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Progress in Neuro-psychopharmacology &... Jun 2024Acute stimulation of M or M muscarinic cholinergic receptors reduces cocaine abuse-related effects in mice and rats. The combined activation of these receptor subtypes...
Acute stimulation of M or M muscarinic cholinergic receptors reduces cocaine abuse-related effects in mice and rats. The combined activation of these receptor subtypes produces synergistic effects on some behavioural endpoints in mice. M and M + M receptor stimulation in a cocaine vs. food choice assay in rats and microdialysis in rats showed delayed and lasting "anticocaine effects". Here, we tested whether these putative lasting neuroplastic changes are sufficient to occlude the reinforcing effects of cocaine at the behavioural level in mice. Mice were pre-treated with the M receptor partial agonist VU0364572, M receptor positive allosteric modulator VU0152100, or VU0364572 + VU0152100 two weeks prior to acquisition of cocaine intravenous self-administration (IVSA). Male C57BL/6JRj mice received vehicle, VU0364572, VU0152100, or VU0364572 + VU0152100. Female mice were tested with two VU0364572 + VU0152100 dose combinations or vehicle. To attribute potential effects to either reduced rewarding effects or increased aversion to cocaine, we tested VU0364572 alone and VU0364572 + VU0152100 in acquisition of cocaine-conditioned place preference (CPP) in male mice using an unbiased design. The acquisition of cocaine IVSA was drastically reduced and/or slowed in male and female mice receiving VU0364572 + VU0152100, but not either drug alone. Food-maintained operant behaviour was unaffected, indicating that the treatment effects were cocaine-specific. No treatment altered the acquisition of cocaine-CPP, neither in the post-test, nor in a challenge 14 days later. The cocaine IVSA findings confirm unusual long-lasting "anticocaine" effects of muscarinic M + M receptor stimulation. Thus, in mice, simultaneous stimulation of both receptor subtypes seems to produce potential neuroplastic changes that yield lasting effects.
PubMed: 38950842
DOI: 10.1016/j.pnpbp.2024.111079 -
European Journal of Pharmacology Jun 2024The link between type 2 diabetes mellitus (T2DM) and an increased risk of breast cancer has prompted the exploration of novel therapeutic strategies targeting shared... (Review)
Review
The link between type 2 diabetes mellitus (T2DM) and an increased risk of breast cancer has prompted the exploration of novel therapeutic strategies targeting shared metabolic pathways. This review focuses on the emerging evidence surrounding the potential anti-cancer effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors in the context of breast cancer. Preclinical studies have demonstrated that various SGLT2 inhibitors, such as canagliflozin, dapagliflozin, ipragliflozin, and empagliflozin, can inhibit the proliferation of breast cancer cells, induce apoptosis, and modulate key cellular signaling pathways. These mechanisms include the activation of AMP-activated protein kinase (AMPK), suppression of mammalian target of rapamycin (mTOR) signaling, and regulation of lipid metabolism and inflammatory mediators. The combination of SGLT2 inhibitors with conventional treatments, including chemotherapy and radiotherapy, as well as targeted therapies like phosphoinositide 3-kinases (PI3K) inhibitors, has shown promising results in enhancing the anti-cancer efficacy and potentially reducing treatment-related toxicities. The identification of specific biomarkers or genetic signatures that predict responsiveness to SGLT2 inhibitor therapy could enable more personalized treatment selection and optimization, particularly for challenging breast cancer subtypes [e, g., triple negative breast cancer (TNBC)]. Ongoing and future clinical trials investigating the use of SGLT2 inhibitors, both as monotherapy and in combination with other agents, will be crucial in elucidating their translational potential and guiding their integration into comprehensive breast cancer care. Overall, SGLT2 inhibitors represent a novel and promising therapeutic approach with the potential to improve clinical outcomes for patients with various subtypes of breast cancer, including the aggressive and chemo-resistant TNBC.
PubMed: 38950839
DOI: 10.1016/j.ejphar.2024.176803 -
Transplant Immunology Jun 2024Systemic lupus erythematosus (SLE) is usually regarded as a relative contraindication for deceased kidney donation. The pathological variations because of the changes in...
Systemic lupus erythematosus (SLE) is usually regarded as a relative contraindication for deceased kidney donation. The pathological variations because of the changes in the immune environment after kidney transplantation (KT) are unclear, and the recovery of renal function is poorly understood. We present a case of KT from a deceased donor with SLE who was followed-up for one year. Although SLE-related hemangioma developed during the perioperative period, it was cured after interventional treatment. A pre-planned biopsy was performed one year after KT, and it was found that most of the pathological changes and immunofluorescent markers of lupus had resolved. Renal function was stable, and urinary protein and occult blood levels reduced one year after KT.
PubMed: 38950754
DOI: 10.1016/j.trim.2024.102077 -
Fitoterapia Jun 2024Brain edema after ischemic stroke could worsen cerebral injury in patients who received intravenous thrombolysis. Cornus officinalis Sieb. et Zucc., a long-established...
Brain edema after ischemic stroke could worsen cerebral injury in patients who received intravenous thrombolysis. Cornus officinalis Sieb. et Zucc., a long-established traditional Chinese medicine, is beneficial to the treatment of neurodegenerative diseases including ischemic stroke. In particular, its major component, cornel iridoid glycoside (CIG), was evidenced to exhibit neuroprotective effects against cerebral ischemic/reperfusion injury (CIR/I). Aimed to explore the effects of the CIG on brain edema of the CIR/I rats, the CIG was analyzed with the main constituents by using HPLC. The molecular docking analysis was performed between the CIG constituents and AQP4-M23. TGN-020, an AQP4 inhibitor, was used as a comparison. In the in vivo experiments, the rats were pre-treated with the CIG and were injured by performing middle cerebral artery occlusion/reperfusion (MCAO/R). After 24 h, the rats were examined for neurological function, pathological changes, brain edema, and polarized Aqp4 expressions in the brain. The HPLC analysis indicated that the CIG was composed of morroniside and loganin. The molecular docking analysis showed that both morroniside and loganin displayed lower binding energies to AQP4-M23 than TGN-020. The CIG pre-treated rats exhibited fewer neurological function deficits, minimized brain swelling, and reduced lesion volumes compared to the MCAO/R rats. In the peri-infarct and infarct regions, the CIG pre-treatment restored the polarized Aqp4 expression which was lost in the MCAO/R rats. The results suggested that the CIG could attenuate brain edema of the cerebral ischemia/reperfusion rats by modulating the polarized Aqp4 through the interaction of AQP4-M23 with morroniside and loganin.
PubMed: 38950636
DOI: 10.1016/j.fitote.2024.106098 -
Klinische Padiatrie Jul 2024We sought to investigate adherence to the current pediatric syncope guideline in the emergency department and its impact on the frequency of missed or unnecessary...
BACKGROUND
We sought to investigate adherence to the current pediatric syncope guideline in the emergency department and its impact on the frequency of missed or unnecessary diagnostic measures. For the first time, in 2014 updated guideline defines indispensable basic diagnostic measures and a consecutive algorithm for safe clinical decision making.
PATIENTS AND METHOD
We analyzed retrospectively 314 pediatric patients, 166 were presented before and 148 after publication of this guideline update.
RESULTS
After guideline publication, 54 patients (36.5%) were not treated in accordance with the guideline and 2 (0.63%) cases caused by epileptic seizures were initially misdiagnosed as reflex syncope. Among these 54 patients, 32 (59.3%) inpatient admissions were inappropriate, as well as 11 (20.4%) electroencephalographies, 4 (7.4%) sleep-deprivation EEGs, 2 (3.7%) magnetic resonance imaging, 5 (9.3%) urine diagnostics and 32 (59.3%) blood tests. In 21 cases (38.9%), the medical history was insufficient. ECG was missed in 42 patients (77.8%). There was no significant difference between the pre- and post-guideline groups concerning diagnostic work-up (p=0,12).
DISCUSSION
This non-compliance with the guideline did not cause a large number of misdiagnosed epileptic seizures (1.4%) or adverse outcomes but led to waste of resources in healthcare system and undue burdens on patients and their families.
CONCLUSION
In addition to establishment of clinical guidelines, the need for additional measures and strategies to promote their implementation seems obvious.
PubMed: 38950601
DOI: 10.1055/a-2345-3343 -
Disability and Rehabilitation Jul 2024Children with Special Health Care Needs (CSHCN) may experience disruptions in education due to extended hospitalizations. The purpose of this study was to describe how...
Experiences of patients, parents, and healthcare professionals in the process of transitioning from hospital to community after inpatient pediatric rehabilitation among children with special health care needs.
PURPOSE
Children with Special Health Care Needs (CSHCN) may experience disruptions in education due to extended hospitalizations. The purpose of this study was to describe how CSHCN experience educational supports during inpatient rehabilitation and identify the ongoing challenges when planning to return to school.
MATERIALS AND METHODS
Semi-structured focus groups were conducted with parents ( = 12), former patients ( = 20), and rehabilitation professionals ( = 8).
RESULTS
Through qualitative thematic analysis based on descriptive phenomenology, we developed three themes: such as instruction and schoolwork helped reduce the learning loss during hospitalization. However, these supports were sometimes complicated by lags in school approvals and challenges in coordination between systems. involved establishing necessary services to support CSHCN's educational and healthcare needs at school re-entry. However, families reported limited information and guidance as key barriers. 3) required continued support after discharge. The participants recommended that reassessment and adjustment of transition plans were often necessary to account for evolving developmental and educational needs but were not always received.
CONCLUSIONS
There is an ongoing need to improve communication between clinicians and educators, information for families, and long-term follow-up on the changing educational needs for CSHCN after rehabilitation.
PubMed: 38950559
DOI: 10.1080/09638288.2024.2362951 -
Spectrochimica Acta. Part A, Molecular... Jun 2024Breath analysis enables rapid, noninvasive diagnosis of human health by identifying and quantifying exhaled biomarker. Here, we demonstrated an exhaled breath sensing...
Breath analysis enables rapid, noninvasive diagnosis of human health by identifying and quantifying exhaled biomarker. Here, we demonstrated an exhaled breath sensing method using the near-infrared laser spectroscopy, and sub parts-per-million (ppm) level ammonia detection inside the exhaled gas was achieved employing a distributed feedback laser centered at 1512 nm and Kalman filtering algorithm. Integration of the ammonia sensor was realized for exhaled breath analysis of kidney patients, and a dual operation mechanism with static and dynamic modes was proposed to make this method applicable for real-time and comprehensive pre-diagnosis of kidney disease.
PubMed: 38950480
DOI: 10.1016/j.saa.2024.124625 -
Medical Education Online Dec 2024To develop and maintain suturing skills, clinical exposure is important. When clinical exposure cannot be guaranteed, an adequate training schedule for suturing skills...
BACKGROUND
To develop and maintain suturing skills, clinical exposure is important. When clinical exposure cannot be guaranteed, an adequate training schedule for suturing skills is required. This study evaluates the effect of continuous training, 'reflection before practice' and self-assessment on basic open suturing skills.
METHODS
Medical students performed four basic suturing tasks on a simulation set up before ('pre-test') and after their surgical rotation ('after-test'). Participants were divided in three groups; the 'clinical exposure group' ( = 44) had clinical exposure during their rotation only, the 'continuous training group' ( = 16) completed a suturing interval training during their rotation and the 'self-assessment group' ( = 16) also completed a suturing interval training, but with the use of reflection before practice and self-assessment. Parameters measured by a tracking system during the suturing tasks and a calculated 'composite score' were compared between groups and test-moments.
RESULTS
A significantly better composite score was found at the after-test compared to the pre-test for all groups for all basic suturing tasks (0.001 ≤ ≤ 0.049). The self-assessment group scored better at the pre-test than the other two groups for all tasks, except for 'knot tying by hand' (0.004 ≤ ≤ 0.063). However, this group did not score better at the after-test for all tasks, compared to the other two groups. This resulted in a smaller delta of time ('transcutaneous suture', = 0.013), distance ('Donati suture' and 'intracutaneous suture', 0.005 ≤ ≤ 0.009) or composite score (all tasks, except for knot tying by hand, 0.007 ≤ ≤ 0.061) in the self-assessment group.
CONCLUSION
Reflection before practice and self-assessment during continuous training of basic open suturing tasks, may improve surgical skills at the start of the learning curve.
Topics: Suture Techniques; Humans; Self-Assessment; Clinical Competence; Students, Medical; Education, Medical, Undergraduate; Simulation Training; Male; Female; Educational Measurement
PubMed: 38950187
DOI: 10.1080/10872981.2024.2374101 -
Rheumatology (Oxford, England) Jul 2024
PubMed: 38950181
DOI: 10.1093/rheumatology/keae350 -
Journal of Managed Care & Specialty... Jul 2024The advent of next-generation imaging will likely reduce nonmetastatic prostate cancer (PC) prevalence and increase identification of metastatic prostate cancer cases,...
Real-world economic burden associated with disease progression from metastatic castration-sensitive to castration-resistant prostate cancer on treatment in the United States.
BACKGROUND
The advent of next-generation imaging will likely reduce nonmetastatic prostate cancer (PC) prevalence and increase identification of metastatic prostate cancer cases, resulting in two predominant advanced stages in the metastatic setting. There is a need to characterize changes in health care resource utilization (HRU) and costs when metastatic castration-sensitive PC (mCSPC) progresses to metastatic castration-resistant PC (mCRPC) to identify value drivers from current and new treatments.
OBJECTIVE
To describe treatment patterns, HRU, and total health care costs among patients with mCSPC, before and after progression to mCRPC.
METHODS
Clinical data from the Flatiron Metastatic PC Core Registry (January 1, 2013, to December 1, 2021) and linked claims from Komodo Health (January 1, 2014, to December 1, 2021) were used to identify patients with progression from mCSPC to mCRPC (date of progression was the index date) and subsequently initiated first-line mCRPC therapy on/after January 1, 2017. Treatment patterns and all-cause/PC-related HRU and health care costs were described per-patient-per-month (PPPM), separately for no more than 12 months pre-index (mCSPC disease state) and post-index (mCRPC disease state). Costs (payer's perspective) included those for services/procedures from medical claims and costs from pharmacy claims. Continuous HRU and costs were compared between the mCSPC and mCRPC disease states using Wilcoxon signed rank tests.
RESULTS
Among 296 patients with mCSPC progressing to mCRPC (median age 69.0 years, 60.5% White, 15.9% Black), use of systemic therapies with androgen deprivation therapy increased dramatically from 35.1% in the mCSPC disease state to 92.9% in the mCRPC disease state, and use of androgen deprivation therapy monotherapy decreased from 25.7% to 2.4%, respectively. Although 39.2% received none of these therapies in the mCSPC disease state, this proportion decreased to 4.7% after transition to mCRPC. The mean number of days with PC-related outpatient visits increased from 1.57 to 2.16 PPPM in the mCSPC and mCRPC disease states ( < 0.001). From the mCSPC to mCRPC disease states, mean all-cause total health care costs PPPM increased from $4,424 (medical costs: $2,846) to $9,717 (medical costs: $4,654), and mean PC-related total health care costs PPPM increased from $2,859 (medical costs: $1,626) to $8,012 (medical costs: $3,285; all < 0.001).
CONCLUSIONS
In this real-world study of patients with disease progression from mCSPC to mCRPC in US clinical practice, nearly 2-in-3 patients did not receive treatment with additional systemic therapies before progression to castration resistance. Post-progression, mean PC-related total costs increased nearly 3-fold, with a more than 2-fold increase in PC-related medical costs. Use of additional systemic therapies may delay the time and cost associated with disease progression to castration resistance.
Topics: Humans; Male; Prostatic Neoplasms, Castration-Resistant; Disease Progression; United States; Aged; Health Care Costs; Middle Aged; Cost of Illness; Retrospective Studies; Aged, 80 and over; Neoplasm Metastasis; Registries
PubMed: 38950154
DOI: 10.18553/jmcp.2024.30.7.684