Age-related differences of γ-aminobutyric acid (GABA)ergic transmission in human colonic smooth muscle

Background: Enteric neurons undergo to functional changes during aging. We investigated the possible age-associated differences in enteric γ-aminobutyric acid (GABA)ergic transmission evaluating function and distribution of GABAergic receptors in human colon. Methods: Mechanical responses to GABA and GABA receptor agonists on slow phasic contractions were examined in vitro as changes in isometric tension in colonic muscle strips from young (<65 years old) and aged patients (>65 years old). GABAergic receptor expression was assessed by quantitative RT-PCR. Key Results: In both preparations GABA induced an excitatory effect, consisting in an increase in the basal tone, antagonized by the GABAA receptor antagonist, bicuculline, and potentiated by phaclofen, GABAB receptor antagonist.Tetrodotoxin (TTX) and atropine-sensitive contractile responses to GABA and GABAA receptor agonist, muscimol, were more pronounced in old compared to young subjects. Baclofen, GABAB receptor agonist, induced a TTX-sensitive reduction of the amplitude of the spontaneous. Nω–nitro-l-arginine methyl ester (L-NAME), nitric oxide (NO) synthase inhibitor abolished the inhibitory responses in old preparations, but a residual responses persisted in young preparations, which in turn was abolished by suramin, purinergic receptor antagonist. α3–GABAA receptor subunit expression tends to change in an age-dependent manner. Conclusions and inferences: Our results reveal age-related differences in GABAergic transmission in human colon. At all the age tested GABA regulates muscular contractility modulating the activity of the intrinsic neurons. Activation of GABAA receptor, through acetylcholine release, induces contraction, which increases in amplitude with age. GABAB receptor activation leads to neural release of NO and purines, being a loss of purinergic-component in aged group

DNA damage response at telomeres boosts the transcription of SARS-CoV-2 receptor ACE2 during aging

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19), known to be more common in the elderly, who also show more severe symptoms and are at higher risk of hospitalization and death. Here, we show that the expression of the angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 cell receptor, increases during aging in mouse and human lungs. ACE2 expression increases upon telomere shortening or dysfunction in both cultured mammalian cells and in vivo in mice. This increase is controlled at the transcriptional level, and Ace2 promoter activity is DNA damage response (DDR)-dependent. Both pharmacological global DDR inhibition of ATM kinase activity and selective telomeric DDR inhibition by the use of antisense oligonucleotides prevent Ace2 upregulation following telomere damage in cultured cells and in mice. We propose that during aging telomere dysfunction due to telomeric shortening or damage triggers DDR activation and this causes the upregulation of ACE2, the SARS-CoV-2 cell receptor, thus contributing to make the elderly more susceptible to the infection

SARS-CoV-2 infection induces DNA damage, through CHK1 degradation and impaired 53BP1 recruitment, and cellular senescence

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the RNA virus responsible for the coronavirus disease 2019 (COVID-19) pandemic. Although SARS-CoV-2 was reported to alter several cellular pathways, its impact on DNA integrity and the mechanisms involved remain unknown. Here we show that SARS-CoV-2 causes DNA damage and elicits an altered DNA damage response. Mechanistically, SARS-CoV-2 proteins ORF6 and NSP13 cause degradation of the DNA damage response kinase CHK1 through proteasome and autophagy, respectively. CHK1 loss leads to deoxynucleoside triphosphate (dNTP) shortage, causing impaired S-phase progression, DNA damage, pro-inflammatory pathways activation and cellular senescence. Supplementation of deoxynucleosides reduces that. Furthermore, SARS-CoV-2 N-protein impairs 53BP1 focal recruitment by interfering with damage-induced long non-coding RNAs, thus reducing DNA repair. Key observations are recapitulated in SARS-CoV-2-infected mice and patients with COVID-19. We propose that SARS-CoV-2, by boosting ribonucleoside triphosphate levels to promote its replication at the expense of dNTPs and by hijacking damage-induced long non-coding RNAs’ biology, threatens genome integrity and causes altered DNA damage response activation, induction of inflammation and cellular senescence

Pengaruh Model Pembelajaran Matematika Knisley terhadap Pemahaman Konsep Matematis Siswa Kelas X

This research aims to determine the effect of the Knisley mathematics learning model on the understanding of mathematical concepts in class X SMA Negeri 2 Kabanjahe. This research was conducted using a sample of 2 classes, namely the Experiment class and the Control class. The form of test that is tested on students is an initial test (pretest), then the researcher provides treatment in the experimental teaching class using the Knisley Mathematics Learning Model and in the control class using the direct learning model, Then a posttest was given to both classes. The data obtained were analyzed using the t test. The results showed that the pretest average in the experimental and control classes was the same as tested using the average similarity test (two-way test) and met   namely so  accepted. For the posttest average equality test (right side test), it was concluded that the posttest average in the experimental class was greater than the control class because it met the requirements, namely 11.6111559 > 1.66907, so  was rejected and the conclusion was obtained that there was an influence Knisley's mathematics learning model for understanding mathematical concepts for class X

The chemical composition of the aerial parts essential oil of Ammi crinitum Guss. (Apiaceae) endemic of Sicily (Italy)

Ammi L. is a small genus of economically important plants belonging to Apiaceae family that includes only six taxa. In the present study the chemical composition of the essential oil from aerial parts of Ammi crinitum Guss., a very rare plant, endemic of Sicily, was analyzed by GC–MS. No previously paper has been published on this species. The results showed the presence of large quantity of monoterpene hydrocarbons with sabinene (63.9%), as the most abundant component. Other metabolites present in good quantity were γ-terpinene (8.0%), and 4-terpineol (3.7%). Based on the composition of the essential oil of all the other Ammi taxa, several considerations have been carried out

[Ultrasonography features of the diaphragmatic crura: normal anatomy and its variants].

To report the various US patterns of the diaphragmatic crura and the changes occurring during the different phases of respirations. The diaphragm has two US patterns: the central membranous part appears highly reflective while the posterior, upper and lateral muscular portions are hypoechoic and thick. The crura can sometimes appear quite bulky, which appearance is easy to misinterpret.We carried out a three-stage work: first we reviewed the US examinations of 23 subjects with a nodular appearance of the posteromedial bundles and studied the changes in thickness during respiration. Second we studied the diaphragmatic crura in 30 subjects aged 18-71 years, 15 men and 15 women. We used a commercially available unit with sector and convex 3.5 MHz probes at baseline and during breath hold and acquired multiple parasagittal and transverse scans. The crura thickness was measured in all patients. Last, we studied the diaphragmatic regions of 10 patients with right pleural effusion and of 8 patients with associated ascites and pleural effusion using 2.0-5.0 MHz convex phased-array transducers.We found focal thickening of the crura in 11 of 23 patients with US findings of diaphragmatic nodules, but only in deep inspiration. The thickening was 1.5-2.2 cm long and maximum thickness was 10 mm. In the other 12 subjects we found 9 small lobules in the right and 3 in the left crus. In the anatomic study, we observed a 3-band appearance of the diaphragmatic crura, probably referable to muscle bundles, in 30 subjects on sagittal images, in 12 on coronal images and in 28 on anterior transverse images. The diaphragmatic crura were identified in 26 subjects only. The left posterior crus was identified in 29 subjects on left coronal images and in 15 on anterior transverse images; it was demonstrated on anterior sagittal images in close proximity to the aorta in only 4 subjects. Right crus thickness, measured on sagittal scans, ranged 3-10 mm in deep inspiration and 1-4 mm in expiration while the left crus was 3-6 mm in inspiration and 1-2 mm in expiration. The length of the right crus, studied in the preaortic portion, ranged from 7 cm in deep inspiration to 9.7 cm in expiration while the left one was 6.5 to 8.8 cm. The right lateral diaphragmatic bundles were seen in 28 subjects only on repeated subcostal oblique scans and the the left ones in 11 subjects only. Finally the thin anterior bundles were shown on parasagittal images in 13 cases in the right side and in 2 in the left. A 2-band appearance of the diaphragm was seen in 10 patients with pleural effusion and in 8 patients with associated ascites. A single band was found only in the tendinous portion of the diaphragm.US is presently considered the imaging method of choice in the assessment of changes in thickness and length of the diaphragmatic crura. These structures have different US patterns and can sometimes appear quite bulky and thus be easily mistaken for other anatomic or abnormal structures; orthogonal scans may be required for the differential diagnosis

Preoperative Risk Factors for Periprosthetic Joint Infection: A Narrative Review of the Literature

Periprosthetic joint infection (PJI) poses a challenging complication for many patients undergoing arthroplasty, and the literature identifies numerous risk factors. A comprehensive understanding of the primary risk and protective factors for PJI is valuable for surgeons. This article aims to compile and summarize the key risk factors for PJI documented in the literature. Some risk factors are related to the nutritional status of patients, with obesity, weight loss, hypovitaminosis, and malnutrition being frequently reported. Pathologies affecting patients also contribute to PJI risk, including septic arthritis, hepatitis, diabetes, urinary tract infections, anemia, hypothyroidism, osteoporosis, and dental pathologies. Unhealthy habits, such as tobacco and drug abuse, are significant factors. Previous corticosteroid injections may also play a role in infection development. A few protective factors are also reported in the literature (use of statins, preoperative decolonization, and preadmission skin preparation). The identification of risk factors and the implementation of evidence-based preoperative protocols are essential steps in reducing the incidence of PJI

Myelolipoma of the adrenal gland: sonographic and CT features.

The radiologic findings in 13 patients with pathologically proved adrenal myelolipomas were reviewed. All lesions involved the right adrenal gland; they ranged from 2 to 9 cm in diameter. Sonograms showed hyperechoic tumors in 11 cases (five homogeneous, six heterogeneous). Two myelolipomas composed primarily of myeloid tissue were hypoechoic. A propagation speed artifact was seen in seven lesions, all of which were composed primarily of fat and larger than 4 cm. CT identified fat-density tissues in all lesions. Contrast-enhanced CT showed positive attenuation values in the two predominantly myeloid tumors. CT appears to be sensitive for the diagnosis of adrenal myelolipomas. However, precontrast images are required to avoid error