behavior.

PURPOSE: To evaluate the relationship of various psychosocial factors on HIV sexual risk behavior in a sample of 169 "inner city" male and female adolescents mandated into in court-ordered substance abuse treatment. METHOD: The Millon Adolescent Clinical Inventory (MACI) and measures of sexual behavior, condom attitudes and skills, HIV knowledge, and substance abuse were administered. Data were evaluated according to five HIV risk groups: abstinent (n = 37); monogamous and practicing only protected sex (n = 19); monogamous and practicing unprotected sex (n = 45); multiple partners and practicing only protected sex (n = 11); and multiple partners and having only unprotected sex (n = 57). RESULTS: Significant main effects were found for impulsive propensity, submissiveness, marijuana and alcohol use, condom attitudes, and intentions to engage in safer sex. Protective behavior was directly associated with submissiveness and inversely associated with impulsive personality profiles, with increased marijuana use emerging as a significant predictive factor in the choice for sexual activity vs. abstinence. More alcohol use was predictive of choosing multiple partners vs. monogamy. IMPLICATIONS: Factoring risk variation into the design of HIV psychosocial research may enhance the tailoring of effective prevention strategies.

Effects of a cognitive-behavioral HIV prevention intervention among HIV negative male substance abusers in VA residential treatment.

This investigation compared the effectiveness of a cognitive-behavioral HIV risk reduction intervention with a standard care (SC) comparison condition in modifying HIV risk related knowledge, beliefs, attitudes, and behavior at 6-month and 12-month follow-ups among 149 HIV seronegative males. The two intervention conditions were administered while participants were in inpatient alcohol and other drug abuse treatment. Global drug abuse severity, as well as injection drug abuse, decreased significantly from preintervention to follow-up across conditions. There were significant increases in the proportions reporting sexual activity and increases in levels of unprotected sex acts between baseline and follow-up across conditions. However, no changes in sex risk behavior were found among those who reported sexual activity both prior to and after intervention across conditions. Participants revealed relatively adequate knowledge regarding HIV and HIV risk reduction practices, strong belief in the utility of safer practices and in their ability to enact such practices, and relatively strong commitment to practice safer sex across conditions at baseline assessment. In general, substantial postintervention improvements over baseline levels in these areas were not found. Relatively modest changes in sexual self-efficacy and in safe-sex guidelines were identified in analyses involving the total sample. Exploratory subgroup analysis suggested increases in knowledge and reductions in susceptibility and anxiety among those who reported sexual activity both prior to and after intervention. Among participants reporting initiation of sexual activity after intervention, those receiving SC revealed changes in perceived susceptibility and in condom attitudes. A discussion is presented of challenges associated with providing meaningful HIV risk reduction intervention when baseline levels of sex risk behavior, perceived HIV infection susceptibility, and HIV anxiety are only moderate and when initial levels of sexual self-efficacy and commitment are relatively high.

Prostaglandin endoperoxide H synthase expression in human thyroid epithelial cells.

KAT-50, an established human thyrocyte cell line, expresses constitutively high levels of prostaglandin endoperoxide H synthase-2 (PGHS-2), the inflammatory cyclooxygenase. Here, we examine primary human thyrocytes. We find that they, too, express PGHS-2 mRNA and protein under control culture conditions. A substantial fraction of the basal prostaglandin E(2) (PGE(2)) produced by these cells can be inhibited by SC-58125 (5 microM), a PGHS-2-selective inhibitor. Interleukin (IL)-1beta (10 ng/ml) induces PGHS-2 expression and PGE(2) production in primary thyrocytes. The induction of PGHS-2 and PGE(2) synthesis by IL-1beta could be blocked by glucocorticoid treatment. Unlike KAT-50, most of the culture strains also express PGHS-1 protein. Our observations suggest that both cyclooxygenase isoforms may have functional roles in primary human thyroid epithelial cells, and PGHS-2 might predominate under basal and cytokine-activated culture conditions.