Chronic neck and upper thoracic pain are common and frequently classified as non-specific when no single structural lesion explains the presentation. Although forward-head posture, prolonged device use, sedentary behaviour, and occupational loading are often considered contributors, the association between static posture and chronic neck pain is inconsistent. This narrative review examines persistent cervicothoracic muscle mechanical stiffness as a potential time-dependent mechanism linking cumulative postural loading to chronic symptoms. The central construct is persistent or repeatedly elevated mechanical stiffness, particularly passive stiffness assessed under standardised resting conditions; active stiffness related to ongoing activation or guarding is considered distinct but potentially relevant. PubMed, Scopus, and Web of Science were searched for English-language articles published from January 1990 to June 2026 addressing cervicothoracic posture, loading, fatigue, muscle mechanical properties, and chronic neck or upper thoracic pain. Findings were synthesised narratively without meta-analysis. Static posture alone does not consistently predict chronic neck pain. Sustained or repeated cervicothoracic loading may nevertheless increase muscular demand and contribute to fatigue, altered recruitment, impaired relaxation, reduced movement variability, and mechanical stiffness when exposure exceeds tissue tolerance and recovery capacity. Persistent mechanical stiffness has been proposed as a possible contributor to pain through mechanical sensitivity, altered perfusion relative to demand, metabolic stress, nociceptive sensitisation, and pain-related guarding. However, direct cervicothoracic evidence in patients with chronic neck pain remains limited; much of the biological rationale is extrapolated from studies of general muscle pain, myofascial pain, trapezius myalgia, and experimental models. In the absence of an identified neurological or vascular cause, alterations in neural-interface mechanics have been hypothesised to contribute to nerve-like symptoms; however, any relationship with surrounding muscle mechanical stiffness remains theoretical and has not been directly established. This review proposes a testable conceptual model in which cumulative postural loading, recovery capacity, neuromuscular adaptation, cervicothoracic muscle mechanical stiffness, and pain-related mechanisms interact over time. Objective assessment may help determine whether cervicothoracic muscle mechanical stiffness precedes pain, contributes to the proposed pathway, or identifies a clinically relevant subgroup. Direct longitudinal evidence validating this proposed pathway remains limited.

Objective This study investigated the efficacy, safety, and tolerability of hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) 10% as maintenance therapy in Japanese patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN).Methods This phase 3, multicenter, open-label study (NCT05084053, jRCT2051210110) comprised a ≤8-week screening/baseline period, a 6-month fSCIG 10% treatment period (Epoch 1), and ≥6 months' extended treatment (Epoch 2). fSCIG 10% was administered at each patient's previous intravenous immunoglobulin (IVIG) dose and interval. The primary endpoints were relapse rate (≥1-point increase in adjusted Inflammatory Neuropathy Cause and Treatment disability score) for CIDP and change from baseline in maximum handgrip strength (more affected hand) for MMN.Patients Adults with CIDP (N=19) or MMN (N=7) on stable IVIG dose.Results In the CIDP group, no patient developed a relapse during Epoch 1; the upper bound of the 95% confidence interval (CI) was 17.65%, below the preset efficacy threshold (57%). For MMN, median (range) and mean (95% CI) change from baseline in maximum grip strength (more affected hand) was 0.0 (-16, 18) and -1.1 (-12.9, 10.6) kPa, respectively. In the CIDP/MMN combined safety analysis across 12 months, 262 treatment-emergent adverse events (TEAEs; 96 systemic, 166 local) in 18 patients (69.2%) were considered fSCIG 10% related. No severe or serious TEAEs occurred.Conclusion fSCIG 10% prevented CIDP relapse and maintained a stable disease course in MMN in Japanese patients. The treatment was well tolerated, with no severe or serious adverse events related to the treatment.

Climate change is expected to profoundly influence high-elevation Himalayan ecosystems, where steep environmental gradients and narrow climatic tolerances render alpine plant communities particularly sensitive to environmental changes. Many threatened Himalayan medicinal plants occur near alpine-sub-alpine ecotones associated with upper forest limits, and shifts in their distribution may reflect broader ecosystem responses to climate change. Anticipating such range dynamics is essential for biodiversity conservation and sustainable resource management in climate-sensitive mountain landscapes. We assessed the current and future habitat suitability of three threatened Himalayan medicinal plants, Aconitum heterophyllum, Lilium polyphyllum, and Picrorhiza kurroa, in Himachal Pradesh, Western Himalaya, using an ensemble species distribution modelling framework. Species occurrence records were combined with climatic and topographic predictors to model the current and future habitat suitability. In addition to habitat suitability projections, we integrated model uncertainty, centroid displacement, and climatic niche overlap analyses to assess the robustness and spatial dynamics of future habitat changes. Ensemble models showed strong predictive performance, with the best-performing algorithms (Random Forest and MaxEnt) achieving ROC values of up to 0.90 and TSS values of up to 0.55. Habitat suitability was primarily influenced by precipitation seasonality (BIO15; importance up to ~ 0.45) and the mean diurnal temperature range (BIO2; up to ~ 0.28). Future suitability became increasingly concentrated in high-elevation districts, such as Lahaul and Spiti and Kinnaur, with suitable habitat declining by approximately 33-57% across most future scenarios. A. heterophyllum was the only species to show a temporary increase in suitable area (+ 35.7%) under SSP126 in 2050, before declining under later projections. Centroid shifts ranged from 9.4-19.4 km, while Schoener's D declined from 0.59 to 0.47 across species and scenarios, indicating increasing divergence from current suitability patterns. These findings indicate that climate change may substantially reorganise habitat suitability for threatened Himalayan medicinal plants, highlighting the potential for high-elevation refugia and providing a framework for climate-informed conservation planning in Himachal Pradesh and other Himalayan mountain ecosystems.

Marine heatwaves are increasing in frequency and intensity worldwide and represent a growing threat to coastal ecosystems and the animals inhabiting them. The vulnerability of marine species to these events depends on several factors, including upper thermal tolerance, the thermal sensitivity of physiological performance, and the capacity for rapid physiological acclimation. We examined upper thermal tolerance and short-term acclimation capacity in 10 mobile macroinvertebrate species inhabiting shallow coastal ecosystems in the Northeast Atlantic. Individuals were exposed either to ambient thermal conditions at 15°C or to a simulated short-term marine heatwave of 5 days at 5°C above ambient temperature. We then measured critical thermal maxima (CTmax) to quantify thermal limits and acclimation responses. Across species, CTmax increased significantly following heatwave exposure, showing that these coastal invertebrates can undergo rapid physiological adjustment. However, the magnitude of the acclimation response was modest, indicating that short-term plasticity provides only limited protection against acute thermal extremes. These limited acclimation responses suggest that some coastal invertebrates may remain vulnerable to intensifying marine heatwaves, particularly taxa with narrow thermal safety margins. Our findings provide an ecologically relevant assessment of thermal performance in coastal invertebrates and contribute to predictions of how nearshore communities may respond to accelerating ocean warming.

Explaining the low-temperature limit of trees requires in situ information on the actual temperature conditions, the trees' phenology and freezing tolerance. Here, we report the seasonal course of freezing resistance and its response to local temperature in species of Larix and Abies, forming the treeline (4350-4400 m) in the south-eastern Himalayas, and Quercus and tree-size Rhododendron, reaching their upper limit in the immediate neighborhood (4270-4290 m). By linking tree-crown temperatures with on-site air temperature, we can utilize long-term meteorological records to hindcast critical freezing events. Deciduous Larix flushes earliest and exhibits the greatest freezing tolerance and largest safety margin. The evergreen species flush 2 months later and operate near their freezing damage limit. The conifers can compensate for freezing damage by rapid resprouting from small auxiliary buds, not an option for Quercus and Rhododendron with their bigger buds. Freezing damage does not appear to constrain the two treeline conifers. Their range limit most likely reflects the general low-temperature growth limit of the tree life form. Freezing tolerance is most likely controlling the upper limits of the evergreen broad-leaved species. The results offer a mechanistic explanation of the range limit of these high-elevation tree species.

Understanding coral-climate interactions through deep time is essential for evaluating reef resilience under ongoing climate change. Rejuvenescence is a rare and poorly documented phenomenon in fossil and extant reef-building scleractinian corals, involving polyp contraction followed by regeneration, and has previously been described as a survival strategy for coping with acute thermal stress in a living species. Here, we report evidence of rejuvenescence from a fossil reef in the Makran region of Iran, dated to the Miocene Climatic Optimum, and place it within an ecological and evolutionary framework. Its occurrence in both Miocene Iranian Acanthastrea cf. polygonalis and modern Mediterranean Cladocora caespitosa, despite their phylogenetic, temporal, and biogeographic separation, suggests a recurrent morphogenetic response associated with inferred thermal stress and potentially linked to metabolic downregulation, while its evolutionary origin remains unresolved between deep homology and convergent evolution. This putative role of rejuvenescence in promoting survival appears to be restricted to individual colonies or species and does not translate into thermal resilience at the reef-community scale. Accordingly, current evidence does not support rejuvenescence as a mechanism enhancing coral reef climate resistance but instead identifies it as an indicator of conditions approaching upper thermal tolerance limits in reef ecosystems across geological timescales.

Recent evidence suggests that higher-than-recommended intakes of long-chain n-3 polyunsaturated fatty acids (PUFA), specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are both safe and effective in supporting health conditions such as inflammatory diseases in adult humans. For adult dogs at maintenance, the National Research Council (NRC, 2006) recommends a safe upper limit of EPA+DHA of 0.37 g/kg body weight (BW)0.75, a value based on limited evidence. This study aimed to investigate how low, moderate and high dietary intakes of EPA+DHA affected oxidative balance through α-tocopherol and malondialdehyde (MDA) concentrations, lipid incorporation into circulating phospholipid fractions, and serum cytokines in healthy adult dogs over 8 weeks. Twenty-seven client-owned dogs were enrolled and, following a 4-week diet acclimation phase, were allocated into three groups balanced for age and BW and then randomly assigned to 1 of 3 dosage groups, consisting of 0.03 g/kg BW0.75 (LOW) of EPA+DHA, 0.45 g/kg BW[0]·[75] (MOD), and 0.71 g/kg BW[0]·[75] (HIGH). Fasted blood samples were collected at weeks 0, 4, and 8 to evaluate serum fatty acid (FA) composition within circulating phospholipid fractions, whole blood α-tocopherol, malondialdehyde (MDA), and cytokine concentrations. Data were analyzed using PROC GLIMMIX in SAS, with dog treated as a random effect, week as a repeated measure, and dosage group (DG), week, sex, and their interactions as fixed effects. In serum phosphatidylcholine (PC) and lysophosphatidylcholine (LysoPC) fractions, EPA and DHA incorperation increased from baseline to week 4 across all dosage groups, with no changes observed between weeks 4 and 8. Total FA analysis showed that dietary EPA+DHA increased total n-3 PUFA and reduced total n-6 PUFA, with both the MOD and HIGH being greater than the LOW treatment. Whole blood α-tocopherol concentrations showed a DG × week interaction (p = 0.034), with the LOW group (5.82 µg/mL) maintaining higher concentrations at week 8 than the HIGH group (3.52 µg/mL) and not differing from the MOD group (5.00 µg/mL). Overall, increasing dietary EPA+DHA intake in adult dogs enriched circulating and membrane-associated n-3 PUFA pools while maintaining MDA and inflammatory cytokine concentrations despite reduced α-tocopherol concentrations. This suggests that higher EPA+DHA intakes were well tolerated over the 8-week study period when interpreted alongside antioxidant status.

Aqueous four-electron zinc-iodine batteries (4eZIBs) hold great promise for long-term energy storage, but their practical application is severely hindered by the multiple drawbacks, including Zn dendrite growth, polyiodide shuttle, and I[+] hydrolysis. Such limitations can be effectively mitigated by employing biphasic electrolytes featuring a liquid-liquid interface, which enables efficient immobilization of the dissolved reaction intermediates. However, such systems frequently employ toxic organic solvents, which not only pose flammability risks but also struggle to adapt to extreme temperature conditions. Herein, we design a novel self-stratified biphasic electrolyte via liquid-liquid phase separation of choline chloride (ChCl)-trifluoroacetamide (TFA) deep eutectic solvent (DES) and ZnSO4/H2O/ ethylene glycol solution. The upper DES phase effectively confines polyiodide anions, suppresses shuttle effect and stabilizes I[+] species, while the bottom aqueous phase regulates Zn[2+] solvation structure and inhibits dendrite formation and side reactions. Benefiting from the synergistic functional separation, the Zn-I2 battery realizes highly reversible four-electron conversion, effectively suppresses battery self-discharge, and delivers superior cycling stability over 21000 cycles as well as wide temperature tolerance ranging from -30°C to 50°C. This work offers novel insights into the design of safe and eco-friendly biphasic electrolytes and provides an effective strategy for the construction of high-performance 4eZIBs.

Intra- and inter-specific differences in upper thermal limits, such as thermal tolerance, can impact conservation decision-making, yet values are typically obtained from a single population. In this study, we assessed the intra- and inter-specific variation of critical thermal maximum (CTmax) and agitation temperature (Tag) among two eastern sand darter (Ammocrypta pellucida) populations (intra-specific) and five species of sand darters (genus Ammocrypta; inter-specific). The Ammocrypta genus is a monophyletic clade of ecologically similar benthic fishes demonstrating high niche conservatism. Field based CTmax trials were conducted stream-side across seasons (April-August 2019 and 2023) to encompass a range of ambient water temperatures (12-28°C). No intra-specific differences in CTmax or Tag between eastern sand darter populations were observed, but population was important in predicting Tag. Minimal inter-specific differences were observed within Ammocrypta with only eastern and naked sand darters (A. pellucida and Ammocrypta beanii) having consistent differences in CTmax, while the southern sand darter (Ammocrypta meridiana) had lower acclimation capacity. Overall, study results provide a better understanding of thermal tolerance differences within Ammocrypta and underline the need for estimates of population- and species-specific tolerances for conservation-based decisions regarding species capacities to withstand climate change.

Cannabigerol (CBG) is a minor cannabinoid that has been considered as a potential therapeutic, yet basic acute pharmacodynamics and pharmacokinetics across commercially available doses have not been examined. To complete this critical step, healthy adults (n = 12) were enrolled in a single ascending dose human laboratory study where they consumed 0, 25, 50, 100, and 200 mg of CBG isolate suspended in medium-chain triglyceride oil. The placebo administration occurred randomly within the dosing sequence. Standardizing flavor and solution volume facilitated blinding. Adverse events were recorded throughout to characterize safety and tolerability. Pharmacodynamic outcomes (ie, subjective, cognitive, and physiological responses) and plasma samples were collected at baseline and regular intervals after drug administration (0.5-, 1-, 1.5-, 2-, 3-, 4- , 5-, 6-, and 8-hours). Pharmacokinetic parameters (eg, peak plasma CBG concentration) were also measured. Liver function tests were characterized at baseline and after acute administration of the 2 highest doses. No drug-related adverse events occurred. Subjective effects associated with CBG administration were minimal with the exception of significant decreases in self-reported ratings of Jittery and Active associated with 50 mg, significant decreases in Calm associated with 100 mg, and increases in Appetite associated with 200 mg of CBG. Pharmacokinetics were dose-orderly, but significant individual variability was observed. Liver function tests never exceeded the upper limit of normal following acute administration of the highest doses. Overall CBG was well-tolerated with no robust pharmacodynamic effects; chronic dosing studies are needed to more fully characterize the safety and pharmacodynamic profile of oral CBG. SIGNIFICANCE STATEMENT: Cannabigerol has garnered attention as a potential therapeutic for many diagnoses before the fundamental studies investigating its pharmacokinetics and pharmacodynamics have been completed. We aimed to provide this information through a single ascending dose study, finding that cannabigerol is well-tolerated while yielding few pharmacodynamic or psychoactive effects.

Primary biliary cholangitis (PBC) is an autoimmune liver disease that targets the small intrahepatic bile ducts with diagnosis based on elevated serum alkaline phosphatase (ALP) levels and the presence of anti-mitochondrial antibodies. Untreated, it may run a progressive course to cirrhosis and hepatic decompensation, at which point liver transplantation is the only effective treatment. This review provides discussion of PBC treatment goals in the Australian context. People with PBC often experience a quality of life burden characterized by fatigue and itch. Extra-hepatic associations may include osteoporosis, Sjögren's syndrome, and thyroid dysfunction. Established baseline risk factors for progression are male gender, young age at onset (< 45 years), ALP > 1.5 × upper limit of normal (ULN), presence of anti-gp210 antibodies, and significant liver fibrosis at diagnosis. Ursodeoxycholic acid (UDCA) is the mainstay of therapy and improves outcomes including transplant-free survival. Patients with inadequate response to UDCA (about 40%), disease progression, or bothersome symptoms require additional second-line (2L) therapy. Second-line treatments include selective peroxisome proliferator-associated receptor (PPAR) agonists, obeticholic acid (OCA; subject to precautions), and off-label use of fenofibrate. In Australia, reimbursement for 2L therapies relies on ALP ≥ 1.67 × ULN or total bilirubin between 1 and 2 × ULN after 1 year of UDCA therapy. Normalization of ALP is an aspirational treatment target with increasing evidence for improved outcomes. Proactive and diligent monitoring of patients with PBC allows personalized selection and early initiation of effective and well-tolerated 2L therapies with potential for improved outcomes.