Exploring the parity paradox: Differential effects on neuroplasticity and inflammation by APOEe4 genotype at middle age.

Female sex and Apolipoprotein E (APOE) ε4 genotype are top non-modifiable risk factors for Alzheimer's disease (AD). Although female-unique experiences like parity (pregnancy and motherhood) have positive effects on neuroplasticity at middle age, previous pregnancy may also contribute to AD risk. To explore these seemingly paradoxical long-term effects of parity, we investigated the impact of parity with APOEε4 genotype by examining behavioural and neural biomarkers of brain health in middle-aged female rats. Our findings show that primiparous (parous one time) hAPOEε4 rats display increased use of a non-spatial cognitive strategy and exhibit decreased number and recruitment of new-born neurons in the ventral dentate gyrus of the hippocampus in response to spatial working memory retrieval. Furthermore, primiparity and hAPOEε4 genotype synergistically modulate inflammatory markers in the ventral hippocampus. Collectively, these findings demonstrate that previous parity in hAPOEε4 rats confers an added risk to present with reduced activity and engagement of the hippocampus as well as elevated pro-inflammatory signaling, and underscore the importance of considering female-specific factors and genotype in health research.

Menopausal hormone therapy and the female brain: leveraging neuroimaging and prescription registry data from the UK Biobank cohort.

Background and Objectives: Menopausal hormone therapy (MHT) is generally thought to be neuroprotective, yet results have been inconsistent. Here, we present a comprehensive study of MHT use and brain characteristics in middle- to older aged females from the UK Biobank, assessing detailed MHT data, APOE ε4 genotype, and tissue-specific gray (GM) and white matter (WM) brain age gap (BAG), as well as hippocampal and white matter hyperintensity (WMH) volumes. Methods: A total of 19,846 females with magnetic resonance imaging data were included (current-users = 1,153, 60.1 ± 6.8 years; past-users = 6,681, 67.5 ± 6.2 years; never-users = 12,012, mean age 61.6 ± 7.1 years). For a sub-sample (n = 538), MHT prescription data was extracted from primary care records. Brain measures were derived from T1-, T2- and diffusion-weighted images. We fitted regression models to test for associations between the brain measures and MHT variables including user status, age at initiation, dosage and duration, formulation, route of administration, and type (i.e., bioidentical vs synthetic), as well as active ingredient (e.g., estradiol hemihydrate). We further tested for differences in brain measures among MHT users with and without a history of hysterectomy ± bilateral oophorectomy and examined associations by APOE ε4 status. Results: We found significantly higher GM and WM BAG (i.e., older brain age relative to chronological age) as well as smaller left and right hippocampus volumes in current MHT users, not past users, compared to never-users. Effects were modest, with the largest effect size indicating a group difference of 0.77 years (~9 months) for GM BAG. Among MHT users, we found no significant associations between age at MHT initiation and brain measures. Longer duration of use and older age at last use post menopause was associated with higher GM and WM BAG, larger WMH volume, and smaller left and right hippocampal volumes. MHT users with a history of hysterectomy ± bilateral oophorectomy showed lower GM BAG relative to MHT users without such history. Although we found smaller hippocampus volumes in carriers of two APOE ε4 alleles compared to non-carriers, we found no interactions with MHT variables. In the sub-sample with prescription data, we found no significant associations between detailed MHT variables and brain measures after adjusting for multiple comparisons. Discussion: Our results indicate that population-level associations between MHT use, and female brain health might vary depending on duration of use and past surgical history. Future research is crucial to establish causality, dissect interactions between menopause-related neurological changes and MHT use, and determine individual-level implications to advance precision medicine in female health care.

Round Bodies Detected by Treponema pallidum Immunohistochemical Stain in Two Cases of Cutaneous Syphilitic Gummata.

ABSTRACT: Tertiary syphilis may present a diagnostic challenge due to negative nontreponemal serologies in up to 30% of cases and frequent lack of identifiable spirochetes on histopathology or other direct detection tests. We report 2 cases of round bodies staining with Treponema pallidum immunohistochemistry by light microscopy in biopsies from cutaneous syphilitic gummata. In 1 case, the finding was validated 3 times by 2 independent laboratories; in the other case, T. pallidum was detected by polymerase chain reaction in the biopsy sample. Spirochete round bodies have previously been reported in the setting of electron microscopy and fluorography, but to the best of our knowledge, have not been reported by light microscopy in a routine skin biopsy. Although the clinical implications are unclear, this may represent a helpful new paradigm for the diagnosis of tertiary syphilis.

Teaching a Canadian Experiential Course in Religion and Spirituality for Undergraduates in Addiction Counseling and Health Sciences: A Social Constructivist Framework.

Religion and spirituality (RS) are integral to counseling and health but their incorporation into the curricula of these professions is still lacking. Limited literature is available on how to effectively teach such courses. This article presents a promising experiential, interactive model for an RS course designed for undergraduate students pursuing careers in addictions counseling, therapeutic recreation, and public health. An online course conducted during the COVID-19 pandemic adopted a social constructivist framework that encompassed four key components in its design and delivery: assessing prior knowledge, creating cognitive dissonance, applying new knowledge with feedback, reflecting on learning. Students' feedback in the course indicated their broadened understanding of the plurality of RS orientations and their acquisition of foundational skills with an increased confidence in bringing RS conversations into their practice. This article provides a conceptual and practical framework for educators to develop an RS course for a diverse representation of students and encourages further evaluation of the proposed model to assess its impact on learning outcomes.

Dermatomyositis with Eosinophils.

Dermatomyositis is an idiopathic inflammatory myopathy that often presents with symmetric proximal skeletal muscle weakness and characteristic skin findings. Typical skin biopsy findings include vacuolar changes of the basal layer, increased dermal mucin, and a predominantly lymphocytic infiltrate. We report a case of dermatomyositis presenting as intensely pruritic papules and plaques, with initial histopathology being atypical of dermatomyositis due to the presence of eosinophils. The initial biopsy demonstrated a superficial dermatitis with eosinophils, initially thought to represent a drug eruption. A second biopsy of the same cutaneous manifestation was performed at a later time given high clinical suspicion for dermatomyositis and demonstrated a more classic vacuolar interface dermatitis with increased mucin and an absence of eosinophils. Notably, increased pruritus was specifically associated with the lesion that demonstrated tissue eosinophilia. The case illustrates the importance of considering tissue eosinophilia in the histologic presentation of dermatomyositis.

Evaluation of the efficacy of the Lentulo spiral filler operated at four different speeds and with two different techniques in cadaveric canine teeth of dogs.

This study evaluated the effect of filling technique and rotational speed on the efficacy of sealer cement placement using the Lentulo spiral filler. Cadaveric maxillary and mandibular canine teeth (n = 74) from age and breed matched fresh-frozen adult canine cadaver heads were utilized. Following routine mechano-chemical preparation, teeth were randomly divided into 8 treatment groups with varying rotational speeds [250-2,000 revolutions per minute (RPM)] and fill techniques (backfill technique versus pumping technique). The quality of the sealer cement fill was evaluated radiographically before and after master gutta percha cone placement. Percentage of voids present in the apical, midbody, and coronal portions of the tooth were subjectively scored as: no voids present, voids present in less than 25% of the area, voids present in 25-50% of the area, voids present in greater than 50% of the area. The apex was also scored as underfilled, adequately filled, or overfilled. Operating the Lentulo spiral filler at 2,000 RPM resulted in the best quality fill regardless of filling technique. The pumping technique with placement of the master gutta percha cone had a higher probability of success as compared to the backfill technique, but this finding lacked significance. Regardless of speed or technique, the apical region had the highest quality of fill. The addition of the master gutta percha cone improved the quality of fill. Therefore, we recommend using the Lentulo spiral filler at higher speeds with a pumping technique (followed by addition of a master gutta percha cone) to improve the quality of epoxy resin-based sealer cement placement.

Eosinophils in Traditionally Noneosinophil-Rich Dermatoses.

ABSTRACT: The presence or absence of tissue eosinophilia has previously aided in the diagnosis of inflammatory skin conditions. However, recent studies have elucidated the presence of eosinophils in traditionally eosinophil-poor inflammatory skin diseases, such as dermatomyositis (DM), psoriasis, and lichen sclerosus (LS). This systematic review of the literature explores previous studies of tissue eosinophilia in skin biopsies of dermatoses that are believed to be classically poor in eosinophil. We identified 26 studies, the majority of which were retrospective reviews. The percent of specimens with increased eosinophils in psoriasis ranged from 18%-73%, pityriasis rubra pilaris (PRP) 22%-63%, LS 29%-53%, DM 15%-44%, morphea 8%-45%, hypertrophic lichen planus (LP) 0%-21%, and oral LP 0%-4%. These reports of tissue eosinophilia in reputed eosinophil-poor dermatologic conditions present a diagnostic pitfall and suggest that tissue eosinophilia itself should not be used to rule out a diagnosis of one of these conditions.

Clinical success of guided tissue regeneration for treating vertical bone and furcation defects in dogs.

This study evaluated the clinical success rate of guided tissue regeneration (GTR) for treating advanced periodontal disease in a large canine cohort. A total of 112 GTR procedures performed from 2003-2021 were retrospectively evaluated, including pre- and post-treatment (3-12 months) periodontal probing depths of 104 treated teeth, dental radiographs of 73 treated teeth, and both diagnostic modalities in 64 treated teeth. Probing depth, radiographically apparent bone height, bone graft material, barrier membrane material, and tooth extraction adjacent to the GTR site were investigated as factors affecting success. Vertical bone defects were evaluated separately from furcation defects. GTR was clinically successful, defined as objective improvement in probing depth, objective decrease in radiographic vertical bone defect, and subjective radiographic gain in bone height in 90.3% of vertical bone defects. Success was significantly associated with the magnitude of initial probing depth and the type of barrier membrane used. GTR was clinically successful, defined as objective improvement in furcation probing and subjective radiographic improvement of the bone in the furcation in 22.2% of furcation defects. When F3 lesions were excluded, GTR was successful in 64.3% of furcation defects. GTR is an appropriate treatment to maintain teeth in the oral cavity of dogs with proper client counseling and patient selection, but it is most likely to be successful in vertical defects.

An Anaplastic Thyroid Carcinoma of the Giant-Cell Type from a Mediastinal Ectopic Thyroid Gland.

Anaplastic thyroid carcinoma is a rare, aggressive form of thyroid carcinoma with a mean survival of less than 6 months. Ectopic thyroid tissue can be present in the mediastinum due to faulty embryogenesis with improper descent. Primary thyroid malignancies may arise from this ectopic tissue. A 90-year-old male with a history of prostatic adenocarcinoma, hypothyroidism, and occupational and therapeutic exposure to radiation presented with a rash on his chest. A review of the dermatopathology and excised mediastinal specimen revealed rare papillary foci that tested positive for thyroid markers from a background of poorly differentiated components. Molecular analysis confirmed a BRAF V600E mutation in the specimen. The final diagnosis was anaplastic thyroid carcinoma of the giant-cell type. Given the atrophic cervical thyroid tissue in the patient's neck with no evidence of previous surgery, this carcinoma was believed to arise from ectopic mediastinal tissue associated with cutaneous and bony metastasis. In conclusion, anaplastic thyroid carcinoma is an aggressive and rare thyroid malignancy that can arise from ectopic thyroid tissue in the mediastinum and should be considered in the differential diagnosis of primary undifferentiated mediastinal malignancies with bony involvement.

Genetic variants in the vitamin D pathway and their association with vitamin D metabolite levels: Detailed studies of an inner-city pediatric population suggest a modest but significant effect in early childhood.

OBJECTIVES: In a large cohort of healthy infants and toddlers 6-36 months of age (n = 776), we have been exploring the potential role of genetic variation in predisposition to vitamin D insufficiency. The genes encoding the key cytochrome P450 hydroxylases (CYP2R1, CYP24A1, and CYP27B1) harbour recurrent mutations of uncertain effect. This study was undertaken to look for biochemically relevant associations of these variants with inter-individual differences in vitamin D metabolism in an at-risk pediatric population. METHODS: Genotyping for CYP2R1-CT (c.-1127 C>T, rs10741657), CYP24A1-AG (c.-686A>G, rs111622401), and CYP27B1-CA (c.-1261 C>A, rs10877012) mutations were performed using SNaPshot assay, followed by Sanger sequencing confirmation. Vitamin D metabolites and vitamin D binding protein (DBP) were measured by established methods. RESULTS: In a multivariate regression model, with corrections for co-variates, subjects with the homozygous CYP2R1-TT variant had significantly higher concentrations of 25(OH)D, free 25(OH)D, and 24,25(OH)2D levels. In subjects with the CYP24A1-AG mutation, concentrations of 25(OH)D were significantly higher. CONCLUSIONS: The CYP2R1-TT and CYP24A1-AG variants have measurable effects on the vitamin D pathway. It seems unlikely that they will be clinically relevant in isolation, but they may be members of the large pool of infrequent mutations contributing to different risks for the vitamin D deficiency phenotype.