Search Results (321)

Background/Objective: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting adverse effect of various chemotherapeutic agents. Previous work demonstrated that cannabis alleviates symptoms of oxaliplatin-induced CIPN. To evaluate the effects of cannabis components, cannabidiol (CBD) and tetrahydrocannabinol (THC), on CIPN-related symptoms. Methods: We reviewed a patient-reported outcomes dataset from “Tikun Olam,” a major medical cannabis provider. Of 1493 patients, 802 reported at least one CIPN symptom at baseline, including a burning sensation, cold sensation, paresthesia (prickling) and numbness, and 751 of them met the study inclusion criteria. Patients were categorized into THC-high/CBD-low and CBD-high/THC-low groups. Symptom changes after six months of cannabis use were analyzed using K-means clustering and logistic regression, incorporating interactions between baseline symptoms and THC and CBD doses. Linear regression assessed changes in activities of daily living (ADL) and quality of life (QOL). Results: Both groups reported symptom improvement. The THC-high group showed significantly greater improvement in burning sensation and cold sensation (p = 0.024 and p = 0.008). Improvements in ADL and QOL were also significantly higher in the THC group (p = 0.029 and p = 0.006). A significant interaction between THC and CBD was observed for symptom improvement (p < 0.0001). Conclusion: Cannabis effectively reduces CIPN symptoms and improves QOL and ADL. Higher THC doses were more effective than lower doses, with combined CBD and THC doses yielding greater symptom relief. Full article

Climate change is one of the most important current threats to global health. Outdoor workers are among the most vulnerable people to its effects. The aim of this systematic review is to assess the occupational risks related to climate change, investigating health outcomes in outdoor workers and estimating its impact in the occupational context. The review was performed following PRISMA guidelines, screening three databases (PubMed, Web of Science, and Scopus). Studies written in English or Italian languages, performed on outdoor workers, assessing occupational risks linked to climate change, and reporting on health outcomes were included. A quality assessment was performed using the Newcastle–Ottawa Scale. Thirteen studies were included in the review, performed mostly on construction (seven studies, 53.8%) and agricultural (five studies, 38.5%) workers. Twelve of the included studies (92.3%) reported on occupational risks related to heat stress, one on the effects of cold weather. Four studies (30.8%) reported a high prevalence of heat-related symptoms, ranging from 64.0% to 90.3% of workers. This systematic review highlights heat-related stress in outdoor workers as an important occupational risk, but it also underlines an important gap in scientific knowledge regarding other occupational risks relating to climate change. Full article

Background: Hand–arm vibration syndrome (HAVS) is a well-recognized occupational condition resulting from prolonged exposure to hand-transmitted vibration (HTV), characterized by vascular, neurological, and musculoskeletal impairments. While vibration exposure is a known risk factor for HAVS, less is understood about the role of personal risk factors and, particularly regarding neurosensory dysfunction. This study aimed to examine the association between vibrotactile (VPT) and thermotactile perception thresholds (TPT) and individual risk factors and comorbidities in HTV-exposed workers. Methods: A total of 235 male HTV workers were evaluated between 1995 and 2005 at the University of Trieste’s Occupational Medicine Unit. Personal, occupational, and health-related data were collected, and sensory function was assessed in both hands. VPTs at 31.5 and 125 Hz and TPTs (for warm and cold) were measured on fingers innervated by the median and ulnar nerves. Results: Multivariable regression analysis revealed that impaired VPTs were significantly associated with age, higher daily vibration exposure (expressed as 8 h energy-equivalent A(8) values), BMI ≥ 25, smoking, vascular/metabolic disorders, and neurosensory symptoms. In contrast, TPTs showed weaker and less consistent associations, with some links to smoking and alcohol use. Conclusions: These findings suggest that, in addition to vibration exposure, individual factors such as aging, overweight, smoking, and underlying health conditions significantly contribute to neurosensory impairment and may exacerbate neurosensory dysfunction in a context of HAVS. The results underscore the importance of including personal health risk factors in both clinical assessment and preventive strategies for HAVS and may inform future research on its pathogenesis. Full article

Objective: The aim of this study was to assess the effects of vestibular stimulation (semicircular canals/utricles) compared to cochlear stimulation on phantom pain and depersonalization/derealization symptoms after ≥3 months since traumatic amputation of hand-finger(s). Methods: A total of 125 adults (38.2 ± 8.1 years old) with phantom pain after amputation of one to four fingers agreed to participate. None of them wore prosthetic devices or had history of otology/audiology/vestibular/neurology/rheumatology/orthopedic/psychiatry disorders or psychopharmacological treatment. After a preliminary assessment, in a random order, they were exposed to caloric stimulation (right/left 44 °C/30 °C), centrifuge (right/left), and transient evoked otoacoustic emissions (TOAEs, right/left) with a follow-up of three days in between. Immediately before and after each stimulus, they reported on their pain characteristics and depersonalization/derealization symptoms. Results: After vestibular stimulation, a decrease in pain intensity was reported by at least one-third of the participants, which persisted for at least one day in the majority of them. Less than one-sixth of the participants reported pain decrease after cochlear stimulation. No influence was observed based on the side of the stimulation or the temperature, but the stimuli sequence had an effect. The centrifuge and TOAE effects were related to anxiety/depression symptoms and mainly observed when they were the first stimulus used. After caloric stimulation, pain decrease was independent from the sequence of the stimuli, and it was related to reports of feeling estrangement from the body. Conclusions: Mild caloric vestibular stimulation, whether applied to the right or left side and using warm or cold temperature, can modulate phantom pain after amputation of hand-finger(s) in patients with altered bodily sensations. However, individual cofactors may influence one’s susceptibility to experiencing this effect. Full article

Background/Objectives: Patients with Parkinson’s disease (PD) often have cold hands and experience frostbite. The diagnostic criteria for multiple system atrophy (MSA) also describe cold and discolored hands; however, in our clinical experience, the hands are relatively warm. These symptoms are thought to be caused by autonomic dysfunction; however, the detailed mechanisms and differences in cold hands between MSA and PD remain unclear. We aimed to identify an appropriate cold stimulation test to differentiate patients with PD and MSA using finger surface temperature (FST). Methods: We included a total of 34 patients, 27 with PD and 7 with MSA diagnosed at least 5 years after disease onset. After 15 min in a room with constant temperature and humidity, the patient’s hand was placed in cold water at 4 °C for 10 s as the cold water stress test (10sec-CWST). FST was captured using a thermal imaging camera every minute for 15 min, and the recovery of FST was analyzed. The association between the clinical characteristics of each patient and the degree of FST recovery was examined. Results: All patients completed the 10sec-CWST without adverse events. Patients with PD showed a significantly slower recovery of FST after 7 min compared to those with MSA, with a maximum difference at 11 min (PD: 8.1 ± 0.6 °C; MSA: 10.5 ± 0.3 °C; p < 0.01). FST recovery at 11 min was negatively correlated with the degree of resting hand tremor (r = −0.585, p < 0.01). Conclusions: FST after 10sec-CWST may be a safe and efficient test to differentiate PD and MSA. Full article

Previously, we reported that Lactobacillus paragasseri SBT2055 (LG2055) activates plasmacytoid dendritic cells (pDCs) and induces interferon alpha (IFN-α) in vitro. Our clinical trial suggested that LG2055 intake may enhance pDC activity, supporting immune maintenance and reducing subjective common cold symptoms. However, the precise mechanisms remain unclear. In this study, we investigated how LG2055 engages with pDCs to stimulate IFN-α production. We evaluated LG2055-induced pDC activation using flow cytometry, ELISA, and phagocytosis assays. Human peripheral blood mononuclear cells (PBMCs) were stimulated with LG2055 and its components to evaluate immune responses. An in vitro M cell model was used to examine LG2055 translocation. We found that DNA extracted from LG2055 activated pDCs and enhanced IFN-α production via Toll-like receptor 9 (TLR9). Phagocytosis assays demonstrated that LG2055 DNA was internalized by PBMC-derived pDCs, enabling TLR9-mediated signaling. Additionally, LG2055 translocated across M cells in vitro, suggesting potential transport into Peyer’s patches, where it may interact with pDCs. These findings demonstrate that intestinal LG2055 can translocate across M cells, interact with pDCs, and exert immune-stimulatory effects to enhance host antiviral immunity. This study provides mechanistic insight into how dietary components support immune health and could inform the development of novel functional foods or therapeutic strategies. Full article

Background and Objectives: The common cold (acute rhinopharyngitis) and acute rhinosinusitis are highly prevalent conditions that significantly impact quality of life, often leading to nasal congestion, inflammation, and discomfort. Given the growing demand for non-pharmacological treatment options, particularly for vulnerable populations such as children and pregnant women, alternative therapies are increasingly being explored. NESOSPRAY HE-C, a nasal spray formulated with a glycerol-based filmogenic solution, acts by forming a protective osmotic film on the nasal mucosa. This mechanism facilitates mechanical cleansing, enhances decongestion, and reduces inflammation while preserving mucosal integrity. Its purely topical and mechanical mode of action provides a non-systemic alternative for symptom management. Materials and Methods: This randomized, double-blind, parallel-group clinical trial evaluated the efficacy and safety of NESOSPRAY HE-C (n = 29) compared to a placebo nasal spray (n = 26) in patients aged ≥ 3 years diagnosed with the common cold or acute rhinosinusitis. Participants had a baseline Rhinosinusitis Symptom Severity Score (RSSS) of ≥25/50. Treatment consisted of administering 2–3 sprays per nostril, four times daily, every 4 to 6 h, for up to 8 days or until symptom resolution. The primary outcomes included changes in total RSSS, Wisconsin Upper Respiratory Symptom Survey (WURSS) score, and individual symptom scores (rhinorrhea, nasal congestion, cough, poor sleep, facial pain, and fever). Safety assessments included adverse event monitoring and treatment tolerability, with subgroup analyses performed for children and pregnant women. Results: Baseline demographics were comparable between the treatment groups. NESOSPRAY HE-C demonstrated a significantly greater reduction in total RSSS from Day 3 onward (p = 0.0008), with sustained superiority through Day 8 (p < 0.0001). Significant improvements in rhinorrhea and nasal congestion were observed within 2 h of administration (p = 0.0089), while reductions in cough (p = 0.0052), poor sleep (p = 0.0005), and facial pain (p = 0.0111) emerged by Day 3. Fever reduction was most pronounced on Days 6 (p = 0.0001) and 8 (p = 0.0312), indicating a delayed but significant effect. In terms of the WURSS score, NESOSPRAY HE-C showed a significant improvement from Day 1, with a greater reduction in symptom severity compared to placebo. This trend of greater improvement continued through Day 8. The treatment was well tolerated, with no reports of serious adverse events or allergic reactions. Efficacy was consistent across all subgroups, including children, pregnant women, and adults. Conclusions: NESOSPRAY HE-C provides rapid and sustained symptom relief for the common cold and acute rhinosinusitis, serving as a safe and effective non-pharmacological alternative to conventional treatments. By leveraging its osmotic action and barrier-forming properties, it facilitates mechanical cleansing, enhances decongestion, and reduces inflammation while preserving mucosal integrity. Additionally, by forming a protective film on the nasal mucosa, it protects against future irritations, further supporting its role as a valuable therapeutic option, particularly for individuals seeking non-systemic symptom management. Full article

Background: Self-medication is the use of medicinal products to treat self-diagnosed disorders or symptoms without the prescription or supervision of a healthcare professional. There is a lack of data about self-medication knowledge, attitudes, and practices among pharmacy undergraduates in Malaysia. This study assessed the knowledge, attitudes, and practices among undergraduate pharmacy students in Penang regarding self-medication. Method: A descriptive cross-sectional study was conducted using a self-administered, web-based survey (Google Forms), which was completed and responded to by 203 undergraduate pharmacy students from Penang, Malaysia, between October and December 2023. Descriptive statistics were used to summarize the socio-demographic characteristics of the participants. Associations between the socio-demographic characteristics of the participants and the knowledge, attitudes, and practices regarding self-medication were assessed using a chi-square test. Regression analyses were carried out to determine whether the socio-demographic characteristics of the participants were associated with practices of self-medication. Results: A total of 203 of the undergraduate pharmacy students completed the questionnaire. More than half of the participants’ age ranged between 19 and 21 years old, the majority were females (77.3%), and 31.5% of the participants had family members employed in the healthcare sector. Most respondents showed good knowledge in a variety of domains: 97.5% acknowledged the potential for drug interaction with other medications, indicating a high awareness of proper self-medication practices. A positive attitude was found regarding participants’ attitudes toward self-medication, and 65.5% practiced self-medication, primarily for treating minor illnesses (75.9%). Common conditions included fever (83.3%), cough/cold/flu (76.8%), and headache (71.4%). Reasons for not self-medicating included the absence of illness (20.2%), lack of knowledge/prior experience (19.2%), and fear of using the wrong medication (18.7%). Only academic year level was the predictor of practicing self-medication within the last six months among the participants. Conclusions: Generally, the participants possessed good knowledge and positive attitudes toward self-medication. The study revealed no significant associations between demographic characteristics and knowledge or attitudes. Insights from this research contribute to understanding self-medication practices among pharmacy students in Penang, informing potential interventions to promote responsible self-medication practices. Full article

Enteroviruses are a group of highly prevalent human pathogens responsible for a wide range of illnesses, ranging from common cold symptoms to life-threatening diseases. A deep understanding of enterovirus biology, evolution, and host interaction is required for the development of effective vaccines and antivirals. Recombinant reporter viruses encoding luminescent or fluorescent proteins have been developed to facilitate such investigation. In this work, using coxsackievirus B3 as our model, we analyze how the insertion of fluorescent reporter genes at three distinct sites within the viral polyprotein affects viral fitness, identifying the most tolerant site for reporter insertion. We then describe a set of experimental workflows for measuring viral fitness, sera neutralization, antiviral efficacy, and recombination using fluorescent reporter viruses. The high homology between different enteroviruses suggests these assays can be readily adapted to study additional members of this medically and economically relevant group of viruses. Full article

Fibromyalgia, one of the most challenging pains to treat, lacks impartial considerations for diagnosis and useful assessment. The core symptoms are persistent extensive pain accompanied by fatigue, psychological disorders, sleep disturbance, and obesity. This study aims to explore the role of cannabinoid receptor 1 (CB1) on transient receptor potential V1 (TRPV1) signaling pathways in a mouse model of fibromyalgia. This model was subjected to intermittent cold stress (ICS) to induce fibromyalgia, as measured by the nociceptive behavior determined by von Frey and Hargreaves’ tests. Our results showed a lower mechanical threshold (2.32 ± 0.12 g) and thermal latency (4.14 ± 0.26 s) in ICS-induced fibromyalgia mice. The hyperalgesia could be alleviated by 2 Hz electroacupuncture (EA) or by TRPV1 knockout. We found decreased CB1 receptors, upregulated TRPV1, and related kinases in the dorsal root ganglion, spinal cord, hypothalamus, and periaqueductal gray in fibromyalgia mice. EA reversed these effects associated with fibromyalgia, aligning with observations in Trpv1^−/− mice. Peripheral acupoint or the intracerebral ventricle injection of a CB1 agonist significantly attenuated mechanical and thermal hyperalgesia. The EA analgesic effect was reversed by a CB1 antagonist injection, suggesting the involvement of the CB1 signaling pathway. The accurate chemogenetic activation of paraventricular nucleus (PVN), which is a structure of the hypothalamus, initiated fibromyalgia pain. The chemogenetic inhibition of PVN attenuated fibromyalgia pain via the downregulation of TRPV1 pathway. Our discoveries shed light on the involvement of CB1 in the TRPV1 signaling pathway in the effects of EA in fibromyalgia, suggesting its potential as a treatment target. Full article

Raynaud’s Phenomenon (RP), characterized by episodic reductions in peripheral blood flow, leads to significant discomfort and functional impairment. Existing therapeutic strategies focus on pharmacological treatments, external heat supplementation and exercise-based rehabilitation, but fail to address biomechanical contributions to vascular dysfunction. We introduce a computational approach rooted in topological transformations of hand prehension, hypothesizing that specific hand postures can generate transient geometric structures that enhance thermal and hemodynamic properties. We examine whether a flexed hand posture—where fingers are brought together to form a closed-loop toroidal shape—may modify heat transfer patterns and blood microcirculation. Using a combination of heat diffusion equations, fluid dynamics models and topological transformations, we implement a heat transfer and blood flow simulation to examine the differential thermodynamic behavior of the open and closed hand postures. We show that the closed-hand posture may preserve significantly more heat than the open-hand posture, reducing temperature loss by an average of 1.1 ± 0.3 °C compared to 3.2 ± 0.5 °C in the open-hand condition (p < 0.01). Microvascular circulation is also enhanced, with a 53% increase in blood flow in the closed-hand configuration (p < 0.01). Therefore, our findings support the hypothesis that maintaining a closed-hand posture may help mitigate RP symptoms by preserving warmth, reducing cold-induced vasoconstriction and optimizing peripheral flow. Overall, our topologically framed approach provides quantitative evidence that postural modifications may influence peripheral vascular function through biomechanical and thermodynamic mechanisms, elucidating how shape-induced transformations may affect physiological and pathological dynamics. Full article

Platycladus orientalis, an evergreen tree belonging to the Cupressaceae family, has been traditionally used to treat various ailments, including fever, cough, diarrhea, diuresis, cold symptoms, and gastrointestinal disorders in folk medicine. As part of our ongoing investigation aimed at discovering bioactive natural products and elucidating their mechanisms of action from various natural sources, we investigated a methanol (MeOH) extract of P. orientalis leaves. This investigation led to the isolation and identification of a labdane-type diterpene, lambertianic acid (LA), via column chromatography and HPLC purification. The structure of LA was elucidated using LC/MS and NMR spectroscopic analyses, including HR-ESIMS, while its absolute configuration was confirmed through electronic circular dichroism (ECD) calculations. Recent studies have reported that labdane-type diterpenes exhibit diverse pharmacological activities, such as anticancer, anti-inflammatory, anti-obesity, and hypolipidemic effects. Notably, LA has been shown to modulate adipocyte metabolism via AMPK signaling; however, its role in skeletal muscle atrophy remains unexplored. Therefore, in this study, we investigated the effects of LA on dexamethasone (Dex)-induced muscle atrophy in C2C12 myotubes. Treatment with LA at concentrations of 25 µM and 50 µM significantly rescued myotube diameter and reduced the expression of atrophy-related proteins, including MuRF-1 and atrogin-1/MAFbx, without compromising cell viability at these moderate concentrations. These findings suggest that LA derived from P. orientalis exerts protective effects against skeletal muscle atrophy, highlighting its potential as a promising natural therapeutic candidate for muscle-wasting disorders. Full article

Background: Colds are widespread infectious diseases that affect daily life, increasing healthcare costs and limiting productivity. Objectives: The aim of this study was to investigate the effects of a dietary supplement containing specific probiotic strains (L. plantarum PBS067, L. acidophilus PBS066, B. lactis BL050) on cold symptom relief, immune response enhancement, and quality of life. Methods This randomized, double-blind, placebo-controlled trial included 65 healthy volunteers (age range: 18–44 years), divided into two groups: 40 received the probiotic treatment (with vitamins and bulking agents), and 25 received placebo (vitamins and bulking agents only) for 12 weeks. Cold symptoms and systemic inflammation were assessed at three time points (baseline T0, post-treatment T1, and 6 weeks after treatment T2). Results: Probiotics were associated with a shorter average duration of cold symptoms (4.5 vs. 6.7% for Placebo, p < 0.05). At T1, fever and muscle pain occurred in 20% of participants in the Probiotic group vs. 28% and 44% in the Placebo group, respectively (p < 0.05 for muscle pain vs. Placebo). For muscle pain, a trend was maintained also at T2 (17.5% vs. 20%). The pro-inflammatory cytokine IFN-γ levels significantly decreased in the Probiotic group vs. T0 (p < 0.0001 at T1 and p < 0.01 at T2), while they increased in the Placebo group (22.279 ± 3.538 vs. 19.432 ± 3.143 pg/mL, p = NS). Although not statistically significant, at T1 the Probiotic group had higher levels of IL-10 vs. T0 (266.98 ± 78.432 vs. 240.967 ± 70.238, pg/mL p = NS). Conclusions: The probiotic mix effectively alleviated cold symptoms and reduced pro-inflammatory cytokine levels, suggesting anti-inflammatory effects. Full article

Background: Dried ivy leaf extract EA 575^® (Prospan^®) is commonly used to treat coughs and may help reduce inappropriate antibiotic use for the common cold. This retrospective study investigated whether prescribing EA 575 is associated with reduced subsequent antibiotic use in children and adolescents with the common cold. Repeated EA 575 prescriptions were also analyzed to estimate treatment satisfaction. Methods: Data were sourced from the IQVIA Disease Analyzer database, including patients under 18 diagnosed with a common cold and prescribed either EA 575 or antibiotics between 2017 and 2020 (index date). Propensity score matching controlled for confounding factors. Antibiotic prescriptions were assessed 4–30 and 31–365 days after the index date, along with bacterial infections 4–40 days post-index. Repeated EA 575 prescriptions 2–5 years post-index were analyzed as a proxy for treatment satisfaction. Results: Overall, 10,390 children and adolescents were included in each matched cohort. Compared to antibiotics, EA 575 prescriptions were associated with significantly lower odds of antibiotic use 4–30 days (OR: 0.56; 95% CI: 0.49–0.64; p < 0.001) and 31–365 days (OR: 0.58; 95% CI: 0.54–0.62; p < 0.001) after the index date. The odds of bacterial infection 4–30 days after EA 575 prescription were also lower (OR: 0.67; 95% CI: 0.45–0.99; p = 0.047). Of the 42,677 patients in the EA 575 analysis, 50.5% had at least one repeated prescription, with the highest rates among children aged 0–2 years (54.7%) and the lowest in those aged 13–17 years (19.9%). Conclusions: EA 575 prescription was associated with reduced subsequent antibiotic use in children and adolescents with common colds. Frequent repeated prescription rates emphasize the therapeutic value of EA 575 as a treatment option for cold symptoms, especially in younger children. Full article

The Hami melon is a characteristic economic crop in Xinjiang. Long-term storage at low temperatures can cause cold damage and significantly impact the storage quality of Hami melon fruits. This study investigated the cold resistance of two Hami melon varieties under low temperatures, screened key genes, and further explored their resistance mechanisms. By comparing and analyzing the relationship between phenotypic morphology, physiological indicators, and storage time, it was found that the symptoms of cold damage in Hami melons are related to both storage time and variety. To analyze the response mechanisms of Hami melons to cold stress at the molecular level, we conducted transcriptome sequencing analysis on the cold-sensitive Hami melon variety Gold Queen and the cold-resistant variety Jia Shi. The analysis shows that cold stress induces the expression of these differentially expressed genes, which participate in the AsA-GSH cycling system, form the NADPH-P450 pathway, and establish the ERF-WRKY cold resistance pathway. This, in turn, increases the content of free proline in the fruits, clears denatured proteins within the fruit, maintains the stability of the redox system, and inhibits certain differentially expressed genes that regulate cell wall metabolism, thereby alleviating fruit softening and improving cold resistance. Full article