Rejected

Rheumatoid arthritis (RA) is a progressive articular disease. In addition to damaging the joints, it may cause multiple organ complications, and considerably impair the patient's functioning. Elderly patients with RA report pain, fatigue, mood disorders, sleep disorders and insomnia, accompanied by weakness, poor appetite, and weight loss. All these factors combined have an adverse effect on the patient's perceived quality of life (QoL). Due to the chronic nature of RA and the high risk of malnutrition in this patient group, the present study investigated QoL, activities of daily living, and frailty syndrome severity in relation to MNA (Mini Nutritional Assessment) questionnaire scores among elderly RA patients. The study included 98 patients (aged over 60) diagnosed with RA per the ARA (American Rheumatism Association) criteria. The following standardized instruments were used: WHOQoL-BREF for QoL, the Edmonton Frail Scale for frailty syndrome severity, MNA for nutritional status assessment, and MMSE (Mini-Mental State Examination) to assess any cognitive impairment. Medical data were obtained from hospital records. Patients with a different nutritional status differed significantly in terms of limitations in activities of daily living (ADL) and instrumental activities of daily living (IADL). Higher levels of malnutrition were associated with greater limitations in activity. An adverse impact of lower body weight on cognitive function was also observed (dementia was identified in 33.33% of malnourished patients vs. 1.79% in patients with a normal body weight). Likewise, frailty was more common in malnourished patients (mild frailty syndrome in 33.3%, moderate in 16.67%, and severe in 16.67%). Malnourished patients had significantly lower QoL scores in all WHOQoL-BREF questionnaire domains than those with a normal body weight, and multiple-factor analysis for the impact of selected variables on QoL in each domain demonstrated that frailty was a significant independent determinant of poorer QoL in all domains: perceived quality of life (β = -0.069), perceived health (β = -0.172), physical domain (β = -0.425), psychological domain (β = -0.432), social domain (β = -0.415), environmental domain (β = -0.317). Malnutrition was a significant independent determinant of QoL in the "perceived health" domain (β = -0.08). In addition, regression analysis demonstrated the positive impact of male sex on QoL scores in the psychological (β = 1.414) and environmental domains (β = 1.123). Malnourished patients have a lower QoL than those with a normal body weight. Malnutrition adversely affects daily functioning, cognitive function, and the severity of frailty syndrome. Frailty syndrome is a significant independent determinant of poorer QoL in all WHOQoL BREF domains.

Streptococcus suis (S. suis), a gram-positive facultative anaerobe, has emerged as a zoonotic pathogen of suppurative infections in various human organs. Never reported is human primary ventriculitis caused by S. suis. A 70-year-old Chinese woman with a history of eating undercooked pork tongue was admitted to our hospital due to vomiting, headache and high fever. Brain magnetic resonance imaging (MRI) revealed intraventricular empyema and hydrocephalus, while cerebrospinal fluid (CSF) analysis showed purulent changes. S. suis was cultured in the CSF and blood samples of the patient, and confirmed as serotype 2 by real-time polymerase chain reaction (PCR). Therefore, the diagnosis of primary ventriculitis caused by S. suis was established. She was treated with intravenous (IV) meropenem for six weeks. To solve hydrocephalus, external ventricular drain (EVD) was performed, followed by ventriculoperitoneal shunt. Finally, the patient achieved a good outcome after a 6-month follow-up. S. suis is a rare pathogen in northern China but can cause severe infection and complications. S. suis infection should be considered when a patient with bacterial infection has a history of eating undercooked pork. MRI can help detect ventriculitis. It is worth noting that rapid and prolongated administration of IV antibiotics and timely neurosurgical intervention can achieve desirable outcomes.

To describe the epidemiological characteristics and clinical features of patients with fatal coronavirus disease (COVID-19), in order to provide evidence for clinical diagnosis and treatment. In this retrospective study, we analyzed data on 141 fatal cases of confirmed COVID-19 that occurred among patients in Jinyintan Hospital in Wuhan, China, from January 20 to March 6, 2020. We analyzed their epidemiological characteristics, clinical and radiological features, laboratory results, and treatment. Of the 141 patients (49 females, 92 males), the median age was 77 years (range: 24-92 years). The most likely source of exposure included the Huanan seafood market (3, 2%), family members (6, 4%), and hospital-acquired infection (8, 6%). The remaining 116 patients (72%) had no known source of exposure. Of the patients, 101 (72%) had chronic diseases. The most common comorbidities were hypertension, diabetes and coronary heart disease. The most common clinical manifestations were fever (121, 85%), dry cough (77, 54%), shortness of breath (23, 16%), and chest pain (15, 10%). Less common clinical manifestations included fatigue (7, 4%), headache (3, 2%), disorders of consciousness (2, 1%), diarrhea (2, 1%) and lumbago (1, 0.7%). In terms of laboratory tests, the absolute value of lymphocytes in most patients was reduced (132, 94%), but C-reactive protein (141, 100%), procalcitonin(121, 89%), serum amyloid (140, 99%) were significantly increased. The most common findings on imaging of the lungs were bilateral multiple mottling and ground-glass opacity (101, 72%), mainly in the lower lobes (15, 10%), with lesions being more common on the right. Other imaging findings included diffuse consolidation (4, 3%), ground-glass opacity and consolidation (20, 14%), and pneumothorax (1, 0.7%). All patients were treated with antibiotics and antiviral drugs. Other treatments included immunoglobulin (49, 35%), corticosteroids (45, 32%), continuous renal replacement therapy (24, 17%), and extracorporeal membrane oxygenation (12, 9%). All patients were treated with oxygen therapy. The mode of administration included invasive mechanical ventilation (61, 43%), noninvasive mechanical ventilation (65, 46%), and nasal catheter oxygen inhalation (15, 11%). The direct causes of death were acute respiratory distress syndrome (90, 64%), multiple organ failure (24, 17%), sudden cardiac arrest (11, 8%), viral myocarditis (8, 5%), acute myocardial infarction (4, 3%), cerebrovascular accident (3, 2%), and acute gastrointestinal bleeding (1, 0.7%). Risk factors for death due to COVID-19 included older age, male sex, and the presence of comorbidities. The most common direct causes of death were acute respiratory distress syndrome, multiple organ failure, sudden cardiac arrest, and viral myocarditis.

First-line analgetic medication used in the field of musculoskeletal degenerative diseases, like Nonsteroidal anti-inflammatory drugs (NSAIDs), reduces pain and prostaglandin synthesis, whereby peptic ulcers are a severe adverse effect. Therefore, proton pump inhibitors (PPI) are frequently used as a concomitant medication to reduce this risk. However, the impact of NSAIDs or metamizole, in combination with PPIs, on bone metabolism is still unclear. Therefore, human mesenchymal stem cells (hMSCs) were cultured in monolayer cultures in 10 different groups for 21 days. New bone formation was induced as follows: Group 1 negative control group, group 2 osteogenic differentiation media (OSM), group 3 OSM with pantoprazole (PAN), group 4 OSM with ibuprofen (IBU), group 5 OSM with diclofenac (DIC), group 6 OSM with metamizole (MET), group 7 OSM with ibuprofen and pantoprazole (IBU + PAN), group 8 OSM with diclofenac and pantoprazole (DIC + PAN), group 9 OSM with metamizole and pantoprazole (MET + PAN) and group 10 OSM with diclofenac, metamizole and pantoprazole (DIC + MET + PAN). Hydroxyapatite content was evaluated using high-sensitive radioactive Tc-HDP labeling. Within this study, no evidence was found that the common analgetic medication, using NSAIDs alone or in combination with pantoprazole and/or metamizole, has any negative impact on the osteogenic differentiation of mesenchymal stem cells in vitro. To the contrary, the statistical results indicate that pantoprazole alone (group 3 (PAN) ( = 0.016)) or diclofenac alone (group 5 (DIC) ( = 0.008)) enhances the deposition of minerals by hMSCS in vitro. There is an ongoing discussion between clinicians in the field of orthopaedics and traumatology as to whether post-surgical (pain) medication has a negative impact on bone healing. This is the first hMSC in vitro study that investigates the effects of pain medication in combination with PPIs on bone metabolism. Our in vitro data indicates that the assumed negative impact on bone metabolism is subsidiary. These findings substantiate the thesis that, in clinical medicine, the patient can receive every pain medication needed, whether or not in combination with PPIs, without any negative effects for the osteo-regenerative potential.

1,4-Dihydropyridines (DHPs) are the most important class of L-type calcium channel blockers that are employed for the treatment of cardiovascular diseases, particularly hypertension. Various modifications on this scaffold lead to the discovery of new DHPs blocking different types of calcium channels. Among them, the T-type calcium channel has recently attracted great interest due to its role in chronic pain conditions. In this study, we selected three newly synthesized DHPs (HM8, HM10 and MD20) with different selectivity profiles to the T-type calcium channel and formulated them in micellar solutions and micellar-in-gel matrices to be tested for potential topical use in the treatment of neuropathic pain. To prevent the well-known sensitivity to light of the DHPs, the studied compounds were entrapped in colloidal aggregates obtained by using edible Pluronic surfactants and adding α-tocopherol as an antioxidant. All the prepared formulations were exposed to stressing light, according to international rules. Along with the degradation experiments, the concentrations of the parent compounds and by-products were calculated by multivariate curve resolution-alternating least squares (MCR-ALS) applied to the spectral data. The defined formulations proved suitable as light-stable matrices for the DHP compounds, showing an increase in stability for HM8 and MD20 and an almost complete photoprotection for HM10, compared to ethanol solutions and standard gel formulations.

Chemotherapy-induced neuropathy is a common, dose-dependent adverse effect of several antineoplastics, such as oxaliplatin (L-OHP). The aim of the present work was to evaluate the potential beneficial effects of 2-pentadecyl-2-oxazoline (PEA-OXA) in a murine model of oxaliplatin-induced peripheral neuropathy (OIPN). OIPN was induced by an intraperitoneally injection of L-OHP in rats on five consecutive days (D0-4) for a final cumulative dose of 10 mg/kg. PEA-OXA and ultramicronized palmitoylethanolamide (PEAum), both 10 mg/kg, were given orally 15-20 min prior (L-OHP) and sacrifice was made on day 25. Our results demonstrated that PEA-OXA, more than PEAum, reduced the development of hypersensitivity in rats; this was associated with the reduction in hyperactivation of glia cells and the increased production of proinflammatory cytokines in the dorsal horn of the spinal cord, accompanied by an upregulation of neurotrophic factors in the dorsal root ganglia (DRG). Moreover, we showed that PEA-OXA reduced L-OHP damage via a reduction in NF-κB pathway activation and a modulation of Nrf-2 pathways. Our findings identify PEA-OXA as a therapeutic target in chemotherapy-induced painful neuropathy, through the biomolecular signaling NF-κB/Nrf-2 axis, thanks to its abilities to counteract L-OHP damage. Therefore, we can consider PEA-OXA as a promising adjunct to chemotherapy to reduce chronic pain in patients.

Endometriosis is a chronic inflammatory condition, which is distinguished by the presence of the endometrial-like glands and stroma outside the uterine cavity. Pain and infertility are the most commonly expressed symptoms, occurring in 60% and 40% of cases, respectively. Women with endometriosis, especially those with pelvic pain, also have a greater vulnerability to several psychiatric disorders. There is, in particular, a tendency to contract affective or anxiety disorders as well as panic-agoraphobic and substance use disorders. Endometriosis with pelvic pain, infertility and psychic vulnerability usually leads to disability and a markedly lower quality of life for women of reproductive age. Thus, the burden of endometriosis is not limited to the symptoms and dysfunctions of the disease; it extends to the social, working and emotional spheres, leading to a severe impairment of global functioning. An analysis of scientific literature revealed a close relationship between specific temperamental traits, the expression of several psychiatric symptoms, chronicity of pain, risk of substance use and lower probability of a positive outcome. Endometriosis symptoms and the impact of related psychological consequences, increased vulnerability and the possible onset of psychiatric symptoms may influence coping strategies and weaken resilience, so triggering a vicious cycle leading to a marked deterioration in the quality of life. A multidisciplinary approach consisting of a medical team composed of gynecologists, psychologists, psychiatrists, experts in Dual Disorder, algologists and sexologists, would guarantee the setting of a target and taking the best decision on a personalized treatment plan. That approach would allow the prompt detection of any psychopathological symptoms and improve the endometriosis-related physical symptoms, bringing a healthier quality of life and a greater likelihood of a positive outcome.

Health complaints are increasing among adolescents and are recognized as a global public health issue. Health complaints are an indicator for subjective ill-being, but little is known about the relationship between sadness and other health complaints. The aim of this study was to investigate sadness and other health complaints among Swedish adolescents. A survey with a cross-sectional design was completed by adolescents ( = 1489, 15-17 years old) in the south of Sweden. A logistic regression analysis was used to analyze the relationship between sadness and other health complaints. The result show that sadness and other health complaints were common among adolescents, and sadness was related to health complaints (headache (OR: 1.58), sleeping difficulties (OR: 2.00), reduced appetite (OR: 1.43), tension (OR: 2.44), and concentration difficulties (OR: 2.75)). When adolescents express sadness or other health complaints it is important to reflect on what these complaints are an expression of, and take into account the body as physical and psychological intertwined. This might entail person-centered support that hopefully leads to an improvement in adolescents' well-being. Future research that profoundly highlights adolescents' existential health is needed.

We pose, based on a neurobiological examination, that events that occur around the time of slaughter have the potential to intensify the pain response, through the processes of sensitisation and enhanced transmission. Sensitisation, or an enhanced response to painful stimuli, is a well-discussed phenomenon in the human medical literature, which can arise from previous injury to an area, inflammatory reactions, or previous overstimulation of the stress axes. A number of events that occur prior to arrival at, or in the slaughterhouse, may lead to presence of these factors. This includes previous on-farm pathology, injuries arising from transport and handling and lack of habituation to humans. Whilst there is limited evidence of a direct effect of these on the processes of sensitisation in animals at slaughter, by analogy with the human neurobiology literature the connection seems plausible. In this review a neurobiological approach is taken to discuss this hypothesis in the light of basic science, and extrapolations from existing literature on the slaughter of ruminants. To confirm the postulated link between events at slaughter, and processes of hypersensitisation, further dedicated study is required.

The study aims to assess the impact of the second COVID-19 pandemic wave on migraine characteristics.