Soelbergholt2389

The epidemiological transition to non-communicable diseases in the 20th century necessitated the development of new public health approaches to address the problems of the new age. As understanding of the determinants of health became more sophisticated, so did public health practice. Thus, palliative care became an integral component of the health definition. It is an approach which improves quality of life of patients and their families facing chronic serious illness and life-threatening diseases. This is performed through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychological and spiritual. Palliative care is provided without giving up cure or slowing disease progression.Chronic kidney disease (CKD) is often associated with muscle atrophy. However, the underlying molecular mechanisms are still not well understood. Here, we treated 5/6-nephrectomized (5/6Nx) rats with resveratrol and found that this treatment greatly improves renal function as evidenced by reduced proteinuria and cystatin C. Moreover, resveratrol ameliorates renal fibrosis by reducing transforming growth factor β (TGF-β) and connective tissue growth factor (CTGF). Meanwhile, muscle atrophy in these 5/6Nx rats was largely attenuated by resveratrol. Immunoprecipitation revealed that SIRT1 physically interacts with FoxO1 in muscle, and this interaction was weakened in 5/6Nx rats. As a consequence, acetylated FoxO1 was increased in muscle of 5/6Nx rats. The application of resveratrol markedly reverses this trend. These data point out that SIRT1 is a key factor for linking renal disease and muscle atrophy. Indeed, both renal dysfunction and muscle atrophy were further aggravated by 5/6Nx in Sirt1+/- mice. Taken together, our data indicate that SIRT1 plays a pivotal role in muscle atrophy in CKD, and FoxO1 might be a substrate of SIRT1 in this process. Furthermore, resveratrol, together with other agonists of SIRT1, may hold great therapeutic potentials for treating CKD and its related muscle atrophy.Trichinellosis in humans is most often caused by the parasite Trichinella spiralis. The clinical course of the disease is diverse and the symptoms can vary from mild to severe. Symptoms usually disappear within a few months, but encysted larvae in the muscles can cause myalgia and weakness that last for years. However, the existence of chronic trichinellosis as a disease is still debatable. This study presents the results obtained at the National Reference Laboratory for Trichinellosis - INEP, Serbia. The study was conducted to assess the immunoserological, biochemical and symptomatic disease parameters of twelve patients who acquired trichinellosis 13 and 18 years ago, respectively. They were involved in two T. spiralis outbreaks in Serbia, at the village of Kumane and the city of Belgrade (nine and three patients, respectively). Results indicated the presence of specific anti-Trichinella antibodies in 83% of the total number of patients. However, while the humoral immune response to Trichinella lasted for more than a decade reaching almost two decades after the acute infection phase (7/9 and 3/3 respectively, in two outbreaks), persistence of chronic muscular pain, as the most prolonged symptom of trichinellosis, could be found in the majority of patients from the Kumane outbreak (7/9). As a consequence, these patients suffered from limitations in daily living activities for the same period of time. The results presented in this paper are our contribution to the view that trichinellosis as a chronic disease with symptoms exists and may be related to the severity of the disease in the acute phase.In basic and applied sciences, genome editing has become an indispensable tool, especially the versatile and adaptable CRISPR/Cas9 system. Using CRISPR/Cas9 in plants has enabled modifications of many valuable traits, including environmental stress tolerance, an essential aspect when it comes to ensuring food security under climate change pressure. The CRISPR toolbox enables faster and more precise plant breeding by facilitating multiplex gene editing, gene pyramiding, and de novo domestication. In this paper, we discuss the most recent advances in CRISPR/Cas9 and alternative CRISPR-based systems, along with the technical challenges that remain to be overcome. A revision of the latest proof-of-concept and functional characterization studies has indeed provided more insight into the quantitative traits affecting crop yield and stress tolerance. Additionally, we focus on the applications of CRISPR/Cas9 technology in regard to extremophile plants, due to their significance on industrial, ecological and economic levels. These still unexplored genetic resources could provide the means to harden our crops against the threat of climate change, thus ensuring food security over the next century.

Despite the common use of cyclosporine (CsA) for acute graft-versus-host disease (aGVHD) prophylaxis following allogeneic stem cell transplant, the optimal CsA trough target remains unknown.

Here, we report on outcomes of adult patients following myeloablative conditioning to identify an optimal CsA trough target and characterize the most relevant timeframe post-transplant for CsA trough targeting to minimize aGVHD. S-Adenosyl-L-homocysteine We retrospectively reviewed 399 consecutive patients who underwent first peripheral blood allogeneic stem cell transplant for hematological malignancies between January 2009 and December 2018.

In the unadjusted and adjusted analyses, the incidence of grades 2-4 aGVHD was significantly higher among patients with an average CsA trough concentration <250mcg/L compared to patients with an average CsA trough concentration ≥250mcg/L during days 15-28 post-transplant (31.5% versus 18.8%, P = 0.037), with an odds ratio (OR) of 1.97 (95% confidence interval 1.04-3.71). In contrast, no correlations between CsA trough concentration and relapse, non-relapse mortality and overall survival was found.

In conclusion, early post-transplant CsA trough concentrations are an important factor in the prophylaxis against aGVHD. Our findings suggest that CsA trough concentrations should be maximized between days 15-28 post-myeloablative transplant.

In conclusion, early post-transplant CsA trough concentrations are an important factor in the prophylaxis against aGVHD. Our findings suggest that CsA trough concentrations should be maximized between days 15-28 post-myeloablative transplant.

Aortic surgery is often performed in elderly patients, and these patients have a high risk of postsurgical muscle weakness. To reinforce purposeful postsurgical rehabilitation, we aimed to investigate the factors associated with postsurgical muscle weakness in patients who underwent thoracic aortic surgery.

This retrospective cohort study analyzed data of consecutive patients who underwent elective thoracic aortic surgery with cardiopulmonary bypass, and whose knee extensor isometric muscle strength (KEIS) were measured pre- and postoperatively at University Hospital between January 2012 and December 2018. The primary outcome was percent change in KEIS (% change in KEIS). Multivariate linear regression analysis was used to identify independent risk factors for % change in KEIS.

Overall, 218 patients were included. Multivariate linear regression analysis showed that mechanical ventilation time, days from initial sitting to 100 m walking, and the number of exercises in the rehabilitation room were associated with % change in KEIS.

This study may serve as a reference to stratify patients at risk of postsurgical muscle weakness. The preventive or alternative interventions in patients undergoing thoracic aortic surgery will be assessed in future studies.

This study may serve as a reference to stratify patients at risk of postsurgical muscle weakness. The preventive or alternative interventions in patients undergoing thoracic aortic surgery will be assessed in future studies.Ectopic expression of a single neural transcription factor NeuroD1 can reprogram reactive glial cells into functional neurons both in vitro and in vivo, but the underlying mechanisms are not well understood yet. Here, we used RNA-sequencing technology to capture the transcriptomic changes at different time points during the reprogramming process. We found that following NeuroD1 overexpression, astroglial genes (ACTG1, ALDH1A3, EMP1, CLDN6, SOX21) were significantly downregulated, whereas neuronal genes (DCX, RBFOX3/NeuN, CUX2, RELN, SNAP25) were significantly upregulated. NeuroD family members (NeuroD1/2/6) and signaling pathways (Wnt, MAPK, cAMP) as well as neurotransmitter receptors (acetylcholine, somatostatin, dopamine) were also significantly upregulated. Gene co-expression analysis identified many central genes among the NeuroD1-interacting network, including CABP7, KIAA1456, SSTR2, GADD45G, LRRTM2, and INSM1. Compared to chemical conversion, we found that NeuroD1 acted as a strong driving force and triggered fast transcriptomic changes during astrocyte-to-neuron conversion process. Together, this study reveals many important downstream targets of NeuroD1 such as HES6, BHLHE22, INSM1, CHRNA1/3, CABP7, and SSTR2, which may play critical roles during the transcriptomic landscape shift from a glial profile to a neuronal profile.

This study aimed to determine the implications of including tympanometry in the Rapid Assessment of Hearing Loss survey protocol. A comparative study design was employed, with findings from otoscopy compared with the results of tympanometry.

A population-based survey of the prevalence and causes of hearing loss among adults aged over 35 years in The Gambia was conducted. Clinical assessments included air conduction audiometry, otoscopy and clinical history. Otoscopy outcome was recorded and for those with hearing loss, a probable cause was assigned. Following otoscopy, tympanometry was completed. Otoscopy outcome was not changed as a result of tympanometry. Clinician assigned cause was compared to the results of tympanometry. The proportion of causes potentially misclassified by excluding tympanometry was determined.

Among people with hearing loss, including tympanometry led to a higher proportion diagnosed with middle-ear conditions.

The value of adding tympanometry to population-based survey protocols is a higher estimated proportion of hearing loss being attributed to middle-ear disease rather than sensorineural causes. This can inform service needs as more people will be classified as needing medical or surgical services, and a slightly lower number will need rehabilitative services, such as hearing assistive devices. It is highly recommended that tympanometry is included in the protocol.

The value of adding tympanometry to population-based survey protocols is a higher estimated proportion of hearing loss being attributed to middle-ear disease rather than sensorineural causes. This can inform service needs as more people will be classified as needing medical or surgical services, and a slightly lower number will need rehabilitative services, such as hearing assistive devices. It is highly recommended that tympanometry is included in the protocol.