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Lei Gao,1,2,&ast; Jian-Feng Zhang,3,&ast; John P Williams,4 Yi-Ning Yan,1 Xi-Lai Xiao,1 Wan-Rui Shi,5 Xiao-Yan Qian,1 Jian-Xiong An1– 3,6 1Department of Anesthesiology, Pain and Sleep Medicine, Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine, Chinese Academy of Sciences, Beijing, People’s Republic of China; 2School of Anesthesiology, Weifang Medical University, Weifang, Shangdong, People’s Republic of China; 3Savaid Medical School, University of Chinese Academy of Sciences, Beijing, People’s Republic of China; 4Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; 5Department of Anesthesiology, Peking University Third Hospital, Beijing, People’s Republic of China; 6School of Medical Science & Engineering, Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian-Xiong AnDepartment of Anesthesiology, Pain and Sleep Medicine, Aviation General Hospital of China Medical University, Beiyuan Road 3#, Beijing, 100012, People’s Republic of ChinaTel +86 13801281750Fax +86 59520233Email anjianxiong@yeah.netPurpose: It is unclear whether neuropathological structural changes in the peripheral nervous system and central nervous system can occur in the spared nerve injury model. In this study, we investigated the pathological changes in the nervous system in a model of neuropathic pain as well as the effects of electroacupuncture (EA) and pregabalin (PGB) administration as regards pain relief and tissue repair.Patients and Methods: Forty adult male SD rats were equally and randomly divided into 4 groups: spared nerve injury group (SNI, n = 10), SNI with electroacupuncture group (EA, n = 10), SNI with pregabalin group (PGB, n =10) and sham-operated group (Sham, n=10). EA and PGB were given from postoperative day (POD) 14 to 36. EA (2 Hz and 100 Hz alternating frequencies, intensities ranging from 1– 1.5– 2 mA) was applied to the left “zusanli” (ST36) and “Yanglingquan” (GB34) acupoints for 30 minutes. The mechanical withdrawal thresholds (MWTs) were tested with von Frey filaments. Moreover, the organizational and structural alterations of the bilateral prefrontal cortex, hippocampus, sciatic nerves and the thoracic, lumbar spinal cords and dorsal root ganglions (DRGs) were examined via light and electron microscopy.Results: MWTs of left hind paw demonstrated a remarkable decrease in the SNI model (P < 0.05). In the SNI model, ultrastructural changes including demyelination and damaged neurons were observed at all levels of the peripheral nervous system (PNS) and central nervous system (CNS). In addition, EA improved MWTs and restored the normal structure of neurons. However, the effect was not found in the PGB treatment group.Conclusion: Chronic pain can induce extensive damage to the central and peripheral nervous systems. Meanwhile, EA and PGB can both alleviate chronic pain syndromes in rats, but EA also restores the normal cellular structures, while PGB is associated with no improvement.Keywords: neuropathic pain, structural changes, electroacupuncture, pregabalin

Jian-Xiong An,1– 3 John P Williams,4 Qi-Wu Fang,1 Yong Wang,1 Hui Liu,1 Le Shi,5 Wen-Hao Zhang1,2 1Department of Anesthesiology, Pain and Sleep Medicine, Aviation General Hospital of China Medical University & Beijing Institute of Translational Medicine, Chinese Academy of Sciences, Beijing, People’s Republic of China; 2Savaid Medical School, University of Chinese Academy of Sciences, Beijing, People’s Republic of China; 3School of Medical Science & Engineering, Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing, People’s Republic of China; 4Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; 5Key Laboratory of Mental Health, Peking University Sixth Hospital, Peking University Institute of Mental Health, Ministry of Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, People’s Republic of ChinaCorrespondence: Wen-Hao Zhang Tel +86 159 1096 3901Email zhangwenhao18@mails.ucas.ac.cnBackground: Patient-controlled analgesia (PCA) is an “on-demand” system which allows patients to self-administer intravenous medications in small bolus doses. Based on the principles of PCA, we developed Patient-Controlled Sleep (PCSL) for chronic intractable insomnia where the traditional analgesics in PCA were replaced with dexmedetomidine (Dex), an alpha-2 agonist widely used for premedication, sedation, anxiolysis and analgesia. The purpose of this study was to assess the feasibility of the new method for the treatment of chronic intractable insomnia.Patients and Methods: Patients with chronic intractable insomnia undergoing PCSL (n=20) were evaluated with the Pittsburgh Sleep Quality Index (PSQI), Symptom Checklist 90 (SCL-90), Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) before and after the treatment. The patient characteristics, overall outcomes and related side effects were also assessed.Results: Fifteen patients completed the treatment protocol. The duration of PCSL varied from a few days to four months, and the dosage of Dex gradually decreased without eliciting signs or symptoms of tolerance or physical dependence. The sleep quality improvement occurred immediately after the therapy in 12/15 patients, and of which, 7/12 patients achieved continuously improved sleep quality in follow-up.Conclusion: PCSL with Dex might be a potential treatment for patients with chronic intractable insomnia. However, it is an off-label use, and the potential side effects of dexmedetomidine with long-term use needs further evaluation.Keywords: insomnia, dexmedetomidine, Patient-Controlled Sleep, biomimetic sleep

Lei Gao,1,2 Ruo-Wen Chen,2 John P Williams,3 Tong Li,4 Wei-Jiang Han,5 Qian-Nan Zhao,2 Yong Wang,2 Jian-Xiong An1,2 1Department of Anesthesiology, Weifang Medical University, Weifang City 261000, Shangdong, People’s Republic of China; 2Department of Anesthesiology, Pain and Sleep Medicine, Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine, Chinese Academy of Sciences, Beijing, 100012, People’s Republic of China; 3Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; 4Department of Pain, Lanzhou Maternity and Child Healthcare Hospital, Lanzhou, 730030, People’s Republic of China; 5Department of Pain, Xishuangbanna Dai Nationality Autonomous Prefecture People’s Hospital, Xishuangbanna, 666100, People’s Republic of ChinaCorrespondence: Jian-Xiong AnDepartment of Anesthesiology, Pain and Sleep Medicine, Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine, Chinese Academy of Sciences, Beiyuan Road 3, Beijing 100012, People’s Republic of ChinaTel +86 138 0128 1750Fax +86 10 5952 0393Email anjianxiong@yeah.netBackground: Ozone injection around Gasserian ganglion (OIAGG) has been reported to be an effective treatment for trigeminal neuralgia (TN); however, there remain areas for improvement. To overcome one of these limitations, a multicenter examination of application would be extremely helpful.Objective: The goal of this report was to assess the efficacy of OIAGG for refractory TN across multiple centers and to explore factors predictive of successful treatment.Design: A multicenter, retrospective study.Setting: The study was conducted across 3 pain centers across China.Patients and Methods: A total of 103 subjects from 3 pain centers were enrolled in the study. An ozone-oxygen mixture gas at a concentration of 30 μg/mL was injected into the area around the Gasserian ganglion performed under C-arm X-ray guidance. Primary outcome measures included a pain assessment using a visual analog scale (VAS) and the Barrow Neurological Institute (BNI) pain intensity scale. Clinical assessment of patients for these outcome measures was performed at pretreatment, post-treatment, 6 months, 1 year and 2 years after the OIAGG.Results: Successful pain relief was defined as a score within BNI grades I–IIIa. The pain relief rates at post-treatment, 6 months, 1 year and 2 years after the procedure were 88.35%, 86.87%, 84.46% and 83.30%, respectively. The VAS at each observation time point was significantly different from the preoperative levels (P< 0.05). Logistic regression analysis showed that previous nerve damage had a significant effect on the treatment results. No significant complications or side effects were found during or after treatment.Conclusion: This multicenter research confirms our previous single center results that OIAGG is both effective and safe for patients with TN.Keywords: trigeminal neuralgia, trigeminal post-herpetic neuralgia, ozone therapy, Gasserian ganglion

Si-Yu Lin,1,2 Shi-Zhong Zhang,1 Jian-Xiong An,1,2 Xiao-Yan Qian,2 Xin-You Gao,2 Yong Wang,2 Wen-Xing Zhao,2 Derek Eastwood,3 Doris K Cope,4 John P Williams4 1China Three Gorges, University School of Medicine, Yichang, China; 2Department of Anesthesiology, Pain Medicine and Critical Care Medicine, Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine, Chinese Academy of Sciences, Beijing, China; 3Department of Pain Services, Wirral University Teaching Hospital, Wirral, Merseyside, UK; 4Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Objective: This study was to evaluate the effectiveness of ultrasound-guided percutaneous ozone injections around the cervical dorsal root ganglions of zoster-associated pain (ZAP) patients.Study design: Retrospective comparative study.Settings: The study was conducted at a pain center of a university hospital.Patients and methods: From June 2016 to July 2017, a total number of 30 patients with ZAP were treated with ultrasound-guided percutaneous ozone injection around the cervical dorsal root ganglion (DRG) at the injured nerve level (C2-C8). A volume of 3 mL ozone-oxygen mixture at a concentration of 30 µg/mL was injected into the area around the DRG. Patients were divided into two groups according to their disease duration: group A (at or 3 months). The pain severity was assessed according to a visual analog scale, and imaging changes were evaluated by ultrasound. Patient improvements in pain and neurologic function were evaluated during a follow-up period from 1 to 3 months.Results: The data showed that ozone injections reduced pain in patients with ZAP. However, the success rate of group A was higher than group B. After the injection, the von Frey data demonstrated decreases in both groups, but, there were no significant differences between the groups. Moreover, univariate logistic regression analysis and multivariate regression analysis showed a history of diabetes mellitus had a significant effect on the treatment results.Conclusions: Percutaneous ozone injection around the DRG might be a useful method for treatment-resistant cases of ZAP at the cervical level. Institutional Review Board (IRB) approval number: HK2017-1130. Keywords: herpes zoster, neuropathic pain, post-herpetic neuralgia, ozone injection

Jian-Xiong An,1,2 Hui Liu,1 Ruo-Wen Chen,1,2 Yong Wang,1 Wen-Xing Zhao,1 Derek Eastwood,3 John P Williams4 1Department of Anesthesiology, Pain Medicine & Critical Care Medicine, Aviation General Hospital of China Medical University & Beijing Institute of Translational Medicine, Chinese Academy of Sciences, 2Department of Anesthesiology, Weifang Medical University, Beijing, People’s Republic of China; 3Department of Pain Services, Wirral University Teaching Hospital, Wirral, Merseyside, UK; 4Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Objective: The aim of this study was to evaluate the therapeutic effect of computed tomography (CT)-guided percutaneous ozone injection for refractory trigeminal neuralgia. Design: A retrospective evaluation was performed in the study. Setting: The study was conducted at a university hospital pain center. Patients and methods: A total of 29 patients with a clinical diagnosis of refractory trigeminal neuralgia were enrolled. All patients were treated with a percutaneous ozone injection and one patient was excluded. There were 21 patients with classical trigeminal neuralgia (group A) and seven patients with painful trigeminal neuropathy caused by post-herpetic neuralgia (group B). The percutaneous injection was an oxygen–ozone mixture at an ozone concentration of 30 mg/­mL into the Gasserian ganglion performed under CT guidance. The number of ­procedures performed varied from one to as many as 16. Outcomes were evaluated using visual analog scale (VAS) pain scores. Results: The combined VAS scores were 7.11 ± 1.23 pretreatment, 2.86 ± 1.69 posttreatment (P < 0.05) and 3.25 ± 2.01 after 6-month follow-up (P < 0.05). In group A, the VAS scores were 7.10 ± 1.04 pretreatment and 2.90 ± 1.84 posttreatment (P < 0.05). In group B, the VAS scores were 7.14 ± 1.77 pretreatment and 2.71 ± 1.25 posttreatment (P < 0.05). After 6-months follow-up, the VAS score was 3.38 ± 2.18 in group A and 2.86 ± 1.46 in group B, a decrease compared to pretreatment (P < 0.05). VAS of Group A and B showed no difference not only in pretreatment but also in postreatment and follow-up. Conclusion: Percutaneous ozone injection is a safe and effective treatment for patients with refractory trigeminal neuralgia. Keywords: trigeminal neuralgia, percutaneous ozone injection, Gasserian ganglion

Ruo-Wen Chen,1,2 Hui Liu,2 Jian-Xiong An,1,2 Xiao-Yan Qian,2 Yi-De Jiang,2 Doris K Cope,3 John P Williams,3 Rui Zhang,1 Li-Na Sun1 1Department of Anesthesiology, Weifang Medical University, Weifang City, Shandong, 2Department of Anesthesiology, Pain Medicine and Critical Care Medicine, Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine, Chinese Academy of Sciences, Beijing, China; 3Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Objective: The objective of this study was to investigate the effects of electro-acupuncture (EA) and pregabalin on cognition impairment induced by chronic trigeminal neuralgia (TN) in rats. Design: Controlled animal study. Setting: Department of Anesthesiology, Pain Medicine and Critical Care Medicine, Aviation General Hospital of China Medical University. Subjects: Forty adult male Sprague Dawley rats. Methods: Rats were randomly divided into four groups. The TN model was induced by administration of cobra venom to the left infraorbital nerve. On postoperative day 14, either EA or pregabalin was administered, free behavioral activities were observed. Spatial learning and memory abilities were determined in the Morris water maze. The ultrastructural alterations of the Gasserian ganglion, medulla oblongata and hippocampus were examined by electron microscopy. The changes on long-term potentiation were investigated. Results: After treatment, the exploratory behavior increased and the grooming behavior decreased (P0.05). Vacuolar degeneration in the hippocampal neurons was mild in the EA group, while it was severe in the pregabalin group.Conclusion: EA and pregabalin could alleviate TN induced by cobra venom. EA could also inhibit the cognition deficit induced by TN, while pregabalin could not. Keywords: TN, cognition dysfunction, EA, pregabalin, LTP

James P Williams,1 Paul Southern,2 Anya Lissina,3 Helen C Christian,4 Andrew K Sewell,3 Rodney Phillips,1,5,6 Quentin Pankhurst,2 John Frater1,5,6 1Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, UK; 2Davy-Faraday Research Laboratory, Royal Institution of Great Britain, London, UK; 3Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK; 4Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK; 5James Martin 21st Century School, John Radcliffe Hospital, Oxford, UK; 6Oxford NIHR Biomedical Research Centre, Oxford, UK Abstract: The latent HIV-1 reservoir remains the major barrier to HIV-1 eradication. Although successful at limiting HIV replication, highly active antiretroviral therapy is unable to cure HIV infection, thus novel therapeutic strategies are needed to eliminate the virus. Magnetic field hyperthermia (MFH) generates thermoablative cytotoxic temperatures in target-cell populations, and has delivered promising outcomes in animal models, as well as in several cancer clinical trials. MFH has been proposed as a strategy to improve the killing of HIV-infected cells and for targeting the HIV latent reservoirs. We wished to determine whether MFH could be used to enhance cytotoxic T-lymphocyte (CTL) targeting of HIV-infected cells in a proof-of-concept study. Here, for the first time, we apply MFH to an infectious disease (HIV-1) using the superparamagnetic iron oxide nanoparticle FeraSpin R. We attempt to improve the cytotoxic potential of T-cell receptor-transfected HIV-specific CTLs using thermotherapy, and assess superparamagnetic iron oxide nanoparticle toxicity, uptake, and effect on cell function using more sensitive methods than previously described. FeraSpin R exhibited only limited toxicity, demonstrated efficient uptake and cell-surface attachment, and only modestly impacted T-cell function. In contrast to the cancer models, insufficient MFH was generated to enhance CTL killing of HIV-infected cells. MFH remains an exciting new technology in the field of cancer therapeutics, which, as technology improves, may have significant potential to enhance CTL function and act as an adjunctive therapy in the eradication of latently infected HIV-positive cells. Keywords: nanoparticles, HIV-1, thermotherapy, cytotoxic T-cell

A range of sleep disorders has the potential to adversely affect cognitive function. This study was undertaken with the objective of investigating the effects of ozone rectal insufflation (O3-RI) on cognitive dysfunction induced by chronic REM sleep deprivation, as well as elucidating possible underlying mechanisms. O3-RI ameliorated cognitive dysfunction in chronic REM sleep deprived mice, improved the neuronal damage in the hippocampus region and decreased neuronal loss. Administration of O3-RI may protect against chronic REM sleep deprivation induced cognitive dysfunction by reversing the abnormal expression of Occludin and leucine-rich repeat and pyrin domain-containing protein 3 inflammasome as well as interleukin-1β in the hippocampus and colon tissues. Moreover, the microbiota diversity and composition of sleep deprivation mice were significantly affected by O3-RI intervention, as evidenced by the reversal of the Firmicutes/Bacteroidetes abundance ratio and the relative abundance of the Bacteroides genus. In particular, the relative abundance of the Bacteroides genus demonstrated a pronounced correlation with cognitive impairment and inflammation. Our findings suggested that O3-RI can improve cognitive dysfunction in sleep deprivation mice, and its mechanisms may be related to regulating gut microbiota and alleviating inflammation and damage in the hippocampus and colon., (Copyright © 2024 Copyright: © 2024 Medical Gas Research.)

While regular physical activity is a cornerstone of health, wellness, and vitality, the impact of endurance exercise training on molecular signaling within and across tissues remains to be delineated. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to characterize molecular networks underlying the adaptive response to exercise. Here, we describe the endurance exercise training studies undertaken by the Preclinical Animal Sites Studies component of MoTrPAC, in which we sought to develop and implement a standardized endurance exercise protocol in a large cohort of rats. To this end, Adult (6-mo) and Aged (18-mo) female (n = 151) and male (n = 143) Fischer 344 rats were subjected to progressive treadmill training (5 d/wk, ∼70%-75% VO2max) for 1, 2, 4, or 8 wk; sedentary rats were studied as the control group. A total of 18 solid tissues, as well as blood, plasma, and feces, were collected to establish a publicly accessible biorepository and for extensive omics-based analyses by MoTrPAC. Treadmill training was highly effective, with robust improvements in skeletal muscle citrate synthase activity in as little as 1-2 wk and improvements in maximum run speed and maximal oxygen uptake by 4-8 wk. For body mass and composition, notable age- and sex-dependent responses were observed. This work in mature, treadmill-trained rats represents the most comprehensive and publicly accessible tissue biorepository, to date, and provides an unprecedented resource for studying temporal-, sex-, and age-specific responses to endurance exercise training in a preclinical rat model., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Physiological Society.)

Introduction: Point-of-care ultrasound (POCUS) can assist rheumatologists in monitoring disease activity, establishing diagnoses, and guiding procedural interventions. POCUS use has been increasing, but little is known about current use and barriers among rheumatologists. The purpose of this study was to characterize current POCUS use, training needs, and barriers to use among rheumatologists in practice., Methods: A prospective observational study of all Veterans Affairs (VA) medical centers was conducted using a web-based survey sent to all chiefs of staff and rheumatology chiefs about current POCUS use, training needs, barriers, and policies., Results: All chiefs of staff (n = 130) and rheumatology chiefs at VA medical centers (n = 95) were surveyed with 100% and 84% response rates, respectively. The most common diagnostic POCUS applications were evaluation of synovitis, joint effusion, tendinopathies, bursitis, and rotator cuff. The most common procedural applications were arthrocentesis and joint, bursa, and tendon injection. Most rheumatology chiefs (69%) expressed interest in training for their group. The most common barriers to POCUS use were lack of trained providers (68%), funding for training (54%), training opportunities (38%), funding for travel (38%), and ultrasound equipment (31%). Lack of POCUS infrastructure was common, and few facilities had POCUS policies (20%), image archiving (25%), or quality assurance processes (6%)., Conclusion: Currently, half of rheumatology groups use diagnostic and procedural ultrasound applications. Most rheumatology groups desire training, and lack of training and equipment were the most common barriers to ultrasound use. Deliberate investment is needed in ultrasound training and infrastructure for systematic adoption of POCUS in rheumatology. Graphical Abstract available for this article., Trial Registration: NCT03296280., (© 2024. The Author(s).)

Background: Acute appendicitis is one of the most common emergency general surgical conditions worldwide. Uncomplicated/simple appendicitis can be treated with appendectomy or antibiotics. Some studies have suggested possible benefits with antibiotics with reduced complications, length of hospital stay, and the number of days off work. However, surgery may improve success of treatment as antibiotic treatment is associated with recurrence and future need for surgery., Objectives: To assess the effects of antibiotic treatment for uncomplicated/simple acute appendicitis compared with appendectomy for resolution of symptoms and complications., Search Methods: We searched CENTRAL, MEDLINE, Embase, and two trial registers (World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov) on 19 July 2022. We also searched for unpublished studies in conference proceedings together with reference checking and citation search. There were no restrictions on date, publication status, or language of publication., Selection Criteria: We included parallel-group randomised controlled trials (RCTs) only. We included studies where most participants were adults with uncomplicated/simple appendicitis. Interventions included antibiotics (by any route) compared with appendectomy (open or laparoscopic)., Data Collection and Analysis: We used standard methodology expected by Cochrane. We used GRADE to assess the certainty of evidence for each outcome. Primary outcomes included mortality and success of treatment, and secondary outcomes included number of participants requiring appendectomy in the antibiotic group, complications, pain, length of hospital stay, sick leave, malignancy in the antibiotic group, negative appendectomy rate, and quality of life. Success of treatment definitions were heterogeneous although mainly based on resolution of symptoms rather than incorporation of long-term recurrence or need for surgery in the antibiotic group., Main Results: We included 13 studies in the review covering 1675 participants randomised to antibiotics and 1683 participants randomised to appendectomy. One study was unpublished. All were conducted in secondary care and two studies received pharmaceutical funding. All studies used broad-spectrum antibiotic regimens expected to cover gastrointestinal bacteria. Most studies used predominantly laparoscopic surgery, but some included mainly open procedures. Six studies included adults and children. Almost all studies aimed to exclude participants with complicated appendicitis prior to randomisation, although one study included 12% with perforation. The diagnostic technique was clinical assessment and imaging in most studies. Only one study limited inclusion by sex (male only). Follow-up ranged from hospital admission only to seven years. Certainty of evidence was mainly affected by risk of bias (due to lack of blinding and loss to follow-up) and imprecision. Primary outcomes It is uncertain whether there was any difference in mortality due to the very low-certainty evidence (Peto odds ratio (OR) 0.51, 95% confidence interval (CI) 0.05 to 4.95; 1 study, 492 participants). There may be 76 more people per 1000 having unsuccessful treatment in the antibiotic group compared with surgery, which did not reach our predefined level for clinical significance (risk ratio (RR) 0.91, 95% CI 0.87 to 0.96; I 2 = 69%; 7 studies, 2471 participants; low-certainty evidence). Secondary outcomes At one year, 30.7% (95% CI 24.0 to 37.8; I 2 = 80%; 9 studies, 1396 participants) of participants in the antibiotic group required appendectomy or, alternatively, more than two-thirds of antibiotic-treated participants avoided surgery in the first year, but the evidence is very uncertain. Regarding complications, it is uncertain whether there is any difference in episodes of Clostridium difficile diarrhoea due to very low-certainty evidence (Peto OR 0.97, 95% CI 0.24 to 3.89; 1 study, 1332 participants). There may be a clinically significant reduction in wound infections with antibiotics (RR 0.25, 95% CI 0.09 to 0.68; I 2 = 16%; 9 studies, 2606 participants; low-certainty evidence). It is uncertain whether antibiotics affect the incidence of intra-abdominal abscess or collection (RR 1.58, 95% CI 0.61 to 4.07; I 2 = 19%; 6 studies, 1831 participants), or reoperation (Peto OR 0.13, 95% CI 0.01 to 2.16; 1 study, 492 participants) due to very low-certainty evidence, mainly due to rare events causing imprecision and risk of bias. It is uncertain if antibiotics prolonged length of hospital stay by half a day due to the very low-certainty evidence (MD 0.54, 95% CI 0.06 to 1.01; I 2 = 97%; 11 studies, 3192 participants). The incidence of malignancy was 0.3% (95% CI 0 to 1.5; 5 studies, 403 participants) in the antibiotic group although follow-up was variable. Antibiotics probably increased the number of negative appendectomies at surgery (RR 3.16, 95% CI 1.54 to 6.49; I 2 = 17%; 5 studies, 707 participants; moderate-certainty evidence)., Authors' Conclusions: Antibiotics may be associated with higher rates of unsuccessful treatment for 76 per 1000 people, although differences may not be clinically significant. It is uncertain if antibiotics increase length of hospital stay by half a day. Antibiotics may reduce wound infections. A third of the participants initially treated with antibiotics required subsequent appendectomy or two-thirds avoided surgery within one year, but the evidence is very uncertain. There were too few data from the included studies to comment on major complications., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objectives: Cardiorespiratory fitness (CRF) declines with advancing and has also, independent of age, been shown to be predictive of all-cause mortality, morbidity, and poor clinical outcomes. In relation to the older patient, there is a particular wealth of evidence highlighting the relationship between low CRF and poor surgical outcomes. Cardiopulmonary exercise testing (CPET) is accepted as the gold-standard measure of CRF. However, this form of assessment has significant personnel and equipment demands and is not feasible for those with certain age-associated physical limitations, including joint and cardiovascular comorbidities. As such, alternative ways to assess the CRF of older patients are very much needed., Methods: Sixty-four participants (45% female) with a median age of 74 (65-90) years were recruited to this study via community-based advertisements. All participants completed three tests of physical function: (1) a step-box test; (2) handgrip strength dynamometry; and (3) a CPET on a cycle ergometer; and also had their muscle architecture (vastus lateralis) assessed by B-mode ultrasonography to provide measures of muscle thickness, pennation angle, and fascicle length. Multivariate linear regression was then used to ascertain bedside predictors of CPET parameters from the alternative measures of physical function and demographic (age, gender, body mass index (BMI)) data., Results: There was no significant association between ultrasound-assessed parameters of muscle architecture and measures of CRF. VO 2peak was predicted to some extent from fast step time during the step-box test, gender, and BMI, leading to a model that achieved an R 2 of 0.40 ( p  < 0.001). Further, in aiming to develop a model with minimal assessment demands (i.e., using handgrip dynamometry rather than the step-box test), replacing fast step time with non-dominant HGS led to a model which achieved an R 2 of 0.36 ( p  < 0.001). Non-dominant handgrip strength combined with the step-box test parameter of fast step time and BMI delivered the most predictive model for VO 2peak with an R 2 of 0.45 ( p  < 0.001)., Conclusions: Our findings show that simple-to-ascertain patient characteristics and bedside assessments of physical function are able to predict CPET-derived CRF. Combined with gender and BMI, both handgrip strength and fast step time during a step-box test were predictive for VO 2peak . Future work should apply this model to a clinical population to determine its utility in this setting and to explore if simple bedside tests are predictive of important clinical outcomes in older adults (i.e., post-surgical complications)., Competing Interests: All authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 The Authors. Aging Medicine published by Beijing Hospital and John Wiley & Sons Australia, Ltd.)

Background: Point-of-care ultrasound (POCUS) can aid geriatricians in caring for complex, older patients. Currently, there is limited literature on POCUS use by geriatricians. We conducted a national survey to assess current POCUS use, training desired, and barriers among Geriatrics and Extended Care ("geriatric") clinics at Veterans Affairs Medical Centers (VAMCs)., Methods: We conducted a prospective observational study of all VAMCs between August 2019 and March 2020 using a web-based survey sent to all VAMC Chiefs of Staff and Chiefs of geriatric clinics., Results: All Chiefs of Staff (n=130) completed the survey (100% response rate). Chiefs of geriatric clinics ("chiefs") at 76 VAMCs were surveyed and 52 completed the survey (68% response rate). Geriatric clinics were located throughout the United States, mostly at high-complexity, urban VAMCs. Only 15% of chiefs responded that there was some POCUS usage in their geriatric clinic, but more than 60% of chiefs would support the implementation of POCUS use. The most common POCUS applications used in geriatric clinics were the evaluation of the bladder and urinary obstruction. Barriers to POCUS use included a lack of trained providers (56%), ultrasound equipment (50%), and funding for training (35%). Additionally, chiefs reported time utilization, clinical indications, and low patient census as barriers., Conclusions: POCUS has several potential applications for clinicians caring for geriatric patients. Though only 15% of geriatric clinics at VAMCs currently use POCUS, most geriatric chiefs would support implementing POCUS use as a diagnostic tool. The greatest barriers to POCUS implementation in geriatric clinics were a lack of training and ultrasound equipment. Addressing these barriers systematically can facilitate implementation of POCUS use into practice and permit assessment of the impact of POCUS on geriatric care in the future., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Landmark-based geometric morphometrics (LGM) is most often used in archaeology to characterize and differentiate groups of artifacts, but it can be used for much more. We demonstrate LGM's power to uncover new insights by exploring stone-tool allometry, modularity, and integration using a sample of 100 western North American Clovis points. Here, allometry concerns how stone tools change in shape as their size changes through their use-lives, and modularity and integration concern how the constituent parts of a tool work together. We show that Clovis points are surprisingly complex tools. When their blades and hafts are defined technologically, rather than arbitrarily, they unambiguously exhibit allometry, and their hafts and blades are modular and highly integrated. We use these analyses to further explore questions about Clovis points, including the differences between cache and non-cache points. Finally, we use heuristic haft-size categories to examine functional constraints on the shape and size of hafts and blades. This work illustrates the importance of using accurate measurements of point components rather than estimates or proxies, which can lead to unfounded inferences. These analytical approaches and accompanying R code are easily transferable to other research questions of stone-tool use., Competing Interests: NO authors have competing interests., (Copyright: © 2023 Thulman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Chronic postsurgical pain is common after surgery. Identification of non-opioid analgesics with potential for preventing chronic postsurgical pain is important, although trials are often underpowered. Network meta-analysis offers an opportunity to improve power and to identify the most promising therapy for clinical use and future studies., Methods: We conducted a PRISMA-NMA-compliant systematic review and network meta-analysis of randomised controlled trials of non-opioid analgesics for chronic postsurgical pain. Outcomes included incidence and severity of chronic postsurgical pain, serious adverse events, and chronic opioid use., Results: We included 132 randomised controlled trials with 23 902 participants. In order of efficacy, i.v. lidocaine (odds ratio [OR] 0.32; 95% credible interval [CrI] 0.17-0.58), ketamine (OR 0.64; 95% CrI 0.44-0.92), gabapentinoids (OR 0.67; 95% CrI 0.47-0.92), and possibly dexmedetomidine (OR 0.36; 95% CrI 0.12-1.00) reduced the incidence of chronic postsurgical pain at ≤6 months. There was little available evidence for chronic postsurgical pain at >6 months, combinations agents, chronic opioid use, and serious adverse events. Variable baseline risk was identified as a potential violation to the network meta-analysis transitivity assumption, so results are reported from a fixed value of this, with analgesics more effective at higher baseline risk. The confidence in these findings was low because of problems with risk of bias and imprecision., Conclusions: Lidocaine (most effective), ketamine, and gabapentinoids could be effective in reducing chronic postsurgical pain ≤6 months although confidence is low. Moreover, variable baseline risk might violate transitivity in network meta-analysis of analgesics; this recommends use of our methods in future network meta-analyses., Systematic Review Protocol: PROSPERO CRD42021269642., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Resistance exercise training (RET) can counteract negative features of muscle ageing but older age associates with reduced adaptive capacity to RET. Altered muscle protein networks likely contribute to ageing RET adaptation; therefore, associated proteome-wide responses warrant exploration. We employed quantitative sarcoplasmic proteomics to compare age-related proteome and phosphoproteome responses to RET. Thigh muscle biopsies were collected from eight young (25 ± 1.1 years) and eight older (67.5 ± 2.6 years) adults before and after 20 weeks supervised RET. Muscle sarcoplasmic fractions were pooled for each condition and analysed using Isobaric Tags for Relative and Absolute Quantification (iTRAQ) labelling, tandem mass spectrometry and network-based hub protein identification. Older adults displayed impaired RET-induced adaptations in whole-body lean mass, body fat percentage and thigh lean mass (P > 0.05). iTRAQ identified 73 differentially expressed proteins with age and/or RET. Despite possible proteomic stochasticity, RET improved ageing profiles for mitochondrial function and glucose metabolism (top hub; PYK (pyruvate kinase)) but failed to correct altered ageing expression of cytoskeletal proteins (top hub; YWHAZ (14-3-3 protein zeta/delta)). These ageing RET proteomic profiles were generally unchanged or oppositely regulated post-RET in younger muscle. Similarly, RET corrected expression of 10 phosphoproteins altered in ageing, but these responses were again different vs. younger adults. Older muscle is characterised by RET-induced metabolic protein profiles that, whilst not present in younger muscle, improve untrained age-related proteomic deficits. Combined with impaired cytoskeletal adhesion responses, these results provide a proteomic framework for understanding and optimising ageing muscle RET adaptation., (© 2022. The Author(s).)

The study was attempted to investigate the effect on and mechanisms of action of dexmedetomidine with regard to learning and memory impairment in rats with chronic rapid eye movement (REM) sleep deprivation. A total of 50 male Sprague Dawley rats were randomly divided into five groups. Modified multiple platform method was conducted to cause the sleep deprivation of rats. Dexmedetomidine and midazolam were administered by intraperitoneal injection. Learning and memory ability was assessed through Morris water maze. Morphological changes of rat hippocampal neurons and synaptic were detected by transmission electron microscope and Golgi staining. The gene expression in hippocampus of each group was detected by RNA-seq and verified by RT-PCR and western blot. REM Sleep-deprived rats exhibited spatial learning and memory deficits. Furthermore, there was decreased density of synaptic spinous in the hippocampal CA1 region of the sleep deprivation group compared with the control. Additionally, transmission electron microscopy showed that the synaptic gaps of hippocampal neurons in REM sleep deprivation group were loose and fuzzy. Interestingly, dexmedetomidine treatment normalized these events to control levels following REM sleep deprivation. Molecular biological methods showed that Alox15 expression increased significantly after REM sleep deprivation as compared to control, while dexmedetomidine administration reversed the expression of Alox15. Dexmedetomidine alleviated the spatial learning and memory dysfunction induced with chronic REM sleep deprivation in rats. This protective effect may be related to the down-regulation of Alox15 expression and thereby the enhancement of synaptic structural plasticity in the hippocampal CA1 area of rats., Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-023-00450-8., Competing Interests: Conflict of interestThe authors declare no conflicts of interest., (© The Author(s), under exclusive licence to Japanese Society of Sleep Research 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Whole-body exposure to high-energy particle radiation remains an unmitigated hazard to human health in space. Ongoing experiments at the NASA Space Radiation Laboratory and elsewhere repeatedly show persistent changes in brain function long after exposure to simulations of this unique radiation environment, although, as is also the case with proton radiotherapy sequelae, how this occurs and especially how it interacts with common comorbidities is not well-understood. Here, we report modest differential changes in behavior and brain pathology between male and female Alzheimer's-like and wildtype littermate mice 7-8 months after exposure to 0, 0.5, or 2 Gy of 1 GeV proton radiation. The mice were examined with a battery of behavior tests and assayed for amyloid beta pathology, synaptic markers, microbleeds, microglial reactivity, and plasma cytokines. In general, the Alzheimer's model mice were more prone than their wildtype littermates to radiation-induced behavior changes, and hippocampal staining for amyloid beta pathology and microglial activation in these mice revealed a dose-dependent reduction in males but not in females. In summary, radiation-induced, long-term changes in behavior and pathology, although modest, appear specific to both sex and the underlying disease state.

Postherpetic neuralgia (PHN) is a devastating disease with extraordinarily poor treatment outcomes. Both pulsed radiofrequency (PRF) and ozone have good effects on the treatment of the disease. However, whether PRF and ozone have a synergistic effect on PHN remains unclear. Therefore, this study aimed to assess the therapeutic effects of ozone alone and in combination with PRF in the treatment of PHN. Ninety-one patients with PHN were assigned into two groups: PRF combined with ozone (PRF + ozone group, n = 44) and ozone therapy alone (ozone group, n = 47). In PRF + ozone group, the high-voltage, long-duration PRF was applied to the target dorsal root ganglions. Then ozonated water (11.5 µg/mL) was injected through the inner cannula. In the ozone group, all other processes were the same as those in the PRF + ozone group apart from the electrical stimulation. The therapeutic efficacy was evaluated by visual analog scale and tactile sensation at pre-treatment and post-treatment 3, 6, and 12 months. Compared with pre-treatment data, the visual analog scale score was significantly decreased in both groups after treatment. Compared with the ozone group, the visual analog scale score was significantly decreased in the PRF + ozone group at 3, 6, and 12 months. Similarly, the tactile sensation was also significantly decreased at post-treatment when compared to pre-treatment. However, there were no statistical differences between the two groups. Regression analysis results showed that the history of diabetes mellitus and age had significant negative and positive effects, respectively, on the treatment results. To conclude, the administration of PRF + ozone and ozone therapy alone could both improve pain symptoms. Moreover, treatment effects and total efficacy rates tended to be higher for the combination of PRF and ozone than ozone alone. This conclusion was especially true for long-term therapeutic effects., Competing Interests: None

In recent decades, the principal goals of participants in the field of radiation biologists have included defining dose thresholds for cancer and non-cancer endpoints to be used by regulators, clinicians and industry, as well as informing on best practice radiation utilization and protection applications. Importantly, much of this work has required an intimate relationship between "bench" radiation biology scientists and their target audiences (such as physicists, medical practitioners and epidemiologists) in order to ensure that the requisite gaps in knowledge are adequately addressed. However, despite the growing risk for public exposure to higher-than-background levels of radiation, e.g. from long-distance travel, the increasing use of ionizing radiation during medical procedures, the threat from geopolitical instability, and so forth, there has been a dramatic decline in the number of qualified radiation biologists in the U.S. Contributing factors are thought to include the loss of applicable training programs, loss of jobs, and declining opportunities for advancement. This report was undertaken in order to begin addressing this situation since inaction may threaten the viability of radiation biology as a scientific discipline., (© 2023 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Vitamin D (VD) deficiency is a highly prevalent worldwide phenomenon and is extensively discussed as a risk factor for the development of systemic lupus erythematosus (SLE) and other immune-mediated diseases. In addition, it is now appreciated that VD possesses multiple immunomodulatory effects. This study aims to explore the impact of dietary VD intake on lupus manifestation and pathology in lupus-prone NZB/W F1 mice and identify the underlying immunological mechanisms modulated by VD. Here, we show that low VD intake accelerates lupus progression, reflected in reduced overall survival and an earlier onset of proteinuria, as well higher concentrations of anti-double-stranded DNA autoantibodies. This unfavorable effect gained statistical significance with additional low maternal VD intake during the prenatal period. Among examined immunological effects, we found that low VD intake consistently hampered the adoption of a regulatory phenotype in lymphocytes, significantly reducing both IL-10-expressing and regulatory CD4 + T cells. This goes along with a mildly decreased frequency of IL-10-expressing B cells. We did not observe consistent effects on the phenotype and function of innate immune cells, including cytokine production, costimulatory molecule expression, and phagocytic capacity. Hence, our study reveals that low VD intake promotes lupus pathology, likely via the deviation of adaptive immunity, and suggests that the correction of VD deficiency might not only exert beneficial functions by preventing osteoporosis but also serve as an important module in prophylaxis and as an add-on in the treatment of lupus and possibly other immune-mediated diseases. Further research is required to determine the most appropriate dosage, as too-high VD serum levels may also induce adverse effects, possibly also on lupus pathology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kraemer, Schäfer, Sprenger, Sehnert, Williams, Luo, Riechert, Al-Kayyal, Dumortier, Fauny, Winter, Heim, Hofmann, Herrmann, Heine, Voll and Chevalier.)

Objectives: Sleep deprivation is a common health problem in modern society and is negatively associated with deleterious effects on cognitive functions such as learning and memory ability. This study was undertaken to provide a detailed account of the effect of chronic ozone intraperitoneal injection on the deleterious effects of sleep deprivation on brain function in rats., Materials and Methods: Sleep deprivation was induced using the modified multiple platform model. The rats received REM sleep deprivation with an intraperitoneal injection of ozone or midazolam for 28 days. The effects of ozone on REM sleep deprivation-induced hippocampus-dependent learning and memory deficits were studied by the following approaches: Morris water maze (MWM) tests were used to evaluate spatial learning and memory of rats. Morphological changes in the brain were evaluated using hematoxylin and eosin (HE) staining. RNA-sequence was performed to seek a common mechanism. The expression of the targeted gene was examined by qPCR and Western blotting., Results: Ozone intraperitoneal injection reversed spatial learning and memory deficits associated with REM sleep deprivation, ameliorating pathological brain damage and down-regulating the hippocampal expression of Sema3A in rats after REM sleep deprivation., Conclusion: Ozone intraperitoneal injection alleviated sleep deprivation-induced spatial learning and memory deficits by protecting hippocampal neurons via down-regulation of the expression of Sema3A in the hippocampus., Competing Interests: The authors declare that they have no competing interests.

Background: Thalamic pain (TP), also known as central post-stroke pain, is a chronic neuropathic pain syndrome that follows a stroke and is a severe pain that is usually intractable. No universally applicable and effective therapies have been proposed. Emerging studies have reported that electroacupuncture (EA) can potentially be used as an effective therapy for the treatment of neuropathic pain. However, whether EA influences TP and if so, by what potential mechanism, remains poorly understood., Objective: The aim of this study was to detect the efficacy of EA and explore possible mechanisms for treating TP., Study Design: Controlled animal study., Setting: The laboratory at the Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine., Methods: Male Sprague Dawley rats were randomly divided into 3 groups (n = 15 / group): sham-operated (SH) group, thalamic pain model (TP) group, EA treatment (EA) group. After the TP rat model was successfully established, EA was used for intervention. During the experiment, the mechanical pain thresholds of rats were detected among the groups. The right thalamus of the rats was extracted on postoperative day 28 for RNA-sequencing (RNA-Seq) analysis to find the changes in gene expression in different groups of rats. The key genes were screened using reverse transcription-polymerase chain reaction (RT-PCR) detection and subsequently identified with western blotting and immunofluorescence., Results: The mechanical withdrawal threshold (MWT) value of the right facial skin in the TP group and the EA group decreased significantly on the 3rd day after surgery, compared to the SH group (P < 0.01). From 7 to 28 days, the MWT value increased continually in the EA group; however, there was no significant change in the TP group. The results of RNA-seq showed that compared to the TP group, 377 genes changed in the EA group. Moreover, ADCY1 expression increased significantly in the TP group as compared to the SH group, while EA treatment reversed the expression of ADCY1., Limitations: In addition to ADCY1, the mechanism(s) of other signaling pathways in TP need to be explored in future research., Conclusions: EA treatment may promote the recovery of TP model rat by regulating ADCY1 expression.