Sulfhemoglobinemia in a 53-Year-Old With a History of Phenazopyridine Misuse.

Sulfhemoglobin is formed by the irreversible bonding of sulfur atoms to the heme molecule. Oxygen is then unable to bind the heme molecule, rendering the hemoglobin molecule unable to carry oxygen. The most common etiology of sulfhemoglobinemia is the use/misuse of sulfur-containing medications such as AZO. Unlike methemoglobin, sulfhemoglobin, due to its irreversible binding, has no antidote, and the treatment is ultimately supportive. We present a case of a 53-year-old female who presented to the emergency room endorsing dysuria and was noted to have abnormally low oxygen saturation (SpO2) despite having high arterial oxygen pressure (PaO2) on blood gas. History was significant for dysuria developed while traveling and the use of over-the-counter AZO four times daily for the past 10 days. She was diagnosed with a presumed dyshemoglobinemia and, upon return of send-out labs, was confirmed to have sulfhemoglobinemia attributed to phenazopyridine. This case highlights the importance of the recognition of potential dyshemoglobinemias and consideration of sulfhemoglobinemia as a potential causative etiology, especially in patients taking sulfur-containing medications.

Whole-Exome Sequencing Analyses Support a Role of Vitamin D Metabolism in Ischemic Stroke.

BACKGROUND: Ischemic stroke (IS) is a highly heritable trait, and genome-wide association studies have identified several commonly occurring susceptibility risk loci for this condition. However, there are limited data on the contribution of rare genetic variation to IS. METHODS: We conducted an exome-wide study using whole-exome sequencing data from 152 058 UK Biobank participants, including 1777 IS cases. We performed single-variant analyses for rare variants and gene-based analyses for loss-of-function and deleterious missense rare variants. We validated these results through (1) gene-based testing using summary statistics from MEGASTROKE-a genome-wide association study of IS that included 67 162 IS cases and 454 450 controls, (2) gene-based testing using individual-level data from 1706 IS survivors, including 142 recurrent IS cases, enrolled in the VISP trial (Vitamin Intervention for Stroke Prevention); and (3) gene-based testing against neuroimaging phenotypes related to cerebrovascular disease using summary-level data from 42 310 UK Biobank participants with available magnetic resonance imaging data. RESULTS: In single-variant association analyses, none of the evaluated variants were associated with IS at genome-wide significance levels (P<5×10-8). In the gene-based analysis focused on loss-of-function and deleterious missense variants, rare genetic variation at CYP2R1 was significantly associated with IS risk (P=2.6×10-6), exceeding the Bonferroni-corrected threshold for 16 074 tests (P<3.1×10-6). Validations analyses indicated that CYP2R1 was associated with IS risk in MEGASTROKE (gene-based test, P=0.003), with IS recurrence in the VISP trial (gene-based test, P=0.001) and with neuroimaging traits (white matter hyperintensity, mean diffusivity, and fractional anisotropy) in the UK Biobank neuroimaging study (all gene-based tests, P<0.05). CONCLUSIONS: Because CYP2R1 plays an important role in vitamin D metabolism and existing observational evidence suggests an association between vitamin D levels and cerebrovascular disease, our results support a role of this pathway in the occurrence of IS.

Polygenic Susceptibility to Hypertension and Blood Pressure Control in Stroke Survivors.

BACKGROUND AND OBJECTIVES: Blood pressure (BP) is often not at goal in stroke survivors, leaving individuals vulnerable to additional vascular events. Given that BP is a highly heritable trait, we hypothesize that a higher polygenic susceptibility to hypertension (PSH) leads to worse BP control in stroke survivors. METHODS: We conducted a study within the UK Biobank evaluating persons of European ancestry who survived an ischemic or hemorrhagic stroke. To model the PSH, we created polygenic risk scores (PRSs) for systolic and diastolic BP using 732 genetic variants. We divided the PRSs into quintiles and used linear/logistic regression to test whether higher PSH led to higher observed BP, uncontrolled BP (systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg), and resistant BP (uncontrolled BP despite being on ≥3 antihypertensive drugs). We conducted an independent replication using data from the Vitamin Intervention for Stroke Prevention (VISP) trial. RESULTS: We analyzed 5,940 stroke survivors. When comparing stroke survivors with very low vs very high PSH, the mean systolic BP was 137 (SD 18) vs 143 (SD 20, p < 0.001), the mean diastolic BP was 81 (SD 10) vs 84 (SD 11, p < 0.001), the prevalence of uncontrolled BP was 42.8% vs 57.2% (p < 0.001), and the prevalence of resistant hypertension was 3.9% vs 11% (p < 0.001). Results remained significant using multivariable models (p < 0.001) and were replicated in the VISP study (all tests with p < 0.05). DISCUSSION: A higher PSH is associated with worse BP control in stroke survivors. These findings point to genetic predisposition as an important determinant of poorly controlled BP in this population.

Shingles: a harbinger of chronic HIV infection.

Early diagnosis and treatment are essential to reduce the risk of community transmission and morbidity and mortality of individuals infected with HIV. A 49-year-old woman presented with a painful, vesicular rash on the left side of her neck after being treated with valacyclovir for a separate perianal rash. She admitted recent weight loss and diffuse lymphadenopathy. She reported one family member with HIV but denied intravenous drug use or recently new sexual partners. Serum HIV-1 antibody screen was positive. Herpes zoster reactivation is associated with waning immunity in chronic HIV and should prompt testing. Delays in treatment impacts short-term and long-term prognosis for patients infected with HIV.

Sex difference in initial thermoregulatory response to dehydrated exercise in the heat.

Although it is well established that dehydration has a negative impact on thermoregulation during exercise in the heat, it is unclear whether this effect of dehydration is different between men and women, or across the phases of the menstrual cycle (MC). Twelve men and seven women (men: 20 ± 2 years, 70.13 ± 10.5 kg, 173.4 ± 6.0 cm, 54.2 ± 8.6 ml kg-1  min-1 ; women: 20 ± 2 years, 57.21 ± 7.58 kg, 161 ± 5 cm, 40.39 ± 3.26 ml kg-1  min-1 ) completed trials either euhydrated (urine specific gravity, USG ≤ 1.020, Euhy) or dehydrated (USG > 1.020, Dehy). Trial order was randomized and counterbalanced; men completed two trials (MEuhy and MDehy) and women completed four over two MC phases (late follicular: days 10-13, FDehy, FEuhy; midluteal: days 18-22, LDehy, LEuhy). Each trial consisted of 1.5 h, split into two 30 min blocks of exercise (B1 and B2, 15 min at 11 W/kg & 15 min at 7 W/kg) separated by 15 min rest in between and after. Rectal temperature (Tre ) was measured continuously and estimated sweat loss was calculated from the body mass measured before and after each block of exercise. When dehydrated, the rate of rise in Tre was greater in women in the first block of exercise compared to men, independently of the MC phase (MDehy: 0.03 ± 0.03°C/min, FDehy: 0.06 ± 0.02, LDehy: 0.06 ± 0.02, p = 0.03). Estimated sweat loss was lower in all groups in B1 compared to B2 when dehydrated (p < 0.05), with no difference between sexes for either hydration condition. These data suggest that women may be more sensitive to the negative thermoregulatory effects of dehydration during the early stages of exercise in the heat.

Mineral and Heavy Metal Composition of Oil Shale Ash from Oxyfuel Combustion.

Oxyfuel combustion can reduce CO2 emissions from fossil fuels. Hence, it is currently being investigated for potential use in oil shale-fired power plants, which currently produce most of Estonia's electricity. Here, experiments were performed with kukersite oil shale for both oxyfuel and conventional combustion in a 60 kWth circulating fluidized bed combustor. In this paper, we provide data on the ash composition including mineral compositions and heavy metal concentrations. Oxyfuel conditions did not noticeably influence the concentrations of heavy metals in the ash but did have significantly lower amounts of free lime because of inhibition of the carbonate decomposition reactions. The results suggest that oxyfuel combustion would produce no significant problems in terms of the behavior of the ash or the fate of heavy metals contained in the ash.

Evaluation of an Online Educational Intervention to Increase Knowledge and Self-efficacy in Disaster Responders and Critical Care Transporters Caring for Individuals with Developmental Disabilities.

OBJECTIVE: Disability-related education is essential for disaster responders and critical care transporters to ensure positive patient outcomes. This pilot study evaluated the effect of an online educational intervention on disaster responders and critical care transporters' knowledge of and feelings of self-efficacy about caring for individuals with developmental disabilities. METHODS: A 1-group, pretest-posttest, quasi-experimental design was used. A convenience sample of 33 disaster responders and critical care transporters participated. RESULTS: Of the 33 participants, only 24% had received prior education on this topic, and 88% stated that such education would be beneficial to their care of patients. Nineteen participants completed both the pretest and posttest, and overall performance on knowledge items improved from 66% correct to 81% correct. Self-efficacy for caring for developmentally disabled individuals improved, with all 10 items showing a statistically significant improvement. CONCLUSION: Online education is recommended to improve the knowledge and self-efficacy of disaster responders and critical care transporters who care for this vulnerable population after disasters and emergencies. (Disaster Med Public Health Preparedness. 2019;13:677-681).

Chondral Lesions of the Hip.

The treatment of chondral hip injuries is challenging. However, for young patients with hip disorders, orthopedic surgeons now have the opportunity to intervene early in the development of debilitating joint disease. As understanding of the hip joint continues to evolve, more effective treatment strategies are emerging. There are several reportedly successful options for surgical treatment. This article reviews the clinical presentation of chondral injuries and the surgical modalities, arthroscopic and open, available to treat them.

Inflated applicants: attribution errors in performance evaluation by professionals.

When explaining others' behaviors, achievements, and failures, it is common for people to attribute too much influence to disposition and too little influence to structural and situational factors. We examine whether this tendency leads even experienced professionals to make systematic mistakes in their selection decisions, favoring alumni from academic institutions with high grade distributions and employees from forgiving business environments. We find that candidates benefiting from favorable situations are more likely to be admitted and promoted than their equivalently skilled peers. The results suggest that decision-makers take high nominal performance as evidence of high ability and do not discount it by the ease with which it was achieved. These results clarify our understanding of the correspondence bias using evidence from both archival studies and experiments with experienced professionals. We discuss implications for both admissions and personnel selection practices.

Correspondence bias in performance evaluation: why grade inflation works.

Performance (such as a course grade) is a joint function of an individual's ability (such as intelligence) and the situation (such as the instructor's grading leniency). Prior research has documented a human bias toward dispositional inference, which ascribes performance to individual ability, even when it is better explained through situational influences on performance. It is hypothesized here that this tendency leads admissions decisions to favor students coming from institutions with lenient grading because those students have their high grades mistaken for evidence of high ability. Three experiments show that those who obtain high scores simply because of lenient grading are favored in selection. These results have implications for research on attribution because they provide a more stringent test of the correspondence bias and allow for a more precise measure of its size. Implications for university admissions and personnel selection decisions are also discussed.

Latent autoimmune diabetes in the young.

This case represents latent autoimmune diabetes in the young (LADY), and demonstrates that autoimmune diabetes can be slowly progressive even in younger patients with insulin independency period lasting for more than two years.

Changes in interface pressures and shear stresses over time on trans-tibial amputee subjects ambulating with prosthetic limbs: comparison of diurnal and six-month differences.

For trans-tibial amputees maintenance over time of a quality fit of the prosthesis to the residual limb is an important clinical challenge. The purpose of this research was to compare diurnal and long-term (5 weeks to 6 months) interface stress changes as well as variance in the change in cross-sectional area down the length of the residual limb. If long-term changes were simply accentuated diurnal fluctuations then this result would suggest similar treatment methods should be used for both conditions. Interface pressures and shear stresses at 13 sites and residual limb shape were measured on eight trans-tibial amputee subjects using patellar-tendon-bearing prostheses. Data were collected at diurnal intervals (within the same day at least 5 h apart) as well as at long-term intervals (5, 10, 15, 20, and 25 weeks apart). Absolute diurnal interface stress changes were not significantly different from those at 5-weeks intervals but were significantly smaller than those at 15, 20, and 25-weeks intervals. Mean interface stress changes increased significantly (p<0.05) for increased session-to-session intervals. Variance of the change in cross-sectional area down the length of the residual limb was significantly smaller for diurnal intervals than for 6-months intervals, indicating that long-term changes were more localized than diurnal changes. These results indicate that long-term changes are not simply accentuated diurnal fluctuations, suggesting that different treatment methods should be used to treat each condition.

Relative influence of polymer fiber diameter and surface charge on fibrous capsule thickness and vessel density for single-fiber implants.

Single polypropylene microfibers plasma-coated with polymers of different surface charge [N,N-dimethylaminoethyl methacrylate (NN) (positive charge), methacrylic acid (MA) (negative charge), and hexafluoropropylene (HF) (neutral)] were implanted in the subcutaneous dorsum of Sprague-Dawley rats for 5-week intervals. Thee groups of fiber diameters were used: (I) 1.0 to 5.9 microm; (II) 6.0 to 10.9 microm; and (III) 11.0 to 15.9 microm. Fibrous capsule thickness and blood-vessel density (number of vessels within 100 microm of the fiber) were assessed in tissue sections in the planes of microfiber cross-sections. Results from a multifactorial analysis of variance demonstrated statistically significant main effects (p < 0.05) for microfiber diameter but not for surface-charge coating. The mean differences in capsule thickness among the microfiber diameter groups were: between groups II and I: 5.4 microm; between groups III and I: 10.2 microm; and between groups III and II: 4.7 microm. The mean differences in capsule thickness among surface-charge coatings were: between MA and NN: 0.7 microm; between MA and HF: 1.4 microm; and between NN and HF: 0.7 microm. Many of the 1.0 to 5.9 microm-in-diameter fibers had no capsule and no sign of a foreign-body reaction. For the vessel density analysis, neither microfiber diameter nor surface-charge coating had a statistically significant effect. Thus the geometric feature of microfiber diameter was more important than was surface charge relative to fibrous capsule formation but not relative to local vessel density. This ranking of the relative influence of design features in relation to tissue response provides useful information for prioritization in biomaterial design.

Evaluation of ventilator-associated lower respiratory tract infection and tracheobronchial aspiration of gastrointestinal contents.

STUDY OBJECTIVE: Ventilator-associated lower respiratory tract infection (LRTI) in a set up of respiratory intensive care unit was evaluated. Also the incidence of tracheobronchial aspiration of gastrointestinal contents was explored among these patients. DESIGN: Twenty eight patients admitted in the respiratory intensive care unit of referral teaching hospital were studied. All patients were evaluated for tracheobronchial aspiration of gastrointestinal contents in the initial 48 hours of initiating mechanical ventilation using methylene blue as marker and glucostix reagent strip. Protected endotracheal aspirate was secured after 48 hours of beginning of mechanical ventilation and was submitted for microbiological assay. RESULTS: Of the 28 mechanically ventilated patients, 82% were found to have developed LRTI. Aerobic gram-negative bacilli accounted for 79% of the infections, Klesiella responsible for 39% while Pseudomonas and Escherichia accounted for 18% each. The remaining 4% were caused by Acinetobacter. Gram-positive cocci were responsible for 21% of infection with Staphylococcus and enterococci 14% and 7% respectively. Tracheobronchial aspiration of GI contents was found to be present in 72% of the patients which was significantly correlated with the incidence of LRTI (p=0.014). Significant association was also found between the incidence of LRTI and mortality (p=0.05). CONCLUSION: The incidence of gastrointestinal aspiration was found to be high and correlation with LRTI was significant. Both glucostix reagent strip and methylene blue were observed to have same positivity rate.

Interface pressure and shear stress changes with amputee weight loss: case studies from two trans-tibial amputee subjects.

Interface pressures and shear stresses were measured at monthly intervals on two trans-tibial amputee subjects who lost more than 12% of their body weight over the course of the study. For one subject interface pressures and shear stresses during the weight-acceptance phase of gait decreased over the study interval at all 13 sites monitored, while the other subject experienced increased pressures distally but decreased pressures proximally. Subjects' stumps appeared to atrophy over the study interval, increasing distal end and patellar tendon loading, but not increasing interface shear stresses at other locations. Adding socks at the end of the study did not return interface pressures to first session values at all sites. It is expected that local stump shape changes occurred, causing a non-uniform change in interface stress patterns.

Influence of different biodegradable carriers on the in vivo behavior of human adipose precursor cells.

The correction of soft-tissue defects presents a challenge in plastic and reconstructive surgery. The implantation of isolated and culture-expanded adipose precursor cells is a solution to this problem because these cells differentiate into adipocytes when implanted in vivo. Appropriate scaffolds are needed in soft-tissue engineering to allow the differentiation of precursor cells. The optimal carrier needs to be defined. In this study, human preadipocytes were isolated and cultured. Three different carrier materials were seeded with 106 preadipocytes each and implanted in 42 nude mice. Sponges and nonwoven carriers based on hyaluronic acid modified by esterification (HYAFF 11) were compared with collagen sponges. Scaffolds without cells served as negative controls in the same animal. After 3 and 8 weeks, the grafts were explanted. Macroscopic appearance, weight, thickness, microscopy, immunohistochemistry, and TEM (scaffold structure, cellularity, penetration depth of the seeded cells, vascularization) were assessed and evaluated for differences in scaffold-cell interactions.Preadipocytes differentiated earlier in vitro when attached to HYAFF 11 scaffolds than to other carrier materials. Macroscopically, all preadipocyte constructs were yellowish and well vascularized, and the controls were white and avascular. Vessel formation was more pronounced around mature adipocytes. Microscopically, HYAFF 11 constructs showed a higher cell density than collagen constructs. The pores of the sponges contained more differentiated adipocytes than the nonwoven carriers, whereas the undifferentiated preadipocytes were more numerous in the nonwoven material. Penetration of adipose precursor cells was deeper and more homogeneous in HYAFF 11 scaffolds. Electron microscopy demonstrated well-differentiated adipocytes and large amounts of extracellular matrix in HYAFF 11 sponges.HYAFF 11 sponges supported the expansion and differentiation of the adipose precursor cells. This carrier is superior to the nonwoven carrier with regard to adipocyte differentiation and superior to the collagen sponge with regard to cellularity. This is a promising method for the reconstruction of soft-tissue defects. Modifications of the scaffold (larger pore size and coating with adipogenic factors) will be examined in further experiments.

Standing interface stresses as a predictor of walking interface stresses in the trans-tibial prosthesis.

Interface pressures and shear stresses within the socket, in standing and walking, were measured for two unilateral, male, trans-tibial amputee subjects, during two sessions each. The ratios of equal weight-bearing standing stresses to peak walking stresses showed regional variation, ranging from 0.24:1 for pressure over the anterior region to 1.01:1 for resultant interface shear stress over the lateral region. Interface stresses in standing were only moderate predictors of peak walking stresses. The best correlation coefficient between standing in full weight-bearing and peak walking stress was 0.88 for pressure over the lateral region. As the amputees progressed from minimal to full weight-bearing in standing, and then to walking, the interface stresses increased in a nonlinear fashion, consistent with the assumption that the anterior tibia provides much resistance to the bending moment in the sagittal plane during walking.

Human preadipocytes seeded on freeze-dried collagen scaffolds investigated in vitro and in vivo.

Currently, there is no adequate implant material for the correction of soft tissue defects such as after extensive deep burns, after tumor resection and in hereditary and congenital defects (e.g. Romberg's disease, Poland syndrome). The autologous transplantation of mature adipose tissue has poor results. In this study human preadipocytes of young adults were isolated and cultured. 10(6) preadipocytes were seeded onto collagen sponges with uniform 40 microm pore size and regular lamellar structure and implanted into immunodeficient mice. Collagen sponges without preadipocytes were used in the controls. Macroscopical impression, weight, thickness, histology, immunohistochemistry (scaffold structure, cellularity, penetration depth of the seeded cells) and ultrastructure were assessed after 24 h in vitro and after explantation at 3 and 8 weeks. Preadipocytes penetrated the scaffolds 24 h after seeding at a depth of 299+/-55 microm before implantation. Macroscopically after 3 and 8 weeks in vivo layers of adipose tissue accompanied by new vessels were found on all preadipocyte/collagen grafts. The control grafts appeared unchanged without vessel ingrowth. There was a significant weight loss of all grafts between 24 h in vitro and 3 weeks in vivo (p < 0.05), whereas there was only a slight weight reduction from week 3 to 8. The thickness decreased in the first 3 weeks (p < 0.05) in all grafts. The preadipocyte/collagen grafts were thinner but had a higher weight than the controls at this point in time. The histology showed adipose tissue and a rich vascularisation adherent to the scaffolds under a capsule. The control sponges contained only few cells and a capsule but no adipose tissue. Human-vimentin positive cells were found in all preadipocyte/collagen grafts but not in the controls, penetrating 1188+/-498 microm (3 weeks) and 1433+/-685 microm (8 weeks). Ultrastructural analysis showed complete in vivo differentiation of viable adipocytes in the sponge seeded with preadipocytes. Formation of extracellular matrix was more pronounced in the preadipocyte/collagen grafts. The transplantation of isolated and cultured preadipocytes within a standardised collagen matrix resulted in well-vascularised adipose-like tissue. It is assumed that a pore size greater than 40 microm is required, as preadipocytes enlarge during differentiation due to incorporation of lipids.