The Physical and Psychological Effects of Telerehabilitation-Based Exercise for Patients With Nonspecific Low Back Pain: Prospective Randomized Controlled Trial.

Background: Physical therapy has demonstrated efficacy in managing nonspecific low back pain (NLBP) among patients. Nevertheless, the prevalence of NLBP poses a challenge, as the existing medical infrastructure may be insufficient to care for the large patient population, particularly in geographically remote regions. Telerehabilitation emerges as a promising method to address this concern by offering a method to deliver superior medical care to a greater number of patients with NLBP. Objective: The purpose of this study is to demonstrate the physical and psychological effectiveness of a user-centered telerehabilitation program, consisting of a smartphone app and integrated sensors, for patients with NLBP. Methods: This was a single-center, prospective, randomized controlled trial for individuals with NLBP for a duration exceeding 3 months. All participants were assigned randomly to either the telerehabilitation-based exercise group (TBEG) or the outpatient-based exercise group (OBEG). All participants completed a 30-minute regimen of strength and stretching exercises 3 times per week, for a total of 8 weeks, and were required to complete assessment questionnaires at 0, 2, 4, and 8 weeks. The TBEG completed home-based exercises and questionnaires using a telerehabilitation program, while the OBEG completed them in outpatient rehabilitation. The Oswestry Disability Index (ODI) served as the primary outcome measure, assessing physical disability. Secondary outcomes included the Numeric Pain Rating Scale, Fear-Avoidance Beliefs Questionnaire, and 36-item Short-Form Health Survey. Results: In total, 54 of 129 eligible patients were enrolled and randomly assigned to the study. The completion of all the interventions and assessments in the TBEG and OBEG was 89% (24/27) and 81% (22/27). The findings indicate that no statistical significance was found in the difference of ODI scores between the TBEG and the OBEG at 2 weeks (mean difference -0.91; odds ratio [OR] 0.78, 95% CI -5.96 to 4.14; P=.72), 4 weeks (mean difference -3.80; OR 1.33, 95% CI -9.86 to -2.25; P=.21), and 8 weeks (mean difference -3.24; OR 0.92, 95% CI -8.65 to 2.17; P=.24). The improvement of the ODI in the TBEG (mean -16.42, SD 7.30) and OBEG (mean -13.18, SD 8.48) was higher than 10 after an 8-week intervention. No statistically significant differences were observed between the 2 groups at the 8-week mark regarding the Fear-Avoidance Beliefs Questionnaire (mean difference 8.88; OR 1.04, 95% CI -2.29 to 20.06; P=.12) and Numeric Pain Rating Scale (mean difference -0.39; OR 0.44, 95% CI -2.10 to 1.31; P=.64). In the subgroup analysis, there was no statistically significant difference in outcomes between the 2 groups. Conclusions: Telerehabilitation interventions demonstrate comparable therapeutic efficacy for individuals with NLBP when compared to conventional outpatient-based physical therapy, yielding comparable outcomes in pain reduction and improvement in functional limitations.

Comparing the effects of neck stabilization exercises versus dynamic exercises among patients having nonspecific neck pain with forward head posture: a randomized clinical trial.

BACKGROUND: Nonspecific neck pain (NSNP) is a well-established global burden affecting. It is also a common problem in Pakistan. The burden of neck pain is also increasing day by day due to poor work ergonomics, and increased use of computers and mobiles after the pandemic. An individual's poor posture is often associated with forward head posture (FHP). Limited evidence is available about the effects of neck stabilization (NSE) and dynamic exercises (NDE) for nonspecific neck pain particularly in patients with FHP. This aimed to compare the effects of NSE versus NDE among patients having NSNP with FHP in reducing pain, disability, forward head posture and improving neck range of motion. METHODS: It is a single-blinded randomized clinical trial with 60 patients aged 18-40 years, with moderate intensity NSNP for > 3 weeks and < 6 months along with FHP with a moderate disability on neck disability index (NDI) randomly assigned to the treatment groups. Group 1 was doing NSE and group 2 was doing NDE. Transcutaneous Electical Nerve Stimulation, cold packs, and stretching exercises were given to both groups. A total of 9 sessions (3 sessions/ week) were given to participants. NDI questionnaire, Visual analogue scale (VAS), goniometry, and plumb line measurement tool were used as baseline and assessment at the end of 3rd week. The data was analyzed on SPSS version 21. Descriptive analysis was performed. Independent t-test was used for between group comparison and paired t-test used for within group comparison. A p-value less than 0.05 was considered statistically significant. RESULTS: After treatment within-group analysis of both NSE and NDE showed significant (p < 0.001) improvement in pain on VAS, all ROMs of the neck including flexion, extension, left and right lateral flexion and left rotation, plumb line and NDI score with very large effect size. However, between-group analysis showed non-significant differences (p > 0.05) for post-treatment mean VAS, neck ROM, NDI and plumb line measurement. CONCLUSION: Between NSE and NDE, no one is more beneficial than another. Both are equally effective in alleviating pain, increasing ROM, decreasing functional disability, and improving forward head posture in patients with NSNP. TRIAL REGISTRATION: Registered trial at ClinicalTrials.gov Identifier: NCT05298631, 28/03/2022, prospectively registered.

Differentiation of bacterial orbital cellulitis and diffuse non-specific orbital inflammation on magnetic resonance imaging.

PURPOSE: To examine the radiological differences between bacterial orbital cellulitis (OC) and diffuse non-specific orbital inflammation (DNSOI) on magnetic resonance imaging (MRI). METHODS: Retrospective study of patients with OC and DNSOI with an MRI orbital scan. Localised orbital inflammation (e.g., idiopathic dacryoadenitis and myositis), quiescent orbital inflammation and pre-septal cellulitis were excluded. RESULTS: Thirty-two patients presenting between 2008 and 2023, including twenty-one OC patients (mean age: 42.5 ± 24.9 years old, male: 6), and eleven DNSOI patients (mean age: 52.3 ± 17.8 years old, male: 16). Both OC and DNSOI demonstrate orbital fat contrast-enhancement. However, whilst OC demonstrated a hyperintense T2 signal (P < 0.001), variable signal was observed in DNSOI, with a hypointense T2 signal more suggestive of DNSOI (P = 0.012). When the lacrimal glands were involved, indistinct margins were more likely in OC (P < 0.001), whilst gross enlargement and contrast-enhancement was observed in DNSOI (P = 0.032 and 0.017, respectively). Peripheral contrast-enhancement of the extraocular muscle (EOM) (P = 0.002) was more common in OC, whilst DNSOI demonstrated variable contrast-enhancement throughout the affected EOM (P < 0.001). The presence of contralateral abnormalities, such as lacrimal gland enlargement and EOM involvement, are more suggestive of DNSOI. CONCLUSION: Several MRI features, beyond overt sinogenic disease, may help to differentiate OC from DNSOI, including the orbital fat signal intensity, EOM and/or lacrimal gland involvement, and contralateral orbital abnormalities. However, these features may not be specific, and thus highlights the ongoing radiological dilemma clinicians are faced when tasked with differentiating between infectious and non-infectious orbital inflammatory disease.

Contradictory mortality results in early 2-dose measles vaccine trials: Interactions with oral polio vaccine may explain differences.

OBJECTIVES: Between 2003-2019, three trials (RCTs) in Guinea-Bissau randomised infants to an early 2-dose measles vaccine (MV) schedule at 4 and 9 months vs. standard MV at 9 months. The RCTs produced contradictory mortality results; the effect being beneficial in the 2-dose group in the first but tending to have higher mortality in the last two RCTs. We hypothesised that increased frequency of campaigns with oral polio vaccine (C-OPV) explained the pattern. METHODS: We performed per-protocol analysis of individual-level survival data from the three RCTs in Cox proportional hazards models yielding hazards ratios (HR) for the 2-dose vs. the 1-dose MV group. We examined whether timing of C-OPVs, and early administration of OPV0 (birth to day 14) affected the HRs for 2-dose/1-dose MV. RESULTS: The combined HR(2-dose/1-dose) was 0.79 (95% confidence interval: 0.62-1.00) for children receiving no C-OPV-before-enrolment, but 1.39 (0.97-1.99) for those receiving C-OPV-before-enrolment (homogeneity, p=0.01). C-OPV-before-enrolment had a beneficial effect in the 1-dose group, but tended to have a negative effect in the 2-dose group especially in females. These effects were amplified further by early administration of OPV0. CONCLUSIONS: In the absence of C-OPVs, an early 2-dose MV strategy had beneficial effects on mortality, but frequent C-OPVs may have benefitted the 1-dose group more than the 2-dose MV group, leading to varying results depending on the intensity of C-OPVs.

Lysine methylation: A strategy to improve in-cell NMR spectroscopy of proteins.

BACKGROUND: In-cell NMR is a valuable technique for investigating protein structure and function in cellular environments. However, challenges arise due to highly crowded cellular environment, where nonspecific interactions between the target protein and other cellular components can lead to signals broadening or disappearance in NMR spectra. RESULTS: We implemented chemical reduction methylation to selectively modify lysine residues on protein surfaces aiming to weaken charge interactions and recover obscured NMR signals. This method was tested on six proteins varying in molecular size and lysine content. While methylation did not disrupt the protein's native conformation, it successful restored some previously obscured in-cell NMR signals, particularly for proteins with high isoelectric points that decreased post-methylation. SIGNIFICANCE: This study affirms lysine methylation as a feasible approach to enhance the sensitivity of in-cell NMR spectra for protein studies. By mitigating signal loss due to nonspecific interactions, this method expands the utility of in-cell NMR for investigating proteins in their natural cellular environment, potentially leading to more accurate structural and functional insights.

Chronic nonspecific cheilitis associated with tislelizumab treatment in a patient with a history of tongue squamous cell carcinoma: a case report.

BACKGROUND: Chronic nonspecific cheilitis is a complex condition characterized by persistent lip peeling and discomfort. This case report explores the clinical progression of a patient with history of tongue squamous cell carcinoma and subsequent Tislelizumab treatment, presenting with persistent lip peeling. CASE PRESENTATION: A patient with a history of tongue squamous cell carcinoma (T2N0M0), treated with chemotherapy, surgery, and Tislelizumab, presented with six months of persistent lip peeling. Clinical examination revealed distinct features of chronic nonspecific cheilitis with infectious angular cheilitis (Oral Candidiasis). A tailored treatment plan, emphasizing oral hygiene practices and local treatments with Sodium Bicarbonate, Tacrolimus ointment, and Chlortetracycline ointment. Follow-up visits demonstrated sustained improvement, highlighting the significance of individualized approaches. CONCLUSIONS: This case underscores the importance of recognizing and managing oral manifestations in patients with a history of cancer and immunotherapy. The patient's response to treatment suggests that a multifaceted approach, combining local therapy with lifestyle modifications, can be effective in managing chronic nonspecific cheilitis associated with immunotherapy. Routine follow-up appointments, guided by personalized medicine principles, contribute to sustained patient well-being.

Non-specific phospholipase C3 is involved in endoplasmic reticulum stress tolerance in Arabidopsis.

Non-specific phospholipase C (NPC) is an emerging family of lipolytic enzymes unique to plants and bacteria that play crucial roles in growth and stress responses. Among six copies of NPC isoforms found in Arabidopsis, the role of NPC3 remains elusive to date. Here, we show that NPC3 is a functional non-specific phospholipase C involved in tolerance to tunicamycin (TM)-induced endoplasmic reticulum (ER) stress through the synthesis of phosphocholine (PCho), a reaction product of NPC3. The npc3 mutant exhibited reduced sensitivity to TM treatment. Recombinant NPC3 possessed pronounced phospholipase C activity that hydrolyses phosphatidylcholine (PC). The hyposensitivity of npc3 to TM treatment was complemented by exogenous PCho, suggesting that NPC3-catalysed PCho production is involved in TM-induced ER stress tolerance. NPC3 was localized at the ER and was predominantly expressed in the roots, and it was further induced by TM-induced ER stress. Intriguingly, npc3 mutants showed a markedly reduced PCho content in shoots under ER stress. Our results indicate that ER stress induces NPC3 to produce PCho, which is involved in TM-induced ER stress tolerance.

Substantial benefits of an inert biphenyl column for the analysis of steroids and their phase II metabolites in biological samples.

Steroids can be used as biomarkers in clinical metabolomics and other fields related to human toxicology. This chemical group is known for its complexity, considering its number of isobaric compounds and the wide variety of phases I and II metabolic pathways that parent compounds can undergo. For a successful analysis of steroids in biological samples, liquid chromatography separation must be finely tuned. It is especially challenging for glucuronidated and sulfated steroids derivatives that bear polar heads and can be affected by non-specific adsorption. The benefits of a biphenyl stationary phase chemistry for the selectivity of the separation of steroids and their phase II metabolites and the extent to which nonspecific adsorption phenomena could degrade chromatographic performance were investigated. Replacing a conventional hardware by a passivated hardware allowed to considerably reduce peaks width and asymmetry of sulfated species. The addition of weak ion pairing agents in the mobile phase could also help to reduce non-specific adsorption but are detrimental to mass spectrometry detection. As confirmed by the successful detection of 52 steroids in plasma, the use of a biphenyl stationary phase complemented by a passivated column hardware is of great help for a successful biomedical analysis of steroids and their phase II metabolites.

The effect of core stability training combined with fascial release on patients with nonspecific low back pain.

BACKGROUND: Non-specific lower back pain (NLBP) is treated with a variety of therapies, including health education, exercise therapy, soft tissue release, psychological interventions, and shockwave therapy. However, some studies have shown that core stability training or fascial release therapy alone is not effective in the treatment of low back pain. BJECTIVE: The aim of this study was to investigate the effects of core stability training on patients' inflammatory cytokine levels and lumbar muscle temperature when combined with fascial release for the treatment of non-specific low back pain. METHODS: In this study, a total of 60 patients with non-specific low back pain who were treated in Mindong Hospital of Ningde City between December 2021 and January 2023 were selected and randomly and equally divided into a control group (30 cases) and an experimental group (30 cases). The control group received core stability training, while the experimental group added fascial release surgery to this. We compared and assessed the pain visual analog score (VAS), Oswestry dysfunction index (ODI), lumbar spine mobility (including anterior flexion, posterior extension, left flexion, and right flexion), as well as levels of inflammatory factors IL-6, TNF-a, and muscle tissue temperature in the two groups. RESULTS: This study has been successfully implemented and covered 60 patients throughout the trials. Upon comparison, the two groups did not show statistically significant differences in baseline data such as age, gender and duration of disease (p> 0.05). After four weeks of treatment, the test group showed statistically significant (p< 0.05) differences in VAS scores, ODI scores, and IL-6 and TNF-a levels that were significantly lower than those of the control group. It is worth mentioning that the muscle tissue temperature of the patients in the test group, as well as their performance in lumbar anterior flexion, posterior extension, left flexion, and right flexion mobility, were significantly better than those of the control group, and these differences also showed statistical significance (p< 0.05). CONCLUSION: The combination of core stability training and fascial release demonstrates significant clinical results in the treatment of nonspecific lower back pain. Through medical thermography and serum inflammatory factor testing, we were able to assess the treatment effect more objectively, providing a strong basis for future clinical practice.

Electrodermal lability and sensorimotor preparation: effects on reaction time, contingent negative variation, and heart rate.

Electrodermal lability is a trait-like measure of spontaneous sympathetic resting activity. In the present study, we addressed whether interindividual differences in this lability have an impact on the reaction time (RT) and on two physiological indicators of a goal-oriented sensorimotor preparation in a long-running, forewarned RT task (S1-S2 paradigm). The two indicators were the brain's contingent negative variation (CNV) and a heart rate deceleration (HRD). The interindividual differences were determined by counting spontaneous skin conductance fluctuations during a 5-min resting phase and dividing the subjects into two groups: individuals below (stable) and above (labile) the median of these fluctuations. In the task, labile individuals had a shorter RT compared with stable individuals and showed in the final phase of preparation in both physiological indicators the stronger response. Thus, lability-dependent effects in forewarned RT tasks cannot be explained by differences in stimulus-driven or passively controlled processes alone. Rather, goal-oriented, deliberately controlled processes that serve to adequately prepare for an imperative stimulus-the S2 in our paradigm-also must be considered to explain them. Labile individuals not only react faster than stable ones but also intentionally prepare themselves more appropriately for the imperative stimulus. A norepinephrine hypothesis focusing on the tonic activity of the locus coeruleus (LC) is proposed as an explanation for these and other lability-dependent effects. The frequency of spontaneous electrodermal fluctuations at rest may represent a peripheral, noninvasive, and easily measurable indicator of the baseline LC activity during wakefulness.

Siglec7 functions as an inhibitory receptor of non-specific cytotoxic cells and can regulate the innate immune responses in a primitive vertebrate (Oreochromis niloticus).

In mammals, siglec7, an integral component of the siglecs, is principally found on the surface of natural killer (NK) cells, macrophages, and monocytes, where it interacts with various pathogens to perform immunological regulatory activities. Nonetheless, the immune defense and mechanism of siglec7 in early vertebrates remain unknown. In this study, we identified siglec7 from Oreochromis niloticus (OnSiglec7) and revealed its immune functions. Specifically, OnSiglec7 was abundantly expressed in immune-related tissues of healthy tilapia and its transcription level was strongly activated after being challenged with A. hydrophila, S. agalactiae, and Poly: IC. Meanwhile, OnSiglec7 protein was purified and analyzed, which could recognize multiple pathogens through binding and agglutinating activity. Moreover, OnSiglec7-positive cells were mainly distributed in non-specific cytotoxic cells (NCC) of tilapia HKLs and showed cell membrane localization. Furthermore, OnSiglec7 blockage affected multiple innate immune responses (inflammation, apoptosis, and pyroptosis process) by regulating the activation of MAPK, NF-κB, TLR, and JAK-STAT pathways. Finally, OnSiglec7 blockage also greatly enhanced the cytotoxic effect of tilapia NCC. Summarily, this study uncovers immune functions and mechanisms of siglec7 in primitive vertebrates, thereby enhancing our understanding of the systemic evolution and ancient functions of other siglecs within the host's innate immune system (to our knowledge).

Safety, Pharmacokinetics, and Pharmacodynamics of Efzimfotase Alfa, a Second-generation Enzyme Replacement Therapy: Phase 1, Dose-escalation Study in Adults with Hypophosphatasia.

Hypophosphatasia (HPP) is a rare, inherited metabolic disease caused by deficient activity of tissue-nonspecific alkaline phosphatase (TNSALP). Efzimfotase alfa (ALXN1850) is a second-generation TNSALP enzyme replacement therapy in development for HPP. This first-in-human open-label, dose-escalating phase 1 trial evaluated safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of efzimfotase alfa. Fifteen adults (five per cohort) with HPP received efzimfotase alfa 15 mg (cohort 1), 45 mg (cohort 2), or 90 mg (cohort 3) as one i.v. dose followed by 3 weekly s.c. doses. The primary objective was to assess safety and tolerability. Secondary objectives included pharmacokinetics, pharmacodynamics of ALP substrates known to be biomarkers of disease (inorganic pyrophosphate [PPi] and pyridoxal 5'-phosphate [PLP]), and immunogenicity. Treatment-emergent adverse events (TEAEs) occurred in 12 (80%) participants. Eight (53%) participants had injection site reactions (ISRs), observed after 10 of 41 (24%) s.c. injections. Most ISR TEAEs were mild and resolved within 1-2 days. Peak and total exposures of efzimfotase alfa increased in a greater than dose-proportional manner over 15-90 mg after i.v. and s.c. dosing. Arithmetic mean elimination t½ was approximately 6 days; absolute bioavailability ranged from 28.6% to 36.8% over the s.c. dose range of 15-90 mg. Dose-dependent reductions in plasma concentrations of PPi and PLP relative to baseline reached nadir in the first week after i.v. dosing and were sustained for 3-4 weeks after the last s.c. dose. Four (27%) participants tested positive for antidrug antibodies (ADAs), three of whom were ADA positive before the first dose of efzimfotase alfa. ADAs had no apparent effect on efzimfotase alfa pharmacokinetics/pharmacodynamics. No participants were positive for neutralizing antibodies. Efzimfotase alfa demonstrated acceptable safety, tolerability, and pharmacokinetic profiles and was associated with sustained reductions in biomarkers of disease in adults with HPP, supporting further evaluation in adult and pediatric patients. REGISTRATION: NCT04980248.

Hypophosphatasia (HPP) is a rare metabolic disease caused by low activity of tissue non-specific alkaline phosphatase (TNSALP), which is an enzyme involved in the formation and healing of bone and function of other body systems. People with HPP experience fractures, difficulty moving and walking, muscle weakness, pain, fatigue (tiredness), and teeth problems. Babies with HPP often have life-threatening breathing problems, craniosynostosis (early closure of skull bones), seizures that respond to treatment with vitamin B6, failure to thrive (inability to gain weight), and weak and abnormally shaped bones. Enzyme replacement therapy (ERT) for HPP was developed to supplement defective TNSALP with active enzyme, thus improving bone health and the symptoms of HPP. Asfotase alfa, the first ERT approved for the treatment of HPP is given by subcutaneous injection either 3 or 6 times per week. Efzimfotase alfa is a second-generation ERT that is being developed for the treatment of HPP. While similar to asfotase alfa, efzimfotase alfa has incorporated several changes that have the potential to require lower doses and reduce injection volume and dosing frequency, thereby potentially improving the treatment experience for patients. This first-in-human study investigated the safety, tolerability, pharmacokinetics (how a drug is absorbed into, distributed throughout, and removed from the body), pharmacodynamics (effects of the drug within the body), and immunogenicity (ability of a drug to provoke an undesirable immune response) of four injections of efzimfotase alfa when given by intravenous and subcutaneous routes of administration to adults with HPP. Our results showed that efzimfotase alfa has acceptable safety and pharmacokinetics and is effective for reducing biomarkers (measurable substances that reflect underlying disease) when given once weekly by subcutaneous injection, supporting further evaluation of efzimfotase alfa in planned clinical trials in adult and pediatric patients with HPP.

Vitamin C as a functional enhancer in the non-specific immune defense, antioxidant capacity and resistance to low-temperature stress of juvenile mud crab, Scylla paramamosain.

This experiment was conducted to explore the effects of dietary vitamin C supplementation on non-specific immune defense, antioxidant capacity and resistance to low-temperature stress of juvenile mud crab (Scylla paramamosain). Mud crabs with an initial weight of 14.67 ± 0.13 g were randomly divided into 6 treatments and fed diets with 0.86 (control), 44.79, 98.45, 133.94, 186.36 and 364.28 mg/kg vitamin C, respectively. The experiment consisted of 6 treatments, each treatment was designed with 4 replicates and each replicate was stocked with 8 crabs. After 42 days of feeding experiment, 2 crabs were randomly selected from each replicate, and a total of 8 crabs in each treatment were carried out 72 h low-temperature challenge experiment. The results showed that crabs fed diets with 186.36 and 364.28 mg/kg vitamin C significantly improved the activities of alkaline phosphatase (AKP) and acid phosphatase (ACP) in hemolymph and hepatopancreas (P < 0.05). Crabs fed diet with 133.94 mg/kg vitamin C significantly decreased the concentration of nitric oxide (NO) and the activity of nitric oxide synthase (NOS) in hemolymph (P < 0.05). Diet with 133.94 mg/kg vitamin C was improved the activity of polyphenol oxidase (PPO) and the concentration of albumin (ALB) in hemolymph. Crabs fed diet with 133.94 mg/kg vitamin C showed lower concentration of malondialdehyde (MDA) in hemolymph and hepatopancreas than those fed the other diets. Meanwhile, crabs fed diet with 98.45 mg/kg vitamin C showed higher activity of total superoxide dismutase (T-SOD) in hemolymph, and crabs fed diet with 133.94 mg/kg vitamin C showed higher activity of T-SOD in hepatopancreas. Crabs fed diet with 186.36 mg/kg vitamin C significantly decreased the concentration of reduced glutathione (GSH) and the activity of glutathione peroxidase (GSH-PX) in hepatopancreas (P < 0.05). In normal temperature, crabs fed diets with 133.94 mg/kg vitamin C significantly up-regulated the expression levels of gpx (glutathione peroxidase) and trx (thioredoxin) in hepatopancreas compared with the control treatment (P < 0.05). The highest expression levels of relish, il16 (interleukin 16), caspase 2 (caspase 2), p38 mapk (p38 mitogen-activated protein kinases) and bax (bcl-2 associated x protein) in hepatopancreas were found at crabs fed control diet (P < 0.05). Moreover, crabs fed diet with 133.94 mg/kg vitamin C showed higher expression levels of alf-3 (anti-lipopolysaccharide factor 3) and bcl-2 (B-cell lymphoma 2) in hepatopancreas than those fed the other diets (P < 0.05). Under low-temperature stress, crabs fed diet with 133.94 mg/kg vitamin C significantly improved the expression levels of hsp90 (heat shock protein 90), cat (catalase), gpx, prx (thioredoxin peroxidase) and trx in hepatopancreas (P < 0.05). In addition, dietary with 133.94 vitamin C significantly up-regulated the expression levels of alf-3 and bcl-2 (P < 0.05). Based on two slope broken-line regression analysis of activity of PPO against the dietary vitamin C level, the optimal dietary vitamin C requirement was estimated to be 144.81 mg/kg for juvenile mud crab. In conclusion, dietary 133.94-144.81 mg/kg vitamin C significantly improved the non-specific immune defense, antioxidant capacity and resistance to low-temperature stress of juvenile mud crab.

A Rare Case of Adult-Onset Bilateral Nonspecific Orbital Inflammation (NSOI) With Concomitant Unilateral Third Cranial Nerve Palsy.

Nonspecific orbital inflammation (NSOI), also known as orbital pseudotumor, is a condition characterized by inflammation in the tissues around the eye socket (orbit) without a clearly identifiable cause. This inflammatory disorder can affect various structures within the orbit, including muscles, fat, and connective tissues, leading to symptoms such as pain, swelling, and changes in vision. A 74-year-old man with a history of previous orbital trauma presented with acute-onset head and orbital pain, followed by restricted left eye movements in all directions, left ptosis, and a dilated left pupil. Orbital imaging revealed bilateral inflammation of the lateral rectus muscles and orbital fat, suggestive of bilateral NSOI, while brain and laboratory studies ruled out other differential diagnoses. The presence of left ptosis, a dilated pupil, and limited upward, downward, and inward movements in the left eye suggested intraorbital involvement of both the superior and inferior divisions of the left third nerve. The complete resolution of orbital symptoms and third nerve function after systemic corticosteroid therapy supported the inflammatory nature of the nerve involvement in this case. The case is notable in terms of bilateral involvement in adult-onset NSOI, the possible role of previous orbital trauma in the development of the disease, and the inflammatory involvement of third nerve divisions following the extension of inflammation into the orbital tissues. NSOI can mimic other, more serious conditions, making accurate diagnosis crucial for effective management and treatment. Understanding its presentation, potential causes, and appropriate diagnostic approaches is essential in providing optimal care for patients affected by this complex inflammatory condition.

The Immunomodulatory Function of Assembled Composite Nanopolypeptide Containing Bursal-Derived BP7 (CNPB7) in Promoting the Mucosal Immune Response within Poultry Immunization.

Mucosal immunity is the main defense line against respiratory disease pathogens. Newcastle disease and avian infectious bronchitis are common respiratory diseases in poultry. However, the mucosal immune response is not sufficiently activated and thus fails to achieve the ideal immune protection. Therefore, it is important to develop a suitable mucosal immune adjuvant to enhance the immune response of live vaccines. Here, the bursal-derived peptide BP7, ß-glucan, and hyaluronic acid were selected as the adjuvant to be assembled into the composite nanopolypeptide adjuvant (CNPB7) with ultrasonic dispersion technology. The results showed that after optimizing assembly conditions, the optimal average particle size of nanoparticle CNPB7 was 514.9 nm and PDI was 0.298. To evaluate the non-specific immune responses of nanoparticle CNPB7, the chickens were immunized only with nanoparticle CNPB7. It was confirmed that nanoparticle CNPB7 enhanced the expression of CD3, CD4, CD80, and CD86 factors in the spleen lymphocyte from the chicken immunized with nanoparticle CNPB7. To investigate the mucosal immune response of nanoparticle CNPB7, the chickens were orally immunized with Newcastle disease virus (NDV)-infectious bronchitis virus (IBV) dual vaccines and CNPB7. The results proved that the levels of immunoglobulin SIgA, IL-4, IFN-γ, and IL-13 in the mucus samples from the respiratory and digestive tract in chicken immunized with nanoparticle CNPB7 and vaccines were significantly increased, compared to that of vaccine control. Finally, it was observed that nanoparticle CNPB7 promoted specific increased antibody productions against NDV and IBV in the immunized chicken. These results proved that the assembled nanoparticle CNPB7 could enhance the vaccination efficacy in chicken, which provided the experimental basis for the development of new adjuvants, and offered technical support for preventing virus transmission of avian diseases.

Low Back Pain Caused by Traction Peripheral Neuropathy Due to Chronic Ankle Instability: Three Clinical Cases.

Non-specific low back pain without identifiable causes on imaging is a common and frustrating problem for both patients and physicians. While proximal symptoms such as shoulder pain from distal upper extremity neuropathies such as carpal tunnel syndrome are well-known, peripheral neuropathy of the foot or ankle is rarely considered in the differential diagnosis for low back pain. This study aims to highlight the potential link between chronic ankle instability (CAI) and low back pain. We present three cases: a 32-year-old woman with chronic low back pain for over 10 years, a 59-year-old woman with transient low back pain after long drives, and a 42-year-old woman with acute low back pain while gardening. All patients had normal imaging studies but exhibited CAI on examination. Diagnostic modalities included the ankle anterior drawer test, application of ankle brace, superficial peroneal nerve (SPN) blocks, and assessment of the active straight leg raise (aSLR) angle. In the first case, low back pain disappeared after SPN neurolysis and ankle ligament reconstruction. The second case showed significant improvement in aSLR and pain reduction with SPN block and ankle brace. The third case experienced substantial pain relief with the use of an ankle brace. These findings suggest that addressing ankle instability and associated traction neuropathy can significantly alleviate low back pain symptoms. CAI may be an underrecognized cause of non-specific low back pain. Interventions such as ankle brace, SPN blocks, SPN decompression, and ankle ligament reconstruction can be effective for diagnosis and treatment, potentially offering relief for patients with chronic low back pain.

The Importance of Mind-Body in Pilates Method in Patients with Chronic Non-Specific Low Back Pain-A Randomized Controlled Trial.

Background/Objectives: Chronic non-specific low back pain (CNSLBP) is a prevalent condition causing significant distress and healthcare costs globally. Despite various treatments, effective management remains challenging. Pilates, recognized for its focus on core strength and postural alignment, has emerged as a promising intervention. This study investigates the impact of mind-body in Pilates for directing participants on CNSLBP outcomes. Methods: A randomized controlled trial was conducted with 67 participants, aged 18 to 65 years, suffering from CNSLBP. They were allocated into two groups: Pilates with mind-body cueing (n = 34) and Pilates without cueing (n = 33). Both groups underwent 60 min sessions twice weekly for 8 weeks. Outcome measures included pain intensity (Visual Analogue Scale), functional disability (Roland Morris Disability Questionnaire), fear of movement (Tampa Scale of Kinesiophobia), and adherence (percentage of sessions attended). Statistical significance was determined through repeated measures ANOVA. Results: Both groups showed significant improvement in pain reduction, functional ability, and kinesiophobia. However, the mind-body group demonstrated a statistically significant reduction in kinesiophobia compared to the non-cueing group (p = 0.048), indicating the potential additional benefit of mind-body cueing in managing movement-related fear in CNSLBP. Conclusions: This study underscores the effectiveness of an 8-week Pilates intervention in managing CNSLBP, highlighting the added value of mind-body cueing in reducing fear of movement. These findings suggest incorporating mind-body cueing in Pilates could enhance the therapeutic benefits, particularly for patients with high levels of movement-related fear, potentially improving long-term adherence to physical activity and rehabilitation outcomes.

Effects of Fu's subcutaneous needling on clinical efficacy and psychological cognitive characteristics in patients with chronic non-specific low back pain: A randomized controlled trial.

BACKGROUND AND PURPOSE: Low back pain (LBP) is a major global public health problem. Evidence shows that LBP is also related to cognitive, psychological, and lifestyle factors. Fu's subcutaneous needling (FSN) has been used for the treatment of musculoskeletal problems for many years. This prospective randomized controlled trial aimed to evaluate the clinical efficacy and fear avoidance beliefs of FSN in the treatment of patients with chronic non-specific LBP. MATERIAL AND METHODS: Ninety participants with chronic non-specific LBP were randomly divided into the FSN and the traditional acupuncture (TA) groups (n = 45) and received either FSN or TA treatment for three consecutive days from December 2021 to March 2023. The primary outcome was pain intensity measured by the visual analogue scale (VAS). Secondary outcomes were trunk extensor endurance (TEE), lumbar range of motion (ROM), and the Fear Avoidance Beliefs Questionnaire (FABQ). Outcome measurements were made before the first treatment and after each treatment. Follow-up assessments of VAS and FABQ scores were conducted one month after treatment. RESULTS: The FSN group had significantly lower VAS and FABQ scores at each time point after intervention compared to the TA group (P < 0.01). The scores of TEE and lumbar ROM were higher in the FSN group than those in the TA group (P < 0.01). Repeated measures analysis of variance (ANOVA) showed significant time effects, group effects, and interaction effects for VAS, TEE, lumbar ROM, and FABQ in both groups (P < 0.01). One month after treatment, the FSN group had significantly lower VAS and FABQ scores compared to the TA group (P < 0.05). CONCLUSION: This study suggested that FSN was superior to TA in terms of clinical efficacy and fear-avoidance beliefs in the treatment of chronic non-specific LBP. FSN could be used as an effective clinical treatment.

On-Demand Elongation of Peptide Nanofibrils at Cellular Interfaces to Modulate Cell-Cell Interactions.

Natural cells can achieve specific cell-cell interactions by enriching nonspecific binding molecules on demand at intercellular contact faces, a pathway currently beyond synthetic capabilities. We are inspired to construct responsive peptide fibrils on cell surfaces, which elongate upon encountering target cells while maintaining a short length when contacting competing cells, as directed by a strand-displacement reaction arranged on target cell surfaces. With the display of ligands that bind to both target and competing cells, the contact-induced, region-selective fibril elongation selectively promotes host-target cell interactions via the accumulation of nonspecific ligands between matched cells. This approach is effective in guiding natural killer cells, the broad-spectrum effector lymphocytes, to eliminate specific cancer cells. In contrast to conventional methods relying on target cell-specific binding molecules for the desired cellular interactions, this dynamic scaffold-based approach would broaden the scope of cell combinations for manipulation and enhance the adjustability of cell behaviors for future applications.

Hypoxia-Inducible Factor-1α-Activated Protein Switch Based on Allosteric Self-Splicing Reduces Nonspecific Cytotoxicity of Pharmaceutical Drugs.

Protein-based therapeutic agents currently used for targeted tumor therapy exhibit limited penetrability, nonspecific toxicity, and a short circulation half-life. Although targeting cell surface receptors improves cancer selectivity, the receptors are also slightly expressed in normal cells; consequently, the nonspecific toxicity of recombinant protein-based therapeutic agents has not been eliminated. In this study, an allosteric-regulated protein switch was designed that achieved cytoplasmic reorganization of engineered immunotoxins in tumor cells via interactions between allosteric self-splicing elements and cancer markers. It can target the accumulated HIF-1α in hypoxic cancer cells and undergo allosteric activation, and the splicing products were present in hypoxic cancer cells but were absent in normoxic cells, selectively killing tumor cells and reducing nonspecific toxicity to normal cells. The engineered pro-protein provides a platform for targeted therapy of tumors while offering a novel universal strategy for combining the activation of therapeutic functions with specific cancer markers. The allosteric self-splicing element is a powerful tool that significantly reduces the nonspecific cytotoxicity of therapeutic proteins.