Mucosal preservation is paramount to achieving successful outcomes after endoscopic sinus surgery (ESS). Despite best surgical practices and implementation of evidenced-based postoperative care, ...patients in rare cases might exhibit persistent demucosalization that is recalcitrant to conservative therapies. We retrospectively reviewed the records of 3 patients-a 63-year-old woman, a 67-year-old woman, and a 43-year-old man-who experienced clinically significant local demucosalization after uncomplicated ESS despite routine surgical and postoperative management. We collected data on the characteristics of presentation, wound management strategies, and postoperative care practices. Two patients achieved remucosalization with mechanical debridement, gelatin sponge placement, and intensive moisturization therapy. Our experience suggests that surgical debridement of these chronic, persistent demucosalized wounds may be an effective management strategy for patients who develop this unusual and rare postoperative complication. Biopsy and culture of the persistently demucosalized wound bed may be useful in recognizing the presence of worrisome disease processes and identifying any tenacious infectious agents so that more appropriate therapy can be initiated if necessary.
Recent genome-wide association studies (GWAS) have identified a link between single-nucleotide polymorphisms (SNPs) near the MBOAT7 gene and advanced liver diseases. Specifically, the common MBOAT7 ...variant (rs641738) associated with reduced MBOAT7 expression is implicated in non-alcoholic fatty liver disease (NAFLD), alcohol-associated liver disease (ALD), and liver fibrosis. However, the precise mechanism underlying MBOAT7-driven liver disease progression remains elusive. Previously, we identified MBOAT7-driven acylation of lysophosphatidylinositol lipids as key mechanism suppressing the progression of NAFLD (Gwag et al., 2019). Here, we show that MBOAT7 loss of function promotes ALD via reorganization of lysosomal lipid homeostasis. Circulating levels of MBOAT7 metabolic products are significantly reduced in heavy drinkers compared to healthy controls. Hepatocyte- ( Mboat7 -HSKO), but not myeloid-specific ( Mboat7 -MSKO), deletion of Mboat7 exacerbates ethanol-induced liver injury. Lipidomic profiling reveals a reorganization of the hepatic lipidome in Mboat7 -HSKO mice, characterized by increased endosomal/lysosomal lipids. Ethanol-exposed Mboat7 -HSKO mice exhibit dysregulated autophagic flux and lysosomal biogenesis, associated with impaired transcription factor EB-mediated lysosomal biogenesis and autophagosome accumulation. This study provides mechanistic insights into how MBOAT7 influences ALD progression through dysregulation of lysosomal biogenesis and autophagic flux, highlighting hepatocyte-specific MBOAT7 loss as a key driver of ethanol-induced liver injury.
A total of 66 serovars of potentially pathogenic Leptospira species were examined by slot blot hybridization, and 57 of these serovars were classified in six DNA homology groups. In cases in which ...common serovars were studied, the results were in general agreement with the results of previous workers, who used different DNA homology methods. However, we propose a new species, Leptospira kirschneri, comprising the following serovars: bulgarica, butembo, cynopteri, dania, grippotyphosa, kabura, kambale, ramisi, and tsaratsovo. Seven of these serovars have not had their DNAs studied by other workers.
Drowning is a leading cause of accidental death. In cold-water, sudden skin cooling triggers the life-threatening cold shock response (CSR). The CSR comprises tachycardia, peripheral ...vasoconstriction, hypertension, inspiratory gasp, and hyperventilation with the hyperventilatory component inducing hypocapnia and increasing risk of aspirating water to the lungs. Some CSR components can be reduced by habituation (i.e., reduced response to stimulus of same magnitude) induced by 3-5 short cold-water immersions (CWI). However, high levels of acute anxiety, a plausible emotion on CWI: magnifies the CSR in unhabituated participants, reverses habituated components of the CSR and prevents/delays habituation when high levels of anxiety are experienced concurrent to immersions suggesting anxiety is integral to the CSR.
To examine the predictive relationship that
ratings of acute anxiety have with the CSR. Secondly, to examine whether anxiety ratings correlated with components of the CSR
immersion before and after induction of habituation.
Forty-eight unhabituated participants completed one (CON1) 7-min immersion in to cold water (15°C). Of that cohort, twenty-five completed four further CWIs that would ordinarily induce CSR habituation. They then completed two counter-balanced immersions where anxiety levels were increased (CWI-ANX) or were not manipulated (CON2). Acute anxiety and the cardiorespiratory responses (cardiac frequency
, respiratory frequency
, tidal volume
, minute ventilation
) were measured. Multiple regression was used to identify components of the CSR from the most life-threatening period of immersion (1
minute) predicted by the anxiety rating
immersion. Relationships between anxiety rating and CSR components
immersion were assessed by correlation.
Anxiety rating predicted the
component of the CSR in unhabituated participants (CON1;
< 0.05,
= 0.536,
= 0.190). After habituation immersions (i.e., cohort 2), anxiety rating predicted the
component of the CSR when anxiety levels were lowered (CON2;
< 0.05,
= 0.566,
= 0.320) but predicted the
component of the CSR (
< 0.05,
= 0.518,
= 0.197) when anxiety was increased suggesting different drivers of the CSR when anxiety levels were manipulated; correlation data supported these relationships.
Acute anxiety is integral to the CSR before and after habituation. We offer a new integrated model including neuroanatomical, perceptual and attentional components of the CSR to explain these data.
Positron emission tomography and post-mortem studies of the number of somatodendritic 5-hydroxytryptamine(1A) (5-HT(1A)) autoreceptors in raphé nuclei have found both increases and decreases in ...depression. However, recent genetic studies suggest they may be increased in number and/or function. The current study examined the effect of buspirone on the electroencephalographic (EEG) centroid frequency, a putative index of somatodendritic 5-HT(1A) receptor functional status, in a cohort of medication-free depressed patients and controls.
A total of 15 depressed patients (nine male) and intelligence quotient (IQ)-, gender- and age-matched healthy controls had resting EEG recorded from 29 scalp electrodes prior to and 30, 60 and 90 min after oral buspirone (30 mg) administration. The effect of buspirone on somatodendritic 5-HT(1A) receptors was assessed by calculating the EEG centroid frequency between 6 and 10.5 Hz. The effect of buspirone on postsynaptic 5-HT(1A) receptors was assessed by measuring plasma growth hormone, prolactin and cortisol concentrations.
Analysis of variance revealed a significantly greater effect of buspirone on the EEG centroid frequency in patients compared with controls (F1,28 = 6.55, p = 0.016). There was no significant difference in the neuroendocrine responses between the two groups.
These findings are consistent with an increase in the functional status of somatodendritic, but not postsynaptic, 5-HT1A autoreceptors, in medication-free depressed patients in line with hypotheses based on genetic data. This increase in functional status would be hypothesized to lead to an increase in serotonergic negative feedback, and hence decreased release of 5-HT at raphé projection sites, in depressed patients.
A breed-specific polymyositis is frequently observed in the Hungarian Vizsla. Beneficial clinical response to immunosuppressive therapies has been demonstrated which points to an immune-mediated ...aetiology. Canine inflammatory myopathies share clinical and histological similarities with the human immune-mediated myopathies. As MHC class II associations have been reported in the human conditions we investigated whether an MHC class II association was present in the canine myopathy seen in this breed. 212 Hungarian Vizsla pedigree dogs were stratified both on disease status and degree of relatedness to an affected dog. This generated a group of 29 cases and 183 "graded" controls: 93 unaffected dogs with a first degree affected relative, 44 unaffected dogs with a second degree affected relative, and 46 unaffected dogs with no known affected relatives. Eleven DLA class II haplotypes were identified, of which, DLA-DRB1*02001/DQA1*00401/DQB1*01303, was at significantly raised frequency in cases compared to controls (OR = 1.92, p = 0.032). When only control dogs with no family history of the disease were compared to cases, the association was further strengthened (OR = 4.08, p = 0.00011). Additionally, a single copy of the risk haplotype was sufficient to increase disease risk, with the risk substantially increasing for homozygotes. There was a trend of increasing frequency of this haplotype with degree of relatedness, indicating low disease penetrance. These findings support the hypothesis of an immune-mediated aetiology for this canine myopathy and give credibility to potentially using the Hungarian Vizsla as a genetic model for comparative studies with human myositis.
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