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The best results were obtained for clobazam (already marketed), ganaxolone (in phase III trials), CVL-865 (in phase II trials), and padsevonil (in phase III trials). Several compounds with more selective action on GABA A receptors, perhaps only in certain brain regions, have the potential to become effective drugs against specific subtypes of focal-onset epilepsy. However, their development needs time, and in the near future we can expect only one or two new GABA A agonists to obtain marketing authorization for focal epilepsy, an advance that would be of use for just a fraction of patients with drug-resistant epilepsy.
Given the pressures surrounding women's reproductive role in India, and persistent high rates of perinatal death, the purpose of this study is to describe and compare poor rural and urban Indian women's experiences of perinatal grief.
Two cross-sectional studies were compared on shared quantitative variables. Poor rural (N = 217) and urban, slum-dwelling (N = 149) Central Indian women with a history of stillbirth, and/or infant death were recruited with the aid of local community health workers. Trained, local, gender, and linguistically matched research assistants conducted the structured interviews. Shared quantitative variables include demographics, Social Provision Scale, Shortened Ways of Coping-Revised, Perinatal Grief Scale, social norms and autonomy.
While similar with respect to SES, age, number of living sons and perinatal loss experiences, these samples of poor women differed significantly across many variables, most notably women's household position, joint family living, number of live daugrief was high following perinatal loss. Both groups of women with perinatal loss have increased risk of mental health sequelae. Notably, the context affected how they experienced perinatal grief, with rural women's grief being higher and more affected by their societal pressures and isolation. Such nuances are important considerations for much-needed tailored approaches to future interventions.
Calcium hydroxide is a gold standard dental material generally used for pulpal and periapical therapy including regenerative endodontic procedures because of its positive properties. However, evaluation about this material on stem cells is limited. Human umbilical cord mesenchymal stem cells (HUCMSCs) are potential to be used in regenerative therapy. Regenerative therapy needs a sustainable cell supply to maintain its regenerative capacity. The aim of this study was to ascertain the apoptosis result of calcium hydroxide on HUCMSCs through the expression of apoptotic protease-activating factor-1 (APAF-1), caspase-3, and caspase-9.
This study used a thawed frozen stock of passage 5 HUCMSCs, grown in minimum essential medium (MEM) alpha containing calcium hydroxide at concentration of 0.1 microgram/mL for 1, 3 and 7 days. Polyclonal antibody with fluorescence isothiocyanate (FITC) label was used to evaluate the expressions. APAF-1, caspase-3, and caspase-9 expressions were recorded and compared on every observation day using fluorescence microscope. DNA Repair chemical Analysis of variance was performed to analyze the significance among the results of treatment groups. The results were concluded significant if p<0.05.
The addition of calcium hydroxide in MEM alpha medium increases HUCMSCs expression of APAF-1, caspase-3 and caspase-9 significantly, compared to the control group without calcium hydroxide (p<0.05) in all the times. Day 1 showed the lowest increase followed by higher expressions on day 3 and day 7.
HUCMSCs express increased APAF-1, caspase-3 and caspase-9 after in-vitro calcium hydroxide exposure. This should be considered when using calcium hydroxide on HUCMSCs for regenerative procedures with regard to other positive properties.
HUCMSCs express increased APAF-1, caspase-3 and caspase-9 after in-vitro calcium hydroxide exposure. This should be considered when using calcium hydroxide on HUCMSCs for regenerative procedures with regard to other positive properties.
To assess the association between
and
variants and the incidence of adverse drug reactions in warfarin-treated patients in a real-world setting.
This was a register-based cohort study (PreMed) linking data from Finnish biobanks, national health registries and patient records between January 1st 2007 and June 30th 2018. The inclusion criteria were 1) ≥18 years of age, 2)
and V
genotype information available, 3) a diagnosis of a cardiovascular disease, 4) at least one warfarin purchase, 5) regular INR tests. Eligible individuals were divided into two warfarin sensitivity groups; normal responders, and sensitive and highly sensitive responders based on their
and
genotypes. The incidences of clinical events were compared between the groups using Cox regression models.
The cohort consisted of 2508 participants (45% women, mean age of 69 years), of whom 65% were categorized as normal responders and 35% sensitive or highly sensitive responders. Compared to normal responders, sensitive and highly sensitive responders had fewer INR tests below 2 (median 33.3% vs 43.8%, 95% CI -13.3%, -10.0%) and more above 3 (median 18.2% vs 6.7%, 95% Cl 8.3%, 10.8%). The incidence (per 100 patient-years) of bleeding outcomes was 5.4 for normal responders and 5.6 for the sensitive and highly sensitive responder group (HR=1.03, 95% CI 0.74, 1.44). The incidence of thromboembolic outcomes was 4.9 and 7.8, respectively (HR=1.48, 95% CI 1.08, 2.03).
In a real-world setting, genetically sensitive and highly sensitive responders to warfarin had more high INR tests and required a lower daily dose of warfarin than normal responders. However, the risk for bleeding events was not increased in sensitive and highly sensitive responders. Interestingly, the risk of thromboembolic outcomes was lower in normal responders compared to the sensitive and highly sensitive responders.
NCT04001166.
NCT04001166.
Natural orifice specimen extraction surgery (NOSES) has been successfully applied to the treatment of gastric, colorectal cancer (CRC). However, the development of NOSES is still in the exploratory stage, and there is still no strong evidence-based medical evidence.
From January 2013 to June 2017, consecutive patients with colorectal cancer who underwent transluminal resection, anastomosis, and specimen extraction and those who underwent conventional laparoscopic resection were enrolled. Propensity score matching was used to align clinicopathological features between the two groups.
A total of 372 patients were eventually included in this study, 186 in each group. According to perioperative information and postoperative follow-up in both groups, the NOSES group had less blood loss (P = 0.011), shorter time to recovery of gastrointestinal function (P < 0.001), shorter postoperative hospital stay (P = 0.037). The NOSES group had fewer postoperative analgesics (P < 0.001), lower postoperative pain sc postoperative pain, recovery of gastrointestinal function, postoperative quality of life, and improving patients' satisfaction with abdominal wall aesthetics. There was no difference in long-term survival between NOSES and conventional laparoscopic surgery.
Gallbladder cancer (GBC) is a common malignancy of the biliary tract and is characterized by rapid progression and early metastasis. Elucidating the molecular mechanisms of GBC could help to develop better treatment strategies.
Human GBC cell lines (GBC-SD and NOZ) were applied to determine the capacity of the proliferation and migration of cells using the MTT assay, colony formation, wound-healing assay as well as the Transwell™ assay. A nude xenograft was used to evaluate tumor growth in vivo.
Using two types of GBC cell lines, we found that absence of solute carrier family (SLC) 39A4 (which encodes the zinc transporter ZRT/IRT-like protein [ZIP]4), could suppress the proliferation and migration of cells. Additionally, absence of ZIP4 could impair growth of xenografts in nude mice. While, over-expression of SLC39A4 could promote the GBC cell proliferation and migration, and inhibit apoptosis. We revealed that SLC39A4 might affect GBC progression by modulating the signaling pathways responsible for the survival, energy supply and metastasis of cells, and indicated that SLC39A4 could serve as a novel therapeutic target for GBC.
SLC39A4 promoted the viability and motility of GBC cells, and tumor formation in nude mice. We demonstrated an oncogenic potential for SLC39A4.
SLC39A4 promoted the viability and motility of GBC cells, and tumor formation in nude mice. We demonstrated an oncogenic potential for SLC39A4.
Racial minorities are disproportionally affected by pain. Compared to non-Hispanic Whites (NHWs), non-Hispanic Blacks (NHBs) report higher pain intensity, greater pain-related disability, and higher levels of mood disturbance. While risk factors contribute to these disparities, little is known regarding how sources of resilience influence these differences, despite the growing body of research supporting the protective role of resilience in pain and disability among older adults with chronic pain. The current study examined the association between psychological resilience and pain, and the moderating role of race across these relationships in older adults with chronic low back pain (cLBP).
This is a secondary analysis of the Adaptability and Resilience in Aging Adults (ARIAA). Participants completed measures of resilience (ie, gratitude, trait resilience, emotional support), as well as a performance-based measure assessing lower-extremity function and movement-evoked pain.
There were 45 participants thaight racial differences in the relationship between resilience and pain-related outcomes among older adults with cLBP. Future studies should examine the potential benefits of targeted interventions that improve resilience and ameliorate pain disparities among racial minorities.
Pain is a common occurrence and persistent symptom, which has an adverse impact on individual well-being and quality of life among people living with HIV (PLHIV). Alteration in the activity of the Hypothalamic-Pituitary-Adrenal (HPA) axis resulting in abnormal glucocorticoid levels had been proposed to play important roles in those associations.
This study aimed to investigate whether pain severity was associated with hair glucocorticoid levels, a novel method of measuring long-term glucocorticoid exposure, among a large cohort of Chinese PLHIV.
A measure of pain severity and hair samples were collected from 431 adults PLHIV in Guangxi, China. Glucocorticoid (cortisol and cortisone) in hair were quantified by liquid chromatography-tandem mass spectrometry. The general linear model was used to test the associations of pain severity with hair glucocorticoid levels after adjusting for potential confounding factors.
Of the 431 PLHIV, 273 reported none pain, 87 reported mild pain, and 71 reported moderate-severe pain. Hair cortisone, but not hair cortisol, was found to differ significantly among the three pain severity groups (
=3.90,
=0.021). PLHIV reported moderate-severe pain had higher hair cortisone than those reported mild (
=0.070) or none pain (
=0.014), with no differences between the latter two pain severity groups.
Greater pain severity is associated with higher hair cortisone levels among Chinese PLHIV. In order to reduce the long-term glucocorticoid levels, interventions managing pain should be considered for PLHIV with moderate-severe pain.
Greater pain severity is associated with higher hair cortisone levels among Chinese PLHIV. In order to reduce the long-term glucocorticoid levels, interventions managing pain should be considered for PLHIV with moderate-severe pain.
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