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13%), alcohol use (40% vs. 22%), fighting (13% vs. 5%), suicidal ideation (31% vs. 13%), and suicide attempts (17% vs. 5%), as well as lower school engagement, educational aspirations, and grades than 19,832 students who dated without TDA. The current study emphasized the need for dating aggression to be a focus of secondary school prevention programs due its associations with poorer academic performance, high-risk behavior with potentially serious mental health consequences. Accurate assessment of TDA can also guide the evaluation of intervention programs that target TDA.Posterior reversible encephalopathy syndrome (PRES) is a central nervous system disorder accompanied by vasogenic edema in white matter that is usually located in temporo-parieto-occipital area. Typically, PRES is presented with headaches, seizures, and change of consciousness. The most common etiologic factor is fluctuations in blood pressure. An eighty-eight-year-old female patient was evaluated because of her acute confused state. Medical history revealed hypertension. Blood pressure was 190/100 mmHg. The initial examination showed impaired consciousness. Radiological investigations of brain showed chronic ischemic lesions. Albuminocytological dissociation was detected in CSF examination. On the 6th day of admission, cranial MRI was repeated. Radiological findings were typical for PRES. The cranial MRI is a valuable diagnostic tool for the diagnosis of the PRES but, as in our case, despite the subtle clinical and radiological findings presented during admission, repeated MRI and CSF examination may contribute to a definite diagnosis. This case is remarkable for severe protein elevation in CSF, irreversible fatal course and radiographic evidence of vasogenic edema occurred subsequently.
RAS-RAF-MEK-ERK signaling is implicated in tumor development by promoting cell proliferation and other cancer hallmarks. MEK1/2 kinases are up-regulated in the majority of human cancers due to activation of tyrosine kinase receptors, RAS proteins, BRAF kinase, or some other members of the MAPK pathway. Targeting of MEK1/2 kinases may counterbalance cancer progression.
The authors analyze the scientific publications relevant to selumetinib (AZD6244, ARRY-142886) systematically and provide their expert opinion.
Selumetinib is an oral selective allosteric inhibitor of MEK1 and MEK2 kinases. Single-agent selumetinib is usually administered in hydrogen sulfate capsules 75 mg twice a day; combination with other therapeutic compounds may or may not require reduced dosing of this drug. The established dose for pediatric patients is 25 mg per square meter twice a day. Selumetinib was extensively evaluated in non-small cell lung cancer (NSCLC) patients. Studies utilizing this drug as a monotherapy did not confirmthat the addition of selumetinib to docetaxel improved response rates and progression-free survival (PFS) in chemotherapy-pretreated KRAS-mutated NSCLC patients; however, a subsequent phase III study did not confirm these findings. There are several highly successful non-NSCLC selumetinib trials involving, e.g., patients with neurofibromatosis type 1 related tumors and children with low-grade BRAF-driven gliomas.
Inborn errors of metabolism include several genetic disorders due to disruption of cellular biochemical reactions. Although individually rare, collectively they are a large and heterogenous group of diseases affecting a significant proportion of patients. Available treatments are often unsatisfactory. Liver-directed gene therapy has potential for treatment of several inborn errors of metabolism. While lentiviral vectors and lipid nanoparticle-mRNA have shown attractive features in preclinical studies and still have to be investigated in humans, adeno-associated virus (AAV) vectors have shown clinical success in both preclinical and clinical trials for in vivo liver-directed gene therapy.
In this review, we discussed the most relevant clinical applications and the challenges of liver-directed gene-based approaches for therapy of inborn errors of metabolism.
Challenges and prospects of clinical gene therapy trials and preclinical studies that are believed to have the greatest potential for clinical translation are presented.
Challenges and prospects of clinical gene therapy trials and preclinical studies that are believed to have the greatest potential for clinical translation are presented.Lumbosacral disc herniation (LDH) represents the most common cause of sciatica. Currently, there is limited evidence about minimally invasive interventional therapies for the treatment of this condition. This paper presents the protocol for a multicenter, prospective, randomized, controlled, phase III trial evaluating if PRF in addition to TFESI leads to better outcomes in patients with sciatica due to LDH, compared to TFESI alone, during the first year after treatment (Pulsed Radiofrequency in Addition to TFESI for Sciatica [PRATS]). Eligible patients are between 18 and 75 years of age, suffer from sciatica of less than 12-week duration with pain intensity >4 on the Visual Analogue Scale (VAS) and have unilateral LDH compatible with symptoms at MRI. The Medical Ethics Committee of participating hospitals approved the study protocol. Patients will be randomized to receive either combined treatment (PRF and TFESI) or TFESI alone. The primary outcome will be the assessment of pain intensity with VAS at different timepoints from week-1 to 52 after treatment; secondary outcomes will include Roland Disability Questionnaire for sciatica and Oswestry Disability Index, evaluated at 4, 12 and 52 weeks. The follow-up will last 52 weeks for each patient. Statistical analysis will be performed on a per-protocol basis.
We aimed to determine the concordance between own and perceived partner fertility intentions and identify predictors of contraceptive use among couples receiving antiretroviral therapy in Kano, Nigeria.
A structured, validated questionnaire was used to interview 399 married men and women receiving antiretroviral therapy. Adjusted odds ratios for predictors of contraceptive use were derived from multivariate logistic regression models.
Most couples (68.9%) had concordant fertility intentions. selleck chemical Only 10.0% of couples had discordant fertility intentions. Among 232 couples (58.1%) at least one partner used contraception. Male condoms were used by 45.9% of couples (
= 183). Female methods were used by 175 couples (43.9%). Contraceptive use was significantly higher in participants who were older (≥30 years), better educated (secondary or post-secondary), had a higher monthly income (NGN ≥30,000), longer marriage duration (≥5 years), at least one living child, >1 year of antiretroviral treatment, and who were living with a serodiscordant partner and in circumstances where the decision on contraception was made by the female partner or jointly by both partners (all
< 0.