Chronic Stress as a Risk Factor for Type 2 Diabetes: Endocrine, Metabolic, and Immune Implications.

BACKGROUND: Chronic stress is a condition of pressure on the brain and whole body, which in the long term may lead to a frank disease status, even including type 2 diabetes (T2D). Stress activates the hypothalamus-pituitary-adrenal axis with release of glucocorticoids (GCs) and catecholamines, as well as activation of the inflammatory pathway of the immune system, which alters glucose and lipid metabolism, ultimately leading to beta-cell destruction, insulin resistance and T2D onset. Alteration of the glucose and lipid metabolism accounts for insulin resistance and T2D outcome. Furthermore, stress-related subversion of the intestinal microbiota leads to an imbalance of the gut-brain-immune axis, as evidenced by the stress-related depression often associated with T2D. Inflammatory mechanisms: A condition of generalized inflammation and subversion of the intestinal microbiota represents another facet of stress-induced disease. In fact, chronic stress acts on the gut-brain axis with multi-organ consequences, as evidenced by the association between depression and T2D. Novel Therapeutic Options: Oxidative stress with the production of reactive oxygen species and cytokine-mediated inflammation represents the main hallmarks of chronic stress. ROS production and pro-inflammatory cytokines represent the main hallmarks of stress-related disorders, and therefore, the use of natural antioxidant and anti-inflammatory substances (nutraceuticals) may offer an alternative therapeutic approach to combat stress-related T2D. Single or combined administration of nutraceuticals would be very beneficial in targeting the neuro-endocrine-immune axis, thus, regulating major pathways involved in T2D onset. However, more clinical trials are needed to establish the effectiveness of nutraceutical treatment, dosage, time of administration and the most favorable combinations of compounds. Therefore, in view of their antioxidant and anti-inflammatory properties, the use of natural products or nutraceuticals for the treatment of stress-related diseases, even including T2D, will be discussed. Several evidences suggest that chronic stress represents one of the main factors responsible for the outcome of T2D.

Thyroid and COVID-19: a review on pathophysiological, clinical and organizational aspects.

BACKGROUND: Thyroid dysfunction has been observed in patients with COVID-19, and endocrinologists are requested to understand this clinical issue. Pandemic-related restrictions and reorganization of healthcare services may affect thyroid disease management. OBJECTIVE AND METHODS: To analyze and discuss the relationship between COVID-19 and thyroid diseases from several perspectives. PubMed/MEDLINE, Google Scholar, Scopus, ClinicalTrial.gov were searched for this purpose by using free text words and medical subject headings as follows: "sars cov 2", "covid 19", "subacute thyroiditis", "atypical thyroiditis", "chronic thyroiditis", "hashimoto's thyroiditis", "graves' disease", "thyroid nodule", "differentiated thyroid cancer", "medullary thyroid cancer", "methimazole", "levothyroxine", "multikinase inhibitor", "remdesivir", "tocilizumab". Data were collected, analyzed, and discussed to answer the following clinical questions: "What evidence suggests that COVID-19 may induce detrimental consequences on thyroid function?"; "Could previous or concomitant thyroid diseases deteriorate the prognosis of COVID-19 once the infection has occurred?"; "Could medical management of thyroid diseases influence the clinical course of COVID-19?"; "Does medical management of COVID-19 interfere with thyroid function?"; "Are there defined strategies to better manage endocrine diseases despite restrictive measures and in-hospital and ambulatory activities reorganizations?". RESULTS: SARS-CoV-2 may induce thyroid dysfunction that is usually reversible, including subclinical and atypical thyroiditis. Patients with baseline thyroid diseases are not at higher risk of contracting or transmitting SARS-CoV-2, and baseline thyroid dysfunction does not foster a worse progression of COVID-19. However, it is unclear whether low levels of free triiodothyronine, observed in seriously ill patients with COVID-19, may worsen the disease's clinical progression and, consequently, if triiodothyronine supplementation could be a tool for reducing this burden. Glucocorticoids and heparin may affect thyroid hormone secretion and measurement, respectively, leading to possible misdiagnosis of thyroid dysfunction in severe cases of COVID-19. High-risk thyroid nodules require a fine-needle aspiration without relevant delay, whereas other non-urgent diagnostic procedures and therapeutic interventions should be postponed. DISCUSSION: Currently, we know that SARS-CoV-2 could lead to short-term and reversible thyroid dysfunction, but thyroid diseases seem not to affect the progression of COVID-19. Adequate management of patients with thyroid diseases remains essential during the pandemic, but it could be compromised because of healthcare service restrictions. Endocrine care centers should continuously recognize and classify priority cases for in-person visits and therapeutic procedures. Telemedicine may be a useful tool for managing patients not requiring in-person visits.

Effects of botulinum neurotoxin on spatio-temporal gait parameters of patients with chronic stroke: a prospective open-label study.

BACKGROUND: Nowadays, administration of botulinum neurotoxin type A is considered a safe, well tolerated and effective treatment for muscles tone reduction in focal spasticity care. Lack of evidence regards instead its functional role on gait parameters, as well patterns. AIM: To assess the botulinum neurotoxin treatment efficacy on chronic poststroke subjects, in order to investigate its functional effects on spatio-temporal gait parameters, in addition to the evaluation of spasticity grade based on clinical scales. DESIGN: A prospective open-label study along 16-weeks trials. SETTING: Outpatient neurophysiology rehabilitation structure and laboratory of movement and gait analysis. POPULATION: Twenty chronic poststroke patients, suffering from equinovarus foot deformity, with a stabilized hemiparesis were recruited according to inclusion criteria of the protocol. METHODS: Single neurotoxin-based local intramuscular injections were given according to a specific protocol concerning both the considered muscles and the relative toxin doses, with a maximum total dose ranged between 200 U and 400 U. Patients were observed both at baseline (t0) and for 4 following monthly visits (t1, t2, t3, t4) after injections at baseline. Gait analysis sessions were performed at each visit, by means of a video-cameras based system and body reflective markers attached to the body, based on a protocol. Authors focus on both global and local gait temporospatial parameters, such as walking speed, stride-length, cadence, stride-time, step-width, single limb support, double support and limp index to point out the functional changes due to the treatment. For comparison prior to and after the treatment, clinical scales like Modified Ashworth Scale, Berg Balance Scale and Rivermead Mobility Index have been also considered. RESULTS: Subsequent to the neurotoxin intramuscular injections, patients reported statistical significant gait improvements after 90 days (t3) regarding temporospatial parameters: (P<0.05) for walking speed, single limb support and double support and (P<0.10) for stride-length, stride-time, cadence and step-width. CONCLUSION: The botulinum neurotoxin treatment has demonstrated its efficacy for a functional recovery of gait, as pointed out by a statistically significant improvement of some spatio-temporal parameters. Thus, the analyzed changes reveal an improved balance and self-confidence in gait. Studies involving a wider population data are nevertheless needed to better confirm this efficacy. CLINICAL REHABILITATION IMPACT: The poststroke botulinum neurotoxin-based treatment is a safe and potentially useful neurorehabilitative approach for the analyzed data.