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Mechanistic and thermal characterization of acupuncture for chemotherapy-induced peripheral neuropathy as measured by quantitative sensory testing.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of chemotherapy. Acupuncture is a promising non-pharmacological intervention for CIPN. However, the physiological effects of acupuncture treatment remain poorly understood. We examined the effects of acupuncture on CIPN using semi-objective quantitative sensory testing (QST).

Visible Apical Blebs on CXR: Are Plain Radiographs Under-Utilized in Primary Spontaneous Pneumothorax?

A primary spontaneous pneumothorax (PSP) is caused by rupture of subpleural emphysematous blebs, without inciting event or pre-existing co-morbidity. A previously healthy 16-year-old male presented with upper chest pain. As expected, chest radiographs (CXR) demonstrated a 13 mm pneumothorax. Additionally, a 4.7 cm apical bleb was identified. After six-hours of observation and non-rebreather oxygen mask therapy, follow-up CXR confirmed stable findings. The patient was subsequently discharged home after symptoms improved. Follow-up CXR at 2-weeks confirmed persistent visible apical bleb. After lengthy discussion addressing patient and parental concerns, elective surgical management was pursued. Current literature suggests blebs are not routinely identified on CXR. While there is no universally accepted management algorithm for PSP in children, visible apical blebs on CXR may influence the decision to pursue surgical intervention. Shared decision making should involve counseling regarding the recurrence risk following surgery, and consideration of patient-specific factors including patient and parental anxiety.

Spesolimab improves patient-reported outcomes in patients with generalized pustular psoriasis: results from the Effisayil 1 study.

Generalized pustular psoriasis (GPP) is a rare inflammatory skin disease with a considerable clinical burden. In the Effisayil 1 study, spesolimab, an anti-interleukin-36 receptor monoclonal antibody, demonstrated efficacy in treating GPP flares.

Comparison of two methods for extracting exosomes from the nucleus accumbens in mice.

Exosomes bind to and are endocytosed by neurons of various brain regions. Methods for isolating and extracting exosomes from specific brain samples are critical. At present, the most important extractive methods for exosomes are Ultracentrifugation and exosome isolation kit extraction. Both of these extraction methods have applications in neuroscience. We compare these methods to reveal the differences METHODS: We sectioned the nucleus accumbens of mice, and isolated exosomes. A culture medium containing exosomes was extracted using ultracentrifugation (UC) and a total exosome isolation kit (TEI). The exosomes were examined using transmission electron microscopy (TEM), measurement regarding the diameter of the exosomes was done, and the thermal allodynia and western blotting analysis were also conducted, respectively.

Synthesis, characterization and evaluation of hyaluronic acid-based polymers for nasal delivery.

Epidemiological research has found that between 5 and 12 percent of the population suffers from chronic rhinosinusitis. Patients are dealing with local side effects such as nasal dryness, sporadic sneezing, and nasal pain in addition to the inflammation. The aim of this study was to synthesize a polymer based on hyaluronic acid in order to provide lubrication combined with a ligand leading to a covalent binding on the nasal mucosa. Hyaluronic acid (HA) was modified with L-cysteine ethyl ester hydrochloride (CYS) via amid bond formation. Ellman's assay, together with spectroscopic techniques like IR and H NMR, confirmed that HACys had been successfully synthesized. It was demonstrated that HACys is safe for administration on the nasal mucosa. The mucoadhesive potential was determined by 3.26-fold with the rotating cylinder assay and 1.4-fold in terms of bioadhesive examination, respectively. Further, the stability of the modified polymer was improved by 7.6-fold compared to the unmodified polymer. Spraying the formulation on the nasal mucosa, the residence time of a model drug was 1.74-fold prolonged at the site of action compared to unmodified polymer. In light of these findings, modified hyaluronic acid (HACys) displayed compelling properties such as lubricity, targeted application, long-lasting effect, and safety and therefore could be an excellent candidate for nasal application.

The Aversive Lens: Stress effects on the prefrontal-cingulate cortical pathways that regulate emotion.

ARNSTEN, A.F.T., M.K.P. Joyce and A.C. Roberts. The Aversive Lens: Stress effects on the prefrontal-cingulate cortical pathways that regulate emotion. NEUROSCI BIOBEHAV REV XXX-XXX, 2022. The symptoms of major-depressive-disorder include psychic pain and anhedonia, i.e. seeing the world through an "aversive lens". The neurobiology underlying this shift in worldview is emerging. Here these data are reviewed, focusing on how activation of subgenual cingulate (BA25) induces an "aversive lens", and how higher prefrontal cortical (PFC) areas (BA46/10/32) provide top-down regulation of BA25 but are weakened by excessive dopamine and norepinephrine release during stress exposure, and dendritic spine loss with chronic stress exposure. These changes may generate an attractor state, which maintains the brain under the control of BA25, requiring medication or neuromodulatory treatments to return connectivity to a more flexible state. In line with this hypothesis, effective anti-depressant treatments reduce the activity of BA25 and restore top-down regulation by higher circuits, e.g. as seen with SSRI medications, ketamine, deep brain stimulation of BA25, or rTMS to strengthen dorsolateral PFC. This research has special relevance in an era of chronic stress caused by the COVID19 pandemic, political unrest and threat of climate change.

Photopharmacological manipulation of amygdala metabotropic glutamate receptor mGlu4 alleviates neuropathic pain.

Neuropathic pain is a common health problem resulting in exacerbated response to noxious and non noxious stimuli, as well as impaired emotional and cognitive responses. Unfortunately, neuropathic pain is also one of the most difficult pain syndromes to manage, highlighting the importance of better understanding the brain regions and neuromodulatory mechanisms involved in its regulation. Among the many interconnected brain areas which process pain, the amygdala is known to play an important role in the integration of sensory and emotional pain signals. Here we questioned the ability of a recently identified neuromodulatory mechanism associated with the metabotropic glutamate receptors mGlu in the amygdala to modulate neuropathic pain. In a murine model of peripheral mononeuropathy, we demonstrate that pharmacological activation of amygdala mGlu efficiently alleviates sensory and depressive-like symptoms in both male and female mice. Moreover, we reveal a differential modulation of these symptoms. Activating mGlu in the contralateral amygdala relative to the side of the mononeuropathy, is necessary and sufficient to relieve both sensory and depressive-like symptoms, while ipsilateral activation solely reduces depressive-like symptoms. Furthermore, using photopharmacology, a recent strategy allowing precise photocontrol of endogenous proteins, we further demonstrate the dynamic alleviation of neuropathic pain through light-dependent facilitation of mGlu by a photoswitchable positive allosteric modulator. Finally, coupling photopharmacology and analgesic conditioned place preference, we show a significant pain-reducing effect of mGlu4 activation. Taken together, these data highlight the analgesic potential of enhancing amygdala mGlu activity to counteract neuropathy reinforcing its therapeutic interest for the treatment of pathological pain.

Efficacy of ultrasound-guided pericapsular nerve group (PENG) block combined with local infiltration analgesia on postoperative pain after total hip arthroplasty: a prospective, double-blind, randomized controlled trial.

This study examined whether pericapsular nerve group (PENG) block combined with local infiltration analgesia (LIA) could improve pain management and functional recovery after total hip arthroplasty (THA).

Perioperative Opioid Prescribing Following Male Fertility Procedure are Associated with New Persistent Opioid Use – Retrospective Analysis of a Large Claims Database.

To assess the risk of new persistent opioid use in opioid-naïve men undergoing male fertility procedures DESIGN: Retrospective cohort study using a claims database SETTING: TriNetX Diamond Network – a database linking electronic medical record data and claims – assessing men undergoing fertility procedure between 2010 and 2021.

The impact of ankle haemarthropathy in patients with moderate haemophilia.

Moderate haemophilia has traditionally been associated with less complications than severe haemophilia. Changes in treatment recommendations have highlighted the burden of moderate haemophilia with a subset of patients with a severe bleeding phenotype. The ankle joint is disproportionally affected by ankle haemarthropathy however the impact has not been evaluated in moderate haemophilia, nor the effect on health related quality of life (HRQoL) or foot and ankle outcomes.

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