Out-of-pocket costs for diagnostic testing following abnormal prostate cancer screening among privately insured men.

OBJECTIVE: Prostate cancer is the most common malignancy among men and following a positive prostate-specific antigen (PSA) screening test, patients may undergo more expensive diagnostic testing. However, testing-related out-of-pocket costs (OOPCs), which may preclude patients from completing the screening process, have not been previously quantified. OOPCs for follow-up diagnostic testing (i.e., prostate biopsy and/or magnetic resonance imaging [MRI]) in patients with private insurance undergoing prostate cancer screening were estimated. METHODS: Men ages 55 to 69 years old who underwent PSA-based prostate cancer screening from 2010 to 2020 from the IBM Marketscan database were identified. The number of patients undergoing follow-up diagnostic testing within 12 months of screening was tabulated, dividing patients into three groups: (1) biopsy only, (2) MRI only, and (3) MRI + biopsy. Over the study period, patients with nonzero cost-sharing and calculated inflation-adjusted OOPCs, adding copayment, coinsurance, and deductible payments, for each group were identified. RESULTS: Among screened patients (n = 3,075,841) from 2010 through 2020, 91,850 had a second PSA test and an elevated PSA level, of which 40,329 (43.9%) underwent subsequent diagnostic testing. More than 75% of these patients experienced cost-sharing, and median OOPCs rose substantially over the study period for patients undergoing biopsy only ($79 to $214), MRI only ($81 to $490), and MRI and biopsy ($353 to $620). CONCLUSIONS: OOPCs from diagnostic testing after prostate cancer screening are common and rising. This work aligns with the recent position statement from the American Cancer Society, that payers should eliminate cost-sharing, which may undermine the screening process, for diagnostic testing following cancer screening.

Racial and ethnic disparities in gallbladder cancer: A two-decade analysis of incidence and mortality rates in the US.

BACKGROUND: Gallbladder cancer (GBC) is an aggressive malignancy that is usually diagnosed at a late stage. Prior data showed increasing incidence of GBC in the US. However, little is known about race/ethnic-specific incidence and mortality trends of GBC per stage at diagnosis. Therefore, we aimed to conduct a time-trend analysis of GBC incidence and mortality rates categorized by race/ethnicity and stage-at-diagnosis. METHODS: Age-adjusted GBC incidence and mortality rates were calculated using SEER*Stat software from the United States Cancer Statistics database (covers ~98% of US population between 2001 and 2020) and NCHS (covers ~100% of the US population between 2000 and 2020) databases, respectively. Race/Ethnic groups were Non-Hispanic-White (NHW), Non-Hispanic-Black (NHB), Hispanic, Non-Hispanic-Asian/Pacific-Islander (NHAPI), and Non-Hispanic-American-Indian/Alaska-Native (NHAIAN). Stage-at-diagnoses were all stages, early, regional, and distant stages. Joinpoint regression was used to generate time-trends [annual percentage change (APC) and average APC (AAPC)] with parametric estimations and a two-sided t-test (p-value cut-off 0.05). RESULTS: 76,873 patients were diagnosed with GBC with decreasing incidence rates in all races/ethnicities except NHB who experienced an increasing trend between 2001 and 2014 (APC = 2.08, p < 0.01) and plateauing afterward (APC = -1.21, p = 0.31); (AAPC = 1.03, p = 0.03). Among early-stage tumors (9927 patients), incidence rates were decreasing only in Hispanic (AAPC = -4.24, p = 0.006) while stable in other races/ethnicities (NHW: AAPC = -2.61, p = 0.39; NHB: AAPC = -1.73, p = 0.36). For regional-stage tumors (29,690 patients), GBC incidence rates were decreasing only in NHW (AAPC = -1.61, p < 0.001) while stable in other races/ethnicities (NHB: AAPC = 0.73, p = 0.34; Hispanic: AAPC = -1.58, p = 0.24; NHAPI: AAPC = -1.22, p = 0.07). For distant-stage tumors (31,735 patients), incidence rates were increasing in NHB (AAPC = 2.72, p < 0.001), decreasing in Hispanic (AAPC = -0.64, p = 0.04), and stable in NHW (AAPC = 0.07, p = 0.84) and NHAPI (AAPC = 0.79, p = 0.13). There were 43,411 deaths attributed to GBC with decreasing mortality rates in all races/ethnicities except NHB who experienced a stable trend (AAPC = 0.25, p = 0.25). CONCLUSION: Nationwide data over the last two decades show that NHB patients experienced increasing GBC incidence between 2001 and 2014 followed by stabilization of the rates. This increase was driven by late-stage tumors and occurred in the first decade. NHB also experienced non-improving GBC mortality, compared to other race and ethnic groups who had decreasing mortality. This can be due to lack of timely-access to healthcare leading to delayed diagnosis and worse outcomes. Future studies are warranted to investigate contributions to the revealed racial and ethnic disparities, especially in NHB, to improve early detection.

Minimizing and managing needle and instrument loss during pediatric robotic surgery.

INTRODUCTION: Lost objects and equipment malfunctions during robotic and laparoscopic cases can lead to an increase in operating time and potential risk to the patient. The literature on the management of foreign bodies during pediatric robotic-assisted surgery is limited. The purpose of the video is to review proper instrument handling to prevent loss of an object and to propose our technique for retrieving lost objects through two pediatric case examples. MATERIALS AND METHODS: The first case is a robotic-assisted laparoscopic left pyeloplasty in a 6-week-old male with congenital uteropelvic junction obstruction during which a needle was lost. In the video, we describe our techniques for safe needle passage, proper suturing technique, and recovering a lost needle. The second case is a robotic-assisted right upper pole heminephrectomy in a 14-month-old female with a duplicated renal collecting system and hydroureteronephrosis. We present the management of a rare case during which a harmonic scalpel jaw malfunctioned leading to a lost foreign body. We describe our technique for retrieving the lost fragment. RESULTS: All objects were safely removed, and patients were discharged post-op day one without complication. CONCLUSION: Our video presents two case examples of foreign bodies lost during pediatric robotic surgeries and approaches to manage each of these incidents.

Spatial mapping of mobile genetic elements and their bacterial hosts in complex microbiomes.

The exchange of mobile genetic elements (MGEs) facilitates the spread of functional traits including antimicrobial resistance within bacterial communities. Tools to spatially map MGEs and identify their bacterial hosts in complex microbial communities are currently lacking, limiting our understanding of this process. Here we combined single-molecule DNA fluorescence in situ hybridization (FISH) with multiplexed ribosomal RNA-FISH to enable simultaneous visualization of both MGEs and bacterial taxa. We spatially mapped bacteriophage and antimicrobial resistance (AMR) plasmids and identified their host taxa in human oral biofilms. This revealed distinct clusters of AMR plasmids and prophage, coinciding with densely packed regions of host bacteria. Our data suggest spatial heterogeneity in bacterial taxa results in heterogeneous MGE distribution within the community, with MGE clusters resulting from horizontal gene transfer hotspots or expansion of MGE-carrying strains. Our approach can help advance the study of AMR and phage ecology in biofilms.

Post-Operative Hyperextension Bracing Has the Potential to Reduce Proximal Junctional Kyphosis: A Propensity Matched Analysis of Braced versus Non-braced Cohorts.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: Determine effects of bracing on proximal junctional kyphosis (PJK) after adult deformity correction. METHODS: Patients were identified from a single-surgeon dataset of posterior-only fusions for ASD (pelvis to UIV of T9-12) with a minimum of 1-year follow up. Starting in 2021, all lower thoracic fusions were braced using a hyperextension brace. Patients wore the brace at all times (unless in bed) for the first 6 weeks after surgery. A 1:1 propensity-match was performed based on age, number of levels, 3 column osteotomies, and magnitude of correction to identify a comparative non-braced cohort. RESULTS: 141 patients (113 non-brace, 28 brace) were evaluated. After matching, 56 patients were identified to form similar cohorts. Non-matched and matched groups had no statistically significant differences in demographics, comorbid conditions, surgical characteristics (except shorter operative time and lower EBL in the braced group), and preoperative radiographic parameters. For the overall cohort, the change in proximal junctional angle at 1-year was higher in the non-braced group (7.6° vs 8.1°, P = .047), and non-braced patients had a higher incidence of PJK at 1-year in both the overall cohort (36% vs 14%, P = .045) and matched cohort (43% vs 14%, P = .038). There was no difference in proximal junctional failure between groups. CONCLUSION: This pilot study shows that our protocol for extension bracing may reduce rates of PJK. These findings can form the basis for future multi-center trials examining the effect of extension bracing on junctional complications.

Mid- to Long-Term Outcomes in Patients After Hip Arthroscopy With Labral Reconstruction: A Systematic Review.

Background: There is a paucity of aggregate data documenting mid- to long-term outcomes of patients after hip arthroscopy with labral reconstruction. Purpose: To report mid- to long-term outcomes in patients after undergoing either primary or revision hip arthroscopy with labral reconstruction for the treatment of irreparable labral tears. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review of the PubMed, Cochrane, and Scopus databases in May 2022 was conducted with the following keywords: "hip arthroscopy,""labral reconstruction,""irreparable,""labrum,""reconstruction,""five-year,""midterm,""5 year,""long-term,""10 year," ten-year," and "femoroacetabular impingement" using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Midterm was defined as mean 5-year follow-up, and long-term was defined as mean 10-year or longer follow-up. For each included article, the demographic, radiographic, intraoperative, and surgical variables, as well as patient-reported outcomes (PROs), psychometric thresholds, and secondary surgeries were recorded. Forest plots were created for PROs that were reported in ≥3 studies; heterogeneity was assessed using I2 values. Results: Out of 463 initial articles, 5 studies including 178 hips with primary and 41 hips with revision surgeries were included. One study had an average 5-year follow-up, three studies had a minimum 5-year follow-up and one study had a minimum 10-year follow-up. The most common indications for hip arthroscopy with labral reconstruction were irreparable labral tears. The most common PRO was the modified Harris Hip Score (mHHS), which was reported in all 5 studies. The mean preoperative mHHS ranged from 58.9 to 66, and the mean postoperative mHHS at minimum 5-year follow-up ranged from 80.2 to 89. The preoperative and postoperative mHHSs for the single long-term follow-up study were 60 and 82, respectively. All 5 studies demonstrated significant improvements in reported PROs. All 5 studies reported secondary surgery rates, with 1 study reporting rates at both 5- and 10-year follow-up. Conversion to total hip arthroplasty ranged from 0% to 27%, while overall secondary surgery rates ranged from 0% to 36%. Conclusion: Findings demonstrated that patients undergoing primary and revision hip arthroscopy with labral reconstruction experienced favorable outcomes and high rates of clinical benefit and survivorship at mid- to long-term follow-up.

Balancing innovation and affordability in anti-obesity medications: the role of an alternative weight-maintenance program.

Despite remarkable clinical advances in highly effective anti-obesity medications, their high price and potential budget impact pose a major challenge in balancing equitable access and affordability. While most attention has been focused on the amount of weight loss achieved, less consideration has been paid to interventions to sustain weight loss after an individual stops losing weight. Using a policy simulation model, we quantified the impact of a weight-maintenance program following the weight-loss plateau from the initial full-dose glucagon-like peptide 1 (GLP-1) receptor agonists or incretin mimetic use. We measured long-term health care savings and the loss of some health benefits (eg, maintenance of weight loss, improvements in cardiometabolic risk factors, and reductions in diabetes and cardiovascular events). Our model suggested that, compared with continuous long-term full-dose GLP-1 receptor agonists or incretin mimetic drugs, the alternative weight-maintenance program would generate slightly fewer clinical benefits while generating substantial savings in lifetime health care spending. Using less expensive and potentially less effective alternative weight-maintenance programs may provide additional headroom to expand access to anti-obesity medications during the active weight-loss phase without increasing total health care spending.

X-linked Inhibitor of Apoptosis (XIAP) Deficiency Complicated by Hemophagocytic Lymphohistiocytosis on Immunotherapy Leading to Acute Respiratory Distress Syndrome and Multiorgan Failure Secondary to Opportunistic Infections.

X-linked inhibitor of apoptosis (XIAP) deficiency is a rare primary immunodeficiency with a broad spectrum of clinical manifestations, including susceptibility to hemophagocytic lymphohistiocytosis (HLH), inflammatory bowel disease (IBD), hypogammaglobulinemia, and severe infections. We present a case of a 39-year-old male with a past medical history of XIAP deficiency complicated by HLH, Crohn's disease, and hypogammaglobulinemia, who developed acute respiratory distress syndrome (ARDS) due to Pneumocystis jiroveci pneumonia (PJP) and concurrent multiorgan failure due to disseminated Mycobacterium avium intracellulare (MAI) infection. This case highlights the challenges in managing XIAP deficiency, emphasizing the importance of early recognition, and the need for further research to improve outcomes in this population.

Dual Cardiac Arrests Leading to Hypercoagulability and Extensive Upper Extremity Deep Vein Thrombosis: A Hematological Case Report.

Upper extremity (UE) deep vein thrombosis (DVT) is a rare yet significant complication that can occur following cardiac arrest (CA). CA initiates a prothrombotic state via various processes, including stasis, endothelial damage, and an impaired balance between thrombogenesis and fibrinolysis, which may contribute to UE DVT formation. Inadequate cardiopulmonary resuscitation (CPR) in the field may further exacerbate blood stasis and clot formation. This case report describes an 80-year-old male with a history of bladder cancer who experienced two cardiac arrest events and subsequently developed an extensive left UE DVT. Despite treatment with a heparin drip and other supportive measures, the patient's condition deteriorated, and he passed away on the tenth day of hospitalization. This case is the first to describe UE DVT post-CA. It underscores the importance of recognizing and proactively managing hypercoagulable states post-CA, which can lead to significant DVTs in atypical locations that may evolve into life-threatening conditions.

Cauda Equina Syndrome: Cost Burden After Spinal Decompression.

STUDY DESIGN: Observational cohort study. OBJECTIVE: Cauda equina syndrome (CES) is a rare neurologic condition with potentially devastating consequences. The objective of this study was to compare the 2-year postoperative cost-associated treatments after posterior spinal decompression between patients with and without CES. METHODS: By analyzing a commercial insurance claims database, patients who underwent posterior spinal decompression with a concurrent diagnosis of lumbar spinal stenosis, radiculopathy, or disk herniation in 2017 were identified and included in the study. The primary outcome was the cost of payments for identified treatments in the 2-year period after surgery. Treatments included were (1) physical therapy (PT), (2) pain medication, (3) injections, (4) bladder management, (5) bowel management, (6) sexual dysfunction treatment, and (7) psychological treatment. RESULTS: In total, 3,140 patients (age, 55.3 ± 12.0 years; male, 62.2%) were included in the study. The average total cost of treatments identified was $2,996 ± 6,368 per patient. The overall cost of identified procedures was $2,969 ± 6,356 in non-CES patients, compared with $4,535 ± 6,898 in patients with CES ( P = 0.079). Among identified treatments, only PT and bladder management costs were significantly higher for patients with CES (PT: +115%, P < 0.001; bladder management: +697%, P < 0.001). The difference in overall cost was significant between patients (non-CES: $1,824 ± 3,667; CES: $3,022 ± 4,679; P = 0.020) in the first year. No difference was found in the second year. DISCUSSION: A short-term difference was observed in costs occurring in the first postoperative year. Cost of treatments was similar between patients apart from PT and bladder management.

Medication use before and after bariatric surgery: 5-year results from a randomised controlled trial of banded Roux-en-Y gastric bypass versus sleeve gastrectomy in patients with obesity and type 2 diabetes.

AIM: Bariatric surgery is an effective tool for weight loss and for improving weight related co-morbidities. Changes in medication usage after a silastic ring laparoscopic Roux-en-Y gastric bypass (SR-LRYGB) compared with laparoscopic sleeve gastrectomy (LSG) are unknown. METHODS: This was a single-centre, double-blind, randomised controlled trial. Patients were randomised to either SR-LRYGB or LSG. A medication history was obtained at regular follow-up intervals, and mean numbers of prescribed medications were analysed over 5 years. Poisson regression and generalised estimating equations were used to test for statistically significant changes in usage. RESULTS: After eight patients were lost to follow-up, data from 52 patients in each group were available for analysis. There was no difference between the SR-LRYGB or LSG groups in the number of medications prescribed, with the exception of oral glucose-lowering medications, where there was a greater decrease after SR-LRYGB compared to LSG (79% vs 55% respectively) from baseline to 5 years. At 5 years, total medication prescribed was down 10% from pre-operative levels. Prescribed insulin decreased by 72%, and cardiovascular medication decreased by 56% compared to baseline. Prescriptions for analgesia increased by 50%, psychiatric medications by 133% and proton-pump inhibitors by 81%. CONCLUSION: Both SR-LRYGB and LSG reduced requirement for diabetic and cardiovascular medications, but increased requirement for nutritional supplementation, analgesia and psychiatric medications. There was a greater reduction in oral anti-diabetic medication prescriptions following SR-LRYGB compared to LSG, but no other difference in medication usage between surgical groups was found.

The current state of digital cytology and artificial intelligence (AI): global survey results from the American Society of Cytopathology Digital Cytology Task Force.

INTRODUCTION: The integration of whole slide imaging (WSI) and artificial intelligence (AI) with digital cytology has been growing gradually. Therefore, there is a need to evaluate the current state of digital cytology. This study aimed to determine the current landscape of digital cytology via a survey conducted as part of the American Society of Cytopathology (ASC) Digital Cytology White Paper Task Force. MATERIALS AND METHODS: A survey with 43 questions pertaining to the current practices and experiences of WSI and AI in both surgical pathology and cytology was created. The survey was sent to members of the ASC, the International Academy of Cytology (IAC), and the Papanicolaou Society of Cytopathology (PSC). Responses were recorded and analyzed. RESULTS: In total, 327 individuals participated in the survey, spanning a diverse array of practice settings, roles, and experiences around the globe. The majority of responses indicated there was routine scanning of surgical pathology slides (n = 134; 61%) with fewer respondents scanning cytology slides (n = 150; 46%). The primary challenge for surgical WSI is the need for faster scanning and cost minimization, whereas image quality is the top issue for cytology WSI. AI tools are not widely utilized, with only 16% of participants using AI for surgical pathology samples and 13% for cytology practice. CONCLUSIONS: Utilization of digital pathology is limited in cytology laboratories as compared to surgical pathology. However, as more laboratories are willing to implement digital cytology in the near future, the establishment of practical clinical guidelines is needed.

Transgenic Overexpression of HDAC9 Promotes Adipocyte Hypertrophy, Insulin Resistance and Hepatic Steatosis in Aging Mice.

Histone deacetylase (HDAC) 9 is a negative regulator of adipogenic differentiation, which is required for maintenance of healthy adipose tissues. We reported that HDAC9 expression is upregulated in adipose tissues during obesity, in conjunction with impaired adipogenic differentiation, adipocyte hypertrophy, insulin resistance, and hepatic steatosis, all of which were alleviated by global genetic deletion of Hdac9. Here, we developed a novel transgenic (TG) mouse model to test whether overexpression of Hdac9 is sufficient to induce adipocyte hypertrophy, insulin resistance, and hepatic steatosis in the absence of obesity. HDAC9 TG mice gained less body weight than wild-type (WT) mice when fed a standard laboratory diet for up to 40 weeks, which was attributed to reduced fat mass (primarily inguinal adipose tissue). There was no difference in insulin sensitivity or glucose tolerance in 18-week-old WT and HDAC9 TG mice; however, at 40 weeks of age, HDAC9 TG mice exhibited impaired insulin sensitivity and glucose intolerance. Tissue histology demonstrated adipocyte hypertrophy, along with reduced numbers of mature adipocytes and stromovascular cells, in the HDAC9 TG mouse adipose tissue. Moreover, increased lipids were detected in the livers of aging HDAC9 TG mice, as evaluated by oil red O staining. In conclusion, the experimental aging HDAC9 TG mice developed adipocyte hypertrophy, insulin resistance, and hepatic steatosis, independent of obesity. This novel mouse model may be useful in the investigation of the impact of Hdac9 overexpression associated with metabolic and aging-related diseases.

Successful Management of Impending Skin Necrosis After a Posterolateral Knee Dislocation.

Incarcerated medial soft tissue after posterolateral knee dislocations has been described, but limited information pertaining to the etiology and management of cutaneous injuries from incarceration exists. We present the case of a 64-year-old man, where reduction of a posterolateral knee dislocation resulted in incarceration of medial ligamentous structures and impending skin necrosis. The patient avoided full-thickness skin necrosis, which could have complicated treatment options. Careful consideration of the soft-tissue envelope of the knee for preventing additional skin injury in the perioperative period should be considered to potentially avert additional necrosis in patients with a 'pucker' sign after knee dislocations.

Cold-Induced Reflex Epilepsy.

This case report describes a woman cold-induced reflex seizures.

Probing entanglement in a 2D hard-core Bose-Hubbard lattice.

Entanglement and its propagation are central to understanding many physical properties of quantum systems1-3. Notably, within closed quantum many-body systems, entanglement is believed to yield emergent thermodynamic behaviour4-7. However, a universal understanding remains challenging owing to the non-integrability and computational intractability of most large-scale quantum systems. Quantum hardware platforms provide a means to study the formation and scaling of entanglement in interacting many-body systems8-14. Here we use a controllable 4 × 4 array of superconducting qubits to emulate a 2D hard-core Bose-Hubbard (HCBH) lattice. We generate superposition states by simultaneously driving all lattice sites and extract correlation lengths and entanglement entropy across its many-body energy spectrum. We observe volume-law entanglement scaling for states at the centre of the spectrum and a crossover to the onset of area-law scaling near its edges.

Intermolecular Interactions between Cysteine and Aromatic Amino Acids with a Phenyl Moiety in the DNA-Binding Domain of Heat Shock Factor 1 Regulate Thermal Stress-Induced Trimerization.

In this study, we investigated the trimerization mechanism and structure of heat shock factor 1 (HSF1) using western blotting, tryptophan (Trp) fluorescence spectroscopy, and molecular modeling. First, we examined the DNA-binding domains of human (Homo sapiens), goldfish (Carassius auratus), and walleye pollock (Gadus chalcogrammus) HSF1s by mutating key residues (36 and 103) that are thought to directly affect trimer formation. Human, goldfish, and walleye pollock HSF1s contain cysteine at residue 36 but cysteine (C), tyrosine (Y), and phenylalanine (F), respectively, at residue 103. The optimal trimerization temperatures for the wild-type HSF1s of each species were found to be 42, 37, and 20 °C, respectively. Interestingly, a mutation experiment revealed that trimerization occurred at 42 °C when residue 103 was cysteine, at 37 °C when it was tyrosine, and at 20 °C when it was phenylalanine, regardless of the species. In addition, it was confirmed that when residue 103 of the three species was mutated to alanine, trimerization did not occur. This suggests that in addition to trimerization via disulfide bond formation between the cysteine residues in human HSF1, trimerization can also occur via the formation of a different type of bond between cysteine and aromatic ring residues such as tyrosine and phenylalanine. We also confirmed that at least one cysteine is required for the trimerization of HSF1s, regardless of its position (residue 36 or 103). Additionally, it was shown that the trimer formation temperature is related to growth and survival in fish.

Fibrolamellar Hepatocellular Carcinoma (FLHCC) in a Young Patient Presenting With Nausea and Vomiting After a Greasy Meal.

Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare and distinct subtype of liver cancer, predominantly affecting younger patients without underlying liver diseases. This case report discusses a unique presentation of FLHCC in a 38-year-old male with a past medical history of a well-controlled seizure disorder. The patient presented with nausea, vomiting, and abdominal pain following a fatty meal. Laboratory tests revealed elevated liver enzymes and anemia, and imaging showed a large hepatic lesion. Initial management included a septic workup and broad-spectrum antibiotics. However, a liver biopsy performed subsequently revealed the presence of FLHCC. The patient underwent a successful open right hepatectomy and was managed postoperatively with consideration of his seizure disorder. Follow-up at six months showed a stable postoperative condition without any evidence of recurrence. The diagnosis of FLHCC is challenging due to its rarity and nonspecific presentation. The case emphasizes the importance of considering FLHCC in the differential diagnosis of hepatic lesions, particularly in young patients. Surgical resection remains the primary treatment modality. This case underscores the importance of a thorough evaluation of hepatic lesions, especially in younger patients. It also illustrates the complexities in managing patients with FLHCC, requiring a multidisciplinary approach for optimal outcomes. Further research is necessary to better understand the pathogenesis of FLHCC and to develop more effective treatment strategies.

A systematic review and meta-analysis of synthetic cathinone use and psychosis.

RATIONALE: Synthetic cathinones (SC), commonly referred to as "bath salts", are stimulants resembling the natural alkaloid cathinone found in the khat plant. These substances have the potential to induce serious health risks such as hallucinations, delusions, paranoia and agitation which can lead to substance-induced psychotic disorders. Despite growing concerns, there is a limited understanding of the association between SC consumption and the devolvement of such psychopathologies. METHODS: We conducted a systematic review to investigate the frequency of substance-induced psychotic disorder (SIPD) and associated conditions in humans following synthetic cathinone consumption. We qualitatively and quantitatively analyzed SC exposure cases. RESULTS: A total of 32 studies were included, with a diverse range of demographics, synthetic cathinone types, and consumption patterns. The proportion of individuals developing psychotic symptoms was reported at 0.380 (Random-effects model, 95% CI 0.289 - 0.475). Additionally, the significant heterogeneity in diagnostic approaches limited our ability to provide a precise estimate of prevalence. CONCLUSIONS: Synthetic cathinone consumption is associated with the risk of developing psychotic symptoms as indicated by the prevalence of hallucinations and/or delusions. Due to the lack of information on classifying factors, particularly duration of symptoms, we are unable to conclude synthetic cathinone-induced psychosis. Further research is warranted to elucidate the underlying mechanism linking synthetic cathinone consumption and psychosis. This review underscores the urgency of addressing the growing health risks posed by synthetic cathinone use. Additionally, it highlights the necessity of proper quantification of psychotic symptoms through scales and reporting of classification criteria to accurately diagnose SIPD.

pH Dependence of HSF1 trimerization is shaped by intramolecular interactions.

Heat shock factor 1 (HSF1) primarily regulates various cellular stress responses. Previous studies have shown that low pH within the physiological range directly activates HSF1 function in vitro. However, the detailed molecular mechanisms remain unclear. This study proposes a molecular mechanism based on the trimerization behavior of HSF1 at different pH values. Extensive mutagenesis of human and goldfish HSF1 revealed that the optimal pH for trimerization depended on the identity of residue 103. In particular, when residue 103 was occupied by tyrosine, a significant increase in the optimal pH was observed, regardless of the rest of the sequence. This behavior can be explained by the protonation state of the neighboring histidine residues, His101 and His110. Residue 103 plays a key role in trimerization by forming disulfide or non-covalent bonds with Cys36. If tyrosine resides at residue 103 in an acidic environment, its electrostatic interactions with positively charged histidine residues prevent effective trimerization. His101 and His110 are neutralized at a higher pH, which releases Tyr103 to interact with Cys36 and drives the effective trimerization of HSF1. This study showed that the protonation state of a histidine residue can regulate the intramolecular interactions, which consequently leads to a drastic change in the oligomerization behavior of the entire protein.