Notes

ALSUntangled #63: ketogenic diet plans.
These findings suggest that inhibition of the efflux protein, Pgp by C. rodentium can cause perturbations in the intestinal epithelial integrity, which could further lead to the pathogenesis of intestinal inflammation as observed in infectious colitis.Since the initial discovery of mutations in the Armadillo-containing repeat protein 5 gene (ARMC5) in primary bilateral macronodular adrenocortical hyperplasia (PBMAH), efforts have been made to better understand the molecular mechanisms involving ARMC5 in the development of this rare form of Cushing syndrome. It has now been established that germline ARMC5-inactivating mutations, mostly frameshift and nonsense ones, are responsible for roughly 40% of PBMAH cases. ARMC5 is a tumor suppressor gene responsible for a familial form of PBMAH. Furthermore, the presence of inactivating ARMC5 mutations is associated with a more severe CS and hypertension as well as an overall increase in adrenal mass. find more However, ARMC5 inactivation decreases cortisol secretion both in vitro and in vivo (in mice) suggesting that the way that ARMC5 deficiency leads to Cushing syndrome is complicated and maybe not a direct effect of the ARMC5's loss, requiring additional molecular events to take place. Moreover, in silico predicted damaging ARMC5 variants have been identified in patients of African American descent with primary aldosteronism suggesting a potential role of ARMC5 in predisposing to low renin hypertension. Beyond its role in adrenocortical cells, ARMC5 defects has recently been associated with meningioma and T-cell immune response defects in humans and mice, respectively. Herein, we review recent discoveries in ARMC5's role in adrenal pathophysiology and beyond; clearly, we are only at the beginning of understanding the function of this gene with functions in the adrenal gland, the immune system, and elsewhere.Tumor recurrence as a result of therapy-induced nuclear DNA lesions is a major issue in cancer treatment. Currently, only a few examples of potentially non-genotoxic drugs have been reported. Mitochondrial re-localization of ciprofloxacin, one of the most commonly prescribed synthetic antibiotics, is reported here as a new approach. Conjugating ciprofloxacin to a triphenyl phosphonium group (giving lead Mt-CFX), is used to enhance the concentration of ciprofloxacin in the mitochondria of cancer cells. The localization of Mt-CFX to the mitochondria induces oxidative damage to proteins, mtDNA, and lipids. A large bias in favor of mtDNA damage over nDNA was seen with Mt-CFX, contrary to classic cancer chemotherapeutics. Mt-CFX was found to reduce cancer growth in a xenograft mouse model and proved to be well tolerated. Mitochondrial relocalization of antibiotics could emerge as a useful approach to generating anticancer leads that promote cell death via the selective induction of mitochondrially-mediated oxidative damage.Metal-based drugs and imaging agents are extensively used in the clinic for the treatment and diagnosis of cancers and a wide range of other diseases. The current clinical arsenal of compounds operate via a limited number of mechanisms, whereas new putative compounds explore alternative mechanisms of action, which could potentially bring new chemotherapeutic approaches into the clinic. In this review, metal-based drugs and imaging agents are characterized according to their primary mode of action and the key properties and features of each class of compounds are defined, wherever possible. A better understanding of the roles played by metal compounds at a mechanistic level will help to deliver new metal-based therapies to the clinic, by providing an alternative, targeted and rational approach, to supplement non-targeted screening of novel chemical entities for biological activity.During the first three months of the Temple Vie programme, average weight loss in 36 subjects exceeded 13 kg. There were associated improvements in Patient Reported Outcome Measures, blood pressure and serum lipids. The Covid-19 pandemic may focus attention on programmes that give rise to rapid weight loss and improvements in cardiovascular health parameters.
Spinal malignant peripheral nerve sheath tumors (MPNSTs) are extremely rare. Because of vital surroundings, en bloc resection can be difficult in MPNSTs of the cervical spine. Herein, we report three cases of MPNST followed by radiotherapy or carbon ion radiotherapy (CIRT) after surgery.

In case 1, the patient underwent subtotal resection from both a posterior and anterior approach following by adjuvant X-ray radiotherapy. The patient died 13 years after surgery due to liver cancer unrelated to MPNST. In case 2, recurrence spread to the spinal canal in 10 months after primary CIRT. The patient underwent resection of the spinal canal lesion with the residual lesion treated by additional CIRT. Recurrence could be controlled for at least 1 year. In case 3, the patient underwent partial resection for the spinal canal lesion with the residual lesion treated by CIRT. Intradural and extradural recurrences from outside of the CIRT field were observed at 3 years after surgery.

Complete resection and adjuvant X-ray radiotherapy would be an effective treatment for MPNST of the cervical spine, even if en bloc resection with a wide margin is impossible. CIRT for the residual tumor after incomplete resection may have the potential to be an additional treatment option; however, further investigation is warranted.
Complete resection and adjuvant X-ray radiotherapy would be an effective treatment for MPNST of the cervical spine, even if en bloc resection with a wide margin is impossible. CIRT for the residual tumor after incomplete resection may have the potential to be an additional treatment option; however, further investigation is warranted.
We have developed the single or double endplates penetrating screw (SEPS/DEPS) technique, which is a novel percutaneous pedicle screw (PPS) insertion technique suitable for osteoporotic vertebral body fracture (OVF) patients with diffuse idiopathic skeletal hyperostosis (DISH). This study aims to compare the effectiveness of this SEPS/DEPS technique with the conventional pedicle screw technique.

The screw is inserted upward from the outer caudal side of the pedicle toward the inner cranial side. Vertebrae affected with DISH were inserted with screws using the SEPS/DEPS technique, whereas non-fused vertebrae were inserted with screws using the conventional PPS technique. Twelve OVF patients with DISH were included in this study; three with SEPS/DEPS technique only and nine with a hybrid of both the DEPS and the conventional PPS techniques. As a control group, 12 OVF patients with DISH treated by conventional PPS. The rates of implant failures and of surgical complications were compared between the SEPS/DEPS group and the control group.
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