Trauma, coping, and adjustment when parenting a child with Dravet syndrome.

Objectives: Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy that requires significant caregiver input across the lifespan. This predominantly falls on parents, who are faced with considerable challenges including physical demands, financial burdens, and sustained pressure on mental wellbeing leading to mental health difficulties. We aimed to develop a grounded theory model for the process of coping and adjustment that occurs when caring for a child who has a diagnosis of DS.

Caregiver burden and therapeutic needs in Dravet syndrome - A national UK cross-sectional questionnaire study.

Background And Objectives: Dravet Syndrome is a severe developmental and epileptic encephalopathy with significant care needs for affected individuals and families. Our objective was to characterise the caregiver burden and therapeutic needs of families caring for an individual with Dravet Syndrome from child to adulthood, to examine age related differences in co-morbidities, and identify current gaps in health and social care.

Methods: Cross-sectional national survey conducted by the patient advocacy group Dravet Syndrome UK (DSUK) emailed to registered families caring for an individual with a confirmed diagnosis of Dravet syndrome.

Feeding Difficulties and Gastrostomy in Dravet Syndrome: A UK-Wide Survey and 2-Center Experience.

Background And Objectives: Dravet syndrome (DS) is one of the most common monogenic epilepsies. Alongside the core seizure and developmental phenotypes, problems with appetite, swallowing, and weight loss are frequently reported, necessitating gastrostomy in some. We explored the burden of feeding difficulties and need for gastrostomy across 3 DS populations in the United Kingdom.

Lie-Poisson Neural Networks (LPNets): Data-based computing of Hamiltonian systems with symmetries.

An accurate data-based prediction of the long-term evolution of Hamiltonian systems requires a network that preserves the appropriate structure under each time step. Every Hamiltonian system contains two essential ingredients: the Poisson bracket and the Hamiltonian. Hamiltonian systems with symmetries, whose paradigm examples are the Lie-Poisson systems, have been shown to describe a broad category of physical phenomena, from satellite motion to underwater vehicles, fluids, geophysical applications, complex fluids, and plasma physics.

The impact of SARS-CoV-2 vaccination in Dravet syndrome: A UK survey.

Background: The COVID-19 pandemic led to the urgent need for accelerated vaccine development. Approved vaccines have proved to be safe and well tolerated across millions of people in the general population. Dravet syndrome (DS) is a severe, early onset, developmental and epileptic encephalopathy.

The impact of COVID-19 in Dravet syndrome: A UK survey.

Objectives: To understand the risks, impact and outcome of COVID-19 in people affected by Dravet Syndrome (DS).

Materials And Methods: An anonymous cross-sectional online survey was conducted between June 17 and July 13, 2020, addressed to families of people with DS.

Results: A total of 116 responses were collected, from families of children (n = 86; 74%) and adults (30; 26%) with DS.

Postabortion Care in Humanitarian Emergencies: Improving Treatment and Reducing Recurrence.

Background: Unsafe abortion contributes to maternal mortality worldwide and disproportionately affects the most disadvantaged women and girls; thus, improving the treatment of complications of abortion is essential. Shifting PAC treatment from sharp dilation and curettage (D&C) to the use of aspiration techniques, notably manual vacuum aspiration (MVA), and medical treatment with misoprostol improves health outcomes. Equally critical is ensuring that women have access to voluntary contraception after an abortion to prevent future unintended pregnancies.

Inhibitor of apoptosis proteins (IAPs) mediate collagen type XI alpha 1-driven cisplatin resistance in ovarian cancer.

Although, cisplatin resistance is a major challenge in the treatment of ovarian cancer, the precise mechanisms underlying cisplatin resistance are not fully understood. Collagen type XI alpha 1 (COL11A1), a gene encoding a minor fibrillar collagen of the extracellular matrix, is identified as one of the most upregulated genes in cisplatin-resistant ovarian cancer and recurrent ovarian cancer. However, the exact functions of COL11A1 in cisplatin resistance are unknown.

Stretch activation properties of Drosophila and Lethocerus indirect flight muscle suggest similar calcium-dependent mechanisms.

Muscle stretch activation (SA) is critical for optimal cardiac and insect indirect flight muscle (IFM) power generation. The SA mechanism has been investigated for decades with many theories proposed, but none proven. One reason for the slow progress could be that multiple SA mechanisms may have evolved in multiple species or muscle types.

A quality review of smartphone applications for the management of pain.

Smartphone applications (apps) are recent innovations that have not been studied extensively. The lack of regulatory body assessing the content of existing apps means that their quality is often unknown. This review aims to assess the quality of smartphone apps that claim to provide information and treatment for pain conditions.

Discovery of Tetrahydropyrazolopyridine as Sphingosine 1-Phosphate Receptor 3 (S1P3)-Sparing S1P1 Agonists Active at Low Oral Doses.

FTY720 is the first oral small molecule approved for the treatment of people suffering from relapsing-remitting multiple sclerosis. It is a potent agonist of the S1P1 receptor, but its lack of selectivity against the S1P3 receptor has been linked to most of the cardiovascular side effects observed in the clinic. These findings have triggered intensive efforts toward the identification of a second generation of S1P3-sparing S1P1 agonists.

The roles of troponin C isoforms in the mechanical function of Drosophila indirect flight muscle.

Stretch activation (SA) is a fundamental property of all muscle types that increases power output and efficiency, yet its mechanism is unknown. Recently, studies have implicated troponin isoforms as important in the SA mechanism. The highly stretch-activated Drosophila IFMs express two isoforms of the Ca(2+)-binding subunit of troponin (TnC).

Adjusting to persistent post-concussive symptoms following mild traumatic brain injury and subsequent psycho-educational intervention: a qualitative analysis in military personnel.

Objective: Best practice guidelines outline ways in which mild traumatic brain injury (mTBI) and persistent post-concussive symptoms (PPCS) should be managed. In line with the existing evidence base, DMRC Headley Court established a treatment programme for UK servicemen and women with mTBI. This study explored the experiences of a sample of UK military personnel living with PPCS, who also received psycho-educational intervention (Phase 2) at this unit.

Conformational changes at the nucleotide site in the presence of bound ADP do not set the velocity of fast Drosophila myosins.

The conformational changes in myosin associated with ADP release and their influence on actin sliding velocity are not understood. Following actin binding, the myosin active site is in equilibrium between a closed and open ADP bound state, with the open state previously thought to favor ADP release and thus expected to be favored in faster myosins. However, our recent work with a variety of myosins suggests the opposite, that the open conformation is dominant in slower myosins, which have higher ADP affinities.

Nucleotide pocket thermodynamics measured by EPR reveal how energy partitioning relates myosin speed to efficiency.

We have used spin-labeled ADP to investigate the dynamics of the nucleotide-binding pocket in a series of myosins, which have a range of velocities. Electron paramagnetic resonance spectroscopy reveals that the pocket is in equilibrium between open and closed conformations. In the absence of actin, the closed conformation is favored.

The mechanical properties of Drosophila jump muscle expressing wild-type and embryonic Myosin isoforms.

Transgenic Drosophila are highly useful for structure-function studies of muscle proteins. However, our ability to mechanically analyze transgenically expressed mutant proteins in Drosophila muscles has been limited to the skinned indirect flight muscle preparation. We have developed a new muscle preparation using the Drosophila tergal depressor of the trochanter (TDT or jump) muscle that increases our experimental repertoire to include maximum shortening velocity (V(slack)), force-velocity curves and steady-state power generation; experiments not possible using indirect flight muscle fibers.

Addressing species specific metabolism and solubility issues in a quinoline series of oral PDE4 inhibitors.

Species specific conversion of the lead PDE4 inhibitor 1 to the quinolone 3 was identified as the major route of metabolism in the cynomolgus monkey. Modification of the template to give the cinnoline 9 retained potency and selectivity, and greatly improved the pharmacokinetic profile in the cynomolgus monkey compared with 1. Additional SAR studies aimed at improving the solubility of 9 are also described.

Quinolines as a novel structural class of potent and selective PDE4 inhibitors: optimisation for oral administration.

Crystallography-driven optimisation of a lead derived from similarity searching of the GSK compound collection resulted in the discovery of a series of quinoline derivatives that were highly potent and selective inhibitors of PDE4 with a good pharmacokinetic profile in the rat. Quinolines 43 and 48 have potential as oral medicines for the treatment of COPD.

Psychosocial interventions for carers of survivors of stroke: a systematic review of interventions based on psychological principles and theoretical frameworks.

Purpose: Most stroke survivors are cared for at home by informal carers, usually their partners or children. The chronic burden of meeting these care needs can have a significant impact on the psychological well-being of the carer. The aim of this review is to analyse interventions that target psychosocial functioning in carers of stroke survivors to understand how such interventions can reduce the burden of caring.

Impacts on children of a policy to promote employment and reduce poverty for low-income parents: new hope after 5 years.

The impacts of New Hope, a program to increase parent employment and reduce poverty, were measured 5 years after parents were randomly assigned to program or control groups. New Hope had positive effects on children's school achievement, motivation, and social behavior, primarily for boys, across the age range 6-16. In comparison to impacts measured 2 years after program onset, effects on achievement were robust, but effects on social behavior were reduced.

Patient access. To the ENT degree.

Evaluation of six pilot schemes using specialist GPs to provide ENT services in the community suggests these innovations are popular with patients and have the potential to reduce waiting times. Waiting times in one area, where a specialist GP had been in post for three years, were down to 24 days. The schemes need champions in primary and secondary care and must fit well with the strategy of the local health economy.

Some aspects of adoption in selected samples of adult adoptees.

Various aspects of adoption--psychopathology, age at placement, agency versus independent placement, best age to tell child he is adopted, etc.--are studied in three groups of adoptees: biological parent schizophrenic or manic-depressive; adoptive parent schizoprenic or manic-depressive; biological parent with no psychiatric history. Findings raise questions about a number of common assumptions regarding adoptees.

Interpersonal relationships in heroin use by men and women and their role in treatment outcome.

The majority of both male and female heroin addicts entering a city treatment program were introduced to heroin by a male. But by contrast with the males, females were in many cases introduced to heroin by another woman, more often used drugs with persons of both sexes, and were more likely to be living with a current or former heroin user at intake. Encouragement to give up drugs was reported more frequently by both men and women than attempts to discourage their entry into treatment, but only the encouragement of the spouse or opposite-sexed partner was significantly related to treatment outcome.