Notes

Exactly what do men and women want within a stop smoking software? The investigation regarding user feedback as well as application quality.
We found a remarkable overlap between Washington EHD cumulative impact rankings and COVID-19 positivity in King County. Census tracts with ≥ 10 % COVID-19 positivity had significantly lower COVID-19 testing rates and higher proportions of people of color and faced a combination of low socioeconomic status-related outcomes, poor community health outcomes, and significantly higher concentrations of fine particulate matter (PM2.5). King County communities experiencing high rates of COVID-19 face a disproportionate cumulative burden of environmental and social inequities. Cumulative environmental health impacts should therefore systematically be considered when assessing for risk of exposure to and health complications resulting from COVID-19.
First-generation somatostatin analogs, octreotide (OCT) and lanreotide, are the cornerstone for the medical treatment of growth hormone (GH)-secreting pituitary tumors. A new multireceptor analog, such as pasireotide (PAS), showed better activity than OCT in long-term treatment of patients with acromegaly, but modulation of intracellular key processes is still unclear in vitro. In this study, we evaluated the antitumor activity of OCT and PAS in two GH-secreting pituitary tumor cell lines, GH3 and GH4C1, after a long-term incubation.

The effects of PAS and OCT on the cell viability, cell cycle, apoptosis, GH secretion, and tumor-induced angiogenesis have been evaluated through a colorimetric method (MTS Assay), DNA flow cytometry with propidium iodide, and Annexin V-FITC/propidium iodide staining, ELISA assay and zebrafish platform, respectively.

PAS showed a more potent antitumor activity compared to OCT in GH3 cell line exerted through inhibition of cell viability, perturbation of cell cycle progression, and induction of apoptosis after 6days of incubation. A concomitant decrease in GH secretion has been observed after 2days of incubation only with PAS. No effect on tumor-induced angiogenesis has been reported after treatment with OCT or PAS in zebrafish/tumor xenograft model.

Long-term incubation with PAS showed a more potent antitumor activity than that reported after OCT in GH3 cells, mainly modulated by a cell cycle perturbation and a relevant induction in apoptosis.
Long-term incubation with PAS showed a more potent antitumor activity than that reported after OCT in GH3 cells, mainly modulated by a cell cycle perturbation and a relevant induction in apoptosis.
Elevated fasting plasma glucose has been associated with increased risk for development of type 2 diabetes (T2D). The balance between glucokinase (GCK) and glucose-6-phosphate catalytic subunit 2 (G6PC2) activity are involved in glucose homeostasis through glycolytic flux, and subsequent insulin secretion.

In this study, we evaluated the association between the genetic variability of G6PC2 and GCK genes and T2D-related quantitative traits.

In 794 drug-naïve, GADA-negative, newly diagnosed T2D patients (VNDS; NTC01526720) we performed genotyping of 6 independent tag-SNPs within GCK gene and 5 tag-SNPs within G6PC2 gene; euglycaemic insulin clamp to assess insulin sensitivity; OGTT to estimate beta-cell function (derivative and proportional control; DC, PC) by mathematical modeling. Genetic association analysis has been conducted using Plink software.

Two SNPs within GCK gene (rs882019 and rs1303722) were associated to DC in opposite way (both p < 0.004). Two G6PC2 variants (rs13387347 and rs560887) were associated to both parameters of insulin secretion (DC and PC) and to fasting C-peptide levels (all p < 0.038). Moreover, subjects carrying the A allele of rs560887 showed higher values of 2h-plasma glucose (2hPG) (p = 0.033). Haplotype analysis revealed that GCK (AACAAA) haplotype was associated to decreased fasting C-peptide levels, whereas, the most frequent haplotype of G6PC2 (GGAAG) was associated with higher fasting C-peptide levels (p = 0.001), higher PC (β = 6.87, p = 0.022) and the lower 2hPG (p = 0.012).

Our findings confirmed the role of GCK and G6PC2 in regulating the pulsatility in insulin secretion thereby influencing insulin-signaling and leading to a gradual modulation in glucose levels in Italian patients with newly diagnosed T2D.
Our findings confirmed the role of GCK and G6PC2 in regulating the pulsatility in insulin secretion thereby influencing insulin-signaling and leading to a gradual modulation in glucose levels in Italian patients with newly diagnosed T2D.
Sinking of the diaphragma sellae (DS) may stretch the pituitary stalk, which in turn impairs neurohypophyseal function; thus, it may play a role in the development of postoperative hyponatremia. We aimed to assess the factors influencing the development of hyponatremia after transsphenoidal surgery (TSS) for pituitary adenomas and analyze the effect of DS sinking on hyponatremia.

After applying the inclusion and exclusion criteria, we retrospectively analyzed the clinical data of patients with pituitary adenoma who underwent TSS. The pituitary gland was scanned using a 3.0-T magnetic resonance imaging, and sagittal and coronal images were acquired. We evaluated the following preoperative and postoperative hypothalamus‒pituitary‒thyroid axis function, hypothalamus‒pituitary‒adrenal axis function, intra-operative cerebrospinal fluid leaks, diabetes insipidus, hyponatremia, time from the day of surgery to the day of discharge, and time of hyponatremia onset.

Of the 460 patients who had microscopic TSS for pituitary adenoma, 83 experienced postoperative hyponatremia. Hyponatremia occurred approximately 5.25days postoperatively and persisted for 5.54days. The lowest average blood sodium level was 123.9mEq/L, which occurred at 7.49days after surgery. Logistic regression analysis showed that the risk of hyponatremia was greater for patients with a significant DS sinking depth, a large pituitary stalk deviation angle difference, and a longer postoperative "measurable pituitary stalk". The difference in blood sodium levels between pre-TSS and 2days post-TSS was also an independent predictor of postoperative hyponatremia onset.

DS sinking plays an important role in predicting hyponatremia onset after TSS for pituitary adenomas.
DS sinking plays an important role in predicting hyponatremia onset after TSS for pituitary adenomas.Research productivity and outcomes of junior researchers are usually correlated with the degree and quality of mentorship they receive. A bottom-up approach was followed to develop a research group at the Ocean Road Cancer Institute (ORCI), the major cancer center in Tanzania, to build upon the existing clinical and research resources and institutional global collaborations. The ORCI is a clinical center focused on radio- and chemo-therapy treatment of cancer patients from all over Tanzania. click here In addition, ORCI has a long-standing early detection program for educating women and screening them for cervical cancer. The ORCI physicians have been exposed to cancer research for the past 20 years through non-degree and degree training in the USA and Europe. In addition, US and European groups have been conducting collaborative research and training of oncologists and graduate students at ORCI. The exposure to research through the above-listed venues motivated the clinicians at ORCI to develop their own Research Club (RC) to learn about research methods, seek independent funding, and outline a research agenda for cancer research in Tanzania. However, it seems that mentorship is needed to help the RC members apply the lessons learned from didactic teaching. Mentorship is also needed to enable the RC members to utilize the enormous clinical and epidemiologic data generated by the institutional programs for prevention, treatment, and follow up of patients. This manuscript describes the inception of the program and its achievements, limitations, and suggested opportunities for improvement as a possible model for other LMICs.Canine adenoviruses (CAVs) are of two types canine adenovirus type 1 (CAV-1), which causes infectious canine hepatitis, and canine adenovirus type 2 (CAV-2), which is mainly associated with the respiratory type of disease in dogs. Due to the widespread use of modified live vaccines to control canine adenoviral infections and subsequently reduced disease incidence, CAVs are often neglected by clinicians. Although a number of studies are available about CAV-1 prevalence in India, only meagre information is available about CAV-2. This study reports the CAV-2 infection in a vaccinated dog with neurological and respiratory symptoms which was found negative for other canine pathogens like canine distemper virus and canine parvovirus. The virus was successfully isolated from rectal swab in MDCK cells and characterized by immunofluorescence assay and virus neutralization test. On phylogenetic analysis of partial E3 region, the Indian CAV-2 grouped in a separate clade different from established subgroups. An insertion of "G" nucleotide was reported at nucleotide (nt.) position 1077 in the E3 gene of Indian CAV-2 isolates which led to a frameshift in the coding region of E3 gene thereby imparting additional eleven amino acids to its C-terminal end in comparison to isolates from other parts of the world. This may have an implication on the functional role of E3 protein inside the cell. This study reinforces the unique signature insertion in the E3 gene of Indian CAV-2 and is the second study in the world to report the association of CAV-2 with neurological disease in dogs.The study was aimed to determine fluoride levels in plasma, brain, and bones of Wistar rats following chronic administration of fluoride at different dose levels and the consequent oxidative damage inflicted in these tissues. Brain histomorphology and bone radiographs were also evaluated to assess the extent of damage in these organs. Eighteen rats were randomly divided into three groups with six animals in each group. Group I served as control and groups II and III received 50 and 100 ppm fluoride in tap water, respectively for 180 days. A dose-dependent rise in the levels of fluoride in plasma, brain, and bones was observed in rats. Significant (P  less then  0.05) alterations in levels of total thiols, glutathione peroxidase, glutathione reductase, acetylcholinesterase, catalase, superoxide dismutase, lipids, as well as protein peroxidation in blood and brain were observed as compared to control in a dose-dependent manner. Radiological examination of bone revealed thinning of bone cortex with haphazard ossification, reduced bone density, and widening of marrow cavity indicating occurrence of flawed bone remodeling upon chronic fluoride exposure. Improper mineralization in bones of intoxicated rats indirectly reflected reduced bone tensile strength. Moreover, alterations in plasma CaP ratio and high levels of fluoride in bone ash indicated that chronic fluoride exposure leads to alterations in the bone matrix further corroborating the radio-graphical findings. Additionally, severe microscopic alterations were recorded in the cerebrum and cerebellum of treated rats which included neuronal necrosis, gliosis, spongiosis, perivascular cuffing, congestion, and hemorrhage which correlated well with oxidative changes induced by fluoride intoxication in the brain tissue of rats.
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