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Hearing Research May 2024The sensory epithelia of the auditory and vestibular systems of vertebrates have shared developmental and evolutionary histories. However, while the auditory epithelia... (Review)
Review
The sensory epithelia of the auditory and vestibular systems of vertebrates have shared developmental and evolutionary histories. However, while the auditory epithelia show great variation across vertebrates, the vestibular sensory epithelia appear seemingly more conserved. An exploration of the current knowledge of the comparative biology of the amniote utricle, a vestibular sensory epithelium that senses linear acceleration, shows interesting instances of variability between birds and mammals. The distribution of sensory hair cell types, the position of the line of hair bundle polarity reversal and the properties of supporting cells show marked differences, likely impacting vestibular function and hair cell regeneration potential.
PubMed: 38763033
DOI: 10.1016/j.heares.2024.109035 -
Communications Biology May 2024Pending questions regarding cochlear amplification and tuning are hinged upon the organ of Corti (OoC) active mechanics: how outer hair cells modulate OoC vibrations....
Pending questions regarding cochlear amplification and tuning are hinged upon the organ of Corti (OoC) active mechanics: how outer hair cells modulate OoC vibrations. Our knowledge regarding OoC mechanics has advanced over the past decade thanks to the application of tomographic vibrometry. However, recent data from live cochlea experiments often led to diverging interpretations due to complicated interaction between passive and active responses, lack of image resolution in vibrometry, and ambiguous measurement angles. We present motion measurements and analyses of the OoC sub-components at the close-to-true cross-section, measured from acutely excised gerbil cochleae. Specifically, we focused on the vibrating patterns of the reticular lamina, the outer pillar cell, and the basilar membrane because they form a structural frame encasing active outer hair cells. For passive transmission, the OoC frame serves as a rigid truss. In contrast, motile outer hair cells exploit their frame structures to deflect the upper compartment of the OoC while minimally disturbing its bottom side (basilar membrane). Such asymmetric OoC vibrations due to outer hair cell motility explain how recent observations deviate from the classical cochlear amplification theory.
Topics: Animals; Gerbillinae; Hair Cells, Auditory, Outer; Vibration; Organ of Corti; Cochlea; Basilar Membrane
PubMed: 38762693
DOI: 10.1038/s42003-024-06293-4 -
International Journal of Surgery Case... May 2024Epidermoid cysts may occur due to anomalies during fetal development, approximately 1-2 % occur in the oral cavity. A cyst lumen filled with fluid or keratin without...
INTRODUCTION
Epidermoid cysts may occur due to anomalies during fetal development, approximately 1-2 % occur in the oral cavity. A cyst lumen filled with fluid or keratin without skin adnexal structures (such as hair, hair follicle, sweat gland, sebaceous gland) can be defined as epidermoid cyst. 7 % of these cysts occur in the head and neck, 1.6 % of which appear in the oral cavity. Gender distribution is balanced but more prevalent in males. Epidermoid cysts are the most common cutaneous cysts. These cysts are rarely discovered prior to puberty. It has been reported that 1 % of epidermoid cysts will malignantly develop into squamous cell carcinoma (SCC) or basal cell carcinoma (BCC).
CASE PRESENTATION
18-year-old male patient presented with 57.99 × 55.33 × 41.41 mm-sized epidermoid cyst treated at the Regional Hospital in Indonesia. The primary complaint was a painless, asymptomatic lump on the floor of the mouth which was felt 10 years ago. Two years prior, the lump enlarged, and the patient began to feel difficulty in swallowing, and respiratory distress appeared one year later. Supplementary examinations: ultrasonography, fine needle aspiration biopsy, plain radiography, multiple slice computed tomography scan was performed to support epidermoid cyst diagnosis.
DISCUSSION
An intraoral approach-based cystectomy with a horizontal incision was utilized for surgical treatment to avoid adjacent anatomic structure. Histopathological examination showed a macroscopic image of pouch tissue with approximately 0.2 cm-thick wall, brownish white in color with yellow mass like cheese pulp, and microscopic image of tissue covered with monomorphous complex squamous epithelium with eosinophilic keratinized mass lumen.
CONCLUSION
Following the procedure, there was no longer respiratory distress nor difficulty in swallowing and the patient recovered well with no deficiency in aesthetics.
PubMed: 38761688
DOI: 10.1016/j.ijscr.2024.109729 -
BMC Veterinary Research May 2024The hair follicle is a skin accessory organ that regulates hair development, and its activity varies on a regular basis. However, the significance of metabolites in the...
BACKGROUND
The hair follicle is a skin accessory organ that regulates hair development, and its activity varies on a regular basis. However, the significance of metabolites in the hair follicle cycle has long been unknown.
RESULTS
Targeted metabolomics was used in this investigation to reveal the expression patterns of 1903 metabolites in cashmere goat skin during anagen to telogen. A statistical analysis was used to investigate the potential associations between metabolites and the hair follicle cycle. The findings revealed clear changes in the expression patterns of metabolites at various phases and in various feeding models. The majority of metabolites (primarily amino acids, nucleotides, their metabolites, and lipids) showed downregulated expression from anagen (An) to telogen (Tn), which was associated with gene expression, protein synthesis and transport, and cell structure, which reflected, to some extent, that the cells associated with hair follicle development are active in An and apoptotic in An-Tn. It is worth mentioning that the expression of vitamin D3 and 3,3',5-triiodo-L-thyronine decreased and then increased, which may be related to the shorter and longer duration of outdoor light, which may stimulate the hair follicle to transition from An to catagen (Cn). In the comparison of different hair follicle development stages (An, Cn, and Tn) or feeding modes (grazing and barn feeding), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that common differentially expressed metabolites (DEMs) (2'-deoxyadenosine, L-valine, 2'-deoxyuridine, riboflavin, cytidine, deoxyguanosine, L-tryptophan, and guanosine-5'-monophosphate) were enriched in ABC transporters. This finding suggested that this pathway may be involved in the hair follicle cycle. Among these DEMs, riboflavin is absorbed from food, and the expression of riboflavin and sugars (D-glucose and glycogen) in skin tissue under grazing was greater and lower than that during barn feeding, respectively, suggesting that eating patterns may also alter the hair follicle cycle.
CONCLUSIONS
The expression patterns of metabolites such as sugars, lipids, amino acids, and nucleotides in skin tissue affect hair follicle growth, in which 2'-deoxyadenosine, L-valine, 2'-deoxyuridine, riboflavin, cytidine, deoxyguanosine, L-tryptophan, and guanosine-5'-monophosphate may regulate the hair follicle cycle by participating in ABC transporters. Feeding practices may regulate hair follicle cycles by influencing the amount of hormones and vitamins expressed in the skin of cashmere goats.
Topics: Animals; Hair Follicle; Goats; Metabolomics
PubMed: 38760765
DOI: 10.1186/s12917-024-04057-0 -
Trends in Endocrinology and Metabolism:... May 2024Iron deficiency is globally prevalent, causing an array of developmental, haematological, immunological, neurological, and cardiometabolic impairments, and is associated... (Review)
Review
Iron deficiency is globally prevalent, causing an array of developmental, haematological, immunological, neurological, and cardiometabolic impairments, and is associated with symptoms ranging from chronic fatigue to hair loss. Within cells, iron is utilised in a variety of ways by hundreds of different proteins. Here, we review links between molecular activities regulated by iron and the pathophysiological effects of iron deficiency. We identify specific enzyme groups, biochemical pathways, cellular functions, and cell lineages that are particularly iron dependent. We provide examples of how iron deprivation influences multiple key systems and tissues, including immunity, hormone synthesis, and cholesterol metabolism. We propose that greater mechanistic understanding of how cellular iron influences physiological processes may lead to new therapeutic opportunities across a range of diseases.
PubMed: 38760200
DOI: 10.1016/j.tem.2024.04.015 -
Toxicology May 2024Electronic waste (e-waste) contains numerous metals and organic pollutants that have detrimental impacts on human health. We studied 199 e-waste recycling workers and...
Electronic waste (e-waste) contains numerous metals and organic pollutants that have detrimental impacts on human health. We studied 199 e-waste recycling workers and 104 non-exposed workers; analyzed blood, urine, and hair samples to measure heavy metals, hormonal, liver, and renal function. We used quantile regression models to evaluate the impact of Pb, Cd, and Hg on hormonal, liver and renal function, and the role of DNA oxidative damage in mediating the relationship between exposures and outcomes. Exposed workers had higher blood lead (Pb) (median 11.89 vs 3.63µg/dL), similar blood cadmium (Cd) (1.04 vs 0.99µg/L) and lower total mercury (Hg) in hair (0.38 vs 0.57 ppm) than non-exposed group. Exposed workers also had elevated median concentrations of total triiodothyronine (TT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urinary albumin, albumin creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were significantly higher than non-exposed group (p≤0.05). Sex hormones including luteinizing hormone, follicle stimulating hormone, estrogen, progesterone and testosterone concentrations were not significantly different between exposed and non-exposed (all p≥0.05). The median concentration of ALT was 4.00 (95% CI: 0.23, 7.77), urinary albumin was 0.09 (95% CI: 0.06, 0.12) and ACR was 1.31 (95% CI: 0.57, 2.05) units higher in the exposed group compared to non-exposed group. Pb was associated with a 3.67 unit increase in the ALP (95% CI: 1.53, 5.80), 0.01 unit increase in urinary albumin (95% CI: 0.00, 0.01), and 0.07 unit increase in ACR (95% CI: 0.01, 0.13). However, no hormonal, renal, and hepatic parameters were associated with Cd or Hg. Oxidative DNA damage did not mediate exposure-outcome relationships (p≥0.05). Our data indicate e-waste exposure impairs liver and renal functions secondary to elevated Pb levels. Continuous monitoring, longitudinal studies to evaluate the dose-response relationship and effective control measure are required to protect workers from e-waste exposure.
PubMed: 38759721
DOI: 10.1016/j.tox.2024.153833 -
Frontiers in Molecular Neuroscience 2024Hearing loss constitutes a major global health concern impacting approximately 1.5 billion people worldwide. Its incidence is undergoing a substantial surge with some... (Review)
Review
Hearing loss constitutes a major global health concern impacting approximately 1.5 billion people worldwide. Its incidence is undergoing a substantial surge with some projecting that by 2050, a quarter of the global population will experience varying degrees of hearing deficiency. Environmental factors such as aging, exposure to loud noise, and the intake of ototoxic medications are implicated in the onset of acquired hearing loss. Ototoxicity resulting in inner ear damage is a leading cause of acquired hearing loss worldwide. This could be minimized or avoided by early testing of hearing functions in the preclinical phase of drug development. While the assessment of ototoxicity is well defined for drug candidates in the hearing field - required for drugs that are administered by the otic route and expected to reach the middle or inner ear during clinical use - ototoxicity testing is not required for all other therapeutic areas. Unfortunately, this has resulted in more than 200 ototoxic marketed medications. The aim of this publication is to raise awareness of drug-induced ototoxicity and to formulate some recommendations based on available guidelines and own experience. Ototoxicity testing programs should be adapted to the type of therapy, its indication (targeting the ear or part of other medications classes being potentially ototoxic), and the number of assets to test. For multiple molecules and/or multiple doses, screening options are available: (otic cell assays), (cochlear explant), and (in zebrafish). In assessing the ototoxicity of a candidate drug, it is good practice to compare its ototoxicity to that of a well-known control drug of a similar class. Screening assays provide a streamlined and rapid method to know whether a drug is generally safe for inner ear structures. Mammalian animal models provide a more detailed characterization of drug ototoxicity, with a possibility to localize and quantify the damage using functional, behavioral, and morphological read-outs. Complementary histological measures are routinely conducted notably to quantify hair cells loss with cochleogram. Ototoxicity studies can be performed in rodents (mice, rats), guinea pigs and large species. However, in undertaking, or at the very least attempting, all preclinical investigations within the same species, is crucial. This encompasses starting with pharmacokinetics and pharmacology efficacy studies and extending through to toxicity studies. In life read-outs include Auditory Brainstem Response (ABR) and Distortion Product OtoAcoustic Emissions (DPOAE) measurements that assess the activity and integrity of sensory cells and the auditory nerve, reflecting sensorineural hearing loss. Accurate, reproducible, and high throughput ABR measures are fundamental to the quality and success of these preclinical trials. As in humans, otoscopic evaluations are routinely carried out to observe the tympanic membrane and auditory canal. This is often done to detect signs of inflammation. The cochlea is a tonotopic structure. Hair cell responsiveness is position and frequency dependent, with hair cells located close to the cochlea apex transducing low frequencies and those at the base transducing high frequencies. The cochleogram aims to quantify hair cells all along the cochlea and consequently determine hair cell loss related to specific frequencies. This measure is then correlated with the ABR & DPOAE results. Ototoxicity assessments evaluate the impact of drug candidates on the auditory and vestibular systems, de-risk hearing loss and balance disorders, define a safe dose, and optimize therapeutic benefits. These types of studies can be initiated during early development of a therapeutic solution, with ABR and otoscopic evaluations. Depending on the mechanism of action of the compound, studies can include DPOAE and cochleogram. Later in the development, a GLP (Good Laboratory Practice) ototoxicity study may be required based on otic related route of administration, target, or known potential otic toxicity.
PubMed: 38756707
DOI: 10.3389/fnmol.2024.1379743 -
Frontiers in Veterinary Science 2024Vitamin D deficiency and excess in clinically presented cats conventionally is diagnosed by comparison of patient plasma 25-hydroxyvitamin D (25 (OH)D) concentration...
BACKGROUND
Vitamin D deficiency and excess in clinically presented cats conventionally is diagnosed by comparison of patient plasma 25-hydroxyvitamin D (25 (OH)D) concentration with plasma reference intervals determined in healthy adult cats. For immature cats, validity of this vitamin D status assessment method is uncertain.
OBJECTIVE
The overall objective was determination of whether plasma concentration of 25 (OH) D and other vitamin D metabolites in immature cats markedly change with developmental age as has been reported in other species.
METHODS
Four male and 4 female domestic short-hair kittens from weaning were continuously presented a single nutritionally adequate growth-diet. Concentrations of 25 (OH) D and 24,25-dihydroxyvitamin D (24,25 (OH)D), and calcitriol were quantified in plasma of jugular venous blood collected at 12, 15, 18, and 21 weeks and 1 year of age. Plasma was liquid and solid-phase extracted and fractionation by normal-phase HPLC, and 25 (OH) D and 24,25 OH)D quantified by reverse-phase HPLC-UV and calcitriol by RIA.
RESULTS
Plasma 3-epi-25 (OH) D and 25 (OH) D concentrations increased ( < 0.001) with age so that by study end the concentrations rose by 1-and 2-fold, respectively. Concentrations of 3-epi-25 (OH) D relative to 25 (OH) D were 30% at 12 weeks and 20% at 1 year. Between ages 12 and 21 weeks, rises in 25 (OH) D concentration were positively correlated with body weight gains ( = 0.952, < 0.001) and 24,25 (OH)D concentrations were consistently greater than 25 (OH) D concentrations ( < 0.001). At 1 year of age, concentrations of 24,25 (OH)D declined below those of 25 (OH) D and 3-epi-24,25 (OH)D consistency occurred in low concentrations. Vitamin D metabolites and sex differences in metabolite concentrations were not observed.
CONCLUSION
Reliance on quantification of plasma 25 (OH) D concentration for vitamin D status assessment in kittens may be confounded by developmental changes in 25 (OH) D independent of vitamin D intake. High 24,25 (OH)D concentration and occurrence of 3-epi-25 (OH) D in plasma additionally may interfere with the quantification.
PubMed: 38756523
DOI: 10.3389/fvets.2024.1365204 -
Cureus Apr 2024Hypothyroidism is one of the most common endocrine disorders with a simple therapy, that is levothyroxine (LT4). A normal thyroid-stimulating hormone (TSH) measurement...
BACKGROUND
Hypothyroidism is one of the most common endocrine disorders with a simple therapy, that is levothyroxine (LT4). A normal thyroid-stimulating hormone (TSH) measurement is used as a marker of optimal replacement. But, many patients still have symptoms. Triiodothyronine (T3), thyroxine (T4), and their ratio may correlate with clinical improvement. The study aims to assess the T3/T4 ratio as a marker of clinical response in patients with hypothyroidism. Method: A cross-sectional study was conducted from June to November 2022 at Faiha Specialized Diabetes, Endocrine, and Metabolism Center, in Basrah, southern Iraq. We included 48 adult patients with primary hypothyroidism on LT4 treatment only and TSH within the target reference range for at least within the last six months. Each patient was subjected to a questionnaire that was designed to capture hypothyroidism-related complaints in the form of a five-point Likert scale. Biochemical assessments were done with the measurement of TSH, T3, and T4.
RESULTS
Despite having a normal TSH level, nearly all the patients had persistent and varying severity of clinical complaints of hypothyroidism. Tiredness, hair problems, weight gain, and cold intolerance were the most severely persistent symptoms. Patients with scores of two and more for weight gain, cold intolerance, and skin problems had significantly lower T3/T4 ratios (P = 0.04, 0.002, and 0.02, respectively), while in the remaining clinical symptoms, the T3/T4 ratio did not differ significantly.
CONCLUSION
A low T3/T4 ratio was significantly associated with resistant symptoms of hypothyroidism and may be used as a marker for treatment efficacy with TSH rather than TSH value alone.
PubMed: 38756268
DOI: 10.7759/cureus.58370 -
BMJ Open May 2024Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, can be challenging to diagnose, and treatment outcomes are difficult to predict. In...
Novel biomarker profiles to improve individual diagnosis and prognosis in patients with suspected inflammatory bowel disease: protocol for the Nordic inception cohort study (NORDTREAT).
INTRODUCTION
Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, can be challenging to diagnose, and treatment outcomes are difficult to predict. In the NORDTREAT cohort study, a Nordic prospective multicentre study, we aim to identify novel molecular biomarkers of diagnostic value by assessing the diagnostic test accuracy (cross-sectionally), as well as the prognostic utility when used as prognostic markers in the long-term (cohort study). In the diagnostic test accuracy study, the primary outcome is a successful diagnosis using one or more novel index tests at baseline compared with the ECCO criteria as the reference standard. The composite outcome of the prognostic utility study is 'severe IBD' within 52 weeks from inclusion, defined as one or more of the following three events: IBD-related surgery, IBD-related hospitalisation or IBD-related death.
METHODS AND ANALYSIS
We aim to recruit 800 patients referred on suspicion of IBD to this longitudinal observational study, a collaboration between 11 inclusion sites in Denmark, Iceland, Norway and Sweden. Inclusion will occur from February 2022 until December 2023 with screening and baseline visits for all participants and three outcome visits at weeks 12, 26 and 52 after baseline for IBD-diagnosed patients. Biological material (blood, faeces, biopsies, urine and hair), clinical data and lifestyle information will be collected during these scheduled visits.
ETHICS AND DISSEMINATION
This study will explore novel biomarkers to improve diagnostic accuracy and prediction of disease progression, thereby improving medical therapy and the quality of life for patients with IBD.The study is approved by the Ethics Committee (DK: S-20200051, v1.4, 16.10.2021; IS: VSNb2021070006/03.01, NO: 193064; SE: DNR 2021-05090) and the Danish Data Protecting Agency (20/54594). Results will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences.
CLINICAL TRIAL REGISTRATION NUMBER
NCT05414578; Pre-results.
Topics: Humans; Biomarkers; Prognosis; Prospective Studies; Inflammatory Bowel Diseases; Scandinavian and Nordic Countries; Longitudinal Studies; Research Design; Multicenter Studies as Topic; Crohn Disease
PubMed: 38754881
DOI: 10.1136/bmjopen-2023-083144