Rejected

Quality of life (QoL) is an essential consideration when managing the wellbeing of patients and assists in interpretation of symptoms, functional status and perceptions. Atrial fibrillation (AF) and diabetes demand significant healthcare resources. Existing data demonstrate a negative impact on QoL as individual conditions, but there is less evidence relating to the impact of these disease groups in combination. This study therefore explores QoL in patients with AF and diabetes. This cross-sectional, observational study required participants to complete the short form (SF)-36 survey via an online platform and was offered to people affected by AF alone and people with AF and diabetes in combination. The SF-36 provides a prevalidated tool with eight domains relating to physical and psychological health. A total of 306 surveys were completed (231 AF group, 75 AF and diabetes group).The mean and standard deviation (SD)were calculated for each QoL domain,after re-coding in accordance with SF-36 guidance. Multi-variate analysis of variance (MANOVA) demonstrated an overall significant difference between the groups when considered jointly across all domains.There were significant differences between AF and AF with diabetes QoL responses in physical functioning, energy fatigue,emotional wellbeing, social functioning and pain. In these domains, the mean was highest in the AF group. There were no significant differences in the role physical,role emotional and general health domains. In conclusion, this study demonstrates that diabetes and AF has a more detrimental effect on QoL than AF alone, in the majority of domains. Further research into the general AF population and where chronic conditions co-exist is important to comprehend the true impact this disease combination has on QoL.

Chemotactic cytokines or chemokines are a large family of secreted proteins able to induce chemotaxis. Chemokines are categorized according to their primary amino acid sequence, and in particular their cysteine residues that form disulphide bonds to maintain the structure: CC, CXC, CX3C, and XC, in which X represents variable amino acids. Among their many roles, chemokines are known to be key players in pain modulation in the peripheral and central nervous systems. Thus, they are promising candidates for novel therapeutics that could replace current, often ineffective treatments. The spinal and trigeminal systems are intrinsically different beyond their anatomical location, and it has been suggested that there are also differences in their sensory mechanisms. Hence, understanding the different mechanisms involved in pain modulation for each system could aid in developing appropriate pharmacological alternatives. Here, we aim to describe the current landscape of chemokines that have been studied specifically with regard to trigeminal pain. Searching PubMed and Google Scholar, we identified 30 reports describing chemokines in animal models of trigeminal pain, and 15 reports describing chemokines involved in human pain associated with the trigeminal system. This review highlights the chemokines studied to date at different levels of the trigeminal system, their cellular localization and, where available, their role in a variety of animal pain models.

Cannabinoid receptors have been identified as potential targets for analgesia from studies on animal physiology and behavior, and from human clinical trials. Here, we sought to improve translational understanding of the mechanisms of cannabinoid-mediated peripheral analgesia. Human lumbar dorsal root ganglia were rapidly recovered from organ donors to perform physiological and anatomical investigations into the potential for cannabinoids to mediate analgesia at the level of the peripheral nervous system. Anatomical characterization of gene expression and immunoreactivity showed that 61 and 53% of human sensory neurons express the CB1 gene and receptor, respectively. Calcium influx evoked by the algogen capsaicin was measured by Fura-2AM in dissociated human sensory neurons pre-exposed to the inflammatory mediator prostaglandin E2 (PGE2) alone or together with CB13 (1 μM), a cannabinoid agonist with limited blood-brain barrier permeability. Both a higher proportion of neurons and a greater magnitude of response to capsaicin were observed after exposure to CB13, indicating cannabinoid-mediated sensitization. In contrast, membrane properties measured by patch-clamp electrophysiology demonstrated that CB13 suppressed excitability and reduced action potential discharge in PGE2-pre-incubated sensory neurons, suggesting the suppression of sensitization. This bidirectional modulation of sensory neuron activity suggests that cannabinoids may suppress overall membrane excitability while simultaneously enhancing responsivity to TRPV1-mediated stimuli. We conclude that peripherally restricted cannabinoids may have both pro- and anti-nociceptive effects in human sensory neurons.

Chemotherapy induced peripheral neuropathy (CIPN) is a severe neurodegenerative disorder caused by chemotherapy drugs. Berberine is a natural monomer compound of Coptis chinensis, which has anti-tumor effect and can improve neuropathy through anti-inflammatory mechanisms. Transient receptor potential vanilloid (TRPV1) can sense noxious thermal and chemical stimuli, which is an important target for the study of pathological pain. In both vivo and CIPN models, we found that berberine alleviated peripheral neuropathy associated with dorsal root ganglia inflammation induced by cisplatin. We confirmed that berberine mediated the neuroinflammatory reaction induced by cisplatin by inhibiting the overexpression of TRPV1 and NF-κB and activating the JNK/p38 MAPK pathways in early injury, which inhibited the expression of -JNK and mediated the expression of p38 MAPK/ERK in late injury . Moreover, genetic deletion of significantly reduced the protective effects of berberine on mechanical and heat hyperalgesia in mice. In knockout mice, the expression of NF-κB increased in late stage, and berberine inhibited the overexpression of NF-κB and -ERK in late injury. Our results support berberine can reverse neuropathic inflammatory pain response induced by cisplatin, TRPV1 may be involved in this process.

During the COVID-19 pandemic, physical therapists transitioned to provide telehealth in the United States. We sought to determine the experiences of physical therapists delivering telerehabilitation for vestibular disorders including barriers, preferences, and concerns. A survey was created using the results of a focus group and previously published studies. The survey was distributed across social media sites and through email- the link was sent to the orthopedic, neurologic, and geriatric academies of the American Physical Therapy Association list serves. The email was also shared with each of the 50 state chapters of the American Physical Therapy Association. The survey was broken down into five sections: demographic information, physical therapists' general impressions of telehealth, physical therapists' comfort level treating various vestibular diagnoses, and common barriers physical therapists experienced during telehealth sessions. There were 159 completed surveys. More than 80% of physical therapists surveyed agreed that telehealth was an effective platform for vestibular physical therapy. When asked whether physical therapists felt the patient had similar health outcomes with telehealth versus clinic care 68% of physical therapists agreed. For the physical therapists who treated posterior or horizontal canal benign paroxysmal positional vertigo telehealth, more than 50% were comfortable treating these conditions telehealth. In analyzing common peripheral vestibular diagnoses treated telehealth including bilateral vestibular loss, Meniere's disease, and vestibular neuritis more than 75% of the physical therapists reported comfort treating these diagnoses. Similarly, more than 75% of physical therapists who treated central vestibular diagnoses- including mild traumatic brain injury and vestibular migraine- telehealth reported being comfortable treating these diagnoses. Physical therapists reported several barriers to tele healthcare ranging from concerns about testing balance with no caregiver present (94%) to challenges with providing a written home exercise program (33%). Physical therapists report that telehealth is a viable mechanism for providing rehabilitation for persons with balance and vestibular disorders. For common diagnoses, most physical therapists were comfortable treating vestibular disorders telehealth. While barriers remain including maintaining patient safety and being able to complete a thorough vestibular exam, telehealth for vestibular physical therapy services holds promise for the delivery of virtual care.

Chronic skeletal disorders (CSDs), including degenerative diseases such as osteoporosis (OP) and autoimmune disorders, have become a leading cause of disability in an ageing society, with natural drugs being indispensable therapeutic options. The clinical safety evaluation (CSE) of natural drugs in CSDs has been given priority and has been intensively studied. To provide fundamental evidence for the clinical application of natural drugs in the elderly population, clinical studies of natural drugs in CSDs included in this review were selected from CNKI, Web of Science, PubMed, Science Direct and Google Scholar since 2001. Seventeen randomized controlled trials (RCTs) met our inclusion criteria: four articles were on OP, seven on osteoarthritis (OA), four on rheumatoid arthritis (RA) and two on gout. Common natural drugs used for the treatment of OP include Berberidaceae, Caprifoliaceae root, and Orchidaceae, which have been linked to several mild adverse reactions, such as skin rash, gastric dysfunction, abnormal urine, constipation and irritability. The safety of Araliaceae extract, Burseraceae extract and extract from perna canaliculus was evaluated in OA and upper abdominal pain, and unstable movements were obsrerved as major side effects. Adverse events, including pneumonia, vomiting, diarrhoea and upper respiratory tract infection, were reported when RA was treated with Celastraceae[TwHF] polyglycosides and quercetin (Brassicaceae). The present review aimed to summarize the CSE results of natural drugs in CSDs and could provide evidence-based information for clinicians.

Surgery for chronic anal fissure is challenging for every proctologist. Solving the pain by guaranteeing rapid and effective healing is the objective, but what is the price to pay today in functional terms? Though this result is nowadays partially achievable through interventions that include the execution of an internal sphincterotomy among the procedures, it is necessary to underline the high rate of patients who can present faecal incontinence. The aim of this study is to explore the effectiveness of scanner-assisted CO laser fissurectomy. From April 2021 to September 2021, all consecutive patients who affected by chronic anal fissure suitable for surgery, meeting the inclusion and exclusion criteria, were evaluated. All planned data were recorded before surgery, then at 24 h, 1 week, and 1 month follow-up. A scanner-assisted CO laser was used in this study to achieve a smooth and dried wound with a minimal tissue thermal damage, to ensure good postsurgical pain control, rapid and functional, elastic and stable healing, and to prevent potential relapses. Paracetamol 1 g every 8 h was prescribed for the first 24 h and then continued according to each patient's need. Ketorolac 15 mg was prescribed as rescue. Mean pain intensity ≤3, considered as the principal endpoint, was recorded in 26 out of the 29 patients who enrolled in the study with a final success rate of 89.7% at 1-month follow-up. Pain and anal itching showed a statistically significant reduction while bleeding, burning, and maximum pain, and REALIS score showed a reduction too at the end of the follow-up period. Reepithelisation proved to be extremely fast and effective: 22 of 29 (75.9%) showed a complete healing and 5 showed a partial reepithelisation at 1-month follow-up. Outcomes of this study showed that it is undoubtedly necessary to change the surgical approach in case of anal fissure. The internal sphincterotomy procedure must be most of all questioned, where the availability of cutting-edge technological tools must be avoided and offered only in selected cases. Scanner-assisted CO laser showed great results in terms of pain control and wound healing, secondary to an extremely precise ablation, vaporisation, and debridement procedures with minimal lateral thermal damage.

Although the biological agent ustekinumab (UST) is reported to be effective for Crohn's disease (CD) in pediatric as well as adult patients, data on the efficacy and safety of UST in pediatric patients with CD are limited. Here, we describe the case of a pediatric patient who showed an allergic reaction to UST after subcutaneous (SC) maintenance injections but not immediately after initial intravenous (IV) injection. A 9-year-old boy presented to our hospital with diarrhea lasting 2 years and weight loss, leading to the diagnosis of CD. After prednisolone (PSL) was tapered and discontinued, he promptly relapsed. According to our institution's protocol, we introduced the biological agent infliximab (IFX) with premedication. Coughing and vomiting was observed after the second dose of IFX and it was changed to adalimumab (ADA). However, the effect of ADA gradually disappeared after 18 months; therefore, it was discontinued and he was treated using UST. The first IV UST dose was given after administering hydrocortisone (HDC), an antiallergic and antipyretic analgesic, as premedication, and no obvious adverse reaction was observed. After 8 weeks, UST was subcutaneously injected without premedication. The patient then complained of nausea, dizziness, and headache within 15 min of UST administration. Therefore, for the third dose of UST, HDC was administered again as premedication. However, nausea, dizziness, and headache presented 10 min after UST administration, resulting in discontinuation of further UST treatment. Careful distinction between "true" infusion-related reactions (IRRs) and anaphylaxis or allergic reactions is necessary to determine whether biological agents can be continued after the development of "so-called" IRRs. For true IRRs, it may be possible to continue using the biological agent with appropriate premedication; however, in cases of anaphylaxis, the biological agent itself should be changed.

Despite extensive investigations, the exact etiology of chronic subdural hematoma (CSDH) remains elusive. Organized CSDHs are a distinct but less-understood type of CSDH.

Sciatic nerve injury is often associated with neuropathic pain and neuroinflammation in the central and peripheral nervous systems. In our previous work, L. displayed anti-inflammatory, antipyretic and analgesic properties, predominantly via the inhibition of COX-2 enzyme and attenuation of oxidative stress. Herein, we extended our investigations to study the effects of the plant's extract on pain-related behaviors, oxidative stress, apoptosis markers, GFAP, CD68 and neuro-inflammation in sciatic nerve chronic constriction injury (CCI) rat model. The levels of the pro-inflammatory marker proteins in sciatic nerve and brainstem were measured with ELISA 14 days after CCI induction. Pretreatment with the extract significantly attenuated mechanical and cold allodynia and heat hyperalgesia with better potential than the reference drug, pregabalin. In addition, CCI lead to the overexpression of prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), tumor necrosis alpha (TNFα), nuclear factor κB (NF-κB), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and NADPH oxidase-1 (NOX-1) and decreased the catalase level in sciatic nerve and brainstem. The observed neuro-inflammatory changes were accompanied with glial cells activation (increased GFAP and CD68 positive cells), apoptosis (increased Bax) and structural changes in both brainstem and sciatic nerve. The studied extract attenuated the CCI-induced neuro-inflammatory changes, oxidative stress, and apoptosis while it induced the expression of Bcl-2 and catalase in a dose dependent manner. It also decreased the brainstem expression of CD68 and GFAP indicating a possible neuroprotection effect. Taking together, may be considered as a novel therapy for neuropathic pain patients after performing the required clinical trials.