The decline in stroke hospitalization due to COVID-19 is unrelated to COVID-19 intensity.

BACKGROUND AND PURPOSE: During the coronavirus disease 2019 (COVID-19) pandemic many countries reported a decline in stroke volumes. The aim of this study was to analyze if the decline was related to the intensity of the COVID-19 pandemic. METHODS: The first pandemic year (1 March 2020 to 28 February 2021) overall and during the three COVID-19 waves were compared with the preceding year. Volumes of acute ischaemic stroke (AIS), subarachnoid hemorrhage, intracerebral hemorrhage and recanalization treatments (intravenous thrombolysis [IVT] and mechanical thrombectomy [MT]) were obtained from the National Register of Reimbursed Health Services. Door-to-needle time, onset-to-door time and National Institutes of Health Stroke Scale at admission were obtained from the Registry of Stroke Care Quality. RESULTS: During the pandemic year compared to the preceding year there were 26,453 versus 28,771 stroke admissions, representing an 8.8% decline (p < 0.001). The declines (-10%, -11%, -19%) appeared in COVID-19 waves (spring 2020, autumn 2020, winter 2021) except for an increase (2%) during summer 2020. Admissions for AIS declined by 10.2% (p < 0.001), whilst hemorrhagic stroke volumes were minimally decreased. The absolute volumes of IVT and MT decreased by 9.4% (p < 0.001) and 5.7% (p = 0.16), respectively. However, the proportions of ischaemic stroke patients receiving IVT (18% vs. 18%; p = 0.72) and MT (6% vs. 6%; p = 0.28) remained unchanged. CONCLUSIONS: There was a decline in stroke admissions, but such decline was not related to COVID-19 incidence. The frequency of use of recanalization procedures (IVT, MT) and times (onset-to-door time, door-to-needle time) in AIS were preserved in the Czech Republic during the first year of the pandemic.

Is non-invasive brain stimulation effective for cognitive enhancement in Alzheimer's disease? An updated meta-analysis.

OBJECTIVE: Alzheimer's disease dementia (AD) and its preclinical stage, mild cognitive impairment (MCI), are critical issues confronting the aging society. Non-invasive brain stimulation (NIBS) techniques have the potential to be effective tools for enhancing cognitive functioning. The main objective of our meta-analysis was to quantify and update the status of the efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) and Transcranial Direct Current Stimulation (tDCS) when applied in AD and MCI. METHODS: The systematic literature search was conducted in PubMed and Web of Science according to PRISMA statement. RESULTS: Pooled effect sizes (Hedges' g) from 32 studies were analyzed using random effect models. We found both, rTMS and tDCS to have significant immediate cognition-enhancing effect in AD with rTMS inducing also beneficial long-term effects. We found no evidence for synergistic effect of cognitive training with NIBS. CONCLUSIONS: In AD a clinical recommendation can be made for NEURO-ADTM system and for high-frequency rTMS over the left dorsolateral prefrontal cortex (DLPFC) as probably effective protocols (B-level of evidence) and for anodal tDCS over the left DLPFC as a possibly effective. SIGNIFICANCE: According to scientific literature, NIBS may be an effective method for improving cognition in AD and possibly in MCI.

Delayed timing of successful spawning of an estuarine dependent fish, black bream Acanthopagrus butcheri.

In this paper, we investigate the period of successful spawning for black bream Acanthopagrus butcheri, an obligate estuarine species in southern Australia that typically spawn in spring and early summer. However, back-calculated spawning dates of juveniles sampled in Gippsland Lakes, Victoria from February to May 2016 indicated that spawning was concentrated over a short period in the Austral mid-summer (January), with a second spawning in late summer and early autumn (late February-early March). Ichthyoplankton sampling in the tributary estuaries from October to early December collected substantial numbers of fish larvae, dominated by gobiids, eleotrids and retropinnids of freshwater origin, but no A. butcheri. The lack of A. butcheri larvae was consistent with the delayed successful spawning indicated by juvenile otolith data. Freshwater flows declined from late winter to summer, with consistent salinity stratification of the water column. Dissolved oxygen (DO) concentrations were generally very low below the halocline. These conditions may have delayed the upstream spawning migration of adults or may have been unsuitable for survival of eggs and newly-hatched larvae. Longer-term predictions for climate change in southern Victoria, including the Gippsland Lakes region, are for lower winter-spring freshwater flows, potentially benefiting the reproductive success of A. butcheri through high water-column stratification, but only if DO concentrations are not compromised by a lack of high winter flows needed to flush low DO water from the system.

Chromium is not an essential trace element for mammals: effects of a "low-chromium" diet.

Chromium was proposed to be an essential trace element over 50 years ago and has been accepted as an essential element for over 30 years. However, the studies on which chromium's status are based are methodologically flawed. Whether chromium is an essential element has been examined for the first time in carefully controlled metal-free conditions using a series of purified diets containing various chromium contents. Male Zucker lean rats were housed in specially designed metal-free cages for 6 months and fed the AIN-93G diet with no added chromium in the mineral mix component of the diet, the standard AIN-93G diet, the standard AIN-93G diet supplemented with 200 µg Cr/kg, or the standard AIN-93G diet supplemented with 1,000 µg Cr/kg. The chromium content of the diet had no effect on body mass or food intake. Similarly, the chromium content of the diet had no effect on glucose levels in glucose tolerance or insulin tolerance tests. However, a distinct trend toward lower insulin levels under the curve after a glucose challenge was observed with increasing chromium content in the diet; rats on the supplemented AIN-93G diets had significantly lower areas (P < 0.05) than rats on the low-chromium diet. The studies reveal that a diet with as little chromium as reasonably possible had no effect on body composition, glucose metabolism, or insulin sensitivity compared with a chromium-"sufficient" diet. Together with the results of other recent studies, these results clearly indicate that chromium can no longer be considered an essential element.

Urinary chromium loss associated with diabetes is offset by increases in absorption.

The results of the current study indicate that diabetic rats have increased urinary Cr loss as a result of their diabetes; however, this increased urinary Cr loss is offset by increased absorption of Cr. Insulin resistant, obese rats have alterations in the rates of Cr transport and distribution compared to lean rats but have similar levels of urinary Cr loss and Cr absorption. Thus, any increases in urinary Cr loss associated with insulin resistance or diabetes are offset by increased absorption. Given that dietary chromium is normally absorbed with only approximately 1% efficiency, suitable Cr exists in the diet so that a standard diet possesses sufficient chromium to allow for the increases in absorption associated with diabetes. Consequently, supplementing the diet with nutritionally relevant quantities of chromium is not anticipated to have any beneficial effects. Similarly, beneficial effects on plasma variables, such as cholesterol, triglycerides, and insulin concentrations, from supra-nutritional doses of Cr(III) complexes should not arise from alleviation of chromium deficiency. These beneficial effects must arise from pharmacological effects of high dose Cr(III) administration.

A small molecule antagonist of the alpha(v)beta3 integrin suppresses MDA-MB-435 skeletal metastasis.

INTRODUCTION: Breast cancer is one of the most common malignancies affecting women in the United States and Europe. Approximately three out of every four women with breast cancer develop metastases in bone which, in turn, diminishes quality of life. The alpha(v)beta3 integrin has previously been implicated in multiple aspects of tumor progression, metastasis and osteoclast bone resorption. Therefore, we hypothesized that the alpha(v)beta3-selective inhibitor, S247, would decrease the development of osteolytic breast cancer metastases. MATERIALS AND METHODS: Cells were treated in vitro with S247 and assessed for viability and adhesion to matrix components. Athymic mice received intracardiac (left ventricle) injections of human MDA-MB-435 breast carcinoma cells expressing enhanced green-fluorescent protein. Mice were treated with vehicle (saline) or S247 (1, 10, or 100 mg/kg/d) using osmotic pumps beginning either one week before or one week after tumor cell inoculation. Bones were removed and examined by fluorescence microscopy and histology. The location and size of metastases were recorded. RESULTS AND CONCLUSIONS: IC50 for S247 adhesion to alpha(v)beta3 or alpha(IIB)beta3a substrates was 0.2 nM vs. 244 nM, respectively. Likewise, S247 was not toxic at doses up to 1000 microM. However, osteoclast cultures treated with S247 exhibited marked morphological changes and impaired formation of the actin sealing zone. When S247 was administered prior to tumor cells, there was a significant, dose-dependent reduction (25-50% of vehicle-only-treated mice; P = 0.002) in osseous metastasis. Mice receiving S247 after tumor cell inoculation also developed fewer bone metastases, but the difference was not statistically significant. These data suggest that, in the MDA-MB-435 model, the alpha(v)beta3 integrin plays an important role in early events (e.g., arrest of tumor cells) in bone metastasis. Furthermore, the data suggest that alpha(v)beta3 inhibitors may be useful in the treatment and/or prevention of breast cancer metastases in bone.