Rejected

A systematic overview of mental and physical disorders of informal caregivers based on population-based studies with good methodological quality is lacking. Therefore, our aim was to systematically summarize mortality, incidence, and prevalence estimates of chronic diseases in informal caregivers compared to non-caregivers. Following PRISMA recommendations, we searched major healthcare databases (CINAHL, MEDLINE and Web of Science) systematically for relevant studies published in the last 10 years (without language restrictions) (PROSPERO registration number: CRD42020200314). We included only observational cross-sectional and cohort studies with low risk of bias (risk scores 0-2 out of max 8) that reported the prevalence, incidence, odds ratio (OR), hazard ratio (HR), mean- or sum-scores for health-related outcomes in informal caregivers and non-caregivers. For a thorough methodological quality assessment, we used a validated checklist. The synthesis of the results was conducted by grouping outcomes. We included 22 studies, which came predominately from the USA and Europe. Informal caregivers had a significantly lower mortality than non-caregivers. Regarding chronic morbidity outcomes, the results from a large longitudinal German health-insurance evaluation showed increased and statistically significant incidences of severe stress, adjustment disorders, depression, diseases of the spine and pain conditions among informal caregivers compared to non-caregivers. In cross-sectional evaluations, informal caregiving seemed to be associated with a higher occurrence of depression and of anxiety (ranging from 4 to 51% and 2 to 38%, respectively), pain, hypertension, diabetes and reduced quality of life. Results from our systematic review suggest that informal caregiving may be associated with several mental and physical disorders. However, these results need to be interpreted with caution, as the cross-sectional studies cannot determine temporal relationships. The lower mortality rates compared to non-caregivers may be due to a healthy-carer bias in longitudinal observational studies; however, these and other potential benefits of informal caregiving deserve further attention by researchers.

The physical impairments (e.g., slower walking speed) in patients with chronic obstructive pulmonary disease (COPD) have been attributed to peripheral characteristics (e.g., muscle atrophy). However, cognitive impairment may compromise motor control including walking automaticity. The objective of this study was to investigate PFC neural activity, evaluated using changes in oxygenated hemoglobin (ΔOHb), during preferred paced walking (PPW) in COPD patients and age-matched controls. The ΔOHb from the left and right dorsolateral PFC was measured using functional near-infrared spectroscopy. Fifteen COPD patients (age: 71 ± 8) and twenty age-matched controls (69 ± 7 years) participated. Two-way mixed ANOVA demonstrated that OHb in both groups decreased during PPW from the start (quintile 1; Q1) to the end (quintile 5; Q5) in the left dorsolateral and medial PFC. Q1 was comprised of the data during the first 20% of the task, while Q5 included data collected in the last 20% of the task duration. PPW duration ranged between 30.0 and 61.4 s in the control group and between 28.6 and 73.0 s in COPD patients. COPD patients demonstrated a higher OHb in Q5 compared to the negative OHb in controls in the right medial and dorsolateral PFC during PPW. PPW velocity was lower in COPD patients compared to controls (1.02 ± 0.22 vs. 1.22 ± 0.14 m/s, = 0.005). Healthy older controls exhibited automaticity during walking unlike patients with COPD. The lesser decrease in OHb in COPD patients may be attributed to increased executive demands or affect-related cues (e.g., pain or dyspnea) during walking.

Inflammatory arthritis affects the level of synovial inflammatory factors, which makes it more difficult to diagnose prosthetic joint infection (PJI) patients with inflammatory arthritis. The aim of this study was to analyze synovial interleukin levels to distinguish between PJI and active rheumatoid arthritis (RA) after a hip or knee arthroplasty. From September 2019 to September 2021, we prospectively enrolled patients with joint pain after arthroplasty due to aseptic prosthesis loosening (n = 39), acute RA (n = 26), and PJI (n = 37). Synovial fluid from the affected joint is obtained and tested with a standard enzyme-linked immunosorbent assay. Receiver operating characteristic curve (ROC) was analyzed for each biomarker. Interleukin (IL)-1β, IL-6, and IL-8 showed promising value in differentiating of aseptic loosening from PJI, with areas under the curves (AUCs) of 0.9590, 0.9506, and 0.9616, respectively. Synovial IL-1β, IL-6, and IL-8 showed limited value in distinguishing between PJI and acute episodes of RA after arthroplasty, with AUCs of 0.7507, 0.7069, and 0.7034, respectively. Interleukins showed satisfactory efficacy in differentiating aseptic loosening from PJI. However, when pain after arthroplasty results from an acute episode of RA, current synovial interleukin levels do not accurately rule out the presence of PJI.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) not only affects the respiratory tract but also causes neurological symptoms such as loss of smell and taste, headache, fatigue or severe cerebrovascular complications. Using transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2), we investigated the spatiotemporal distribution and pathomorphological features in the CNS following intranasal infection with SARS-CoV-2 variants, as well as after prior influenza A virus infection. Apart from Omicron, we found all variants to frequently spread to and within the CNS. Infection was restricted to neurons and appeared to spread from the olfactory bulb mainly in basally oriented regions in the brain and into the spinal cord, independent of ACE2 expression and without evidence of neuronal cell death, axonal damage or demyelination. However, microglial activation, microgliosis and a mild macrophage and T cell dominated inflammatory response was consistently observed, accompanied by apoptotic death of endothelial, microglial and immune cells, without their apparent infection. Microgliosis and immune cell apoptosis indicate a potential role of microglia for pathogenesis and viral effect in COVID-19 and the possible impairment of neurological functions, especially in long COVID. These data may also be informative for the selection of therapeutic candidates and broadly support the investigation of agents with adequate penetration into relevant regions of the CNS.

A crescent number of reports describe malignant dermal malignancies presenting as diabetic ulcers, such as melanoma, Kaposi's sarcoma, squamous cell carcinoma and cutaneous lymphoma.

Anal fissure is a linear tear in the distal anoderm most frequently occurring in the posterior midline. Lateral internal sphincterotomy is considered the gold standard for the treatment of this condition. To this date, several pharmacological and neuromodulatory therapies have been tried out as alternative non-invasive treatments for anal fissures, however, the efficacy of some of these methods remains to be understood.

The etiology of chest pain in achalasia-related esophageal motility disorders (AEMDs) and the frequency and risk factors of persistent chest pain after peroral endoscopic myotomy (POEM) remain unclear.

Huangqin decoction (HQD), composed of Scutellaria(Huangqin), Peony(Shaoyao), Liquorice(Gancao) and Jujube(Dazao), is a traditional Chinese medicine prescription, originated from treatise on Febrile Diseases, has the functions of clearing heat, stopping benefits and relieving pain. It is the original prescription for treating heat and relieving dysentery, and is commonly used in clinic for diarrhea and other diseases. In ulcerative colitis, damp-heat syndrome is the most common. However, its mechanism of action is not completely clear.

With the ongoing COVID-19 pandemic, growing evidence shows that a considerable proportion of people who have recovered from COVID-19 have long-term effects on multiple organs and systems. A few longitudinal studies have reported on the persistent health effects of COVID-19, but the follow-up was limited to 1 year after acute infection. The aim of our study was to characterise the longitudinal evolution of health outcomes in hospital survivors with different initial disease severity throughout 2 years after acute COVID-19 infection and to determine their recovery status.