Miller Fisher syndrome and COVID-19: is there a link?

Beyond the typical respiratory symptoms and fever associated with severe acute respiratory syndrome, we may still have much to learn about other manifestations of the novel SARS-CoV-2 infection. A patient presented with Guillain-Barré syndrome in China with a concurrent SARS-CoV-2 infection. The following case report looks at a patient presenting with the rare Miller Fisher syndrome, a variant of Guillain-Barré while also testing positive for COVID-19.

Discovery and Characterization of Bacteriophage LuckyBarnes.

Here, we report the genome sequence of LuckyBarnes, a newly isolated singleton siphovirus that infects Brevibacterium iodinum ATCC 15728 and has a 50,774-bp genome with 67 predicted genes.

Aberrant RNA splicing is the major pathogenic effect in a knock-in mouse model of the dominantly inherited c.1430A>G human RPE65 mutation.

Human RPE65 mutations cause a spectrum of retinal dystrophies that result in blindness. While RPE65 mutations have been almost invariably recessively inherited, a c.1430A>G (p.(D477G)) mutation has been reported to cause autosomal dominant retinitis pigmentosa (adRP). To study the pathogenesis of this human mutation, we have replicated the mutation in a knock-in (KI) mouse model using CRISPR/Cas9-mediated genome editing. Significantly, in contrast to human patients, heterozygous KI mice do not exhibit any phenotypes in visual function tests. When raised in regular vivarium conditions, homozygous KI mice display relatively undisturbed visual functions with minimal retinal structural changes. However, KI/KI mouse retinae are more sensitive to light exposure and exhibit signs of degenerative features when subjected to light stress. We find that instead of merely producing a missense mutant protein, the A>G nucleotide substitution greatly affects appropriate splicing of Rpe65 mRNA by generating an ectopic splice site in comparable context to the canonical one, thereby disrupting RPE65 protein expression. Similar splicing defects were also confirmed for the human RPE65 c.1430G mutant in an in vitro Exontrap assay. Our data demonstrate that a splicing defect is associated with c.1430G pathogenesis, and therefore provide insights in the therapeutic strategy for human patients.

Antibiotic Tissue Penetration in Diabetic Foot Infections A Review of the Microdialysis Literature and Needs for Future Research.

Although many antimicrobial agents display good in vitro activity against the pathogens frequently implicated in diabetic foot infections, effective treatment can be complicated by reduced tissue penetration in this population secondary to peripheral arterial disease and emerging antimicrobial resistance, which can result in clinical failure. Improved characterization of antibiotic tissue pharmacokinetics and penetration ratios in diabetic foot infections is needed. Microdialysis offers advantages over the skin blister and tissue homogenate studies historically used to define antibiotic penetration in skin and soft-tissue infections by defining antibiotic penetration into the interstitial fluid over the entire concentration versus time profile. However, only a select number of agents currently recommended for treating diabetic foot infections have been evaluated using these methods, which are described herein. Better characterization of the tissue penetration of antibiotic agents is needed for the development of methods for maximizing the pharmacodynamic profile of these agents to ultimately improve treatment outcomes for patients with diabetic foot infections.

Hepcidin and iron status among pregnant women in Bangladesh.

Although hepcidin, a recently discovered peptide hormone, is considered a major regulator of iron metabolism and anemia in chronic inflammation, its role in anemia during pregnancy has not been characterized. Our objective was to characterize the role of hepcidin in anemia during pregnancy. We examined the relationships between urinary hepcidin, iron status indicators, hemoglobin, erythropoietin, alpha-1 acid glycoprotein, and C-reactive protein in a cross-sectional study conducted among 149 pregnant rural Bangladeshi women with biospecimens obtained during home visits. Urinary hepcidin was measured using surface-enhanced laser desorption/ ionization time-of-flight mass spectrometry. Urinary hepcidin, as log(intensity per mmol/L creatinine), was correlated with log ferritin (r = 0.33, p <0.001), the transferrin receptor index (r = -0.22, p = 0.007), and log alpha-1 acid glycoprotein (r = 0.20, p = 0.01), but not hemoglobin (r = 0.07, p= 0.40), log transferrin receptor (r = -0.07, p = 0.41), log erythropoietin (r = -0.01, p = 0.88) or log C-reactive protein (r = 0.06, p = 0.48). The strength of the relationship between hepcidin and ferritin was maintained in multiple linear regression analyses after enhancing the sample with data from women selected for low iron stores (n = 41). Among pregnant women in a community-based study in rural Bangladesh, urinary hepcidin levels were related to iron status and AGP but not hemoglobin, erythropoietin, or C-reactive protein.

Low plasma selenium concentrations and mortality among older community-dwelling adults: the InCHIANTI Study.

AIMS: We examined the relationship between plasma selenium levels at enrollment and all-cause mortality over a 6-year period among participants in the InCHIANTI study. METHODS: 1042 men and women > or =65 years from the InCHIANTI study, a population- based study of older adults living in the Chianti region of Tuscany, a population-based cohort in Tuscany, Italy. Plasma selenium was measured at enrollment (1998-2000), and vital status was ascertained until May 2006. RESULTS: During follow-up, 237 participants (22.7%) died. At enrollment, mean (SD) plasma selenium concentrations among participants who survived or died were 0.96 (0.14) and 0.87 (0.18) micromol/L (p<0.0001), respectively. The proportion of participants who died, from lowest to highest quartile of selenium, was 41.3, 27.0, 18.1 and 13.5% (p<0.0001 by Mantel-Haenszel chi-square). After adjusting for age, sex, education, and chronic diseases, adults in the lowest quartile of plasma selenium at enrollment had higher mortality compared with those in the highest quartile (Hazard Ratio (HR) 1.60, 95% Confidence Interval (CI) 1.04-2.47, p=0.034). CONCLUSION: Low plasma selenium may be an independent predictor of mortality among older adults living in the community.

Association of low plasma selenium concentrations with poor muscle strength in older community-dwelling adults: the InCHIANTI Study.

BACKGROUND: Although selenium plays an important role in muscle function, the relation between circulating selenium and muscle strength in elderly adults has not been characterized. OBJECTIVE: The objective was to examine the hypothesis that low plasma selenium is associated with poor muscle strength in older adults. DESIGN: We measured plasma selenium and hip, grip, and knee strength in a cross-sectional study of 891 men and women aged >or=65 y from the Invecchiare in Chianti (InCHIANTI) Study, a population-based cohort study in Tuscany (Italy). Poor muscle strength was defined as the lowest quartile of hip flexion, grip, and knee extension strength. RESULTS: Overall, mean (+/-SD) plasma selenium was 0.95 +/- 0.15 mumol/L. After adjustment for age, sex, education, total energy intake, body mass index, and chronic disease, participants in the lowest versus the highest quartile of plasma selenium were at higher risk of poor hip strength [odds ratio (OR): 1.69; 95% CI: 1.02, 2.83; P = 0.04, P for linear trend = 0.04], knee strength (OR: 1.94; 95% CI: 1.18, 3.19; P = 0.009, P for linear trend = 0.01), and grip strength (OR: 1.94; 95% CI: 1.19, 3.16; P = 0.008, P for linear trend = 0.08). CONCLUSIONS: Low plasma selenium is independently associated with poor skeletal muscle strength in community-dwelling older adults in Tuscany.

Soluble transferrin receptor as an indicator of iron deficiency in HIV-infected infants.

BACKGROUND: Iron deficiency is common in human immunodeficiency virus (HIV)-infected infants in sub-Saharan Africa. It is not known whether soluble transferrin receptor (sTfR) is a good indicator of iron deficiency in infants with HIV. METHODS: We evaluated sTfR as an indicator of iron deficiency in 134 HIV-infected 9-month-old infants in Kampala, Uganda. Ferritin <12 microg/L and microcytic, hypochromic anaemia were used as indicators of iron deficiency, respectively. The presence of inflammation was indicated by C-reactive protein >5 mg/L or alpha1-acid glycoprotein >1 g/L. RESULTS: Receiver operator characteristic curves showed that the area under the curve was 0.67 when sTfR receptor was compared with low ferritin and 0.71 when sTfR was compared with microcytic, hypochromic anaemia. The appropriate calculated cut-offs of sTfR >3.74 microg/mL (43.98 nmol/L) and >3.53 microg/mL (41.55 nmol/L) show adequate specificities of 60% and sensitivities of 63% and 69% for low ferritin and microcytic, hypochromic anaemia, respectively. C-reactive protein and alpha 1-acid glycoprotein were strongly correlated with serum ferritin (r=0.371 and r=0.458, respectively, both p<0.0001) but were not correlated with sTfR (r=0.009 and r= -0.003, respectively, both p=0.9). In all, 78.6% of infants had alpha l-acid glycoprotein >1 g/L and 54.7% had C-reactive protein >5 g/L. CONCLUSIONS: Soluble TfR appears to be an adequate indicator of iron deficiency in HIV-infected infants.

Low Serum Selenium Is Associated with Anemia Among Older Women Living in the Community: the Women's Health and Aging Studies I and II.

Anemia is common among older adults, and a substantial proportion of anemia in the older population is of indeterminate cause. Low selenium levels have been associated with anemia in animals, but this relationship has not been well characterized in humans. The objective was to determine whether low serum selenium concentrations are associated with anemia among older women. We conducted a cross-sectional analysis of participants in the Women's Health and Aging Studies, a population-based sample of women living in the community in Baltimore, MD, USA. Of 632 women, aged 70-79 yr, 14.1% of women were anemic (hemoglobin <120 g/L). The prevalence of anemia among women in the lowest to highest quartile of serum selenium was 22.4%, 14.6%, 11.9% and 6.6%, respectively (p < 0.0001). An increase in loge selenium was associated with a reduced risk of anemia (odds ratio per 1 SD increase = 0.63, 95% confidence interval = 0.47-0.84), adjusting for age, education, chronic diseases, iron status, and serum interleukin-6. We conclude that low serum selenium is independently associated with anemia among older women living in the community.

Low serum selenium and total carotenoids predict mortality among older women living in the community: the women's health and aging studies.

Selenium and the carotenoids play an important role in antioxidant defenses and in the redox regulation involved in inflammation. We tested the hypothesis that low selenium and carotenoids predict mortality in older women living in the community. Women who were enrolled in the Women's Health and Aging Studies I and II in Baltimore, MD (n = 632; 70-79 y old) had serum selenium and carotenoids measured at baseline and were followed for mortality over 60 mo. Median (minimum, maximum) serum selenium and carotenoids were 1.53 (0.73, 2.51) micromol/L and 1.67 (0.13, 9.10) micromol/L; 14.1% of the women died. The 5 major causes of death were heart disease (32.6%), cancer (18.0%), stroke (9.0%), infection (6.7%), and chronic obstructive pulmonary disease (5.6%). Adjusting for age, education, smoking, BMI, poor appetite, and chronic diseases, higher serum selenium [hazard ratio (HR) 0.71, 95% CI 0.56-0.90/1 SD increase in log(e) selenium; P = 0.005] and higher serum total carotenoids (HR 0.77, 95% CI 0.64-0.84/1 SD increase in log(e) total carotenoids; P = 0.009) were associated with a lower risk of mortality. Women living in the community who have higher serum selenium and carotenoids are at a lower risk of death.

Quantitative measures of the effect of the melanocortin 1 receptor on human pigmentary status.

Variation in human hair and skin color is the most striking visible aspect of human genetic variation. The only gene known to exert an effect on pigmentary within the normal population is the melanocortin-1 receptor (MC1R). Previous studies have used a Mendelian framework to relate MC1R genotype to phenotype, by measuring pigmentary status using categorical scales. Such approaches are inadequate. We report results using direct measures of hair color using objective colorimetric dimensions and HPLC determined hair melanins. We have linked MC1R genotype with chemical measures of melanin quantity and type and objective phenotype measures of color. MC1R genotype was predictive of hair melanin expressed as the ratio of the loge of eumelanin to pheomelanin ratio, with a dosage effect evident: MC1R homozygote mean, 1.46; heterozygote, 4.44; and wild type, 5.81 (p<0.001). Approximately 67% of the variance in this model could be accounted for in terms of MC1R genotype. There was also a relation between MC1R status and hair color, most prominently for the b* axis (p<0.001), but also for the a* and L* scales (L*a*b*, CIE). We show for one of the most polymorphic human traits that it is possible to demonstrate meaningful relations between various physical characteristics: DNA sequence diversity, hair-wavelength-specific reflectance patterns, and chemical melanin assays.

Time course of ultraviolet B-induced erythema in people with red hair harbouring homozygous melanocortin 1 receptor mutations.

It has previously been reported that the time course of erythema may be delayed in those with sun-sensitive skin types and those with skin cancer. One molecular explanation for this putative phenotype would be that it is caused by mutations of the melanocortin 1 receptor (MC1R). In the present study of 20 persons, 10 of whom were MC1R homozygous, we measured erythema over a 21-day period in response to a range of ultraviolet B doses using methods that improved on previous studies. We could detect no consistent differences in ultraviolet radiation-induced erythema between the groups studied. The pharmacological mechanisms underpinning such prolonged inflammatory responses merit further investigation.