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Pyogenic (septic) arthritis is a severe joint infection characterized by the invasion of microorganisms into the synovium, causing inflammation and joint destruction. This review article provides a comprehensive overview of pyogenic arthritis, focusing on etiology, pathogenesis, clinical manifestations, diagnosis, and management strategies. This review explores routes of microbial entry into joints, emphasizing the importance of prompt identification and treatment to prevent irreversible joint damage. Clinical manifestations, such as joint pain, swelling, and limited range of motion, are discussed, along with the challenges in differentiating pyogenic arthritis from other joint disorders. Diagnostic approaches, including joint aspiration and imaging modalities, are critically examined for accuracy in confirming diagnosis. This review also addresses the significance of early intervention through antimicrobial therapy and joint drainage, highlighting the role of multidisciplinary collaboration in optimizing patient outcomes. In summary, the present investigation underscores the complexities of pyogenic arthritis and the need for a comprehensive understanding of pathophysiology for timely and effective management to improve patient prognosis and quality of life.

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The second meal phenomenon refers to the improvement in glucose tolerance seen following a second identical meal. We previously showed that 4 hours of morning hyperinsulinemia, but not hyperglycemia, enhanced hepatic glucose uptake (HGU) and glycogen storage during an afternoon hyperinsulinemic-hyperglycemic (HIHG) clamp. Our current aim was to determine if the duration or pattern of morning hyperinsulinemia is important for the afternoon response to a HIHG clamp. To determine this, we administered the same total amount of insulin either over 2h in the first (Ins2h-A) or second (Ins2h-B) half of the morning, or over the entire 4h (Ins4h) of the morning. In the 4h afternoon period, all three groups had 4x-basal insulin, 2x-basal glycemia, and portal glucose infusion to expose the liver to the primary postprandial regulators of hepatic glucose metabolism. During the afternoon clamp, there was a marked increase in HGU and hepatic glycogen synthesis in the Ins4h group compared to the Ins2h-A and Ins2h-B groups, despite matched hepatic glucose loads and total insulin infusion rates. Thus, the longer duration (Ins4h) of lower hyperinsulinemia in the morning seems to be the key to much greater liver glucose uptake during the afternoon clamp.

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In part two of this mini-series, we evaluate the range of machine-learning tools now available for application to veterinary clinical text-mining. These tools will be vital to automate extraction of information from large datasets of veterinary clinical narratives curated by projects such as the Small Animal Veterinary Surveillance Network (SAVSNET) and VetCompass, where volumes of millions of records preclude reading records and the complexities of clinical notes limit usefulness of more "traditional" text-mining approaches. We discuss the application of various machine learning techniques ranging from simple models for identifying words and phrases with similar meanings to expand lexicons for keyword searching, to the use of more complex language models. Specifically, we describe the use of language models for record annotation, unsupervised approaches for identifying topics within large datasets, and discuss more recent developments in the area of generative models (such as ChatGPT). As these models become increasingly complex it is pertinent that researchers and clinicians work together to ensure that the outputs of these models are explainable in order to instill confidence in any conclusions drawn from them.

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Dysphagia after anterior cervical spine surgery has a 5% to 15% incidence beyond 1-year postsurgery, often attributed to mechanical factors such as pharyngeal thickening and epiglottis inversion. Despite normal neurological examination and electromyography, nerve distortion related to stretching also remains a possibility in these patients and may cause allodynia resulting in odynophagia and dysphagia. Current treatment options for dysphagia after anterior cervical discectomy and fusion are limited to local intraoperative steroid injections and tracheal traction exercises. In our patient, a glossopharyngeal nerve block was effectively used to manage the glossopharyngeal allodynia, thereby reducing the odynophagia and dysphagia, ultimately enhancing oral tolerance.

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The species Mimosa gracilis var. capillipes (Benth.) Barneby is used for its antivenom properties in the Coqueiros community, municipality of Catalão, state of Goiás. This study focused on three varieties: M. gracilis Benth. var. gracilis, M. gracilis var. capillipes (Benth.) Barneby, and M. gracilis var. invisiformis Barneby. The chemical profiles of extracts from these varieties were analysed using molecular networking through liquid chromatography with tandem mass spectrometry. Additionally, the study investigated the inhibitory potential of these three varieties against the proteolytic, coagulant, and phospholipase activities of Bothrops and Crotalus venoms. In vitro results confirmed the antivenom potential of nine extracts. Remarkably, the ethanolic extracts of roots from M. gracilis var. capillipes (Benth.) Barneby and the leaves from M. gracilis Benth. var. gracilis exhibited 100 % inhibition of the tested activities. The study also revealed 19 annotated compounds through molecular networking, reported for the first time in the species M. gracilis.

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People with epilepsy often report experiencing memory problems though these are not always detectable using standard neuropsychological measures. One form of difficulty that may be relatively prevalent in epilepsy is termed accelerated long-term forgetting (ALF), typically described as relatively greater loss of memory over days or weeks following initial encoding. The current study used remote assessment to examine memory and forgetting over one week in a broad community sample of people with epilepsy and healthy control participants, using two recently developed tests, one verbal (the Crimes test) and one visual (the Four Doors test). These were administered as part of a short battery of cognitive measures, run remotely with participants over Zoom. Across this community-derived sample, people with epilepsy reported more memory complaints and demonstrated significantly faster forgetting on both the verbal and visual tests. This difference was not attributable to level of initial learning performance and was not detectable through delayed recall on a standard existing test. Our results suggests that ALF may be more common than suspected in people with epilepsy, leading to a potentially important source of memory problems that are currently undetected by standard memory tests.

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BACKGROUND: Endoscopic sinus surgery (ESS) maximized for topical steroid irrigations is highly effective for polyp disease. As extent and completeness of ESS varies widely by situation and practitioner, it is important to understand when revision surgery is appropriate, particularly in the era of biologic treatments. METHODS: A Completion of Surgery Index (CoSI) was developed to assess operative changes in polyp patients using pre- and postoperative computed tomography scans. The CoSI was then applied and tested in a cohort of consecutive chronic rhinosinusitis with nasal polyps (CRSwNP) patients, and examined within the context of quality-of-life improvements. RESULTS: The CoSI assesses surgical extent on a scale of 0-100, with 100 representing the highest possible degree of surgical completeness. Among 100 consecutive CRSwNP patients undergoing ESS in 2021 with postoperative topical steroid irrigations, including 75 revision surgeries, SNOT-22 scores improved at 6 months postoperatively, with durable and consistent improvement at 24 months (p < 0.001). Preoperative CoSI scores in revision surgery patients were 49.4 ± 26.0, improving to 91.0 ± 8.1 postoperatively. SNOT-22 scores for primary ESS patients and patients with a preoperative CoSI score of less than 70 improved by 26.4 and 28.1 points, respectively, in contrast to patients with a preoperative CoSI of 70 or greater (14.1 points, p = 0.029). CONCLUSIONS: It is important to define extent of surgery in CRSwNP to stratify postsurgical patients based on likelihood to benefit from revision surgery or alternative medications. The CoSI can be utilized to identify patients who are likely to improve significantly with revision surgical intervention.

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A low-cost novel spectral camera able to be used for near infrared spectroscopy was made by using a Jetson Nano to synchronize a Sony IMX219 NOIR autofocus image sensor, an AMS AS7265x 18-channel spectral sensor and Osram SFH 4737 broadband infrared LED's. Synchronizing an image sensor and spectral sensor augments a standard RGB image with light spectrum information; capturing the light distribution information normally lost in RGB image capture. Sutherland et al. [1] used this novel spectral camera to examine the dorsal surface of juvenile lobsters as a possible pre-moult detector. Having the image and spectrum in combination allowed the incomplete and unmineralized post-moult dorsal surface to be characterized with 86.7% accuracy for the first time. A proposed application for the spectral camera is to omit the local SFH 4737 light source and use the camera in daylight, effectively making a low-cost substitute hyperspectral snapshot camera. In this configuration the camera may have application for low-cost drone deployment for small scale agriculture.

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CDK1 has been known to be the sole cyclin-dependent kinase (CDK) partner of cyclin B1 to drive mitotic progression1. Here we demonstrate that CDK5 is active during mitosis and is necessary for maintaining mitotic fidelity. CDK5 is an atypical CDK owing to its high expression in post-mitotic neurons and activation by non-cyclin proteins p35 and p392. Here, using independent chemical genetic approaches, we specifically abrogated CDK5 activity during mitosis, and observed mitotic defects, nuclear atypia and substantial alterations in the mitotic phosphoproteome. Notably, cyclin B1 is a mitotic co-factor of CDK5. Computational modelling, comparison with experimentally derived structures of CDK-cyclin complexes and validation with mutational analysis indicate that CDK5-cyclin B1 can form a functional complex. Disruption of the CDK5-cyclin B1 complex phenocopies CDK5 abrogation in mitosis. Together, our results demonstrate that cyclin B1 partners with both CDK5 and CDK1, and CDK5-cyclin B1 functions as a canonical CDK-cyclin complex to ensure mitotic fidelity.

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BACKGROUND: This analysis is a systematic literature review assessing efficacy and adverse effects of three alpha-2 agonists for the symptomatic management of autism spectrum disorder (ASD). METHODS: The present investigation involved an extensive systematic search for eligible studies in PubMed, Embase, Cochrane Library, and Google Scholar. Nine studies, collectively incorporating 226 patients, were assessed. RESULTS: The results demonstrated promising indications for use of alpha-2 agonists in the symptomatic management of autism spectrum disorders, including improvement of hyperactivity, impulsivity, attention deficit symptoms, irritability, and stereotypies in many of the participants studied. CONCLUSION: The present investigation encourages physicians to consider treatment outcomes of clonidine, guanfacine, and lofexidine to determine the most effective management of ASD-related symptoms and to minimize adverse effects. However, our review cannot provide definitive treatment protocols related to various study limitations.

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We analyzed genomic data from the prostate cancer of African- and European American men to identify differences contributing to racial disparity of outcome. We also performed FISH-based studies of Chromodomain helicase DNA-binding protein 1 (CHD1) loss on prostate cancer tissue microarrays. We created CHD1-deficient prostate cancer cell lines for genomic, drug sensitivity and functional homologous recombination (HR) activity analysis. Subclonal deletion of CHD1 was nearly three times as frequent in prostate tumors of African American than in European American men and it associates with rapid disease progression. CHD1 deletion was not associated with HR deficiency associated mutational signatures or HR deficiency as detected by RAD51 foci formation. This was consistent with the moderate increase of olaparib and talazoparib sensitivity with several CHD1 deficient cell lines showing talazoparib sensitivity in the clinically relevant concentration range. CHD1 loss may contribute to worse disease outcome in African American men.

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Osteoarthritis, the most common joint disease of adults worldwide, is increasing in prevalence due to an increase in aging and rates of obesity in developed countries. Treatment options include physical therapy, pharmacologic management, non-pharmacologic management, and total knee replacement surgery. When conservative measures fail, total knee replacement surgery is pursued. The patient is a 61-year-old woman with a history of severe chronic osteoarthritic knee pain following total left and right knee arthroplasty in 2016 and 2019, respectively, who presents with refractory post-total knee replacement pain. Following her surgeries, the patient was in excruciating 10/10 pain on the numerical rating scale (NRS) and was unable to walk or stand. She underwent revisions which, unfortunately, did not ameliorate her pain. She was later referred to chronic pain management in which a peripheral nerve stimulator (PNS) was offered and implanted. Following her PNS trial, the patient achieved >80% pain relief in her left knee. After the permanent PNS implant, the patient noted she had 100% pain relief (0/10 on the NRS) in her left knee and was able to regain mobility. Here, we discuss a case demonstrating rapid pain relief following the minimally invasive PNS implantation for refractory pain following total knee arthroplasty. Refractory pain following total knee arthroplasty can increase morbidity and mortality as a consequence. Thus, proper management is needed to reduce these adverse outcomes. In patients who have failed conservative medical management, PNS may be an alternative, efficacious treatment option for refractory knee pain. Despite the efficacy in our case, further research is needed to define the optimal patient group that would benefit from PNS for refractory knee pain following total knee arthroplasty.

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BACKGROUND: Atopic dermatitis (AD) is the most common inflammatory skin condition which affects all ages. New therapies, including the monoclonal antibody therapy dupilumab, offer excellent efficacy. However, in clinical trials, and emphasised in real-world observations, the unexpected increased frequency of ocular adverse effects became apparent. The effectiveness of dupilumab and the unpredictability of ocular adverse effects mean that clinicians need guidance on counselling patients prior to treatment and on managing them if they arise. OBJECTIVES: The British Association of Dermatologists (BAD) and Royal College of Ophthalmologists collaborated on this consensus guidance on managing dupilumab-related ocular surface disorders (DROSD). METHODS: A multidisciplinary group was formed of adult and paediatric dermatologists and ophthalmologists with DROSD expertise, patient representation, and BAD Clinical Standards Unit. A literature search was conducted, and the results reviewed. All recommendations were reviewed, discussed and voted on. RESULTS: The recommendations pertain to dermatology and ophthalmology management, and apply to all ages, unless otherwise stated. Importantly, initiation of dupilumab for AD should not be delayed for most eye disorders except acute new problems, e.g. infections, or potentially severe conditions, e.g. a history of corneal transplant (ophthalmology advice should be sought first). There is insufficient evidence to recommend lubricant drops prophylactically. Dermatologists should assess eye complaints to diagnose DROSD; a severity grading system is provided. DROSD management differs slightly in those aged <7 years as ocular complications may affect neuro-ocular development; therefore, irrespective of DROSD severity, this population should be referred for ophthalmology advice. In those aged ≥7 years, dermatologists should feel confident to trial treatment and reserve ophthalmology advice for severe or non-responding cases. Discussion about dupilumab withdrawal should be prompted by a significant impact on quality of life, threat to sight, or other complications. CONCLUSIONS: Although dupilumab is a highly effective agent for treating AD, the risk of ocular adverse effects should not inhibit clinicians or patients from using it, but clinicians should be aware of them. If a patient develops DROSD, there are clear pathways to assess severity and offer initial management; where ineffective, dermatologists should assess the urgency and seek advice from or initiate referral to ophthalmology. While the evidence reviewed for these guidelines reflects the extensive literature on dupilumab, we believe our advice has relevance for ocular surface disorders in atopic dermatitis (AD) patients treated with tralokinumab and lebrikizumab.

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BACKGROUND: Dermatoporosis (DP) is a condition associated with thinning skin layers and resultant fragility. Much of the thinning is related to fibroblast dysfunction, production of destructive inflammatory cytokines, breakdown of the extracellular matrix (ECM), and weakening of the dermo-epidermal junction. A major contributor to this change in the ECM milieu, previously under-considered, is cellular senescence, particularly involving the papillary dermal fibroblasts. METHODS: A series of experiments were undertaken to explore the impact of a combination of known actives on senescent cell status. Human keratinocytes and fibroblasts were cultured, and cytotoxicity tests were performed to determine the ideal concentration to avoid cell toxicity. Microdoses of Centella asiatica (0.005%) and mandelic acid (0.05%) were found to be ideal in avoiding any cytotoxicity. However, the challenge was then to assess the efficacy of these actives in this microdosed form. After exposing the cells to the compounds, RNA was isolated and sequenced. Moreover, a well-described ex vivo model using photodamaged skin was subjected to immunofluorescence to identify senescent cells (via p16INK4a), particularly in the papillary dermis, using the microdose formulation compared to untreated skin. In addition, JAG/NOTCH expression in the epidermal basal cells was evaluated to further understand the cellular senescence signaling mechanism. RESULTS: Microdosing these two well-known agents had surprisingly significant synergistic effects in vitro, decreasing senescence-associated secretory phenotype (SASP) cytokines and the associated inflammation involved in the process. The ex vivo model revealed a significant (P<0.05) decrease in senescent cells in the papillary dermis and a significant increase (P<0.001) of JAG/NOTCH expression in the basal cells of the epidermis. CONCLUSION: Using microdoses of two known agents, a novel approach produced an unexpected effect of reversal of dermal senescent cells and promoting an anti-inflammatory milieu. A gene expression analysis of the individual and combined actives validated these observations, followed by full formulation testing in an ex vivo model. The approach of limiting cellular senescence in dermal fibroblasts for managing DP is novel and provides an exciting new direction to address dermatoporosis. Clinical studies will follow. J Drugs Dermatol. 2024;23(9):748-756. doi:10.36849/JDD.8388.

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Allopurinol lowers urate production through the inhibition of xanthine oxidase. It is oxidatively hydroxylated to oxypurinol and is the most prescribed medication for gout treatment. Although it has a beneficial effect in the treatment of this common disease, like many medications, it is also known for having numerous adverse effects. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), diseases that exist on a spectrum, are two of the most dangerous adverse effects associated with allopurinol use. These immune-mediated disease processes involve almost every organ system. They are essential to recognize as early as possible, as they could potentially be deadly, requiring cessation of the medication with initial signs of rash or other early manifestations of SJS/TEN. One major consideration in the increased risk of allopurinol-mediated or modulated SJS/TEN is the need to have a lower dose in the setting of renal disease. The purpose of this review is not only to examine the involvement of allopurinol in SJS/TEN but also to provide detailed information about the drug, allopurinol, and general features and characteristics of SJS/TEN and other associated drug reactions.

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Hypertension is attributable long-term to various negative health outcomes, including atherosclerotic cardiovascular disease and, more broadly, to cardiovascular events such as congestive heart disease, myocardial infarction, heart failure, and stroke. Effective hypertension treatment is essential to lower the risk of these outcomes. Treatment of hypertension includes both nonpharmacologic and, if necessary, pharmacologic interventions. The drug classes proven in trials to decrease the risk of cardiovascular disease events in cases with hypertension include angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, thiazide diuretics, and calcium channel blockers. When considering thiazide diuretics as a first-line treatment, chlorthalidone (CTD) is currently recommended by the American College of Cardiology over hydrochlorothiazide (HCTZ). Previous studies have demonstrated that CTD is superior to HCTZ in preventing cardiovascular disease events. However, more recent studies have revealed that there is no significant difference in the results of patients treated with HCTZ versus those treated with CTD. Additionally, studies have revealed CTD has worse outcomes regarding side effects when compared to HCTZ. In this regard, it is essential to carefully consider which medication will best improve the outcomes of patients with hypertension while also causing few or easily manageable side effects.

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Background: Burn care has long been an integral part of the scope of plastic surgery, but the time allocated to exposure for plastic surgery residents is under threat due to the range of sub-specialities competing for their time. As part of the Competence by Design approach to plastic surgical training, residents are provided with a list of 52 "Entrustable professional activities' (EPA's) to ensure that core skills and knowledge are acquired. Methods: This survey, distributed via email using a link to Survey MonkeyTM, sought to determine which EPA's were available for completion by plastic surgeons in training during the burn rotation at a major academic burn centre in Canada. Via investigator consensus, 26 of the 52 EPA's were included for assessment; the remaining 26 were not regarded as relevant to the burn centre rotation and therefore better acquired elsewhere. Results: Thirty two residents who underwent a burn rotation between 1 January 2015 and 31 December 2021 completed the anonymous survey. Seventeen of the 26 EPA's evaluated were judged by more than 75% of respondents as being readily amenable to completion during the burn rotation. Most of these EPA's relate to the comprehensive care of patients with acute burn injuries, the management of an in-patient plastic surgery service, and associated quality improvement processes. Residents who completed rotations less than three months in duration had less opportunity to complete a further 8 EPA's in comparison to those who had longer rotations, especially with respect to the care of patients undergoing complex wound care and burn reconstruction. Conclusions: In addition to threatening seamless service delivery at burn centres, reduced resident exposure to the burn rotation may compromise the delivery of burn care in the community. The results of this survey refute any argument that the burn service is a "low yield" rotation from an EPA acquisition perspective.

Historique: Les soins aux grands brûlés font partie intégrante de la chirurgie plastique depuis longtemps, mais le temps alloué à y exposer les résidents en chirurgie plastique est menacé en raison de l'éventail de surspécialités. Dans le cadre de l'approche de compétence par conception à la formation en chirurgie plastique, les résultats reçoivent une liste de 52 « activités professionnelles confiables ¼ (APC) pour assurer qu'ils acquièrent les compétences et le savoir de base. Méthodologie : Ce sondage, distribué par courriel grâce à un lien vers la plateforme Survey MonkeyMD, visait à déterminer quelles APC étaient offertes aux chirurgiens plastiques en formation pendant leur rotation dans un grand centre universitaire pour grands brûlés du Canada. Par consensus des chercheurs, 26 des 52 APC ont été incluses dans l'évaluation. Les 26 autres n'ont pas été considérées comme pertinentes pour la rotation au centre pour grands brûlés, mais mieux à même d'être acquises ailleurs. Résultats:  Au total, 32 résidents qui ont participé à une rotation auprès des grands brûlés entre le 1er janvier 2015 et le 31 décembre 2021 ont rempli le sondage anonyme. Selon plus de 75% d'entre eux, 17 des 26 APC évaluées peuvent facilement être effectuées pendant la rotation auprès des grands brûlés. La plupart de ces APC portent sur les soins complets aux patients atteints de brûlures aiguës, la gestion d'un service de chirurgie plastique aux patients hospitalisés et les processus d'amélioration de la qualité qui s'y associent. Les résidents qui ont effectué leur rotation en moins de trois mois avaient moins l'occasion d'effectuer huit APC de plus par rapport à ceux qui avaient vécu des rotations plus longues, particulièrement à l'égard des soins des plaies complexes aux patients et de la reconstruction après leurs brûlures. Conclusions : En plus de menacer la prestation harmonieuse des services dans les centres pour grands brûlés, la moins grande exposition des résidents à la rotation des grands brûlés peut compromettre la prestation des soins aux grands brûlés dans la communauté. Les résultats de ce sondage réfutent toute prétention selon laquelle les services aux grands brûlés est une rotation « à faible rendement ¼ selon le point de vue de l'acquisition des APC.

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Neurodegenerative diseases are broadly hallmarked by impaired energy metabolism and toxic intracellular accumulations such as damaged organelles or reactive oxygen species (ROS). Gold nanoparticles readily cross the blood-brain barrier and increase nicotinamide adenine dinucleotide + hydrogen (NADH) oxidation to nicotinamide adenine dinucleotide (NAD+), which is vital for intracellular energy generation, cellular repair, and protection from ROS. Thus, the use of gold nanoparticles to treat and potentially reverse cellular injury seen in neurodegenerative disease has been an area of ongoing research. This systematic review explores current literature regarding the use of gold nanoparticle therapy in the treatment of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). In vitro studies of CNM-Au8 (Clene Nanomedicine, Salt Lake City, UT) have been shown to reduce TDP-43 aggregates associated with ALS. These studies also exhibited the neuroprotective effects of CNM-Au8 in rat primary neurons exposed to amyloid-beta peptides, which are associated with Alzheimer's disease. In animal models of MS, oral delivery of CNM-Au8 was demonstrated to produce robust and significant remyelination activity, oligodendrocyte maturation, and expression of myelin markers. In these same MS animal models, CNM-Au8 improved the motor function of cuprizone-treated mice in both open-field and kinematic gait studies. Recent phase II trials of CNM-Au8 in 13 patients with Parkinson's disease and 11 patients with stable relapsing MS demonstrated a statistically significant increase in the NAD+/NADH ratio across two cohorts. As the current data repeatedly suggest, these gold nanoparticles are efficacious for the treatment and reversal of symptoms across these varying neurodegenerative pathologies. Further opportunities exist for increasing human trials and eventually incorporating this new technology into existing treatment regimens.

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To generate movements, the brain must combine information about movement goal and body posture. Motor cortex (M1) is a key node for the convergence of these information streams. How are posture and goal information organized within M1's activity to permit the flexible generation of movement commands? To answer this question, we recorded M1 activity while monkeys performed a variety of tasks with the forearm in a range of postures. We found that posture- and goal-related components of neural population activity were separable and resided in nearly orthogonal subspaces. The posture subspace was stable across tasks. Within each task, neural trajectories for each goal had similar shapes across postures. Our results reveal a simpler organization of posture information in M1 than previously recognized. The compartmentalization of posture and goal information might allow the two to be flexibly combined in the service of our broad repertoire of actions.