Expansile Sphenoid Mycetoma Presenting With Headache and Galactorrhea.

This case report describes an immunocompetent woman in her 30s with daily vertex headaches over 13 months duration who developed spontaneous galactorrhea and was diagnosed with noninvasive fungal sinusitis.

Normocephalic sagittal craniosynostosis in young children is common and unrecognized.

OBJECTIVE: Sagittal craniosynostosis (SC) is usually diagnosed during early childhood by the presence of scaphocephaly. Recently, our group found 3.3% of children under 5 years of age with normocephalic sagittal craniosynostosis (NSC) using computed tomography (CT) scans. This paper aims to validate our preliminary findings using a larger cohort of patients, and analyze factors associated with incidental NSC. METHODS: A retrospective review of head CT scans in patients aged 0 to 71 months who presented to the emergency department of our tertiary care institution between 2008 and 2020 was completed. Patients with syndromes associated with craniosynostosis (CS), history of hydrocephalus, or other brain/cranial abnormalities were excluded. Two craniofacial surgeons reviewed the CT scans to evaluate the presence and extent of CS. Demographic information, gestational age, past medical and family history, medications, and chief complaint were recorded as covariates, and differences between patients with and without CS were analyzed. Furthermore, comparison of the prevalence of CS across age groups was studied. Additional analysis exploring association between independent covariates and the presence of CS was performed in two sub-cohorts: patients ≤ 24 months of age and patients > 24 months of age. RESULTS: A total of 870 scans were reviewed. SC was observed in 41 patients (4.71% - 25 complete, 16 incomplete), all with a normal cranial index (width/length > 0.7). The prevalence of SC increased up to 36 months of age, then plateaued through 72 months of age. Patients under 2 years of age with family history of neurodevelopmental disease had 49.32 (95% CI [4.28, 567.2]) times higher odds of developing CS. Sub-cohort of patients above 24 months of age showed no variable independently predicted developing CS. CONCLUSION: NSC in young children is common. While the impact of this condition is unknown, the correlation with family history of neurodevelopmental disease is concerning.

"Poison" or "protection"? A mixed methods exploration of Australian parents' COVID-19 vaccination intentions.

OBJECTIVE: The success of COVID-19 vaccination programs relies on community attitudes, yet little is known about parents' views. We aimed to explore the reasons behind Australian parents' vaccine intentions for themselves and for their children. METHOD: This mixed methods study relates to Wave 13 (January 2021) of a longitudinal study of Australian parents' experiences during COVID-19 and contained 1094 participants (83% mothers). We used multinomial logistic regression to understand demographic predictors of vaccine intention, and a descriptive template thematic analysis to analyse open-ended questions about parents' reasons for vaccine intentions for themselves and their children. RESULTS: 64% of Australian parents intend on vaccination, 26% are unsure and 9% intend to decline; 48% intend to vaccinate their children, 38% are unsure, and 14% intend to decline. Relative to those intending to vaccinate, parents unsure (OR = -0.63, 95% CI: 0.46, -0.84, p = .002) or not intending (OR = -0.41, 95% CI: 0.24, 0.67 p < .001) to vaccinate were more likely to have lower trust in doctors. Similar predictors emerged for parents who did not intend to vaccinate their children (OR = 0.47, 95% CI: 0.31, 0.70, p < .001). Qualitative data indicated that many parents had not made a firm decision, including a lack of alignment between intentions and reasons. For example, parents who said 'yes' to vaccination, often then expressed hesitance and a focus on risks in their written response. Reasons for hesitancy for themselves included concerns about testing, side effects, and long-term outcomes. Similar themes were present for children, but parents expressed a strong desire to protect their children, and an eagerness for health information. CONCLUSION: Based on prior research and the themes identified here, a multipronged campaign that includes education/promotion, good access to vaccines and role models, is likely to support parents to make informed decisions regarding COVID-19 vaccination.

Nutrient adequacy, dietary patterns and diet quality among children with and without intellectual disabilities.

BACKGROUND: Children with intellectual disabilities (ID) frequently have feeding problems, but there has been limited research on nutrient intake, dietary patterns and diet quality in this population. METHOD: Nutrient intakes, dietary patterns and the Healthy Eating Index were compared between 48 children with ID and 55 typically developing (TD) children aged 3-8 years who participated in the Children's Mealtime Study. Three-day food records that included two weekdays and one weekend day were used to assess dietary intake. Food intake was entered into the Nutrition Data System for Research for analysis of nutrient intake, dietary patterns and diet quality. Height and weight were measured to determine body mass index (BMI). The relation of dietary patterns to weight status was also assessed. RESULTS: Typically developing children and children with ID met the Estimated Average Requirement/Adequate Intake (EAR/AI) for most nutrients. However, a substantial number of children in both groups did not meet the EAR for vitamins E and D and calcium and the AI for vitamin K. Only one TD child met the AI for potassium. A small percentage of children in both groups did not meet the EAR for vitamin A and vitamin C, and in the ID group, a small percentage did not meet the EAR for vitamin B12 . Children in the ID group consumed, on average, fewer servings of vegetables than TD children (0.5 vs. 1.2, P < 0.001), but there was no significant difference in servings of fruit (0.8 vs. 1.1, respectively), fruit juice (less than a half serving in both groups), sugar-sweetened beverages (less than a half serving in both groups) or snacks (1.1 vs. 1.4, respectively) after adjusting for BMI z-score, parental education and race. We found a significant correlation between snack intake and BMI z-score among children with ID but not among TD children (r = 0.48, P < 0.0001 vs. r = 0.19, P = 0.16, respectively). The Healthy Eating Index indicated, on average, poor overall diet quality in both groups (58.2 in the ID group and 59.1 in the TD group). CONCLUSIONS: This study suggests that the diets of children with ID, as in TD children, need improvement. Targeting healthy eating in children with ID would improve diet quality and overall health.

Acute kidney injury: prevention, detection, and management. Summary of updated NICE guidance for adults receiving iodine-based contrast media.

The National Institute for Health and Care Excellence (NICE) has recently updated the guideline for Acute kidney injury: prevention, detection and management (NG148), providing new recommendations on preventing acute kidney injury (AKI) in adults receiving intravenous iodine-based contrast media. The association between intravenous iodinated contrast media and AKI is controversial, particularly with widespread use of iso-osmolar agents. Associations between contrast media administration and AKI are largely based on observational studies, with inherent heterogeneity in patient populations, definitions applied, and timing of laboratory investigations. In an attempt to mitigate risk, kidney protection has typically been employed using intravenous volume expansion and/or oral acetylcysteine. Such interventions are in widespread use, despite lacking high-quality evidence of benefit. In the non-emergency setting, glomerular filtration rate (GFR) measurements should be obtained within the preceding 3 months before offering intravenous iodine-based contrast media. In the acute setting, adults should also have their risk of AKI assessed before offering intravenous iodine-based contrast media; however, this should not delay emergency imaging. Based on the evidence available from randomised controlled trials, the NICE committee recommends that oral hydration should be encouraged in adults at increased risk of AKI and that volume expansion with intravenous V fluids should only be considered for inpatients at particularly high risk.

Short communication: Genetic lag represents commercial herd genetic merit more accurately than the 4-path selection model.

Expectation of genetic merit in commercial dairy herds is routinely estimated using a 4-path genetic selection model that was derived for a closed population, but commercial herds using artificial insemination sires are not closed. The 4-path model also predicts a higher rate of genetic progress in elite herds that provide artificial insemination sires than in commercial herds that use such sires, which counters other theoretical assumptions and observations of realized genetic responses. The aim of this work is to clarify whether genetic merit in commercial herds is more accurately reflected under the assumptions of the 4-path genetic response formula or by a genetic lag formula. We demonstrate by tracing the transmission of genetic merit from parents to offspring that the rate of genetic progress in commercial dairy farms is expected to be the same as that in the genetic nucleus. The lag in genetic merit between the nucleus and commercial farms is a function of sire and dam generation interval, the rate of genetic progress in elite artificial insemination herds, and genetic merit of sires and dams. To predict how strategies such as the use of young versus daughter-proven sires, culling heifers following genomic testing, or selective use of sexed semen will alter genetic merit in commercial herds, genetic merit expectations for commercial herds should be modeled using genetic lag expectations.

B-Vitamin Therapy for Kidney Transplant Recipients Lowers Homocysteine and Improves Selective Cognitive Outcomes in the Randomized FAVORIT Ancillary Cognitive Trial.

BACKGROUND: Objectives: Elevated plasma total homocysteine (tHcy) is associated with increased risk of cardiovascular disease, stroke and dementia. Results of clinical trials using B-vitamins to reduce the cognitive risks attributed to tHcy have been inconsistent. The high prevalence of both hyperhomocysteinemia and cognitive impairment among kidney transplant recipients makes them an important population in which to evaluate the effect of lowering homocysteine on cognitive function. We therefore evaluated whether B-vitamin therapy to lower tHcy would prevent cognitive-decline in a cohort of stable kidney transplant recipients. DESIGN: The study was a longitudinal ancillary of the FAVORIT trial, a randomized, placebo-controlled multi-site trial of high-dose B vitamins to reduce cardiovascular and cerebrovascular events in clinically stable kidney transplant recipients with elevated tHcy. PARTICIPANTS: 584 participants from 18 sites across North America. INTERVENTION: The intervention consisted of a daily multivitamin containing high-doses of folate (5.0 mg), vitamin B12 (1.0 mg) and vitamin B6 (50 mg). The placebo consisted of a daily multi-vitamin containing no folate and recommended daily allowances of vitamins B12 and B6 (0 mg folate; 2.0 µg vitamin B12; 1.4 mg vitamin B6). MEASUREMENTS: Annual neuropsychological assessment for up to 5 years (mean 3.3 years) using a standardized test battery. Efficacy was analyzed on an intention-to-treat basis using end-of-trial data. Subgroup analyses included stratification for baseline plasma B-vitamin and tHcy concentrations. RESULTS: At baseline, cognitive impairment was common with 61% of participants falling more than one standard deviation below published norms for at least one cognitive test. Fewer than 1% of participants had insufficient plasma folate < 5 ng/ml or vitamin B12 < 148 pmol/L. However, 44.6% had plasma B6 concentrations < 30 nmol/L. At follow-up, processing speed and memory scores were modestly but significantly better in the B-vitamin supplement group than in controls (p≤0.05). There was no interaction between baseline tHcy, B-vitamin status and treatment on the cognitive outcomes. CONCLUSIONS: High-dose B-vitamin supplementation provided modest cognitive benefit for kidney transplant recipients with elevated baseline tHcy. Since nearly all participants were folate and vitamin B12 sufficient at baseline, the potential cognitive benefits of folate and B12 supplementation in individuals with poor B-vitamin status remains to be determined.

Acute photosensitisation and mortality in a herd of dairy cattle in Tasmania.

CASE HISTORY: A herd of Holstein, Jersey, or Holstein-Jersey cross lactating cattle of mixed ages presented with a sudden drop in milk yield in 94/678 cows on 3 October 2014 (Day 0). The herd was located in Gretna in the Derwent Valley (Tasmania, Australia) and had been grazing dryland pasture. CLINICAL FINDINGS: On Day 0 the cows variably showed recumbency, peracute photosensitisation, inflamed coronary bands, conjunctival erythema, periauricular oedema, distress indicated by kicking at the flank, bruxism, discomfort, weight shifting, vocalisation indicating pain and depression. Blood samples collected on Day 4 from five clinically affected cows showed high activities of aspartate aminotransferase, glutamate dehydrogenase and gamma-glutamyl transferase. Morbidity, based on the number of treated cases within 72 hours of clinical onset, was estimated at 165/678 cows (24.3%). Mortality over the first 30 days was 19/678 cows (2.8%). PATHOLOGICAL FINDINGS: Necropsies of two cows on Day 4 showed marked distension of the gall bladder and extensive icterus. Necropsies of another two cows on Day 5 showed enlarged livers with severe damage and oedema of the distal abomasum. Severe ulcerative abomasal gastritis was present in both cows. Hepatic histopathology was consistent with chronic cholangiohepatitis. MYCOTOXICOLOGY: Fifty-five different mycotoxins were detected from a barley grass (Hordeum murinum) sample from the presumably contaminated pasture. Concentrations of B-trichothecenes, fumonisins, and zearalenone metabolites from this sample were remarkably high. The leaf smut, Jamesdicksonia dactylidis, that has not been previously reported in Tasmania, was identified from the sample of barley grass, but it is not known whether the smut can produce toxins. DIAGNOSIS: Probably an undescribed peracute mycotoxicosis associated with the ingestion of contaminated dryland pasture. CLINICAL RELEVANCE: A definitive diagnosis could not be reached in this case of acute photosensitisation and mortality in dairy cattle grazing possibly contaminated dryland pasture. The findings differed from both facial eczema and acute bovine liver disease, suggesting an undescribed mycotoxicosis.

Inflammasome signaling affects anxiety- and depressive-like behavior and gut microbiome composition.

The inflammasome is hypothesized to be a key mediator of the response to physiological and psychological stressors, and its dysregulation may be implicated in major depressive disorder. Inflammasome activation causes the maturation of caspase-1 and activation of interleukin (IL)-1ß and IL-18, two proinflammatory cytokines involved in neuroimmunomodulation, neuroinflammation and neurodegeneration. In this study, C57BL/6 mice with genetic deficiency or pharmacological inhibition of caspase-1 were screened for anxiety- and depressive-like behaviors, and locomotion at baseline and after chronic stress. We found that genetic deficiency of caspase-1 decreased depressive- and anxiety-like behaviors, and conversely increased locomotor activity and skills. Caspase-1 deficiency also prevented the exacerbation of depressive-like behaviors following chronic stress. Furthermore, pharmacological caspase-1 antagonism with minocycline ameliorated stress-induced depressive-like behavior in wild-type mice. Interestingly, chronic stress or pharmacological inhibition of caspase-1 per se altered the fecal microbiome in a very similar manner. When stressed mice were treated with minocycline, the observed gut microbiota changes included increase in relative abundance of Akkermansia spp. and Blautia spp., which are compatible with beneficial effects of attenuated inflammation and rebalance of gut microbiota, respectively, and the increment in Lachnospiracea abundance was consistent with microbiota changes of caspase-1 deficiency. Our results suggest that the protective effect of caspase-1 inhibition involves the modulation of the relationship between stress and gut microbiota composition, and establishes the basis for a gut microbiota-inflammasome-brain axis, whereby the gut microbiota via inflammasome signaling modulate pathways that will alter brain function, and affect depressive- and anxiety-like behaviors. Our data also suggest that further elucidation of the gut microbiota-inflammasome-brain axis may offer novel therapeutic targets for psychiatric disorders.

From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways.

The human body hosts an enormous abundance and diversity of microbes, which perform a range of essential and beneficial functions. Our appreciation of the importance of these microbial communities to many aspects of human physiology has grown dramatically in recent years. We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases. Evidence is now emerging that, through interactions with the gut-brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behaviour, with recent evidence that changes in behaviour alter gut microbiota composition, while modifications of the microbiome can induce depressive-like behaviours. Although an association between enteropathy and certain psychiatric conditions has long been recognized, it now appears that gut microbes represent direct mediators of psychopathology. Here, we examine roles of gut microbiome in shaping brain development and neurological function, and the mechanisms by which it can contribute to mental illness. Further, we discuss how the insight provided by this new and exciting field of research can inform care and provide a basis for the design of novel, microbiota-targeted, therapies.

Comparison of Holstein-Friesian and Norwegian Red dairy cattle for estrus length and estrous signs.

This study addressed the effect of breed on estrus length and estrous behavior by observing 20 Holstein-Friesian (HF) and 20 Norwegian Red (NRF) cows on an outdoor wood-chip pad through 1 estrous cycle (22d). Detailed behavioral data were collected by continuous (24 h) video monitoring of all cows. Accurate estimation of duration of estrous periods, behavioral signs (sum per period and counts per hour), and duration and number of sexually active groups were reported through all stages of mount estrus (prestand, standing estrus, and poststand). These dependent variables were analyzed with a basic statistical model that included fixed effects for breed and lactation group. Other independent variables (milk yield, body condition score, and number of cows in standing estrus) were added to the basic model one by one and included in an expanded model if they had an effect on the respective dependent variables. Estrus duration was considerably shorter in HF compared with NRF cows for all the major periods: mount estrus (11.2 ± 3.0 vs. 21.3 ± 2.7 h), standing estrus (7.1 ± 1.4 vs. 11.7 ± 1.3 h), mounting period (6.9 ± 2.7 vs. 18.2 ± 2.4 h), and mounted period (9.2 ± 2.8 vs. 17.5 ± 2.6 h). Additionally, the NRF cows spent more time in sexually active groups (36.1 ± 4.0 vs. 17.6 ± 4.8%) during standing estrus compared with HF cows. The NRF cows participated in a greater number of sexually active groups (9.6 ± 1.3 vs. 5.5 ± 1.3) with longer average duration (0.42 ± 0.04 vs. 0.20 ± 0.04 h) and continued to be more active in these groups through late stages of estrus (poststand) compared with the HF breed. Mounting activity differed between breeds as NRF mounted more times in total (46.3 ± 6.2 vs. 18.1 ± 6.3) and per hour (2.6 ± 0.4 vs. 1.5 ± 0.5) during mount estrus. In addition, NRF tended to express the primary estrous sign, standing when mounted, more often during standing estrus (32.4 ± 5.0 vs. 18.5 ± 5.2). The HF initiated more unsuccessful mounts (1.6 ± 0.3 vs. 0.6 ± 0.3) per hour than did NRF during mount estrus. A significant effect of milk yield was demonstrated only on this behavior. For other estrous signs, HF cows initiated chase-up (2.0 ± 0.5 vs. 0.5 ± 0.4) and anogenital sniff (3.7 ± 0.6 vs. 2.0 ± 0.5) more frequently (counts per hour), whereas NRF expressed more total head butt behavior (32.3 ± 4.7 vs. 14.2 ± 4.8) during mount estrus. Body condition score had a significant effect on receptive behavior. Measures of estrus duration, sexually active group activity, and behavior related to estrus should be subjected to larger studies for improved heat detection and possible implementation in breeding programs.

Immune responses to human factor IX in haemophilia B mice of different genetic backgrounds are distinct and modified by TLR4.

Our laboratory develops protocols to prevent or reverse ongoing anti-hFIX IgG inhibitors in haemophilia B mice with a F9 gene deletion on BALB/c and C3H/HeJ backgrounds. C3H/HeJ F9(-/Y) mice develop high titre anti-hFIX IgG1 inhibitors and anaphylaxis, whereas most BALB/c F9(-/Y) mice have mild anti-hFIX IgG1 inhibitors and no anaphylaxis. Our aim was to determine if hFIX-specific B- and T-cell responses in BALB/c and C3H/HeJ F9(-/Y) mice trigger the difference in anti-hFIX immune responses. BALB/c and C3H/HeJ F9(-/Y) mice were challenged weekly with recombinant hFIX protein. Humoral immune responses were determined by IgG1 and IgG2a anti-hFIX ELISA, Bethesda assay for inhibitors and B-cell ELISpot on bone marrow and spleen cells. T-cell studies measured the TH 1 (IFN-γ) and TH 2 (IL-4) cytokine responses in splenocytes at the mRNA and protein level in response to hFIX protein. Antibody responses were also measured in C3H/HeJ/OuJ F9(-/Y) mice with restored toll-like receptor 4 (TLR4) function. BALB/c F9(-/Y) mice have a TH 2 skewed response and a reduction in anti-hFIX secreting plasma cells in the bone marrow. Independent antigen challenge revealed both strains generated equivalent IgG1 antibody titres to an intravenously delivered antigen. C3H/HeJ F9(-/Y) mice have a mixed TH 1 and TH 2 response (mainly TH 2). Importantly, TLR4 signalling has a modulatory role in the C3H background on the levels of anti-hFIX IgG1 and incidence of anaphylaxis. The background strain strongly impacts the immune response to hFIX, which can be significantly impacted by mutations in innate immune sensors.

The human microbiome: opportunities and challenges for clinical care.

There is a growing appreciation of the importance of the human microbiome to our normal physiology. This complex microbial ecosystem plays a range of roles, including influencing the development and function of our immune systems, providing essential nutrients, regulating metabolism and protecting us from opportunistic infections. Our increasing understanding of these processes is due, to a large extent, to the development of high-throughput sequencing technologies, providing for the first time a means by which complex microbial dynamics can be detailed. There is also a growing recognition that disruption of commensal microbiota, a phenomenon known as dysbiosis, is associated with several common disorders, including inflammatory bowel disease, type 2 diabetes and oncogenesis. Further, where innate immunity fails to protect us, the microbial communities that colonise the external surfaces of our bodies represent a ready source of infection. This review discusses the mechanisms that govern our interaction with our resident microbiota, both in health and disease, the technological advances that allow us to gain insight into these relationships, and the way in which our growing understanding can inform clinical practice.

Bilateral superior keratoconus: two case reports.

PURPOSE: To present two cases of the rare entity of bilateral superior keratoconus and to review the literature regarding presentation and clinical findings. METHODS: Case report based on chart review. RESULTS: Two patients presented to our corneal service with clinical and topographical features of superior keratoconus. CONCLUSION: The unusual clinical and topographical findings of superior keratoconus are presented and treatment options are considered.