Search Results (214)

Background: Spinal cord injury is a life-changing condition for individuals who have previously been independent in activities of daily living. Motor recovery prognosis for individuals with complete spinal cord lesion above thoracic level ten is poor after nine months of injury. Although the corticospinal tract is responsible for voluntary mobility functions such as walking, it is possible, through neuroplasticity, that involuntary lower limb movements can be trained. Methods: This case study discusses the use of multi-modal rehabilitation strategies, from weightbearing exercises using traditional manual-controlled exoskeleton to ambulation using advanced automotive exoskeleton. Results: The patient’s perspective showed themes that align with the World Health Organization’s International Classification of Functioning and Disability. In spinal cord injury, majority of concerns are in environmental and personal factors. This could be due to the perceived permanent disability in complete spinal cord lesion. The moderate-intensity two-hour intervention using traditional and advanced exoskeletons during physical rehabilitation showed that it was possible to stimulate deep sensations, and muscle pull and cramp for a patient diagnosed with complete spinal cord lesion. Conclusions: The use of traditional and advanced exoskeletons in weightbearing exercises may benefit patients with complete spinal cord lesions in regaining deep sensations in the lower limbs. Full article

Climate change-related weather extremes and air pollution have wide-ranging health effects, with emerging evidence suggesting a potential influence on pain. This narrative review explores the relationship between climate-related weather parameters/air pollution with pain across various conditions, including chronic and acute musculoskeletal pain, postoperative pain, headache/migraine, dysmenorrhea, and chest pain. Included studies were published in 2014 or later. Findings indicate that higher humidity/dampness may exacerbate pain in individuals with knee osteoarthritis, while extremes in temperature and humidity are linked to a higher risk of gout arthritis attacks. No clinically meaningful associations were found between weather parameters and acute low-back pain. However, lower barometric pressure, elevated temperatures, and possibly higher humidity may influence postoperative pain levels. Headache and migraine episodes were more frequent during heat waves and periods of high humidity or rainfall, as well as in areas with elevated traffic-related air pollutants and particulate matter. Air pollution exposure was also associated with increased risk of dysmenorrhea, while lower temperatures and higher humidity correlated with more severe menstrual cramps. Temperature extremes were linked to chest pain in patients with asthma and other conditions. Overall, this review highlights the disproportionate pain-related burden of climate change and air pollution on women and emphasizes the need for further research. Full article

Furosemide appears to contribute to the accumulation of protein-bound uremic toxins (PBUTs) and to induce adverse drug reactions. We investigated the extent to which the association between the furosemide dose and serum PBUT concentrations mediates the relationship between the furosemide dose and the symptom burden in patients with chronic kidney disease (CKD). This cross-sectional analysis included patients with CKD stages 2 to 5 from the CKD-REIN cohort and with data on the baseline serum concentrations of the free fractions of indoxyl sulphate (IS), kynurenine (KYN), p-cresyl sulphate (PCS), and indole-3-acetic acid (IAA), as measured by liquid chromatography–tandem mass spectrometry. The symptom burden was also assessed with a modified (8-item) symptom subscale from the Kidney Disease Quality of Life-36 (e.g., muscle soreness, cramps, itchy skin, dry skin, dizziness, appetite, numbness, and nausea). We used beta regressions to model the association between the furosemide dose and the symptom burden and used structural equation models to quantify the mediating effect of PBUT on this association. Among the 2053 included patients (males: 66%, median age: 68; mean estimated glomerular filtration rate: 35 mL/min/1.73 m²), those prescribed high-dose furosemide (>120 mg/day) had higher symptom burden than those not prescribed furosemide (i.e., a 5.67-point lower symptom score, 95%CI 1.41–9.93). The sum of PBUTs explained 3.78% (95%CI 0.10–18.01%) of this association. Similar results were observed for IS, KYN, and IAA, considered separately, but not for PCS, whose estimated mediation effect was nearly null. Although high-dose furosemide was associated with a greater symptom burden in patients with CKD, mediation by PBUT accumulation appeared to be minimal. Full article

Background/Objectives: Primary dysmenorrhea is a prevalent condition that causes severe uterine cramps in women worldwide. The objective of this work was to synthesize and characterize a novel immediate-release system using vitexin and ZIF-8, and to evaluate its pharmacological action in a model of primary dysmenorrhea. Methods: A 2² full factorial design guided the synthesis of the system. Physicochemical characterization was performed by FT-IR, TG, DSC, SEM, XRD, and in vitro release tests. Pharmacological activity was assessed in an oxytocin-induced dysmenorrhea model in mice. In addition, in silico molecular docking and molecular dynamics simulations were conducted to explore the potential mechanism of action of vitexin. Results: Optimal yield and loading capacity were achieved at the high levels of the factorial design. Characterization analyses confirmed the successful formation of the vitexin@ZIF-8 (VIT@ZIF-8) system. The release study demonstrated a markedly enhanced dissolution rate of vitexin. Both isolated vitexin and VIT@ZIF-8 reduced abdominal writhing when administered orally at 3 and 30 mg/kg, while intraperitoneal activity was observed only at 30 mg/kg. Computational analyses revealed favorable interactions of vitexin with aldose reductase (AKR1C3), suggesting this enzyme as a potential molecular target in dysmenorrhea. Conclusions: The VIT@ZIF-8 system represents a promising strategy to improve the dissolution profile of vitexin, although pharmacological activity in this model was not superior to the isolated compound. The combined in vivo and in silico evidence supports vitexin as a potential antidysmenorrheic agent, possibly through modulation of AKR1C3. These findings open avenues for future studies addressing the molecular pathways of vitexin and for the development of novel therapeutic approaches for primary dysmenorrhea. Full article

P2X receptors are a family of ATP-gated ion channels widely distributed in various tissues, especially in neuronal cells and hematopoietic cells. ATP activates P2X receptors, causing the opening of an ionic channel with preferential permeability to the passage of mono- and divalent cations. High concentrations of ATP stimulate the P2X7 subtype through prolonged activation, which opens pores and causes inflammation, proalgesic effects, and cell death. Peptides, including antimicrobials (antimicrobial peptides), are present in several organisms, such as amphibians, mammals, fish, arachnids, and plants, where they act as the first line of defense. Thus, these peptides have the capacity to eliminate a wide spectrum of microorganisms, such as bacteria, fungi, and some viruses. In general, the mechanism of action of antimicrobial peptides involves interactions with the lipid bilayer of the cell membrane, which can lead to an increase in the internal liquid content of liposomes. However, many peptides can act on ion channels, such as those of the P2X family, especially the P2X7 receptor. We investigated the action of peptides that directly modulate P2X7 receptors, such as beta-amyloid, LL-37/hCap18, Pep19-2.5, rCRAMP, ADESG, and polymyxin B. Additionally, we evaluated peptides that modulate the activity of P2X family receptor subtypes. In this review, we intend to describe the relationships between peptides with distinct characteristics and how they modulate the functionality of P2X receptors. Full article

Background: Acute aortic occlusion (AAO) is a rare but life-threatening condition which can present with a spectrum of symptoms, ranging from mild cramping pain in the lower extremities (with or without sensory loss) to more dramatic motor loss and paraplegia. Once a diagnosis has been established, the treatment remains ambiguous, especially in a resource-limited setting. Treatment ranges from direct vascular intervention to systemic or directed thrombolysis—however, there is a lack of published literature on systemic thrombolysis, and thereby, consensus guidelines are nonexistent. Additionally, systemic thrombolysis bears a risk of hemorrhagic complications; however, the risk of death due to AAO is up to 57 times greater than the risk of intracerebral hemorrhage from systemic thrombolysis. Methods: This case report explores the prompt diagnosis of an acute aortic occlusion causing bilateral acute lower extremity ischemia in a sixty-three-year-old female patient treated with systemic thrombolysis. Results: The patient received 100 mg of tPA (without a bolus dose, over a two-hour period) in the Emergency Department (similar to that which is administered for the full-dose pulmonary embolism protocol). One hour after administration, the patient had restored flow to the bilateral lower extremities verified using bedside color-flow Doppler, with a drastic improvement in her symptoms. Two days after systemic thrombolysis, a repeat CTA showed evidence of complete resolution of her aortic clot. Her condition was complicated by a brief episode of retroperitoneal bleeding (presenting with flank pain) while on a heparin drip after admission (day two), which was resolved through discontinuation of the heparin drip and a two-unit blood transfusion. Conclusion: The patient was discharged with full function of the lower extremities on day six without anticoagulation. At her 2-week follow-up appointment, she was noted to be ambulatory without any neurodeficit, with a persistently restored arterial flow to the lower extremity. The application of systemic tPA could be paramount in the treatment of AAO in the setting of ischemic limb pathology, particularly at rural hospitals and healthcare centers where urgent direct vascular intervention may not be possible. Full article

Background: Foot injuries are common among Umrah pilgrims due to prolonged walking, overcrowded conditions, and inadequate preventive measures, such as inappropriate footwear or walking barefoot. Despite their potential impact on mobility and overall pilgrimage experience, these conditions remain underreported and insufficiently addressed in public health strategies. Objectives: This study aims to assess the prevalence and types of foot problems among Umrah pilgrims, examine their associations with demographic characteristics and comorbidities, analyze the utilization of medical attention for foot pain, and assess the use of preventive measures to reduce foot-related health risks during the pilgrimage. Methods: A cross-sectional study was conducted throughout the 2024 G (1445 H) Umrah season at the Grand Mosque, Makkah. The study recruited 1138 Umrah pilgrims aged 18 and older who performed the pilgrimage. A structured questionnaire was administered to collect data on demographic characteristics, chronic diseases, foot conditions, medical-attention-seeking behavior, and preventive practices. Pilgrims with pre-existing foot conditions were excluded from participation. Results: Foot diseases were reported by 46% of participants. The most common foot injuries included sprains/strains (18.7%) and muscle pain/cramps (4.9%), with the leg and forefoot being the most affected areas. Significant associations were observed between foot diseases and lower education levels (p = 0.03), chronic liver disease (p = 0.04), and cardiovascular disease (p = 0.04). Despite the high prevalence of foot-related conditions, only 9.6% sought medical attention, and 14.9% reported using preventive measures. Conclusions: The study highlights a substantial burden of foot problems among Umrah pilgrims, with limited utilization of healthcare services and preventive strategies. Targeted interventions, including educational campaigns and improved screening for high-risk individuals, are essential for enhancing foot health and ensuring a safer pilgrimage experience. Full article

Tubular aggregate myopathy (TAM) is an inherited skeletal muscle disease associated with progressive muscle weakness, cramps, and myalgia. Tubular aggregates (TAs) are regular arrays of highly ordered and densely packed straight-tubules observed in muscle biopsies; the extensive presence of TAs represent a key histopathological hallmark of this disease in TAM patients. TAM is caused by gain-of-function mutations in proteins that coordinate store-operated Ca²⁺ entry (SOCE): STIM1 Ca²⁺ sensor proteins in the sarcoplasmic reticulum (SR) and Ca²⁺-permeable ORAI1 channels in the surface membrane. Here, we assessed the therapeutic potential of endurance exercise in the form of voluntary wheel running (VWR) in mitigating TAs and muscle weakness in Orai1^G100S/+ (GS) mice harboring a gain-of-function mutation in the ORAI1 pore. Six months of VWR exercise significantly increased specific force production, upregulated biosynthetic and protein translation pathways, and normalized both mitochondrial protein expression and morphology in the soleus of GS mice. VWR also restored Ca²⁺ store content, reduced the incidence of TAs, and normalized pathways involving the formation of supramolecular complexes in fast twitch muscles of GS mice. In summary, sustained voluntary endurance exercise improved multiple skeletal muscle phenotypes observed in the GS mouse model of TAM. Full article

Background: The primary effect of Botulinum toxin (BoNT) is to cause weakness in the injected muscles by inhibiting the release of acetyl choline from presynaptic nerve terminals. Its effect on sensorimotor integration (SMI) has largely been confined to small studies. The aim of this review is to highlight effect of BoNT on SMI in the context of Parkinson’s disease (PD), Cervical dystonia (CD), and Writer’s cramp (WC). Methods: Using keywords “Botulinum toxin” and “sensorimotor integration” or “Freezing of gait (FOG)” or ‘Tremor”or “Cervical dystonia” or “Parkinson’s disease”, or “Writer’s cramp”, PubMed database was searched for relevant articles supporting our view. The abstracts of all resultant articles (case reports, case series, randomized trials, observational studies) were reviewed to look for evidence of effects of botulinum toxin on SMI. The relevant articles were charted in excel sheet for further full text review. Results: In FOG, chronic BoNT injections may alter central motor patterns with inclusion of alternative striatal systems, cerebellum, and its connections. In tremor, the afferent proprioceptive input may be modified with reduction of intracortical facilitation and increment of intracortical inhibition. In CD, BoNT can restore disorganized cortical somatotrophy, the key pathophysiology behind cervical dystonia. Similarly, in WC, both the deficient sensory system and abnormal reorganization of the sensorimotor cortex may be altered following chronic BoNT injections. Conclusions: There is preliminary evidence that BoNT may modulate SMI in PD, CD, and WC by altering inputs from the muscle spindles in short term and modifying circuits/particular anatomic cerebral cortices in the long term. Properly conducted randomized trials comparing BoNT with placebo or prospective large-scale studies to look for effect on various surrogate markers reflective of changes in SMI should be the next step to confirm these findings. Targeting the system of afferents like spindles and golgi tendon organs in muscles may be a better way of injecting BoNT, with lower amounts of toxin needed and potential for lesser side-effects like weakness and atrophy. However, this needs to be proven in controlled trials. Full article

Osteoarthritis (OA) is the most prevalent form of joint arthritis, frequently associated with aging, mechanical wear, and inflammation. Our previous work demonstrated that cathelicidin-related antimicrobial peptide (Cramp) is upregulated in mouse OA cartilage, and that transient knockdown (KD) of Cramp in cultured chondrocytes decreases IL-1β-induced expression of matrix-degrading enzymes. The aim of this study was to determine the in vivo role of Cramp in OA pathogenesis using whole-body Cramp knockout (KO) mice. Normal skeletal development and growth plate morphology were assessed in E18.5d embryos and 2-week-old mice, respectively. Expression profiles of catabolic and anabolic genes were analyzed in primary chondrocytes derived from Cramp KO mice. OA in mouse knee joints was induced using intra-articular monosodium iodoacetate (MIA) injections or surgical destabilization of the medial meniscus (DMM). We observed that Cramp loss does not impact normal skeletal development. In contrast to our expectations, complete Cramp deficiency in chondrocytes failed to decrease catabolic gene expression upon IL-1β stimulation. Instead, genetic deletion of Cramp significantly worsened OA cartilage degradation in both MIA- and DMM-induced models. The detrimental phenotype observed in Cramp-deficient mice results from enhanced chondrocyte apoptosis. Therefore, even minimal Cramp expression appears essential for maintaining catabolic balance and preventing chondrocyte apoptosis in OA cartilage. Collectively, our data indicate that Cramp may exert multifaceted effects on OA pathogenesis by modulating catabolic pathways and apoptosis. Full article

The application of natural juices in sports nutrition is attracting growing interest due to their potential antioxidant, anti-inflammatory, and ergogenic properties. Exercise, especially when prolonged or intense, increases oxidative stress and muscle damage, leading athletes to explore dietary strategies that support recovery and enhance performance. This systematic review investigates the effectiveness of five widely studied juices—beetroot, pomegranate, cherry, watermelon, and pickle juice—in the context of athletic supplementation and recovery. A thorough search of the PubMed, Scopus, and Web of Science databases was conducted to identify studies published between 2010 and 2025. Fifty peer-reviewed articles met the inclusion criteria, examining various physiological, biochemical, and performance-related outcomes linked to juice consumption. Given the methodological diversity among studies, a qualitative synthesis was employed. The juices were compared across four key outcomes—inflammation, oxidative stress, delayed onset of muscle soreness, and exercise performance—to determine their most consistent benefits. Beetroot juice, noted for its high nitrate content, consistently enhanced oxygen efficiency and submaximal endurance, although benefits in elite or sprint athletes were less evident. Both pomegranate and cherry juices were effective in reducing muscle soreness and inflammatory markers, particularly when consumed over several days surrounding exercise. Watermelon juice, primarily through its L-citrulline content, offered antioxidant and recovery support, although performance outcomes varied. Evidence for pickle juice was limited, with no notable ergogenic effects beyond anecdotal cramp relief. Overall, natural juices can support recovery and occasionally improve performance, depending on the specific juice, dosage, and athlete characteristics. Beetroot juice stands out as the most reliable in enhancing performance, while pomegranate and cherry juices are more beneficial for recovery. Future research with standardized protocols is essential to determine optimal application across diverse athletic contexts. Full article

Background/Objectives: Carnitine deficiency is common in hemodialysis patients and may contribute to anemia, inflammation, dyslipidemia, and muscle symptoms. This review explores the potential benefits of L-carnitine supplementation in this population. Methods: A thorough literature search of the PubMed database was conducted to identify clinical trials and studies assessing the effects of L-carnitine supplementation on adult hemodialysis patients. Key outcomes included the effects on inflammation, lipid profile, anemia, glycemic control, and muscle function. Results: Evidence suggests that L-carnitine may reduce inflammatory markers and improve lipid profiles by lowering triglycerides and increasing high-density lipoprotein (HDL). Several studies reported reduced erythropoietin need and improved hemoglobin levels. However, some studies did not find benefits of carnitine supplementation on the mentioned parameters. Results for muscle cramps, glycemic control, and cardiac function remain inconsistent. Conclusions: L-carnitine supplementation shows potential benefits in the management of hemodialysis complications. However, further well-designed trials are needed to confirm efficacy and optimize treatment protocols. Full article

Primary dysmenorrhea (PD) is characterized by lower abdominal spasms and painful cramps during menstruation in females with a normal pelvic anatomy. Cymbopogon citratus (DC.) Stapf, commonly known as lemongrass, is consumed in the form of herbal tea around the world. It has been traditionally used for menstrual disorders in several communities. This study aims to evaluate the traditional use of C. citratus for its efficacy in alleviating the symptoms of PD. C. citratus extract (CcE) was chemically characterized using HPLC and GCMS, which indicated the presence of several phenolic compounds and long-chain fatty acids. The anti-inflammatory activity of CcE was assessed by COX-I, COX-II, and 5-LOX enzyme inhibition with IC₅₀ values of 143.7, 91.7, and 61.5 µg/mL, respectively, and showed good total antioxidant capacity and free radical scavenging activity. PD was induced in female Wistar rats by administering estradiol valerate followed by oxytocin to induce PD symptoms. CcE efficacy was assessed at 30, 100, and 300 mg/kg concentrations and compared with ibuprofen. CcE 300 mg/kg reduced abdominal contortions and inflammation in the rat uterus. The inflammatory (COX-II, TNFα and IL-10) and oxidative stress (TAC, TOS, MDA and SOD) markers in uterine tissue homogenate were also improved. An in vivo analgesic assessment through hot-plate, tail-flick, and acetic acid-induced writhing assays showed good analgesic activity by CcE, while ex vivo experiments described tocolytic effects in rat uterine muscles. CcE alleviates PD by its antioxidant, anti-inflammatory, analgesic, and tocolytic effects. Full article

Introduction: Spinal and bulbar muscular atrophy (SBMA) is an X-linked neuromuscular disorder characterized by progressive muscle weakness, along with muscle cramps, tremors, and sensory neuropathy. Previous research has shown that patients with SBMA have difficulty with dynamic balance and sensory postural control during quiet stance. There have been no reports on automatic postural reactions in SBMA. Objectives: In this study, we aimed (1) to augment previous findings of sensory postural control, (2) to investigate automatic postural reactions in SBMA, and (3) to explore the relationship between strength and balance. Design: A cross-sectional design was used for the analysis. Participants: The participants were fifty male individuals with a confirmed diagnosis of SBMA. Outcome Measures: Balance testing included the NeuroCom modified Clinical Test of Sensory Interaction on Balance (mCTSIB), which measures sway velocity during quiet stance, and the NeuroCom Motor Control Test (MCT), which measures the latency and strength of postural reactions following sudden perturbations. Strength testing included maximal voluntary isometric contractions measured via fixed-frame dynamometry. Results: Forty-seven out of fifty participants were able to complete the mCTSIB test, but only thirty-eight completed the MCT test. Patients who were unable to complete the MCT were significantly weaker in all lower extremity muscles compared to those who were able to complete testing. Compared to normative data, participants showed significantly higher sway velocity during quiet stance across all conditions of the mCTSIB, except when standing on foam with eyes open. They also exhibited significantly slower postural reactions in response to sudden shifts of the force plate on the MCT. Plantarflexor weakness was significantly correlated with poor postural control on the mCTSIB and MCT. Conclusions: This study confirms previously reported abnormalities of sensory postural control in SBMA and highlights patients’ heavy reliance on visual inputs for postural control. Additionally, this study shows that automatic postural corrections are slower than normal in SBMA and provides a unique approach for measuring the combined sensory and motor components of the disease. Both the sensory and automatic balance abnormalities were found to be associated with plantarflexor weakness and may contribute to a higher risk of falls under challenging situations. Therefore, addressing this weakness may be an important step toward fall prevention in this population. Full article

Background: Gestrinone is a synthetic hormone derived from 19-nortestosterone, exhibiting androgenic, anabolic, anti-progestogenic, and antiestrogenic effects. Gestrinone subcutaneous implants have been used “off label” for aesthetic purposes due to their anabolic action, promoting accelerated metabolism and muscle gain. Objective: Our goal is to conduct a systematic review focused exclusively on identifying the safety profile of gestrinone use, without addressing efficacy. Methods: This systematic review was performed according to the Joanna Briggs Institute and Cochrane Collaboration recommendations and is reported following the Preferred Reporting Items for Systematic Reviews and Network Meta-Analyses. This article’s searches were carried out in the PubMed, Embase, and Web of Science databases. Results: A total of 32 articles were included in this study. The reported adverse events associated with the use of gestrinone were amenorrhea (41.4% of cases), acne, seborrhea (42.7% of reports), decreased libido (26.5%), and hot flushes (24.2%). Other nonspecific symptoms such as hoarseness and cramps were also fairly reported (3.5% and 18.6%, respectively). Other reported effects were associated with breast size reduction (23.7% of patients) and increased transaminases (15.1%). Most studies (40%, n = 24 studies) found significant weight gain (ranging from 0.9 to 8 kg per patient). Abnormalities in bone mineral density were reported in four studies. Conclusions: The evidence remains insufficient to fully understand the risks of gestrinone uses associated with its widespread, unregulated use. Thus, further standardized studies and regulatory oversight to ensure patient safety are needed to mitigate potential health risks. Full article