Rejected

Initial Phase III clinical studies with polidocanol endovenous microfoam (PEM) have demonstrated safety and efficacy in the treatment of superficial venous reflux. In those studies, the primary outcome requirement was to assess improvement in symptoms related to superficial venous disease. The goal of this study was to evaluate the efficacy of PEM technology in routine clinical practice, specifically closure rates following treatment.

The thrombospondin receptor α2δ-1 plays essential roles promoting the activity of SF1 neurons in the ventromedial hypothalamus (VMH) and mediating glucose and lipid metabolism in male mice. Its role in the VMH of female mice remains to be defined, especially considering that this hypothalamic region is sexually dimorphic. We found that α2δ-1 depletion in SF1 neurons differentially affects glucose and lipid balance control and sympathetic tone in females compared to males. Mutant females show a modest increase in relative body weight gain when fed a high fat diet (HFD) and normal energy expenditure, indicating that α2δ-1 is not a critical regulator of energy balance in females, similar to males. However, diminished α2δ-1 function in the VMH leads to enhanced glycemic control in females fed a chow diet, in contrast to the glucose intolerance reported previously in mutant males. Interestingly, the effects of α2δ-1 on glucose balance in females are influenced by diet. Accordingly, females but not males lacking α2δ-1 exhibit diminished glycemic control as well as susceptibility to hepatic steatosis when fed a HFD. Increased hepatic sympathetic tone and CD36 mRNA expression and reduced adiponectin levels underlie these diet-induced metabolic alterations in mutant females. The results indicate that α2δ-1 in VMH SF1 neurons critically regulates metabolic function through sexually dimorphic mechanisms. These findings are clinically relevant as metabolic alterations have been reported as a side effects in human patients prescribed gabapentinoid drugs, known to inhibit α2δ-1 function, for the treatment of seizure disorders, neuropathic pain and anxiety disorders.

The aim of this study was to analyse the epidemiological impact of murine typhus in patients who required hospitalization in the National Health System (SNS) in Spain between 1997 and 2015.

: The pathophysiological relevance of the endocannabinoid system has been widely demonstrated in a variety of diseases including cancer, neurological disorders, and metabolic issues. Therefore, targeting the receptors and the endogenous machinery involved in this system can provide a successful therapeutic outcome. Ligands targeting the canonical cannabinoid receptors, CB and CB, along with inhibitors of the endocannabinoid enzymes have been thoroughly studied in diverse disease models. In fact, phytocannabinoids such as cannabidiol or Δ-tetrahydrocannabinol are currently on the market for the management of neuropathic pain due to spasticity in multiple sclerosis or seizures in children epilepsy amongst others.: Challenges in the pharmacology of cannabinoids arise from its pharmacokinetics, off-target effects, and psychoactive effects. In this context, the current review outlines the novel molecular approaches emerging in the field discussing their clinical potential.: Even if orthosteric CB and CB ligands are on the forefront in cannabinoid clinical research, emerging strategies such as allosteric or biased modulation of these receptors along with controlled off-targets effects may increase the therapeutic potential of cannabinoids.

Although open reduction and internal fixation (ORIF) is an accepted treatment for a proportion of acute rib fractures, there is paucity of literature on its potential to treat chronic, non-union fractures. This study evaluates the outcomes and quality of life of patients who underwent ORIF for chronic, symptomatic non-union rib fractures.

Delirium is highly prevalent in people with advanced life limiting illness(es), and current evidence can inform how we provide best delirium care in this setting. Whilst strategies to prevent and reverse delirium are the cornerstones of optimal care, the care for delirious patients who are approaching the end of life and their families pose specific challenges particularly if delirium is refractory flagging a grave prognosis. These include addressing additional supportive care needs, clinical decision-making about the degree of investigation and intervention, minimising distress from the symptoms of delirium itself and considering other concurrent problems contributing to agitation. A fine balance is needed to address other symptoms such as pain whilst minimizing psychoactive medication load. There is need for regular and clear information and communication about prognosis and goals of care. Witnessing a delirium episode in a loved one in close proximity to death requires consideration of the needs of the family into bereavement care. Palliative care is person and family-centred care provided for a person with an active, progressive, advanced disease; who has little or no prospect of cure and who is expected to die, and for whom the primary treatment goal is to optimise quality of life. It is an approach which can be provided regardless of setting and diagnosis, and by both specialist palliative care teams and other health professionals.

Chronic pelvic pain syndrome (CPPS) is one of the common diseases in urology and gynecology. CPPS is a multifactorial disorder where pain may originate in any of the urogynecological, gastrointestinal, pelvic musculoskeletal, or nervous systems. The symptoms of CPPS appear to result from an interplay between psychological factors and dysfunction in the immune, neurological, and endocrine systems. The aim of this article was to present new insight about CPPS in order to raise awareness of nursing and medical staff in the identification and diagnosis of the syndrome and to promote an appropriate treatment for each woman who suffers from CPPS.

Older adults recently discharged from hospital are at high risk of functional decline and falls. A tailored fall prevention education provided at hospital discharge aimed to improve the capacity of older adults to engage in falls prevention activities. What remains unknown are the factors affecting behaviour change after hospital discharge. This study identified the perceived barriers and enablers of older adults to engagement in fall prevention activities during the 6-month period post-discharge. An exploratory approach using interpretative phenomenological analysis focused on the lived experience of a purposive sample (n = 30) of participants. All were recruited as a part of an RCT (n = 390) that delivered a tailored fall prevention education program at three hospital rehabilitation wards in Perth, Australia. Data were collected at 6-month post-discharge using semi-structured telephone surveys. Personal stories confirmed that some older adults have difficulty recovering functional ability after hospital discharge. Reduced physical capability, such as experiences of fatigue, chronic pain and feeling unsteady when walking were barriers for participants to safely return to their normal daily activities. Participants who received the tailored fall education program reported positive effects on knowledge and motivation to engage in fall prevention. Participants who had opportunities to access therapy or social supports described more positive experiences of recovery compared to individuals who persevered without assistance. A lack of physical and social support was associated with apprehension and fear toward adverse events such as falls, injuries, and hospital readmission. The lived experience of participants following hospital discharge strongly suggested that they required more supports from both healthcare professionals and caregivers to ensure that their needs were met. Further research that evaluates how to assist this population to engage in programs that will mitigate the high risk of falls and hospital readmissions is required.

Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes. Diosgenin is a natural steroidal saponin with a variety of beneficial effects, including antidiabetic effects, and is a raw material for the synthesis of carrier hormones. In our study, we aimed to assess the antioxidant effects of diosgenin in diabetic mice.

To investigate the genetic and environmental factors responsible for phenotype variability in a family carrying a novel CACNA1A missense mutation. Mutations in the CACNA1A gene were identified as responsible for at least three autosomal dominant disorders: FHM1 (Familial Hemiplegic Migraine), EA2 (Episodic Ataxia type 2), and SCA6 (Spinocerebellar Ataxia type 6). Overlapping clinical features within individuals of some families sharing the same CACNA1A mutation are not infrequent. Conversely, reports with distinct phenotypes within the same family associated with a common CACNA1A mutation are very rare.