Influence of altered torsional stiffness through sole modification of air pressure shoes on lower extremity biomechanical behaviour during side-step cutting maneuvers.

Directional changes in cutting maneuvers are critical in sports, where shoe torsional stiffness (STS) is an important factor. Shoes are designed based on different constructions and movement patterns. Hence, it is unclear how adjustable spacers into the sole constructions of air pressure chambers (APC) affect the STS in side-step cutting. Therefore, this study investigated the effects of altered STS through adjustable sole spacers on ground reaction force (GRF) and ankle and knee joint moments in side-step cutting. Seventeen healthy recreational athletes performed side-step cutting with experimental conditions including (i) barefoot (BF), (ii) unaltered shoes (UAS): soles consisting of APC, and (iii) altered shoes (AS): modified UAS by inserting elastomeric spacers into cavities formed by APC. Mechanical and biomechanical variables were measured. Significant differences were revealed across shoe conditions for impact peak (p = 0.009) and impulse (p = 0.018) in vertical GRF, time to achieve peak braking (p = 0.004), and peak propulsion (p = 0.025) for anterior-posterior GRF in ANOVA test. No significant differences were observed in GRF peaks and impulses between UAS and AS except for a trend of differences in impact peak (p = 0.087) for vertical GRF. At the ankle and knee joint, peak ankle power absorption (p = 0.019), peak knee internal rotation moment (p = 0.042), peak knee extension moment (p = 0.001), peak knee flexion moment (0.000), peak knee power absorption (p = 0.047) showed significant difference across three shoe conditions. However, no significant differences between the UAS and AS were noticed for peak joint moments and power. Altered shoe torsional stiffness did not significantly affect the peak forces and peak ankle and knee joint moments or powers; hence sole adjustment did not influence the cutting performance. This study might be insightful in sports footwear design, and adjusting shoe torsional stiffness by sole modification might be advantageous for athletes playing sports with cutting maneuvers to reduce the risk of injuries by controlling the twisting force at the ankle that frequently happens during cutting maneuvers.

Outcomes and clinicopathologic characteristics associated with disseminated tumor cells in bone marrow after neoadjuvant chemotherapy in high-risk early stage breast cancer: the I-SPY SURMOUNT study.

PURPOSE: Disseminated tumor cells (DTCs) expressing epithelial markers in the bone marrow are associated with recurrence and death, but little is known about risk factors predicting their occurrence. We detected EPCAM+/CD45- cells in bone marrow from early stage breast cancer patients after neoadjuvant chemotherapy (NAC) in the I-SPY 2 Trial and examined clinicopathologic factors and outcomes. METHODS: Patients who signed consent for SURMOUNT, a sub-study of the I-SPY 2 Trial (NCT01042379), had bone marrow collected after NAC at the time of surgery. EPCAM+CD45- cells in 4 mLs of bone marrow aspirate were enumerated using immunomagnetic enrichment/flow cytometry (IE/FC). Patients with > 4.16 EPCAM+CD45- cells per mL of bone marrow were classified as DTC-positive. Tumor response was assessed using the residual cancer burden (RCB), a standardized approach to quantitate the extent of residual invasive cancer present in the breast and the axillary lymph nodes after NAC. Association of DTC-positivity with clinicopathologic variables and survival was examined. RESULTS: A total of 73 patients were enrolled, 51 of whom had successful EPCAM+CD45- cell enumeration. Twenty-four of 51 (47.1%) were DTC-positive. The DTC-positivity rate was similar across receptor subtypes, but DTC-positive patients were significantly younger (p = 0.0239) and had larger pretreatment tumors compared to DTC-negative patients (p = 0.0319). Twenty of 51 (39.2%) achieved a pathologic complete response (pCR). While DTC-positivity was not associated with achieving pCR, it was significantly associated with higher RCB class (RCB-II/III, 62.5% vs. RCB-0/I; 33.3%; Chi-squared p = 0.0373). No significant correlation was observed between DTC-positivity and distant recurrence-free survival (p = 0.38, median follow-up = 3.2 years). CONCLUSION: DTC-positivity at surgery after NAC was higher in younger patients, those with larger tumors, and those with residual disease at surgery.

Behavior of medial gastrocnemius muscle beneath kinesio taping during isometric contraction and badminton lunge performance after fatigue induction.

Kinesio taping (KT) is widely used in sports for performance improvement and injury prevention. However, little is known of the behavior of the muscle region beneath the KT with movement, particularly when the muscle is fatigued. Accordingly, this study investigated the changes in the medial gastrocnemius muscle architecture and fascia thickness when using KT during maximum isometric plantar flexion (MVIC) and badminton lunges following heel rise exercises performed to exhaustion. Eleven healthy collegiate badminton players (4 males and 7 females) were recruited. All of the participants performed two tasks (MVIC and badminton lunge) with a randomized sequence of no taping, KT and sham taping and repeated following exhaustive repetitive heel rise exercise. In the MVIC task, the fascia thickness with the medial gastrocnemius muscle at rest significantly decreased following fatigue induction both without taping and with KT and sham taping (p = 0.036, p = 0.028 and p = 0.025, respectively). In the lunge task, the fascia thickness reduced after fatigue induction in the no taping and sham taping trials; however, no significant change in the fascia thickness occurred in the KT trials. Overall, the results indicate that KT provides a better effect during dynamic movement than in isometric contraction.

Force Control Strategy of Five-Digit Precision Grasping With Aligned and Unaligned Configurations.

OBJECTIVE: To investigate the digit force control during a five-digit precision grasp in aligned (AG) and unaligned grasping (UG) configurations. BACKGROUND: The effects of various cylindrical handles for tools on power grasp performance have been previously investigated. However, there is little information on force control strategy of precision grasp to fit various grasping configurations. METHOD: Twenty healthy young adults were recruited to perform a lift-hold-lower task. The AG and UG configurations on a cylindrical simulator with force transducers were adjusted for each individual. The applied force and moment, the force variability during holding, and force correlations between thumb and each finger were measured. RESULT: No differences in applied force, force correlation, repeatability, and variability were found between configurations. However, the moments applied in UG were significantly larger than those in AG. CONCLUSION: The force control during precision grasp did not change significantly across AG and UG except for the digit moment. The simulator is controlled efficiently with large moment during UG, which is thus the optimal configuration for precision grasping with a cylindrical handle. Further research should consider the effects of task type and handle design on force control, especially for individuals with hand disorders. APPLICATION: To design the handle of specific tool, one should consider the appropriate configuration according to the task requirements of precision grasping to reduce the risk of accumulating extra loads on digits with a cylindrical handle.

CCL2: a Chemokine Potentially Promoting Early Seeding of the Latent HIV Reservoir.

HIV infects long-lived CD4 memory T cells, establishing a latent viral reservoir that necessitates lifelong antiretroviral therapy (ART). How this reservoir is formed so quickly after infection remains unclear. We now show the innate inflammatory response to HIV infection results in CCL2 chemokine release, leading to recruitment of cells expressing the CCR2 receptor, including a subset of central memory CD4 T cells. Supporting a role for the CCL2/CCR2 axis in rapid reservoir formation, we find (i) treatment of humanized mice with anti-CCL2 antibodies during early HIV infection decreases reservoir seeding and preserves CCR2/5+ cells and (ii) CCR2/5+ cells from the blood of HIV-infected individuals on long-term ART contain significantly more integrated provirus than CCR2/5-negative memory or naive cells. Together, these studies support a model where the host's innate inflammatory response to HIV infection, including CCL2 production, leads to the recruitment of CCR2/5+ central memory CD4 T cells to zones of virus-associated inflammation, likely contributing to rapid formation of the latent HIV reservoir. IMPORTANCE There are currently over 35 million people living with HIV worldwide, and we still have no vaccine or scalable cure. One of the difficulties with HIV is its ability to rapidly establish a viral reservoir in lymphoid tissues that allows it to elude antivirals and the immune system. Thus, it is important to understand how HIV accomplishes this so we can develop preventive strategies. Our current results show that an early inflammatory response to HIV infection includes production of the chemokine CCL2, which recruits a unique subset of CCR2/5+ CD4+ T cells that become infected and form a significant reservoir for latent infection. Furthermore, we show that blockade of CCL2 in humanized mice significantly reduces persistent HIV infection. This information is relevant to the development of therapeutics to prevent and/or treat chronic HIV infections.

Pregabalin Toxicity-Induced Posterior Reversible Encephalopathy Syndrome.

Pregabalin, a prescription medication typically used for neuropathic pain, has increasingly been overused and abused. We present a unique case of a 51-year-old woman with a history of polysubstance use disorder and on methadone therapy who presented to the emergency department with altered mental status after consuming an unknown supratherapeutic amount of pregabalin. She was stabilized and discharged. Within 24 hours, she ingested another 1000mg of pregabalin, presenting again with altered mental status, along with tachycardia and hypertension. Computed tomography (CT) without contrast and fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR MRI) revealed subcortical white matter edema in the bilateral frontal and occipital lobes as well as the left parietal lobe, suggestive of posterior reversible encephalopathy syndrome (PRES). The patient recovered after four days of supportive treatment with an antihypertensive and an antiepileptic. PRES is a neurological phenomenon in which vasogenic edema, most commonly accumulating in the posterior parieto-occipital white matter, causes headaches, altered mental status, and seizures. To our knowledge, there has not been an established link between pregabalin toxicity and PRES, and the awareness of this potential complication can help in the early diagnosis and management of the disease to prevent further progression.

A substructure-based screening approach to uncover N-nitrosamines in drug substances.

Drug substances are at risk of contamination with N-nitrosamines (NAs), well-known carcinogenic agents, during synthesis processes and/or long-term storage. Therefore, in this study, we developed an efficient data-based screening approach to systemically assess marketed products and investigated its scalability for benefiting both regulatory agencies and pharmaceutical industries. A substructure-based screening method employing DataWarrior, an open-source software, was established to evaluate the risks of NA impurities in drug substances. Eight NA substructures containing susceptible amino sources for N-nitrosation have been identified as screening targets: dimethylamine (DMA), diethylamine, isopropylethylamine, diisopropylamine, N-methyl-2-pyrrolidone, dibutylamine, methylphenylamine, and tetrazoles. Our method detected 192 drug substances with a theoretical possibility of NA impurity, 141 of which had not been reported previously. In addition, the DMA moiety was significantly dominant among the eight NA substructures. The results were validated using data from the literature, and a high detection sensitivity of 0.944 was demonstrated. Furthermore, our approach has the advantage of scalability, owing to which 31 additional drugs with suspected NA-contaminated substructures were identified using the substructures of 1-methyl-4-piperazine in rifampin and 1-cyclopentyl-4-piperazine in rifapentine. In conclusion, the reported substructure-based approach provides an effective and scalable method for the screening and investigation of NA impurities in various pharmaceuticals and might be used as an ancillary technique in the field of pharmaceutical quality control for risk assessments of potential NA impurities.

Are Risk Factors for Postoperative Significant Hemorrhage following Total Knee Arthroplasty Potentially Modifiable? A Retrospective Cohort Study.

Total knee arthroplasty (TKA) is the treatment of choice for end-stage osteoarthritis (OA) of the knee, because it alleviates pain and restores function of the knee. However, TKA-associated hemorrhage and subsequent anemia remain a concern. Most previous studies have defined meaningful postoperative bleeding as blood loss > 500 mL or hemoglobin (Hb) drop > 20 g/L. Therefore, we defined significant hemorrhage as a postoperative Hb drop more than 20 g/L in this study, and we investigated possible risk factors related to significant hemorrhage in TKA and whether these risk factors are modifiable. This retrospective study was conducted through a comprehensive review of the perioperative records of patients with OA of the knee who underwent TKA between January 2009 and December 2015 at our hospital. Patients were allocated into two groups: patients in Group A had their Hb drop ≤ 20 g/L; patients in Group B had their Hb drop > 20 g/L. Factors analyzed included sex, age, body mass index (BMI), the American Society of Anesthesiologists (ASA) classification, comorbidities, preoperative platelet count, use of tranexamic acid (TXA), operation time, and type of anesthesia. A total of 3350 patients met the criteria for analysis, with 1782 patients allocated to Group A and 1568 patients to Group B. Five independent risk factors for significant hemorrhage were identified: male sex (odds ratio(OR), 1.29; 95% confidence interval(CI), 1.08−1.53; p = 0.005), age (OR, 1.02; 95% CI, 1.01−1.03; p = 0.001), use of TXA (OR, 0.39; 95% CI, 0.34−0.45; p < 0.001), spinal anesthesia versus general anesthesia (OR, 0.71; 95% CI, 0.56−0.90; p = 0.004), and preoperative platelet count (OR, 0.96; 95% CI, 0.93−0.98; p = 0.001). Of these identified risk factors, preoperative platelet count, use of TXA, and spinal anesthesia are modifiable. These potentially modifiable risk factors need to be taken into consideration when making both the perioperative care and anesthesia plan by surgeons and anesthesiologists, especially in patients at risk of significant hemorrhage.

Externally applied force helps reduce bowstring effect of flexors in patients with carpal tunnel release surgery.

BACKGROUND: Patients with severe carpal tunnel syndrome (CTS) undergo carpal tunnel release (CTR) surgery to alleviate pressure in the carpal tunnel. However, the subsequent lack of the transverse carpal ligament (TCL) causes the bowstring phenomenon of the flexor tendons and increases the potential incidence of trigger finger. OBJECTIVE: This study aimed to investigate the effects of various compressive forces on the flexor tendon and identify the appropriate force needed to mitigate the bowstring effect of those flexors. DESIGN: Cross-sectional repeated measures comparison. METHOD: Thirteen CTS patients who underwent CTR surgery were asked to flex the middle finger while applying different external compressive forces, just contact, 4N, and 8N force, over the carpal tunnel. Images of the flexor tendon within the carpal tunnel and at the metacarpal phalangeal (MCP) joint were recorded via ultrasound. RESULT: Results show that the compression force limited the volar migration of the flexor tendon under maximal voluntary contraction (MVC) conditions. Entrance angles between the flexor tendon and metacarpal bone also decreased as the external compressive force increased. CONCLUSIONS: Findings of this study may indicate that applying compression force on the carpal tunnel is useful for CTS patients and can inhibit the volar shift of the flexor digitorum superficialis (FDS) tendon after surgery, which may further prevent trigger finger.

A Novel and Clinically Feasible Instrument for Quantifying Upper Limb Muscle Tone and Motor Function via Indirect Measure Methods.

OBJECTIVE: Quantifying muscle tone is often based on a tester's subjective judgment in clinical settings. There is, however, a lack of suitable tools that can be used to objectively assess muscle tone. This study thus introduces a reliable, clinically-feasible device, called the Arm Circumference Motor Evaluation System (ACMES), for quantifying the muscle tone of upper limbs without using mechanical torque transducers. METHODS: While the ACMES conducts continuously passive arm circumduction motions, the voltage and current of the driving motor is transduced into torque values via a least square approximation. A torque sensor and springs with different spring constants were used for the validity and reliability test in the first part of this study. Fifteen healthy adults and two patients who had experienced a stroke participated in the second part, which was a clinical experiment used to examine the in-vivo test-retest reliability and to explore the inspection differences between healthy and patient participants. RESULTS: The results showed that the ACMES has high validity (R2: ~0.99) and reliability (R2: 0.96~0.99). The reliability of the ACMES used on human subjects was acceptable (R2: 0.83~0.85). The various muscle tone patterns could be found among healthy and stroke subjects via the ACMES. CONCLUSION: Clinically, abnormal muscle tone, which seriously affects motion performance, will be found in many diagnoses, such as stroke or cerebral palsy. However, objectively and feasibly measuring abnormal tone in modern clinical settings is still a challenging task. Thus, the ACMES was developed and tested to verify its feasibility as a measurement system for detecting the mechanical torque associated with muscle tone.

Comparison of Back-Propagation Neural Network, LACE Index and HOSPITAL Score in Predicting All-Cause Risk of 30-Day Readmission.

BACKGROUND: The main purpose of this study is to predict the all-cause risk of 30-day readmission by employing the back-propagation neural network (BPNN) in comparison with traditional risk assessment tools of LACE index and HOSPITAL scores. METHODS: This was a retrospective cohort study from January 1st, 2018 to December 31st, 2019. A total of 55,688 hospitalizations from a medical center in Taiwan were examined. The LACE index (length of stay, acute admission, Charlson comorbidity index score, emergency department visits in previous 6 months) and HOSPITAL score (hemoglobin level at discharge, discharge from an Oncology service, sodium level at discharge, procedure during hospital stay, Index admission type, number of hospital admissions during the previous year, length of stay) are calculated. We employed variables from LACE index and HOSPITAL score as the input vector of BPNN for comparison purposes. RESULTS: The BPNN constructed in the current study has a considerably better ability with a C statistics achieved 0.74 (95% CI 0.73 to 0.75), which is statistically significant larger than that of the other two models using DeLong's test. Also, it was possible to achieve higher sensitivity (70.32%) without penalizing the specificity (71.76%) and accuracy (71.68%) at its optimal threshold, which is at the 20% of patients with the highest predicted risk. Moreover, it is much more informative than the other two methods because of a considerably higher LR+ and a lower LR-. CONCLUSION: Our findings suggest that more attention should be paid to methods based on non-linear classification systems, as they lead to substantial differences in risk-scores.

Is There an Optimal Timing of Adductor Canal Block for Total Knee Arthroplasty?-A Retrospective Cohort Study.

Adductor canal block (ACB) has gained popularity for postoperative pain control after total knee arthroplasty (TKA). However, its role in TKA has been questioned recently. Our study aimed to clarify the role of ACB in reducing postoperative pain after TKA and to elucidate an optimal timing to perform ACB for better outcomes. We conducted a comprehensive review of the perioperative records of 652 patients undergoing primary TKA from January 2019 to December 2019. Patients were divided into three groups: Group A received general anesthesia without ACB, Group B received ACB before inducing general anesthesia, and Group C received ACB at the post-anesthesia recovery unit (PACU). Patients in Groups B and C had lower pain visual analogue scale (VAS) scores than patients in Group A at the PACU. Opioid consumption was similar among the three groups; however, a slightly higher dose was required by Group A patients. Higher VAS scores were recorded in the ward in Group A than in Groups B and C with the leg at rest. In addition, higher VAS scores were recorded in Group A than in Groups B and C with the leg in continuous passive motion (CPM) training. More patients in Group A (34.9%) quit their first CPM training after a few cycles than those in Groups B (27.0%) and C (20.1%). Group A patients required a higher per kg dose of opioids in the ward than Groups B and C patients. Additionally, the hourly consumption of sevoflurane was similar among the three groups of patients, while Group A and C patients required a higher hourly per kg dose of intraoperative opioids than Group B patients. More patients in Group A (67.6%) and C (61.7%) developed intraoperative hypertension than patients in Group B (52.7%). There was no significant difference in PON (postoperative nausea), POV (postoperative vomiting), postoperative dizziness, or patient satisfaction among the three groups of patients. Group A patients had a longer length of hospital stay compared to Group B and C patients. In conclusion, preoperative ACB could be a better choice for patients undergoing TKA as it decreases intraoperative opioid consumption and facilitates a stable hemodynamic state during surgery.

Sevoflurane versus desflurane for early postoperative vomiting after general anesthesia in hospitalized adults: A systematic review and meta-analysis of randomized controlled trials.

STUDY OBJECTIVE: This systematic review and meta-analysis aimed at assessing the effects of two commonly used anesthetics in general anesthesia (GA), sevoflurane and desflurane, on early postoperative vomiting (POV) in hospitalized adults. DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). SETTING: Early postoperative vomiting after GA. PATIENTS: A total of 266 adult patients receiving inpatient surgeries under GA maintained with sevoflurane or desflurane. INTERVENTIONS: We searched PubMed, Medline, Cochrane Central Register of Controlled Trials, ScienceDirect, and Embase for eligible RCTs comparing postoperative outcomes following sevoflurane- or desflurane-maintained anesthesia. MEASUREMENTS: The primary outcome was early POV. Secondary outcomes included late POV, early and late postoperative nausea (PON), time to extubation, and emergence time. MAIN RESULTS: Eight trials were included. There was no significant difference in the risk of early POV (risk ratio [RR] 1.03, 95% confidence interval [CI] 0.64-1.64, p = 0.91). No significant difference in early PON was observed (RR 1.09; 95% CI, 0.77-1.56; p = 0.62). Nevertheless, the incidence of late POV and late PON were significantly lower in the sevoflurane group than that in the desflurane group (RR 0.47, 95% CI 0.23-0.94, p = 0.03; RR 0.45, 95% CI 0.24-0.84, p = 0.01, respectively). The extubation time was longer in the sevoflurane group than in the desflurane group (standardized mean difference [SMD] 0.56, 95% CI 0.14-0.97, p = 0.009). The emergence time of patients in the sevoflurane group was longer than that in those receiving desflurane (SMD 0.76, 95% CI 0.1-1.42, p = 0.02). CONCLUSIONS: Desflurane had the same effects on early POV and early PON as sevoflurane. However, the association between late POV and late PON with desflurane was stronger than that with sevoflurane if the effects of opioids were not considered. The desflurane group had shorter time to extubation and emergence time than the sevoflurane group. PROSPERO registration number: CRD42020218988.

Risk Factors of Postoperative Vomiting in the Eye of "Real-World Evidence"-Modifiable and Clinical Setting-Dependent Risk Factors in Surgical Trauma Patients.

Numerous studies on postoperative nausea and vomiting (PONV) have been carried out since the early days of contemporary surgery. The incidence of PONV has been greatly reduced in recent years and new drugs for PONV keep evolving in the market; however, a substantial number of patients are still under the threat of PONV. Female gender, non-smokers, a history of PONV/motion sickness, and postoperative opioid use are four well-recognized risk factors of PONV. Many potential risk factors reported in previous studies were not consistently presented as predictors for PONV. Two questions then arise; are risk factors clinical setting dependent and are risk factors modifiable? We attempted to answer the questions through a comprehensive review of perioperative records of surgical patients from the Trauma Department of our hospital. As nausea is subjective and no standard is applicable for its measurement, postoperative vomiting (POV) was used as an endpoint in this study. To the best of our knowledge, this is the first study to address the POV issue in surgical trauma patients. A total of 855 patients were enrolled in this study after excluding age below 20 years old, total intravenous anesthesia, desflurane anesthesia, or records with missing data. Our results showed that female gender (OR 4.89) is the strongest predicting factor, followed by a less potent predicting factor-more intraoperative opioid consumption (OR 1.07)-which favor more POV. More intraoperative crystalloid supply (OR 0.71) and a higher body weight (OR 0.9) favor less POV. Other potential risk factors did not reach statistical significance in this study as independent risk factors. Our results also showed that when the intraoperative crystalloid infusion rate is greater than 4 mL/kg/h (OR 0.20), it favors a lower rate of POV; when intraoperative opioid consumption is greater than 12 mg morphine equivalents, MME (OR 1.87), it favors a higher rate of POV. We concluded that dominance of any independent risk factor over other risk factors depends on how individual factors interact with the clinical setting. Some risk factors could be modified, and a cut-off value could be derived to facilitate a better plan for POV prevention.

Efficacy and airway complications of Parker Flex-Tip tubes and standard endotracheal tubes during airway manipulation: A meta-analysis and trial sequential analysis.

BACKGROUND: Despite reported superior intubation outcomes associated with Parker Flex-Tip (PFT) tubes compared with those associated with standard polyvinylchloride tubes, the efficacy and safety of PFT tubes remain uncertain. OBJECTIVES: To compare the intubation outcomes between PFT and conventional standard polyvinylchloride tubes. DESIGN: Meta-analysis of randomised controlled trials. DATA SOURCES: Embase, Medline, Google Scholar, PubMed and the Cochrane controlled trials register from inception until 3 January 2021. ELIGIBILITY CRITERIA: All randomised trials comparing intubation outcomes between PFT (PFT group) and standard polyvinylchloride (standard polyvinylchloride group) tubes. RESULTS: Analysis of the 13 eligible trials showed no significant difference in successful first-attempt intubation rate [risk ratio (RR) 1.20, 95% confidence interval (CI) 0.99 to 1.44] (6 trials, 568 participants), trauma risk (RR 0.83, 95% CI 0.67 to 1.03) (5 trials, 501 participants) as well as the overall risks of epistaxis (RR 0.58, 95% CI 0.26 to 1.31) (3 trials, 262 participants), sore throat (RR 0.90, 95% CI 0.70 to 1.17) (4 trials, 451 participants) and hoarseness (RR 0.71, 95% CI 0.44 to 1.14) (4 trials, 451 participants) between the two groups. However, the intubation time was slightly shorter (weighted mean difference -4.2 s, 95% CI -7.4 to -1.0 s) (8 trials, 759 participants) and the risks of severe epistaxis (RR 0.15, 95% CI 0.03 to 0.84) (3 trials, 262 participants) and overall difficulty in airway manipulation (RR 0.48, 95% CI 0.29 to 0.80) (8 trials, 647 participants) were lower in the PFT group than those in the standard polyvinylchloride group. Trial sequential analysis conclusively confirmed a shorter intubation time with PFT tubes than with standard polyvinylchloride tubes, whereas other intubation outcomes were inconclusive. CONCLUSION: The use of PFT tubes for airway manipulation was associated with a shorter intubation time compared with the standard polyvinylchloride tubes. The results of trial sequential analysis suggest the need for further trials and meta-analysis to compare other intubation outcomes associated with the two devices. TRIAL REGISTRATION: PROSPERO CRD42020197670.

Earlier Is Better? Timing of Adductor Canal Block for Arthroscopic Knee Surgery under General Anesthesia: A Retrospective Cohort Study.

The adductor canal block (ACB) is effective for treating postoperative pain during arthroscopic knee surgery, but its impact on anesthesia course and the optimal administration timing are unknown. This retrospective study addressed these questions. The aim of this study was to compare the effects of preoperative ACB and postoperative ACB on anesthesia course and postoperative recovery. We allocated 215 adult patients who underwent arthroscopic knee surgery under sevoflurane anesthesia between January 2019 and December 2019 to three groups. Group A received general anesthesia without ACB, Group B received ACB before general anesthesia induction, and Group C received ACB in the post-anesthesia recovery unit (PACU). Group B consumed significantly less sevoflurane (0.19 mL/kg/h) and milligram morphine equivalents (0.08 MME) intraoperatively than Groups A (0.22 mL/kg/h; 0.10 MME, respectively) and C (0.22 mL/kg/h; 0.09 MME, respectively). Groups B and C had lower visual analogue scale (VAS) scores upon PACU discharge than Group A. Dynamic, but not at-rest VAS scores, were significantly higher in Group A. Opioid consumption was similar in the ward, but Group A requested more intravenous parecoxib for pain relief. Length of hospital stay was similar. Thus, preoperative ACB reduced the amount of volatile anesthetic required and maintained stable hemodynamics intraoperatively. Preoperative or postoperative ACB improved postoperative pain control. Consequently, preoperative ACB is optimal for intraoperative stress suppression and postoperative pain control.

Evaluating a New Class of AKT/mTOR Activators for HIV Latency Reversing Activity Ex Vivo and In Vivo.

An ability to activate latent HIV-1 expression could benefit many HIV cure strategies, but the first generation of latency reversing agents (LRAs) has proven disappointing. We evaluated AKT/mTOR activators as a potential new class of LRAs. Two glycogen synthase kinase-3 inhibitors (GSK-3i's), SB-216763 and tideglusib (the latter already in phase II clinical trials) that activate AKT/mTOR signaling were tested. These GSK-3i's reactivated latent HIV-1 present in blood samples from aviremic individuals on antiretroviral therapy (ART) in the absence of T cell activation, release of inflammatory cytokines, cell toxicity, or impaired effector function of cytotoxic T lymphocytes or NK cells. However, when administered in vivo to SIV-infected rhesus macaques on suppressive ART, tideglusib exhibited poor pharmacodynamic properties and resulted in no clear evidence of significant SIV latency reversal. Whether alternative pharmacological formulations or combinations of this drug with other classes of LRAs will lead to an effective in vivo latency-reversing strategy remains to be determined.IMPORTANCE If combined with immune therapeutics, latency reversing agents (LRAs) have the potential to reduce the size of the reservoir sufficiently that an engineered immune response can control the virus in the absence of antiretroviral therapy. We have identified a new class of LRAs that do not induce T-cell activation and that are able to potentiate, rather than inhibit, CD8+ T and NK cell cytotoxic effector functions. This new class of LRAs corresponds to inhibitors of glycogen synthase kinase-3. In this work, we have also studied the effects of one member of this drug class, tideglusib, in SIV-infected rhesus monkeys. When tested in vivo, however, tideglusib showed unfavorable pharmacokinetic properties, which resulted in lack of SIV latency reversal. The disconnect between our ex vivo and in vivo results highlights the importance of developing next generation LRAs with pharmacological properties that allow systemic drug delivery in relevant anatomical compartments harboring latent reservoirs.

Stimulatory effects of Porphyromonas gingivalis GroEL protein on interleukin-6 and interleukin-8 in human osteoblasts.

BACKGROUND/PURPOSE: Porphyromonas gingivalis is an oral pathogen associated with periodontal diseases. P. gingivalis GroEL protein is a stimulator of inflammatory cytokines in macrophages. This study inspected effects of P. gingivalis GroEL protein on production of interleukin (IL)-6 and IL-8 by human osteoblasts. METHODS: Viability of GroEL-treated osteoblasts was analyzed with 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide. Secretion of IL-6 and IL-8 was analyzed using the enzyme-linked immunosorbent assay. Levels of mRNA were analyzed using the reverse transcription and real-time polymerase chain reaction. The antioxidant (curcumin), the p38 mitogen-activated protein kinase (MAPK) inhibitor (SB203580) and the c-Jun N-terminal kinase (JNK) inhibitor (SP600125) were employed to elucidate possible signaling pathways involved. RESULTS: Treatment with GroEL did not affect morphology and viability of osteoblasts. GroEL significantly induced the secretion of IL-6 and IL-8 by osteoblasts in a concentration-dependent pattern. Moreover, the mRNA levels of IL-6 and IL-8 were stimulated by GroEL. The application of SP600125 (10 µM) significantly suppressed the induction of IL-6 and IL-8 by GroEL-treated cells. However, curcumin (20 µM) and SB203580 (20 µM) only down-regulated the stimulatory effects of GroEL on IL-6. CONCLUSION: GroEL protein stimulated the inflammatory reaction of osteoblasts, probably through the activation of p38 MAPK or JNK pathway. The findings suggest that P. gingivalis GroEL may influence the immune functions of osteoblasts and endanger the periodontal health.

Phenotypic analysis of the unstimulated in vivo HIV CD4 T cell reservoir.

The latent reservoir is a major barrier to HIV cure. As latently infected cells cannot be phenotyped directly, the features of the in vivo reservoir have remained elusive. Here, we describe a method that leverages high-dimensional phenotyping using CyTOF to trace latently infected cells reactivated ex vivo to their original pre-activation states. Our results suggest that, contrary to common assumptions, the reservoir is not randomly distributed among cell subsets, and is remarkably conserved between individuals. However, reservoir composition differs between tissues and blood, as do cells successfully reactivated by different latency reversing agents. By selecting 8-10 of our 39 original CyTOF markers, we were able to isolate highly purified populations of unstimulated in vivo latent cells. These purified populations were highly enriched for replication-competent and intact provirus, transcribed HIV, and displayed clonal expansion. The ability to isolate unstimulated latent cells from infected individuals enables previously impossible studies on HIV persistence.

There is no cure for the human immunodeficiency virus infection (HIV), but anti-retroviral drugs allow infected people to keep the virus at bay and lead a normal life. These drugs suppress the growth of HIV, but they do not eliminate the virus. If the treatment is interrupted, the virus bounces back within weeks in most individuals. HIV can start growing again because it hides within particular immune cells, called T cells. These infected cells stay in the infected person's body for their whole life in a dormant or "latent" state, and represent the main barrier to an HIV cure. If these cells could be eliminated or prevented from producing more virus without daily treatment, then HIV could be cured. The fact that HIV hides inside T cells has been known for a long time, but it has remained unclear exactly what kinds of T cells the virus prefers. One challenge to characterizing latently-infected cells is that there is no single protein made by them that is not also made by uninfected T cells. The latently-infected T cells are also very rare: HIV mainly attaches to a protein called CD4, but only one in about a million T cells with CD4 contain the virus. To figure out which CD4-carrying T cells in a patient sample are latently infected, the cells are extracted from the patient's body and 'reactivated' so the virus will start growing again. Unfortunately, the mixture of drugs used to reactivate the T cells changes the cells and the proteins they are producing, which obscures the features the latently-infected T cells had before reactivation. Neidleman, Luo et al. developed a new approach to trace the infected, reactivated T cells back to their state before reactivation. Using computational methods and a laboratory technique called mass cytometry, the levels of approximately 40 different proteins were measured in millions of T cells from people living with HIV. These experiments provided an 'atlas' of overall T cell features onto which each reactivated cell could be mapped. The population of latently-infected T cells exhibited common features among all the participants. Selecting a few of the most abundant proteins on the surface of the latently-infected cells allowed these cells to be physically separated from all other immune cells. In the future, this relatively pure population of infected T cells could be used to study how HIV can persist for many decades. The 'map' of these cells' features will provide a valuable resource for HIV researchers and might enable the discovery of new drugs to eliminate the latent T cells.