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Cell Reports Jun 2024Timed feeding drives adipose browning, although the integrative mechanisms for the same remain unclear. Here, we show that twice-a-night (TAN) feeding generates biphasic...
Timed feeding drives adipose browning, although the integrative mechanisms for the same remain unclear. Here, we show that twice-a-night (TAN) feeding generates biphasic oscillations of circulating insulin and leptin, representing their entrainment by timed feeding. Insulin and leptin surges lead to marked cellular, functional, and metabolic remodeling of subcutaneous white adipose tissue (sWAT), resulting in increased energy expenditure. Single-cell RNA-sequencing (scRNA-seq) analyses and flow cytometry demonstrate a role for insulin and leptin surges in innate lymphoid type 2 (ILC2) cell recruitment and sWAT browning, since sWAT depot denervation or loss of leptin or insulin receptor signaling or ILC2 recruitment each dampens TAN feeding-induced sWAT remodeling and energy expenditure. Consistently, recreating insulin and leptin oscillations via once-a-day timed co-injections is sufficient to favorably remodel innervated sWAT. Innervation is necessary for sWAT remodeling, since denervation of sWAT, but not brown adipose tissue (BAT), blocks TAN-induced sWAT remodeling and resolution of inflammation. In sum, reorganization of nutrient-sensitive pathways remodels sWAT and drives the metabolic benefits of timed feeding.
PubMed: 38900636
DOI: 10.1016/j.celrep.2024.114390 -
A&A Practice Jun 2024
Topics: Humans; Nerve Block; Female; Pregnancy; Analgesia, Obstetrical; Adult; Paraspinal Muscles; Anesthetics, Local
PubMed: 38899784
DOI: 10.1213/XAA.0000000000001801 -
Indian Journal of Dermatology,... Jun 2024
PubMed: 38899420
DOI: 10.25259/IJDVL_73_2024 -
BMJ (Clinical Research Ed.) Jun 2024Resistant hypertension is defined as blood pressure that remains above the therapeutic goal despite concurrent use of at least three antihypertensive agents of different... (Review)
Review
Resistant hypertension is defined as blood pressure that remains above the therapeutic goal despite concurrent use of at least three antihypertensive agents of different classes, including a diuretic, with all agents administered at maximum or maximally tolerated doses. Resistant hypertension is also diagnosed if blood pressure control requires four or more antihypertensive drugs. Assessment requires the exclusion of apparent treatment resistant hypertension, which is most often the result of non-adherence to treatment. Resistant hypertension is associated with major cardiovascular events in the short and long term, including heart failure, ischemic heart disease, stroke, and renal failure. Guidelines from several professional organizations recommend lifestyle modification and antihypertensive drugs. Medications typically include an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, a calcium channel blocker, and a long acting thiazide-type/like diuretic; if a fourth drug is needed, evidence supports addition of a mineralocorticoid receptor antagonist. After a long pause since 2007 when the last antihypertensive class was approved, several novel agents are now under active development. Some of these may provide potent blood pressure lowering in broad groups of patients, such as aldosterone synthase inhibitors and dual endothelin receptor antagonists, whereas others may provide benefit by allowing treatment of resistant hypertension in special populations, such as non-steroidal mineralocorticoid receptor antagonists in patients with chronic kidney disease. Several device based approaches have been tested, with renal denervation being the best supported and only approved interventional device treatment for resistant hypertension.
Topics: Humans; Hypertension; Antihypertensive Agents; Drug Resistance; Drug Therapy, Combination; Calcium Channel Blockers; Blood Pressure
PubMed: 38897628
DOI: 10.1136/bmj-2023-079108 -
Journal of Orthopaedic Surgery (Hong... 2024Local infiltration analgesia (LIA), adductor canal block (ACB), and infiltration between the popliteal artery and the capsule of the posterior knee (IPACK) are popular...
Efficacy of adding infiltration between the popliteal artery and the capsule of the posterior knee (IPACK) to adductor canal block and local infiltration analgesia in total knee arthroplasty: A retrospective cohort study.
OBJECTIVE
Local infiltration analgesia (LIA), adductor canal block (ACB), and infiltration between the popliteal artery and the capsule of the posterior knee (IPACK) are popular multimodal analgesia techniques used during total knee arthroplasty (TKA). This study aimed to explore the efficacy of adding the IPACK technique to ACB and LIA in patients undergoing TKA.
METHODS
In this retrospective cohort study, patients who underwent primary unilateral TKA were divided into two groups based on their date of admission. Sixty-three patients underwent IPACK, ACB and LIA (IPACK group) during surgery, while 60 patients underwent ACB and LIA (control group). The primary outcome was the postoperative administration of morphine hydrochloride as a rescue analgesic. Secondary outcomes included time to first rescue analgesia, postoperative pain assessed using the visual analog scale (VAS), functional recovery assessed by knee range of motion and ambulation distance, time until hospital discharge, and complication rates.
RESULTS
The two groups were similar in average postoperative 0-to-24-h morphine consumption (11.8 mg for the control group vs 12.7 mg for the IPACK group, = .428) and average total morphine consumption (18.2 mg vs 18.0 mg, = .983) during hospitalization. There were also no significant differences in the secondary outcomes.
CONCLUSIONS
The addition of IPACK to ACB and LIA did not provide any clinical analgesic benefits. Orthopedic surgeons and anesthesiologists are justified in using ACB and LIA without IPACK for TKA.
Topics: Humans; Retrospective Studies; Arthroplasty, Replacement, Knee; Male; Female; Aged; Popliteal Artery; Nerve Block; Pain, Postoperative; Middle Aged; Analgesics, Opioid; Morphine; Anesthetics, Local; Pain Measurement; Anesthesia, Local; Analgesia; Pain Management
PubMed: 38896879
DOI: 10.1177/10225536241265445 -
Canadian Urological Association Journal... Jun 2024We aimed to investigate the surgical outcomes following inguinal and subinguinal urological procedures under deep intravenous sedation (DIVS) with multimodal local...
INTRODUCTION
We aimed to investigate the surgical outcomes following inguinal and subinguinal urological procedures under deep intravenous sedation (DIVS) with multimodal local anesthesia (LA).
METHODS
We conducted a retrospective cohort study from September 2022 to December 2023 including adult patients deemed eligible for day surgery (American Society of Anesthesiologist score 1-3) undergoing radical orchiectomy (RO), microscopic varicocelectomy (MV), or microscopic denervation of spermatic cords (MDSC). All procedures were performed at a single urologic ambulatory surgical center and outpatient clinic, and by a single surgeon (PP). Procedures were performed through a subinguinal or inguinal approach with DIVS and adjunctive multimodal LA. We evaluated intraoperative complications and relevant surgical outcomes and parameters.
RESULTS
A total of 103 patients were included in the analysis with a mean age ± standard deviation of 37.3±9.6. This included 25 patients who underwent RO, 54 patients who underwent MV, and 24 patients who underwent MDSC. All procedures were completed successfully without intraoperative complications. Oncologic outcomes were preserved, fertility outcomes improved, and pain scores reduced similar to the expected rates in the literature.
CONCLUSIONS
Our preliminary results demonstrate the safety, effectiveness, and feasibility of performing inguinal and subinguinal urologic procedures under DIVS with LA. These findings suggest that this technique preserves high-quality care while avoiding unnecessary risks of general or spinal anesthesia, representing an opportunity to transfer these cases outside of hospitals' operating rooms into outpatient ambulatory centers.
PubMed: 38896478
DOI: 10.5489/cuaj.8841 -
BioRxiv : the Preprint Server For... Jun 2024The profound pain accompanying bone fracture is mediated by somatosensory neurons, which also appear to be required to initiate bone regeneration following fracture....
The profound pain accompanying bone fracture is mediated by somatosensory neurons, which also appear to be required to initiate bone regeneration following fracture. Surprisingly, the precise neuroanatomical circuitry mediating skeletal nociception and regeneration remains incompletely understood. Here, we characterized somatosensory dorsal root ganglia (DRG) afferent neurons innervating murine long bones before and after experimental long bone fracture in mice. Retrograde labeling of DRG neurons by an adeno-associated virus with peripheral nerve tropism showed AAV-tdT signal. Single cell transcriptomic profiling of 6,648 DRG neurons showed highest labeling across CGRP+ neuron clusters (6.9-17.2%) belonging to unmyelinated C fibers, thinly myelinated Aδ fibers and Aβ-Field LTMR (9.2%). Gene expression profiles of retrograde labeled DRG neurons over multiple timepoints following experimental stress fracture revealed dynamic changes in gene expression corresponding to the acute inflammatory ( , ) and mechanical force ( ). Reparative phase after fracture included morphogens such as and . Two methods to surgically or genetically denervate fractured bones were used in combination with scRNA-seq to implicate defective mesenchymal cell proliferation and osteodifferentiation as underlying the poor bone repair capacity in the presence of attenuated innervation. Finally, multi-tissue scRNA-seq and interactome analyses implicated neuron-derived FGF9 as a potent regulator of fracture repair, a finding compatible with in vitro assessments of neuron-to-skeletal mesenchyme interactions.
PubMed: 38895367
DOI: 10.1101/2024.06.06.597786 -
Sensors (Basel, Switzerland) Jun 2024Ultrasound imaging is an essential tool in anesthesiology, particularly for ultrasound-guided peripheral nerve blocks (US-PNBs). However, challenges such as speckle...
Ultrasound imaging is an essential tool in anesthesiology, particularly for ultrasound-guided peripheral nerve blocks (US-PNBs). However, challenges such as speckle noise, acoustic shadows, and variability in nerve appearance complicate the accurate localization of nerve tissues. To address this issue, this study introduces a deep convolutional neural network (DCNN), specifically Scaled-YOLOv4, and investigates an appropriate network model and input image scaling for nerve detection on ultrasound images. Utilizing two datasets, a public dataset and an original dataset, we evaluated the effects of model scale and input image size on detection performance. Our findings reveal that smaller input images and larger model scales significantly improve detection accuracy. The optimal configuration of model size and input image size not only achieved high detection accuracy but also demonstrated real-time processing capabilities.
Topics: Nerve Block; Neural Networks, Computer; Humans; Ultrasonography; Image Processing, Computer-Assisted; Peripheral Nerves; Ultrasonography, Interventional
PubMed: 38894486
DOI: 10.3390/s24113696 -
Cells May 2024BAX plays an essential role in retinal ganglion cell (RGC) death induced by optic nerve injury. Recently, we developed M109S, an orally bioactive and cytoprotective...
BAX plays an essential role in retinal ganglion cell (RGC) death induced by optic nerve injury. Recently, we developed M109S, an orally bioactive and cytoprotective small compound (CPSC) that inhibits BAX-mediated cell death. We examined whether M109S can protect RGC from optic nerve crush (ONC)-induced apoptosis. M109S was administered starting 5 h after ONC for 7 days. M109S was orally administered in two groups (5 mg/kg twice a day or 7.5 mg/kg once a day). The retina was stained with anti-BRN3A and cleaved Caspase-3 (active Caspase-3) that are the markers of RGC and apoptotic cells, respectively. ONC decreased the number of BRN3A-positive RGC and increased the number of active Caspase-3-expressing apoptotic cells. In ONC-treated retina, there were cells that were double stained with anti-BRN3A and ant-cleaved Caspase-3, indicating that apoptosis in BRN3A-positive RGCs occurred. M109S inhibited the decrease of BRN3A-positive cells whereas it inhibited the increase of active Caspase-3-positive cells in the retina of ONC-treated mice, suggesting that M109S inhibited apoptosis in RGCs. M109S did not induce detectable histological damage to the lungs or kidneys in mice, suggesting that M109S did not show toxicities in the lung or kidneys when the therapeutic dose was used. The present study suggests that M109S is effective in rescuing damaged RGCs. Since M109S is an orally bioactive small compound, M109S may become the basis for a portable patient-friendly medicine that can be used to prevent blindness by rescuing damaged optic nerve cells from death.
Topics: Animals; Retinal Ganglion Cells; Mice; Optic Nerve Injuries; Apoptosis; Nerve Crush; Male; Caspase 3; Mice, Inbred C57BL; Cytoprotection; Optic Nerve
PubMed: 38891043
DOI: 10.3390/cells13110911 -
BMC Oral Health Jun 2024Surgical extraction of impacted third molars (ITM) often leads to postoperative discomfort including pain, swelling, and limited function. Steroids like dexamethasone... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study Observational Study
Comparison of perineural and systemic dexamethasone use in impacted third molar surgeries in terms of anesthesia duration and postoperative complaints: a controlled, randomized observational study.
BACKGROUND
Surgical extraction of impacted third molars (ITM) often leads to postoperative discomfort including pain, swelling, and limited function. Steroids like dexamethasone (DXN) are commonly used in oral surgery to manage pain and inflammation. Various administration routes for DXN exist, including intravenous (IV), perineural (PN), and oral applications, each with its advantages. Previous studies have shown that adding DXN to local anesthetics can prolong anesthesia duration and reduce postoperative sequelae. However, comparative studies on IV and PN applications with inferior alveolar nerve block (IANB) of DXN in ITM surgeries are limited.
METHODS
This controlled, randomized observational study involved patients undergoing Class II position B ITM extraction. Patients were divided into three groups. IANB (1.8 ml of articaine hydrochloride + 1 ml of saline) was performed 1 h after IV-DXN (4 mg/ml DXN) was administered to the IV group. DXN along with IANB (1.8 ml of articaine hydrochloride + 1 ml of 4 mg/ml DXN) was applied to the PN group. Only IANB (1.8 ml of articaine hydrochloride + 1 ml of saline) was applied to the control group. Anesthesia duration was assessed as primary outcomes. Anesthesia duration was evaluated using a vitalometer from the molars. Secondary outcomes included postoperative pain and edema measured on the 1st, 3rd, and 7th days after surgery. Pain was evaluated postoperatively by using a visual analog scale. A p-value < 0.05 was considered statistically significant.
RESULTS
The study included 45 patients with similar demographic characteristics across groups. IV application significantly prolonged anesthesia duration compared to the control group. (p = 0.049) Both IV and PN administration of DXN reduced postoperative edema at 3rd (p = 0.048) and 7th day (p = 0.01). Post-procedure pain reduction was significant in the IV group (p = 0.011). On the other hand, it was observed that the pain did not decrease in the PN group at 3rd and 7th days compared to the control and IV groups.
CONCLUSIONS
PN and IV DXN administration prolonged anesthesia duration and reduced postoperative edema in ITM surgeries. However, PN DXN administration was associated with increased postoperative pain compared to IV DXN and control groups. Further studies comparing different doses and administration routes of DXN are needed to determine optimal strategies for managing postoperative discomfort in ITM surgeries.
TRIAL REGISTRATION
This study was conducted at Ahmet Keleşoğlu Faculty of Dentistry with the permission of Karamanoğlu Mehmetbey University Faculty of Medicine Ethics Committee (#04-2022/101). Trial registration is also available at clinicaltrail.gov. (NCT06318013, 26/05/2024).
Topics: Humans; Molar, Third; Dexamethasone; Tooth, Impacted; Male; Female; Pain, Postoperative; Tooth Extraction; Nerve Block; Adult; Anesthesia, Dental; Anesthetics, Local; Young Adult; Pain Measurement; Mandibular Nerve; Carticaine; Time Factors; Edema
PubMed: 38890655
DOI: 10.1186/s12903-024-04483-4