How does the formation of the blood-testis barrier (BTB), as reflected by the expression of connexin 43 and claudin 11 proteins during the pubertal transition period, take place in vitro compared to ...samples from a large cohort of pre/peripubertal boys?
The BTB connexin 43 and claudin 11 expression patterns appeared to be partially achieved in organotypic culture when compared to that in samples from 71 pre/peripubertal patients.
Although alterations in the protein expression patterns of the BTB, whose main components are connexin 43 and claudin 11, are known to be associated with impaired spermatogenesis in mice and adult men, there is a lack of knowledge on its formation in pre-peripubertal human tissue both in vitro and in vivo. Moreover, despite Sertoli cell (SC) maturation during long-term organotypic culture of immature testicular tissue (ITT), initiation of spermatogenesis has not yet been achieved.
Histological sections from 71 pre-peripubertal patients were evaluated for the formation of the BTB acting as in vivo controls according to age, SC maturation, clinical signs of puberty and germ cell differentiation. Testicular tissue fragments retrieved from three prepubertal boys were cultured in a long-term organotypic system to analyze the BTB formation and expression pattern in correlation with SC maturation.
Testicular histological sections from 71 patients aged 0-16 years who underwent a biopsy between 2005 and 2014 to preserve their fertility before gonadotoxic treatment were examined. Immunohistochemistry (IHC) results for connexin 43 and claudin 11 as BTB markers, using a semi-quantitative score for their expression, and for Anti-Mullerian hormone (AMH), as SC maturation marker, were analyzed. Germ cell differentiation was evaluated on Hematoxylin-Eosin sections. Tanner stages at the time of biopsy were recorded from medical files. A longitudinal analysis of connexin 43, claudin 11 and AMH expressions on immunohistological sections of organotypic cultured testicular tissue from three prepubertal boys who underwent a biopsy for fertility preservation was performed. Immunostaining was evaluated at culture Days 0, 1, 3, 10, 16, 27, 32, 53, 64 and 139 for two different types of culture media.
Immunohistochemical control sections showed progressive maturation of SCs, as shown by the decrease in AMH expression, with increasing age (P ≤ 0.01) and the AMH expression was negatively correlated with the expression of connexin 43 and claudin 11 (P ≤ 0.01 for both proteins). Androgen receptor (AR) expression increased with age (P ≤ 0.01) and was significantly correlated with the expression of connexin 43 (P = 0.002) and claudin 11 (P = 0.03). A statistical correlation was also found between the reduction of AMH expression and both the advancement of Tanner stages (P ≤ 0.01) and the differentiation of germ cells (P ≤ 0.01). Furthermore, positive correlations between BTB formation (using connexin 43 and claudin 11 expression) and age (P ≤ 0.01 for both the proteins), higher Tanner stages (P ≤ 0.001 and P ≤ 0.01 for connexin 43 and claudin 11, respectively), and presence of more advanced germ cells (P ≤ 0.001 for both proteins) were observed. In the subanalysis on organotypic cultured ITT, where a significant decrease in AMH expression as a marker of SC maturation was already reported, we showed the onset of expression of connexin 43 at Day 16 (P ≤ 0.001) and a constant expression of claudin 11 from Days 0 to 139, for all three patients, without differences between the two types of culture media.
N/A.
Accessibility of prepubertal human testicular tissue is a major limiting factor to the analysis of cultured tissue samples from a wide number of patients, as would be needed to assess the in vitro development of the BTB according to the age. The impossibility of performing longitudinal studies on in vivo BTB formation in the same patient prevents a comparison of the time needed to achieve effective BTB formation and protein expression patterns in vivo and in vitro.
To the best of our knowledge, this is the first report describing the expression of two BTB proteins in samples from a cohort of prepubertal and peripubertal boys, for the in vivo pattern, and in cultured ITT from a few prepubertal boys, for the in vitro evaluation. Since the formation of this barrier is essential for spermatogenesis and because little is known about its protein expression patterns and development in humans, a deeper understanding of the testicular microenvironment is essential to improve ITT in vitro culture conditions. The final aim is to restore fertility by acheiving in vitro differentiation of spermatogonial stem cells, using cryopreserved ITT collected before gonadotoxic therapies.
Funding was received from Fonds National de la Recherche Scientifique de Belgique (Grant Télevie Nos. 7.4554.14F and 7.6511.16) and Fondation Salus Sanguinis. No conflict of interest has to be disclosed.
Psychological characteristics, such as depression, anxiety or negative illness perception are highly prevalent in patients with several types of OA. It is unclear whether there are differences in the ...clinical and psychological characteristics of patients with thumb carpometacarpal (CMC-1) osteoarthritis (OA) scheduled for nonsurgical treatment and those with surgical treatment.
(1) What are the differences in baseline sociodemographic characteristics and clinical characteristics (including pain, hand function, and health-related quality of life) between patients with thumb CMC-1 OA scheduled for surgery and those treated nonoperatively? (2) What are the differences in psychological characteristics between patients scheduled for surgery and those treated nonsurgically, for treatment credibility, expectations, illness perception, pain catastrophizing, and anxiety and depression? (3) What is the relative contribution of baseline sociodemographic, clinical, and psychological characteristics to the probability of being scheduled for surgery?
This was a cross-sectional study using observational data. Patients with CMC-1 OA completed outcome measures before undergoing either nonsurgical or surgical treatment. Between September 2017 and June 2018, 1273 patients were screened for eligibility. In total, 584 participants were included: 208 in the surgery group and 376 in the nonsurgery group. Baseline sociodemographic, clinical, and psychological characteristics were compared between groups, and a hierarchical logistic regression analysis was used to investigate the relative contribution of psychological characteristics to being scheduled for surgery, over and above clinical and sociodemographic variables. Baseline measures included pain, hand function, satisfaction with the patient's hand, health-related quality of life, treatment credibility and expectations, illness perception, pain catastrophizing, and anxiety and depression.
Patients in the surgery group had longer symptom duration, more often a second opinion, higher pain, treatment credibility and expectations and worse hand function, satisfaction, HRQoL, illness perception and pain catastrophizing compared with the non-surgery group (effect sizes ranged from 0.20 to 1.20; p values ranged from < 0.001 to 0.044). After adjusting for sociodemographic, clinical, and psychological factors, we found that the following increased the probability of being scheduled for surgery: longer symptom duration (standardized odds ratio SOR, 1.86; p = 0.004), second-opinion visit (SOR, 3.81; p = 0.027), lower satisfaction with the hand (SOR, 0.65; p = 0.004), higher treatment expectations (SOR, 5.04; p < 0.001), shorter perceived timeline (SOR, 0.70; p = 0.011), worse personal control (SOR, 0.57; p < 0.001) and emotional response (SOR, 1.40; p = 0.040). The hierarchical logistic regression analysis including sociodemographic, clinical, and psychological factors provided the highest area under the curve (sociodemographics alone: 0.663 95% confidence interval 0.618 to 0.709; sociodemographics and clinical: 0.750 95% CI 0.708 to 0.791; sociodemographics, clinical and psychological: 0.900 95% CI 0.875 to 0.925).
Patients scheduled to undergo surgery for CMC-1 OA have a worse psychological profile than those scheduled for nonsurgical treatment. Our findings suggest that psychological characteristics should be considered during shared decision-making, and they might indicate if psychological interventions, training in coping strategies, and patient education are needed. Future studies should prospectively investigate the influence of psychological characteristics on the outcomes of patients with CMC-1 OA.
Level III, therapeutic study.
Vertebrates obtain the prohormone vitamin D primarily by endogenous cutaneous synthesis under ultraviolet b (UVb) exposure. To date, endogenous synthesis of vitamin D in insects has never been ...investigated. In an initial experiment, we exposed four insect species which differ in ecology and morphology (migratory locusts, house crickets, yellow mealworms and black soldier fly larvae (BSFL)) to a low irradiance UVb source. In a second experiment we exposed these species to a higher UV irradiance, and in a third we tested the effect of exposure duration on vitamin D concentrations in yellow mealworms. Low irradiance UVb tended to increase vitamin D
levels in house crickets, vitamin D
levels in BSFL and vitamin D
and D
in yellow mealworms. Higher UVb irradiance increased vitamin D
levels in all species but BSFL. Both BSFL and migratory locusts had increased vitamin D
levels. Longer UVb exposure of yellow mealworms increased vitamin D
and increased vitamin D
until a plateau was reached at 6400 IU/kg. This study shows that insects can synthesize vitamin D de novo and that the amounts depend on UVb irradiance and exposure duration.
There is strong circumstantial evidence that certain heavy, unstable atomic nuclei are 'octupole deformed', that is, distorted into a pear shape. This contrasts with the more prevalent rugby-ball ...shape of nuclei with reflection-symmetric, quadrupole deformations. The elusive octupole deformed nuclei are of importance for nuclear structure theory, and also in searches for physics beyond the standard model; any measurable electric-dipole moment (a signature of the latter) is expected to be amplified in such nuclei. Here we determine electric octupole transition strengths (a direct measure of octupole correlations) for short-lived isotopes of radon and radium. Coulomb excitation experiments were performed using accelerated beams of heavy, radioactive ions. Our data on (220)Rn and (224)Ra show clear evidence for stronger octupole deformation in the latter. The results enable discrimination between differing theoretical approaches to octupole correlations, and help to constrain suitable candidates for experimental studies of atomic electric-dipole moments that might reveal extensions to the standard model.
Background
New dental materials are introduced and promoted in the field without extensive clinical testing. Using those materials in a clinical setting might result in unacceptable early failure ...rates.
Purpose
The purpose of this paper was to analyze bonding of a new dental restorative material to either zirconia stock abutments or zirconia customized abutments.
Materials and Methods
Fifty participants seeking single implant treatment were included in a prospective study. Resin Nano Ceramic (RNC, Lava Ultimate, 3M ESPE, Seefeld, Germany) crowns were digitally manufactured and extraorally bonded to either a stock or a customized zirconia abutment (ZirDesign and ATLANTIS, DENTSPLY Implants, Mölndal, Sweden) by means of a resin composite cement (RelyX Ultimate in combination with Scotchbond Universal, 3M ESPE), strictly following the manufacturer's recommendations. The final restorations were screw‐retained to the implants and followed during 12 months. Primary outcome parameter was uncompromised survival of the restoration, and secondary outcome parameter was mode of failure.
Results
No implants were lost. The uncompromised survival rate of the RNC crowns bonded to zirconia abutments after 1 year of clinical service was only 14% (n = 7). Catastrophic failure occurred in three cases (6%), whereas bonding failure between RNC crowns and zirconia abutments occurred in 80% of the cases (n = 40) within the first year of service. No statistical significant difference in uncompromised survival rate could be identified between abutment types (χ2 = 1.495, p = .209). Uncompromised survival rate after 1 year was highly significantly different (χ2 = 104.173, p < .001) from a reference standard, which was set at 95%.
Conclusion
RNC crowns luted to stock and customized zirconia implant abutments with the particular resin composite cement in this trial have a poor prognosis, regardless of the abutment type used.
Differentiated vulvar intraepithelial neoplasia (dVIN) is the precursor of human papillomavirus (HPV)-independent vulvar squamous cell carcinoma (VSCC). Given the rare incidence of dVIN, limited ...information on the exact cancer risk is available. We systematically reviewed the primary and recurrent VSCC risk in patients with dVIN, as well as the time to cancer development. A systematic search was performed up to July 2021 according to the PRISMA guidelines. Five reviewers independently screened articles on title, abstract and full text, followed by critical appraisal of selected articles using the Quality in Prognostic Studies (QUIPS) tool. Of the 455 screened articles, 7 were included for analysis. The absolute risk for primary VSCC in dVIN varied between 33 and 86%, with a median time to progression to VSCC of 9-23 months. The risk of developing recurrent VSCC in dVIN associated VSCC was 32-94%, with a median time to recurrence of 13-32 months. In conclusion, patients with dVIN have a high risk of developing primary and recurrent VSCC with a short time to cancer progression. Increased awareness, timely recognition, aggressive treatment and close follow-up of HPV-independent vulvar conditions including dVIN is therefore strongly recommended.
The circadian system in mammals ensures adaptation to the light-dark cycle on Earth and imposes 24-h rhythmicity on metabolic, physiological and behavioral processes. The central circadian pacemaker ...is located in the brain and is entrained by environmental signals called Zeitgebers. From here, neural, humoral and systemic signals drive rhythms in peripheral clocks in nearly every mammalian tissue. During pregnancy, disruption of the complex interplay between the mother’s rhythmic signals and the fetal developing circadian system can lead to long-term health consequences in the offspring. When an infant is born very preterm, it loses the temporal signals received from the mother prematurely and becomes totally dependent on 24/7 care in the Neonatal Intensive Care Unit (NICU), where day/night rhythmicity is usually blurred. In this literature review, we provide an overview of the fetal and neonatal development of the circadian system, and short-term consequences of disruption of this process as occurs in the NICU environment. Moreover, we provide a theoretical and molecular framework of how this disruption could lead to later-life disease. Finally, we discuss studies that aim to improve health outcomes after preterm birth by studying the effects of enhancing rhythmicity in light and noise exposure.
In many physical therapy programs for subjects with adhesive capsulitis of the shoulder, mobilization techniques are an important part of the intervention. The purpose of this study was to compare ...the effectiveness of high-grade mobilization techniques (HGMT) with that of low-grade mobilization techniques (LGMT) in subjects with adhesive capsulitis of the shoulder.
One hundred subjects with unilateral adhesive capsulitis lasting 3 months or more and a > or =50% decrease in passive joint mobility relative to the nonaffected side were enrolled in this study.
Subjects randomly assigned to the HGMT group were treated with intensive passive mobilization techniques in end-range positions of the glenohumeral joint, and subjects in the LGMT group were treated with passive mobilization techniques within the pain-free zone. The duration of treatment was a maximum of 12 weeks (24 sessions) in both groups. Subjects were assessed at baseline and at 3, 6, and 12 months by a masked assessor. Primary outcome measures included active and passive range of motion and shoulder disability (Shoulder Rating Questionnaire SRQ and Shoulder Disability Questionnaire SDQ). An analysis of covariance with adjustments for baseline values and a general linear mixed-effect model for repeated measurements were used to compare the change scores for the 2 treatment groups at the various time points and over the total period of 1 year, respectively.
Overall, subjects in both groups improved over 12 months. Statistically significant greater change scores were found in the HGMT group for passive abduction (at the time points 3 and 12 months), and for active and passive external rotation (at 12 months). A statistically significant difference in trend between both groups over the total follow-up period of 12 months was found for passive external rotation, SRQ, and SDQ with greater change scores in the HGMT group.
In subjects with adhesive capsulitis of the shoulder, HGMTs appear to be more effective in improving glenohumeral joint mobility and reducing disability than LGMTs, with the overall differences between the 2 interventions being small.
The amount of time spent living with disease greatly influences elderly people's wellbeing, disability and healthcare costs, but differs by disease, age and sex.
We assessed how various single and ...combined diseases differentially affect life years spent living with disease in Dutch elderly men and women (65+) over their remaining life course. Multistate life table calculations were applied to age and sex-specific disease prevalence, incidence and death rates for the Netherlands in 2007. We distinguished congestive heart failure, coronary heart disease (CHD), breast and prostate cancer, colon cancer, lung cancer, diabetes, COPD, stroke, dementia and osteoarthritis.
Across ages 65, 70, 75, 80 and 85, CHD caused the most time spent living with disease for Dutch men (from 7.6 years at age 65 to 3.7 years at age 85) and osteoarthritis for Dutch women (from 11.7 years at age 65 to 4.8 years at age 85). Of the various co-occurrences of disease, the combination of diabetes and osteoarthritis led to the most time spent living with disease, for both men (from 11.2 years at age 65 to 4.9 -years at age 85) and women (from 14.2 years at age 65 to 6.0 years at age 85).
Specific single and multi-morbid diseases affect men and women differently at different phases in the life course in terms of the time spent living with disease, and consequently, their potential disability. Timely sex and age-specific interventions targeting prevention of the single and combined diseases identified could reduce healthcare costs and increase wellbeing in elderly people.
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