Femoral neuropathy: A clinical and electrodiagnostic review.

INTRODUCTION/AIMS: Femoral neuropathies can cause severe, prolonged debility, yet there have been few clinical and electrodiagnostic (EDx) studies addressing this condition. The aim of this study was to better understand the etiologies, EDx features, and clinical course of femoral neuropathy. METHODS: We identified patients evaluated at Mayo Clinic Rochester between January 1, 1999 and July 31, 2019, with possible new femoral neuropathy ascertained via International Classification of Diseases-versions 9 and 10 diagnosis codes presenting within 6 months of symptom onset. RESULTS: A retrospective review of 1084 records was performed and we ultimately identified 159 patients with isolated femoral neuropathy for inclusion. The most common femoral neuropathy etiologies were compressive (40%), perioperative stretch (35%), and inflammatory (6%). Presenting symptoms included weakness (96%), sensory loss (73%), and pain (53%). Presenting motor physical exam findings demonstrated moderate weakness (34%) or no activation (25%) of knee extension and mild (32%) or moderate (35%) weakness of hip flexion. Seventy-two percent of patients underwent EDx testing, including 22 with femoral motor nerve conduction studies. Treatment often involved physical therapy (89%) and was otherwise etiology-specific. In patients with follow-up data available (n = 154), 83% had subjective clinical improvement at follow-up with a mean time to initial improvement of 3.3 months and mean time to recovery at final follow-up of 14.8 months. Only 48% of patients had nearly complete or complete recovery. DISCUSSION: In our cohort, the most common etiologies of femoral neuropathy were compression or perioperative stretch with high initial morbidity. Although motor recovery is common, improvement is often prolonged and incomplete.

High-content phenotypic screening identifies novel chemistries that disrupt mosquito activity and development.

New classes of chemistries are needed to control insecticide resistant populations of mosquitoes and prevent transmission of vector-borne diseases (VBDs). Organismal screens of chemical collections have played an important role in the search for new vector insecticides and the identification of active ingredients (AIs) that cause rapid mortality of mosquitoes. Advances in image-based screening offer an opportunity to identify chemistries that operate via novel biochemical modes and investigate the range of phenotypes exhibited by mosquitoes following exposure to lethal and sub-lethal chemical dose. An automated, high throughput phenotypic screen (HTS) employing high-content imaging of first instar (L1) Aedes aegypti larvae was developed to identify chemistries associated with mortality and atypical morphological phenotypes. A pilot screen of the Library of Pharmacologically Active Compounds (LOPAC1280) identified 92 chemistries that disrupted larval activity and development, including conventional insecticides and chemistries known to modulate G protein-coupled receptors (GPCRs) and other molecular targets in mammalian systems. Secondary assay series were used to evaluate a selection of chemistries for impacts on mosquito activity, survival and development. Ritodrine hydrochloride reduced mobility of larvae but had no observable effect on survival and development of mosquitoes. High doses of metergoline suppressed larval activity and sub-lethal dose resulted in pupal mortality. Assay data support the utility of phenotypic screening and diverse entomological end-points for discovery of novel insecticidal chemical scaffolds. The insecticide discovery process must consider how multi-modal efficacy spectra contribute to vector and VBD control.

Management of superior mesenteric venous thrombus in cystic fibrosis related liver disease.

Abdominal pain is a common feature in patients with cystic fibrosis (CF) and CF related liver disease (CFLD). Superior mesenteric venous (SMV) thrombosis is an uncommon but important cause of abdominal pain. Management strategies are complicated by an underlying prothrombotic state and increased risk of bleeding from complications of CF and CFLD. This review addresses clinical presentation, detection and management options of an acute SMV thrombus in the context of CF.

Preserving US microbe collections sparks future discoveries.

Collections of micro-organisms are a crucial element of life science research infrastructure but are vulnerable to loss and damage caused by natural or man-made disasters, the untimely death or retirement of personnel, or the loss of research funding. Preservation of biological collections has risen in priority due to a new appreciation for discoveries linked to preserved specimens, emerging hurdles to international collecting and decreased funding for new collecting. While many historic collections have been lost, several have been preserved, some with dramatic rescue stories. Rescued microbes have been used for discoveries in areas of health, biotechnology and basic life science. Suggestions for long-term planning for microbial stocks are listed, as well as inducements for long-term preservation.

Clinical spectrum of neuropathy after primary total knee arthroplasty: A series of 54 cases.

INTRODUCTION: Neuropathy after total knee arthroplasty (TKA) can cause significant morbidity but is inconsistently reported. METHODS: We reviewed the clinical, electrodiagnostic and perioperative features of all patients who underwent primary TKA at our institution and developed a new neuropathy within 8 weeks postoperatively. RESULTS: Fifty-four cases were identified (incidence 0.37% [95% confidence interval, 0.28-0.49]) affecting the following nerve(s): peroneal (37), sciatic (11), ulnar (2), tibial (2), sural (1), and lumbosacral plexus (1). In all cases with follow-up data, motor recovery typically occurred within 1 year and was complete or near-complete. CONCLUSIONS: Post-TKA neuropathy is uncommon, typically does not require intervention and usually resolves within 1 year. Post-TKA neuropathy most often affects the nerves surgically at risk. Anesthesia type does not correlate with post-TKA neuropathy. An inflammatory etiology for post-TKA neuropathy is rare but should be considered in specific cases. Muscle Nerve 59:679-682, 2019.

Comparison of the 18F-FDG avidity at PET of benign and malignant pure ground-glass opacities: a paradox?

AIM: To determine if pure ground-glass opacities (GGOs) and the subgroup of ground-glass nodules (GGNs) typically demonstrate higher 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) uptake at positron-emission tomography (PET) when benign than when malignant. MATERIALS AND METHODS: Informed consent was waived for this institutional review board (IRB)-approved, Health Insurance Portability and Accountability Act (HIPAA) compliant, retrospective study. A review of all 1,864 combined PET/computed tomography (CT) examinations performed in 2011 on a single system to identify pure GGOs with mean diameter ≥1 cm yielded 166 GGOs. Two blinded subspecialty-trained thoracic radiologists independently assessed GGO size, morphology, attenuation, and location on CT. A blinded nuclear radiologist procured the SUVmax for each GGO. Final diagnosis of malignancy (n=21) was made based on histopathology or upon increased size and attenuation; a final diagnosis of benignity (n=106) was made if GGO resolved, was new within 3 months, evolved in a manner consistent with pulmonary fibrosis, or was stable for ≥60 months; 29 were indeterminate and were excluded, along with 10 cases with unreliable SUVmax measurements, yielding 127 GGOs, of which 68 were GGNs, in 76 patients. RESULTS: The SUVmax was significantly higher in benign than malignant GGOs (p=0.0017) and in the GGN subgroup (p=0.03). A threshold SUVmax >1.5 for GGOs, including GGNs, assured benignity in this cohort. CONCLUSION: Benign GGOs and the benign GGN subgroup demonstrated significantly higher FDG uptake at PET than malignant GGOs/GGNs. Awareness of this finding may prevent misinterpretation of highly 18FDG-avid pure GGOs/GGNs as definitively malignant, which could lead to unnecessary thoracic surgery and its associated risks.

Comparison of 18F-FDG avidity at PET of benign and malignant pure ground-glass opacities: a paradox? Part II: artificial neural network integration of the PET/CT characteristics of ground-glass opacities to predict their likelihood of malignancy.

AIM: To assess the ability of artificial neural networks (ANNs) to predict the likelihood of malignancy of pure ground-glass opacities (GGOs), using observations from computed tomography (CT) and 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) images and relevant clinical information. MATERIALS AND METHODS: One hundred and twenty-five cases of pure GGOs described in a previous article were used to train and evaluate the performance of an ANN to predict the likelihood of malignancy in each of the GGOs. Eighty-five cases selected randomly were used for training the network and the remaining 40 cases for testing. The ANN was constructed from the image data and basic clinical information. The predictions of the ANN were compared with blinded expert estimates of the likelihood of malignancy. RESULTS: The ANN showed excellent predictive value in estimating the likelihood of malignancy (AUC = 0.98±0.02). Employing the optimal cut-off point from the receiver operating characteristic (ROC) curve, the ANN correctly identified 11/11 malignant lesions (sensitivity 100%) and 27/29 benign lesions (specificity 93.1%). The expert readers found 23 lesions indeterminate and correctly identified 17 lesions as benign. CONCLUSION: ANNs have potential to improve diagnostic certainty in the classification of pure GGOs, based upon their CT appearance, intensity of FDG uptake, and relevant clinical information, and may therefore, be useful to help direct clinical and imaging follow-up.

Impact of maternal intrapartum antibiotics, method of birth and breastfeeding on gut microbiota during the first year of life: a prospective cohort study.

OBJECTIVE: Dysbiosis of the infant gut microbiota may have long-term health consequences. This study aimed to determine the impact of maternal intrapartum antibiotic prophylaxis (IAP) on infant gut microbiota, and to explore whether breastfeeding modifies these effects. DESIGN: Prospective pregnancy cohort of Canadian infants born in 2010-2012: the Canadian Healthy Infant Longitudinal Development (CHILD) Study. SETTING: General community. SAMPLE: Representative sub-sample of 198 healthy term infants from the CHILD Study. METHODS: Maternal IAP exposures and birth method were documented from hospital records and breastfeeding was reported by mothers. Infant gut microbiota was characterised by Illumina 16S rRNA sequencing of faecal samples at 3 and 12 months. MAIN OUTCOME MEASURES: Infant gut microbiota profiles. RESULTS: In this cohort, 21% of mothers received IAP for Group B Streptococcus prophylaxis or pre-labour rupture of membranes; another 23% received IAP for elective or emergency caesarean section (CS). Infant gut microbiota community structures at 3 months differed significantly with all IAP exposures, and differences persisted to 12 months for infants delivered by emergency CS. Taxon-specific composition also differed, with the genera Bacteroides and Parabacteroides under-represented, and Enterococcus and Clostridium over-represented at 3 months following maternal IAP. Microbiota differences were especially evident following IAP with emergency CS, with some changes (increased Clostridiales and decreased Bacteroidaceae) persisting to 12 months, particularly among non-breastfed infants. CONCLUSIONS: Intrapartum antibiotics in caesarean and vaginal delivery are associated with infant gut microbiota dysbiosis, and breastfeeding modifies some of these effects. Further research is warranted to explore the health consequences of these associations. TWEETABLE ABSTRACT: Maternal #antibiotics during childbirth alter the infant gut #microbiome.

Multilocus DNA sequencing of the whiskey fungus reveals a continental-scale speciation pattern.

Baudoinia was described to accommodate a single species, B. compniacensis. Known as the 'whiskey fungus', this species is the predominant member of a ubiquitous microbial community known colloquially as 'warehouse staining' that develops on outdoor surfaces subject to periodic exposure to ethanolic vapours near distilleries and bakeries. Here we examine 19 strains recovered from environmental samples near industrial settings in North America, South America, the Caribbean, Europe and the Far East. Molecular phylogenetic analysis of a portion of the nucLSU rRNA gene confirms that Baudoinia is a monophyletic lineage within the Teratosphaeriaceae (Capnodiales). Multilocus phylogenetic analysis of nucITS rRNA (ITS1-5.8S-ITS2) and partial nucLSU rRNA, beta-tubulin (TUB) and elongation factor 1-alpha (TEF1) gene sequences further indicates that Baudoinia consists of five strongly supported, geographically patterned lineages representing four new species (viz. Baudoinia antilliensis, B. caledoniensis, B. orientalis and B. panamericana).

10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) induces memory B cell responses in healthy Kenyan toddlers.

Memory B cells are long-lived and could contribute to persistence of humoral immunity by maintaining the plasma-cell pool or making recall responses upon re-exposure to an antigen. We determined the ability of a pneumococcal conjugate vaccine to induce anti-pneumococcal memory B cells. Frequencies of memory B cells against pneumococcal capsular polysaccharides from serotypes 1, 6B, 14, 19F and 23F were determined by cultured B cell enzyme-linked immunospot (ELISPOT) in 35 children aged 12-23 months who received pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV). The relationships between plasma antibodies and memory B cell frequencies were also assessed. After two doses of PHiD-CV, the proportion of subjects with detectable memory B cells against pneumococcal capsular polysaccharides increased significantly for serotypes 1 (3-45%; P < 0·01), 19F (21-66%; P < 0·01) and 23F (13-36%; P = 0·02), but not serotypes 6B (24-42%; P = 0·24) and 14 (21-40%; P = 0·06). Correlations between antibodies and memory B cells were weak. Carriage of serotype 19F at enrolment was associated with poor memory B cell responses against this serotype at subsequent time-points (day 30: non-carriers, 82% versus carriers, 0%, P < 0·01; day 210: non-carriers, 72% versus carriers, 33%, P = 0·07). PHiD-CV is capable of inducing memory B cells against some of the component pneumococcal capsular polysaccharides.

Infant gut microbiota and food sensitization: associations in the first year of life.

BACKGROUND: The gut microbiota is established during infancy and plays a fundamental role in shaping host immunity. Colonization patterns may influence the development of atopic disease, but existing evidence is limited and conflicting. OBJECTIVE: To explore associations of infant gut microbiota and food sensitization. METHODS: Food sensitization at 1 year was determined by skin prick testing in 166 infants from the population-based Canadian Healthy Infant Longitudinal Development (CHILD) study. Faecal samples were collected at 3 and 12 months, and microbiota was characterized by Illumina 16S rRNA sequencing. RESULTS: Twelve infants (7.2%) were sensitized to ≥ 1 common food allergen at 1 year. Enterobacteriaceae were overrepresented and Bacteroidaceae were underrepresented in the gut microbiota of food-sensitized infants at 3 months and 1 year, whereas lower microbiota richness was evident only at 3 months. Each quartile increase in richness at 3 months was associated with a 55% reduction in risk for food sensitization by 1 year (adjusted odds ratio 0.45, 95% confidence interval 0.23-0.87). Independently, each quartile increase in Enterobacteriaceae/Bacteroidaceae ratio was associated with a twofold increase in risk (2.02, 1.07-3.80). These associations were upheld in a sensitivity analysis among infants who were vaginally delivered, exclusively breastfed and unexposed to antibiotics. At 1 year, the Enterobacteriaceae/Bacteroidaceae ratio remained elevated among sensitized infants, who also tended to have decreased abundance of Ruminococcaceae. CONCLUSIONS AND CLINICAL RELEVANCE: Low gut microbiota richness and an elevated Enterobacteriaceae/Bacteroidaceae ratio in early infancy are associated with subsequent food sensitization, suggesting that early gut colonization may contribute to the development of atopic disease, including food allergy.

Asthma and allergy development: contrasting influences of yeasts and other fungal exposures.

BACKGROUND: Infancy is a developmental stage with heightened susceptibility to environmental influences on the risk of chronic childhood disease. Few birth cohort studies have detailed measures of fungal diversity data in infants' bedrooms, limiting the potential to measure long-term associations of these complex exposures with development of asthma or allergy. OBJECTIVE: We evaluated the relation of home fungal levels in infancy to repeated measures of wheeze and development of asthma and rhinitis by age 13, and sensitization by age 12 years. METHODS: In the Epidemiology of Home Allergens and Asthma prospective birth cohort study, we recruited 408 children with family history of allergic disease or asthma. When children were aged 2-3 months, we measured culturable fungi in bedroom air and dust, and in outdoor air. Main outcomes included ascertainment of symptoms/disease onset by questionnaire from birth through age 13. We estimated hazard ratios and, for wheeze and sensitization, odds ratios for an interquartile increase in log-transformed fungal concentrations, adjusting for other outcome predictors and potential confounders. RESULTS: Elevated levels of yeasts in bedroom floor dust were associated with reduced: i) wheeze at any age; ii) fungal sensitization; and iii) asthma development by age 13 (hazard ratio (HR) = 0.86; 95% confidence interval (CI), [0.75 to 0.98]). Outdoor airborne Cladosporium and dustborne Aspergillus predicted increased rhinitis. Risk of fungal sensitization by age 12, in response to environmental Alternaria and Aspergillus, was elevated in children with a maternal history of fungal sensitization. CONCLUSIONS AND CLINICAL RELEVANCE: Despite the irritant and allergenic properties of fungi, early-life elevated dust yeast exposures or their components may be protective against allergy and asthma in children at risk for these outcomes. Ascertainment of fungal components associated with immunoprotective effects may have therapeutic relevance for asthma.

Simeprevir with peginterferon/ribavirin for treatment of chronic hepatitis C virus genotype 1 infection: pooled safety analysis from Phase IIb and III studies.

This pooled analysis of five Phase IIb and III studies evaluated the safety and tolerability of simeprevir, a once daily, oral hepatitis C virus (HCV) NS3/4A protease inhibitor. Data were summarised for patients who received simeprevir 150 mg once daily (n = 924) or placebo (n = 540) plus pegylated interferon-α/ribavirin for 12 weeks. During the first 12 weeks of treatment, few patients discontinued simeprevir or placebo due to adverse events (AEs) (both 2.2%). Pruritus (23.8% vs 17.4%), rash (any; 22.9% vs 16.7%) and photosensitivity (3.2% vs 0.6%) [Correction added on 16 January 2015, after first online publication: In the above sentence, the values in 'Photosensitivity' were previously incorrect and have now been changed to 3.2% vs 0.6%.] were more prevalent in the simeprevir vs the placebo groups. Most AEs were grade 1/2 (72.4% for simeprevir vs 71.3% for placebo). All grade 3/4 AEs occurred in <5.0% of patients, except neutropenia (9.8% vs 7.6%). Overall incidence of neutropenia was similar (17.3% vs 15.7%). Incidence of anaemia was 13.2% for simeprevir vs 10.9% for placebo, and incidence of increased bilirubin was 8.4% vs 2.8%. Bilirubin increases were mild-to-moderate and transient without concurrent transaminase increases or association with hepatic injury. Safety and tolerability did not vary with METAVIR score, although increased bilirubin and anaemia were more frequent in simeprevir-treated patients with METAVIR F4 (increased bilirubin, 13.0% vs 3.3%; anaemia, 19.0% vs 14.8%). Serious AEs were infrequent (2.1% for simeprevir vs 3.0% for placebo). No deaths were reported during the first 12 weeks of treatment. Patient-reported fatigue and other outcomes were comparable for both groups, but were of shorter duration for simeprevir due to the use of response-guided therapy. Simeprevir is well tolerated in HCV genotype 1-infected patients.

Syk mediates airway contractility independent of leukocyte function.

BACKGROUND: Syk, an immune regulatory tyrosine kinase, plays a role in inflammatory disease processes. We recently reported a role for epithelial expression of Syk in the airways hyper-responsiveness in response to air pollution in a mouse model of asthma. The aim of this study was to further investigate the role of Syk in airway contractility in response to methacholine (MCh) and particulate matter (PM) air pollutants, in the absence of underlying inflammation. METHODS: We used Syk(flox/flox) //rosa26CreER(T) (2) conditional Syk knockout mice to evaluate respiratory mechanics and MCh responsiveness following PM exposure in vivo using the ventilator-based flexiVent system. RESULTS: While total and differential cell counts in bronchoalveolar lavage fluid were similar between the Syk(flox/flox) and Syk(del/del) mice, central airways respiratory resistance (RN ) to MCh was significantly augmented following PM exposure between Syk-intact (Syk(flox/flox) ) and Syk-deficient (Syk(del/del) ) mice (RN (max) : 2.06 ± 0.29 vs. 1.29 ± 0.10, respectively; p < 0.05, n = 8-10/group). We employed live videomicroscopy to investigate changes in airway luminal diameter using ex vivo lung slices, which were devoid of circulating leukocytes. MCh reduced the airway luminal area of Syk(flox/flox) mice to 81.1 ± 1.4% of baseline, which was virtually abrogated in Syk(del/del) mice (luminal area = 93.2 ± 0.5%, n = 5/group, p < 0.05). In response to PM exposure, Syk(flox/flox) airways contracted to 73.8 ± 2.7% of baseline luminal diameter, whereas Syk(del/del) airways exhibited minimal contractility to PM and MCh (90.0 ± 1.3% of baseline, n = 5/group, p < 0.05). CONCLUSIONS: These observations suggest that Syk mediates airway contractility in the normal and allergic airways, independent of its role and function in leukocytes, and supports a paracrine role for airway epithelial Syk in modulating airway smooth muscle activity.

The Canadian healthy infant longitudinal development birth cohort study: biological samples and biobanking.

BACKGROUND: It is hypothesised that complex interactions between genetic and environmental factors give rise to allergy and asthma in childhood. The Canadian Healthy Infant Longitudinal Development (CHILD) study was designed to explore these factors. METHODS: CHILD is a longitudinal, general population birth cohort study following infants from mid-pregnancy to age 5 years. Over this time period, biological samples, questionnaires, clinical measures and environmental data are collected. RESULTS: A total of 3624 families have been recruited, and many thousands of samples and questionnaires have been collected, annotated, and archived. This report outlines the rationale and methodology for collecting and storing diverse biological samples from parents and children in this study, and the mechanisms for their release for analyses. CONCLUSIONS: The CHILD sample and data repository is a tremendous current and future resource and will provide a wealth of information not only informing studies of asthma and allergy, but also potentially in many other aspects of health relevant for Canadian infants and children.

Radiology reports: a quantifiable and objective textual approach.

AIM: To examine the feasibility of using automated lexical analysis in conjunction with machine learning to create a means of objectively characterising radiology reports for quality improvement. MATERIALS AND METHODS: Twelve lexical parameters were quantified from the collected reports of four radiologists. These included the number of different words used, number of sentences, reading grade, readability, usage of the passive voice, and lexical metrics of concreteness, ambivalence, complexity, passivity, embellishment, communication and cognition. Each radiologist was statistically compared to the mean of the group for each parameter to determine outlying report characteristics. The reproducibility of these parameters in a given radiologist's reporting style was tested by using only these 12 parameters as input to a neural network designed to establish the authorship of 60 unknown reports. RESULTS: Significant differences in report characteristics were observed between radiologists, quantifying and characterising deviations of individuals from the group reporting style. The 12 metrics employed in a neural network correctly identified the author in each of 60 unknown reports tested, indicating a robust parametric signature. CONCLUSION: Automated and quantifiable methods can be used to analyse reporting style and provide impartial and objective feedback as well as to detect and characterise significant differences from the group. The parameters examined are sufficiently specific to identify the authors of reports and can potentially be useful in quality improvement and residency training.

LAPCs contribute to the pathogenesis of allergen-induced allergic airway inflammation in mice.

BACKGROUND: The inflammatory immune response associated with allergic airway inflammation in asthma involves T helper type 2 (Th2) immunity. Given the data that a newly described late activator antigen-presenting cell (LAPC) population promotes Th2 immunity in viral infections, we undertook studies to investigate whether LAPCs have a pathogenic role in allergic airway inflammation. METHODS: We employed acute ovalbumin (OVA) and house dust mite (HDM) sensitization and challenge models to establish allergic airway inflammation in mice, followed by the analysis of lungs and draining lymph node (DLN) cell infiltrates, immunoglobulin E (IgE) production, and airway hyper-responsiveness (AHR). We tested whether adoptive transfer of LAPCs isolated from mice with established allergic airway inflammation augments the development of sensitization in naïve mice. RESULTS: We provide evidence that in both OVA and HDM mouse models of allergic inflammation, LAPCs accumulate in the lungs and draining lymph nodes (DLNs), concomitant with the onset of lung pathology, allergen-specific IgE production, eosinophilia, and Th2 cytokine production. Adoptive transfer experiments using OVA-activated LAPCs reveal exacerbation of disease pathology with an increase in lung inflammatory cells, eosinophilia, circulating IgE, Th2 cytokine production, and a worsening of AHR. OVA-activated LAPCs preferentially increased GATA-3 induction in naïve CD4(+) T cells. CONCLUSIONS: Together, these data suggest an important role for LAPCs in polarizing the Th2 response in mouse models of allergic airway inflammation.

Associations between bacterial communities of house dust and infant gut.

The human gut is host to a diverse and abundant community of bacteria that influence health and disease susceptibility. This community develops in infancy, and its composition is strongly influenced by environmental factors, notably perinatal anthropogenic exposures such as delivery mode (Cesarean vs. vaginal) and feeding method (breast vs. formula); however, the built environment as a possible source of exposure has not been considered. Here we report on a preliminary investigation of the associations between bacteria in house dust and the nascent fecal microbiota from 20 subjects from the Canadian Healthy Infant Longitudinal Development (CHILD) Study using high-throughput sequence analysis of portions of the 16S rRNA gene. Despite significant differences between the dust and fecal microbiota revealed by Nonmetric Multidimensional Scaling (NMDS) analysis, permutation analysis confirmed that 14 bacterial OTUs representing the classes Actinobacteria (3), Bacilli (3), Clostridia (6) and Gammaproteobacteria (2) co-occurred at a significantly higher frequency in matched dust-stool pairs than in randomly permuted pairs, indicating an association between these dust and stool communities. These associations could indicate a role for the indoor environment in shaping the nascent gut microbiota, but future studies will be needed to confirm that our findings do not solely reflect a reverse pathway. Although pet ownership was strongly associated with the presence of certain genera in the dust for dogs (Agrococcus, Carnobacterium, Exiguobacterium, Herbaspirillum, Leifsonia and Neisseria) and cats (Escherichia), no clear patterns were observed in the NMDS-resolved stool community profiles as a function of pet ownership.

Wheeze in infancy: protection associated with yeasts in house dust contrasts with increased risk associated with yeasts in indoor air and other fungal taxa.

BACKGROUND: While fungal exposures are assumed to provoke wheeze through irritant or allergenic mechanisms, little is known about the differential effects of indoor and outdoor fungi on early-life wheeze. METHODS: In a Boston prospective birth cohort of 499 at-risk infants, culturable fungi in bedroom air and dust and outdoor air were measured at the age of 2-3 months. Wheeze was determined using bimonthly telephone questionnaires. Odds ratios were estimated for an interquartile increase in fungal natural log-transformed concentrations, adjusting for predictors of wheeze and potential confounders. RESULTS: Increased odds of 'any wheeze' (≥1 vs 0 episodes) by age one were positively associated with indoor dust Alternaria [odds ratio (OR) = 1.83; 95% confidence interval (CI), 1.07-3.14], Penicillium [OR = 1.18; (0.98-1.43)], and Cladosporium [OR = 1.47; (1.16-1.85)]; indoor air Penicillium [OR = 1.26; (0.92-1.74)]; and outdoor air Cladosporium [OR = 1.68; (1.04-2.72)]. In contrast, indoor dust yeasts were protective [OR = 0.78; (0.66-0.93)]. 'Frequent wheeze' (≥2 vs <2 episodes) by age one was borderline associated with dust yeasts [OR = 0.86; (0.70-1.04)] and indoor air yeasts [OR = 1.53; (0.93-2.53)]. Alternaria concentration was associated with any wheeze for children with maternal mold sensitization [OR = 9.16; (1.37-61.22)], but not for those without maternal mold sensitization [OR = 1.32; (0.79-2.20)]. CONCLUSIONS: While wheeze rates were higher with exposures to fungal taxa considered to be irritant or allergenic in sensitive subjects, yeasts in the home had a strong protective association with wheeze in infancy. Molecular microbiologic studies may elucidate specific components of innate microbiologic stimulants that lead to contrasting effects on wheeze development.

The impact of the COVID-19 pandemic on vaccine coverage in Kilifi, Kenya: A retrospective cohort study.

The COVID-19 pandemic caused unprecedented disruption in health service delivery, globally. This study sought to provide evidence on the impact of the pandemic on vaccine coverage in Kilifi County, Kenya. We conducted a vaccine coverage survey between April and June 2021 within the Kilifi Health and Demographic Surveillance System (KHDSS). Simple random sampling was used to identify 1500 children aged 6 weeks-59 months. Participants were grouped into three retrospective cohorts based on when they became age-eligible for vaccination: before the pandemic, during the first year, or during the second year of the pandemic. Survival analysis with Cox regression was used to evaluate the association between the time-period at which participants became age-eligible for vaccination and the rate of vaccination within a month of age-eligibility for the third dose of pentavalent vaccine (Pentavalent-3) and within three months of age-eligibility for the first dose of Measles vaccine (MCV-1). A total of 1,341 participants were included in the survey. Compared to the pre-COVID-19 baseline period, the rate of vaccination within a month of age-eligibility for Pentavalent-3 was not significantly different in the first year of the pandemic (adjusted hazard ratio [aHR] 1.03, 95 % confidence interval [CI] 0.90-1.18) and was significantly higher during the second year of the pandemic (aHR 1.33, 95 % CI 1.07-1.65). The rate of vaccination with MCV-1 within three months of age-eligibility was not significantly different among those age-eligible for vaccination during the first year of the pandemic (aHR 1.04, 95 % CI 0.88-1.21) and was 35 % higher during the second year of the pandemic (95 % CI 1.11-1.64), compared to those age-eligible pre-COVID-19. After adjusting for known determinants of vaccination, the COVID-19 pandemic did not adversely affect the rate of vaccination within the KHDSS.