Studies on synthesis and influence of sterically driven Ni(II)-terpyridine (NNN) complexes on BSA/DNA binding and anticancer activity.

The present work demonstrates the synthesis, structural diversity and coordination behavior of some selected new Ni(II)-Tpy complexes. The structural analysis revealed the coordination of the selected terpyridine ligands with the core metal atom in two different modes via dimeric species (1:1 fashion) through the Cl-bridging and a bis(Tpy)-Ni complex (2:1 fashion). Perhaps the most striking manifestations of these Ni(II)-Tpy complexes are BSA/DNA binding ability and anticancer activity. In addition, the cytotoxicity studies of Tpy ligand (4-([2,2':6',2″-terpyridin]-4'-yl)phenyl 5-methylthiophene-2-carboxylate) and the Ni(II) complexes were carried out using lung cancer cell line (A549), breast cancer cell line (MCF-7) and normal cell line (Vero cell). The cytotoxicity results were compared with the cisplatin control group. Notably, bis-terpyridyl complex 3C (R = 4-([2,2':6',2″-terpyridin]-4'-yl)phenyl 4-isopropoxybenzoate) demonstrates better activity with the IC50 value of 23.13 ± 3 µm for A549 and 22.7 ± 3 for MCF-7. The DFT calculations reveal the significant energy differences of HOMO and LUMO for the ligands and their corresponding Ni(II) complexes. The Tpy ligands and Ni(II)-Tpy complexes were investigated for BSA binding and further all the Ni(II) complexes were analyzed for DNA binding studies.

Serum levels of hydroxylated metabolites of arachidonic acid cross-sectionally and longitudinally predict knee pain progression: an observational cohort study.

OBJECTIVE: To examine associations between serum oxylipins, which regulate tissue repair and pain signalling, and knee pain/radiographic osteoarthritis (OA) at baseline and knee pain at 3 year follow-up. METHOD: Baseline, and 3 year follow-up, knee pain phenotypes were assessed from 154 participants in the Knee Pain in the Community (KPIC) cohort study. Serum and radiographic Kellgren and Lawrence (KL) and Nottingham line drawing atlas OA scores were collected at baseline. Oxylipin levels were quantified using liquid chromatography coupled with mass spectrometry. Associations were measured by linear regression and receiver operating characteristics (ROC). RESULTS: Serum levels of 8,9-epoxyeicosatrienoic acid (EET) (ß(95% confidence intervals (CI)) = 1.809 (-0.71 to 2.91)), 14,15-dihydroxyeicosatrienoic acid (DHET) (ß(95%CI) = 0.827 (0.34-1.31)), and 12-hydroxyeicosatetraenoic acid (HETE) (ß(95%CI) = 4.090 (1.92-6.26)) and anandamide (ß(95%CI) = 3.060 (1.35-4.77)) were cross-sectionally associated with current self-reported knee pain scores (numerical rating scale (NRS) item 3, average pain). Serum levels of 9- (ß(95%CI) = 0.467 (0.18-0.75)) and 15-HETE (ß(95%CI) = 0.759 (0.29-1.22)), 14-hydroxydocosahexaenoic acid (ß(95%CI) = 0.483(0.24-0.73)), and the ratio of 8,9-EET:DHET (ß(95%CI) = 0.510(0.19-0.82)) were cross-sectionally associated with KL scores. Baseline serum concentrations of 8,9-EET (ß(95%CI) = 2.166 (0.89-3.44)), 5,6-DHET (ß(95%CI) = 152.179 (69.39-234.97)), and 5-HETE (ß(95%CI) = 1.724 (0.677-2.77) showed positive longitudinal associations with follow-up knee pain scores (NRS item 3, average pain). Combined serum 8,9-EET and 5-HETE concentration showed the strongest longitudinal association (ß(95%CI) = 1.156 (0.54-1.77) with pain scores at 3 years, and ROC curves distinguished between participants with no pain and high pain scores at follow-up (area under curve (95%CI) = 0.71 (0.61-0.82)). CONCLUSIONS: Serum levels of a combination of hydroxylated metabolites of arachidonic acid may have prognostic utility for knee pain, providing a potential novel approach to identify people who are more likely to have debilitating pain in the future.

Exploring kidney dialysis costs in the United States: a scoping review.

AIMS: The increasing prevalence of end-stage renal disease (ESRD) in the United States (US) represents a considerable economic burden due to the high cost of dialysis treatment. This review examines data from real-world studies to identify cost drivers and explore areas where dialysis costs could be reduced. METHODS: We identified and synthesized evidence published from 2016-2023 reporting direct dialysis costs in adult US patients from a comprehensive literature search of MEDLINE, Embase, and grey literature sources (e.g. US Renal Data System reports). RESULTS: Most identified data related to Medicare expenditures. Overall Medicare spending in 2020 was $29B for hemodialysis and $2.8B for peritoneal dialysis (PD). Dialysis costs accounted for almost 80% of total Medicare expenditures on ESRD beneficiaries. Private insurance payers consistently pay more for dialysis; for example, per person per month spending by private insurers on outpatient dialysis was estimated at $10,149 compared with Medicare spending of $3,364. Dialysis costs were higher in specific high-risk patient groups (e.g. type 2 diabetes, hepatitis C). Spending on hemodialysis was higher than on PD, but the gap in spending between PD and hemodialysis is closing. Vascular access costs accounted for a substantial proportion of dialysis costs. LIMITATIONS: Insufficient detail in the identified studies, especially related to outpatient costs, limits opportunities to identify key drivers. Differences between the studies in methods of measuring dialysis costs make generalization of these results difficult. CONCLUSIONS: These findings indicate that prevention of or delay in progression to ESRD could have considerable cost savings for Medicare and private payers, particularly in patients with high-risk conditions such as type 2 diabetes. More efficient use of resources is needed, including low-cost medication, to improve clinical outcomes and lower overall costs, especially in high-risk groups. Widening access to PD where it is safe and appropriate may help to reduce dialysis costs.

Previous papers have studied the cost of treating patients who need dialysis for kidney failure. We reviewed these costs and looked for patterns. Dialysis was the most expensive part of treatment for people with kidney disease who have Medicare. Dialysis with private insurance was much more expensive than with Medicare. People with diabetes experienced higher costs of dialysis than those without diabetes. Dialysis in a hospital costs more than dialysis at home. There are opportunities to reduce the cost of dialysis that should be explored further, such as more use of low-cost medication that can prevent the worsening of kidney disease and reduce the need for dialysis.

A Comparative Study of Acute Invasive Fungal Sinusitis During the First and Second Waves of the COVID-19 Pandemic.

We aimed to compare the demography, clinical profile, histopathology, fungal culture, radiology, surgery performed, medical therapy and outcomes of patients with acute invasive fungal sinusitis seen during the first and second waves of the COVID-19 pandemic by retrospectively reviewing their case records. Of 238 patients, 43(18.1%) presented during the first wave and 195(81.9%) during the second wave. Patients seen during the first wave were older (p = 0.04) and more likely to have visual impairment (p = 0.004), frozen eye (p = 0.012), altered sensorium (p = 0.007) and stage 3 disease (p = 0.03). Those seen during the second wave were more often COVID-19 positive and had newly diagnosed diabetes mellitus (p = 0.04)and stage 1 disease (p = 0.03). Most patients had a positive culture for Rhizopus species during both waves. Histopathology showed broad aseptate hyphae in all patients but angioinvasion was seen more often during the first wave (p = 0.04). The majority of patients were treated with endoscopic+/- open debridement followed by intravenous amphotericin B and oral posaconazole. While the overall survival rate was similar (first wave 65.1%; second wave 79%; p = 0.106), mortality after discharge was greater during the first wave (11.6% vs 1.5%; p = 0.001). Mortality was higher in patients with stage 3 disease (p = 0.003). Significant differences in clinical presentation, histopathology, radiological stage of disease and post-discharge survival were noted between the two waves of the COVID-19 pandemic, the causes for which were multi-factorial.

The Impact of Preoperative Medical Evaluation in an Orthopaedic Perioperative Medical Clinic on Total Joint Arthroplasty Outcomes: An Observational Study.

BACKGROUND: A preoperative medical evaluation (PME) in total joint arthroplasty (TJA) is routine despite considerable variation and uncertainty regarding its benefits. The orthopaedic department in our academic health system established a perioperative medical clinic (PMC) to standardize perioperative management and to study the effect of this intervention on total hip arthroplasty (THA) and total knee arthroplasty (TKA) outcomes. This observational study compared the impact of a PME within 30 days prior to surgery at the PMC (Periop30) versus elsewhere ("Usual Care") on postoperative length of stay (LOS), extended LOS (i.e., a stay of >3 days), and Patient-Reported Outcomes Measurement Information System-10 (PROMIS-10) Global Physical Health (GPH) score improvement in TJA. METHODS: We stratified adult patients (≥18 years of age) who underwent primary TJA between January 2015 and December 2020 into Periop30 or Usual Care. We utilized univariate tests (a chi-square test for categorical variables and a t test for continuous variables) to assess for differences in patient characteristics. For both TKA and THA, LOS was assessed with use of multivariable negative binomial regression models; extended LOS, with use of binary logistic regression; and PROMIS-10 GPH score, with use of mixed-effects models with random intercept and slope. Interaction terms between the focal predictor (Periop30, yes or no) and year of surgery were included in all models. RESULTS: Periop30 comprised 82.3% of TKAs (1,911 of 2,322 ) and 73.8% of THAs (1,876 of 2,541). For THA, the Periop30 group tended to be male (p = 0.005) and had a higher body mass index (p = 0.001) than the Usual Care group. The Periop30 group had a higher rate of staged bilateral THA (10.6% versus 7.5%; p = 0.028) and a lower rate of simultaneous bilateral TKA (5.1% versus 12.2%; p < 0.001) than the Usual Care group. Periop30 was associated with a lower mean LOS for both TKA (43.46 versus 54.15 hours; p < 0.001) and THA (41.07 versus 57.94 hours; p < 0.001). The rate of extended LOS was lower in the Periop30 group than in the Usual Care group for both TKA (15% versus 26.5%; p < 0.001) and THA (13.3% versus 27.4%; p < 0.001). There was no significant difference in GPH score improvement between Periop30 and Usual Care for either TKA or THA. CONCLUSIONS: Periop30 decreased mean LOS and the rate of extended LOS for TJA without an adverse effect on PROMIS-10 GPH scores. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

The Effect of Acute Knee Injuries and Related Knee Surgery on Serum Levels of Pro- and Anti-inflammatory Lipid Mediators and Their Associations With Knee Symptoms.

BACKGROUND: Despite an acute knee injury being a major risk factor for osteoarthritis, the factors that initiate and maintain this risk of longer-term knee symptoms are poorly understood. Bioactive lipids derived from omega-3 and -6 polyunsaturated fatty acids have key roles in the regulation of the inflammatory response and have been linked to joint damage and osteoarthritis pain in translational models. HYPOTHESIS: There would be associations between systemic levels of bioactive lipids and knee symptoms longitudinally after an acute knee injury and related knee surgery. STUDY DESIGN: Controlled laboratory study. METHODS: This study analyzed a subset of young, active adults who had sustained an acute knee injury (recruited via a surgical care pathway) and healthy age- and sex-matched controls. Surgery, if performed, was conducted after the baseline serum sample was taken and before the 3-month and 2-year visits. Liquid chromatography-tandem mass spectrometry of 41 bioactive lipids was carried out in sera of (1) 47 injured participants (median age, 28 years) collected at baseline (median, 24 days after injury), 3 months, and 2 years, along with the Knee injury and Osteoarthritis Outcome Score, and (2) age- and sex-matched controls. RESULTS: Levels of the omega-3 polyunsaturated fatty acids eicosapentaenoic acid (P≤ .0001) and docosahexaenoic acid (P≤ .0001) and the pro-resolving lipid mediators 17- and 14-hydroxydocosahexaenoic acid, and 18-hydroxyeicosapentaenoic acid were all significantly greater at baseline in injured participants compared with the later time points and also higher than in healthy controls (P = .0019 and P≤ .0001, respectively). Levels of pro-inflammatory prostaglandins E2 and D2, leukotriene B4, and thromboxane B2 were significantly lower at baseline compared with the later time points. Higher levels of 8,9-, 11,12-, and 14,15-dihydroxyeicosatrienoic acid (DHET) were cross-sectionally associated with more severe knee pain/symptoms according to the Knee injury and Osteoarthritis Outcome Score at 2 years (P = .0004, R2 = 0.251; P = .0002, R2 = 0.278; and P = .0012, R2 = 0.214, respectively). CONCLUSION: The profile of pro-resolving versus pro-inflammatory lipids at baseline suggests an initial activation of pro-resolution pathways, followed by the later activation of pro-inflammatory pathways. CLINICAL RELEVANCE: In this largely surgically managed cohort, the association of soluble epoxide hydrolase metabolites, the DHETs, with more severe knee symptoms at 2 years provides a rationale for further investigation into the role of this pathway in persisting knee symptoms in this population, including potential therapeutic strategies.

Impact of Insurance Type on Access to Pain Management Specialists for the Treatment of Lower Back Pain.

Background Low back pain is known to be one of the leading causes of disability among the young and elderly population. Low back pain can stem from multiple sources, including spinal degeneration, injury, herniated discs, sciatica, and other contributing causes. This symptom significantly influences the quality of life of affected individuals. Its implications include extensive social and economic costs. Economic considerations arise from the fact that not all healthcare facilities accept the insurance plans available to retired individuals under Medicare. This places an additional burden on patients who must bear the financial responsibility for healthcare services not covered by their insurance plan. Florida, renowned as a favored state for retirement, consists of a demographic composition wherein 21% of its residents are aged 65 or older. A significant proportion of this demographic qualifies for Traditional Medicare (TM) and/or Medicare Advantage (MA) plans. Thus, understanding the disparities in healthcare access between Medicare and Medicare Advantage plans is crucial. This study aims to evaluate different Medicare insurances available in the market and their impact on the ease of accessibility to pain management specialists for the treatment of lower back pain in Florida patients. Methods We analyzed the Florida Department of Health database to identify the four counties in Florida with the highest Medicare enrollment rates in 2022: Miami-Dade, Palm Beach, Broward, and Pinellas County. Using the U.S. News and Report directory, 25 Pain Management-trained anesthesiologists were randomly selected from each of the four counties. Each office was contacted four times via telephone by four different team members to assess appointment availability for a fictional 65-year-old grandfather seeking treatment for chronic low back pain. The study examined appointment availability and accepted insurance types, including Cigna (commercial insurance), TM, Humana Gold Plus HMO (Medicare Advantage plan), and Blue Medicare Select PPO (Medicare Advantage plan). Practices without contact information or retired physicians were excluded from the analysis. Time to appointment was measured in business days. Results Of the 100 Pain Management Physicians contacted, 44 fit the inclusion criteria of being non-retired physicians, still practicing in one of the four counties with open offices and valid contact information. Blue Medicare Select PPO was accepted by 47.73%, Humana Gold Plus HMO by 56.82%, TM by 93.18%, and Cigna by 93.18% of the encounters. Blue Medicare select PPO and Humana Gold Plus HMO were accepted at significantly lower rates when compared to Traditional Medicare and Cigna with P values of P < .00001 and P < .000176, respectively. There was no significant difference found in the time to appointment between insurances with P value < 7. Conclusion The study found that patients enrolled in Medicare Advantage plans have significantly decreased access to care when compared to those enrolled in TM or commercial insurance. Further research is needed to elucidate the reasons behind differences in access to care across different insurances, as identified in the study.

A Rare Case of Ameloblastic Carcinoma of Maxilla.

Ameloblastic carcinoma is an odontogenic neoplasm with combined features of ameloblastoma and carcinoma on histopathological examination. Its prognosis is dominated by risk of local recurrence and distant metastasis. We report our patient because of the rare site and to highlight the importance of early, aggressive surgical treatment and regular follow-up.

Image-Based Communication for Strengthening Patient Health Education in Rural and Underserved Settings.

Effective communication is the cornerstone of efficient patient care. It is vital to obtain a thorough history, build the patient's trust, and ensure compliance to treatment. Image-based communication (IBC) using comic-like strips is better than the conventional verbal and written modes, as it is inexpensive, less human resource dependent, and diversity agnostic. Strips based on local and socioculturally relevant issues and characters grab readers' attention, are relatable and entertaining, and utilize a storyline that invigorates thinking. The medical advice delivered by an ideal IBC strip is easy to comprehend, has a better recall, and promotes patient adherence. With an idea that IBC strips can serve as a vital supportive tool in underserved and overburdened clinics, we have described the nuances of adapting them into the existing physician-patient experience. We utilize a prototype IBC of an elderly woman helping a family whose child developed acute fever, possibly malaria. Various elements of an IBC strip, namely, panels, gutters, background, characters, bubbles, captions, and visual effects, are illustrated, and their variations are described later. Once designed, an IBC strip must be critically evaluated for the accuracy of the educational message, and errors, if any, must be corrected. The images are then subjected to a series of local field tests to ensure that they serve their purpose and have the desired cultural competence. Once ready, IBC strips can be posted in public spaces and outside clinics or distributed to healthcare workers or patients. Here, they serve as educational and health literacy tools. The strips can significantly reduce caregiver-patient interaction time and improve the quality of communication, especially when patients are illiterate or understand a different language. It is easier to develop rapport and partnership with a patient when the communication is presented through a pictorial tool. An IBC strip can be used to train grassroot workers, who subsequently train patients, thereby serving a dual purpose. To obtain tangible clinical and epidemiologic benefits from IBC strips, rigorous evidence building and standardization are a crucial long-term goal.

Hydrosilylation of Terminal Alkynes Catalyzed by an Air-Stable Manganese-NHC Complex.

In recent years, catalysis with base metal manganese has received a significant amount of interest. Catalysis with manganese complexes having N-heterocyclic carbenes (NHCs) is relatively underdeveloped in comparison to the extensively investigated manganese catalysts possessing pincer ligands (particularly phosphine-based ligands). Herein, we describe the synthesis of two imidazolium salts decorated with picolyl arms (L1 and L2) as NHC precursors. Facile coordination of L1 and L2 with MnBr(CO)5 in the presence of a base resulted in the formation manganese(I)-NHC complexes (1 and 2) as an air-stable solid in good isolated yield. Single-crystal X-ray analysis revealed the structure of the cationic complexes [Mn(CO)3(NHC)][PF6] with tridentate N,C,N binding of the NHC ligand in a facile fashion. Along with a few known manganese(I) complexes, these Mn(I)-NHC complexes 1 and 2 were tested for the hydrosilylation of terminal alkynes. Complex 1 was proved to be an effective catalyst for the hydrosilylation of terminal alkynes with good selectivity toward the less thermodynamically stable ß-(Z)-vinylsilanes. This method provided good regioselectivity (anti-Markovnikov addition) and stereoselectivity (ß-(Z)-product). Experimental evidence suggested that the present hydrosilylation pathway involved an organometallic mechanism with manganese(I)-silyl species as a possible reactive intermediate.

Cobalt catalyzed chemoselective reduction of nitroarenes: hydrosilylation under thermal and photochemical reaction conditions.

Commercially available Co2(CO)8 was used as an effective catalyst for the hydrosilylation of nitroarenes under both thermal and photochemical conditions. A wide variety of nitroarenes with various functionalities were selectively reduced to aromatic amines. Syntheses of drug molecules expand the potential utility of this protocol. Experimental evidence suggested a radical pathway.

Inhibition of CXCR4 Enhances the Efficacy of Radiotherapy in Metastatic Prostate Cancer Models.

Radiotherapy (RT) is a standard treatment for patients with advanced prostate cancer (PCa). Previous preclinical studies showed that SDF1α/CXCR4 axis could mediate PCa metastasis (most often to the bones) and cancer resistance to RT. We found high levels of expression for both SDF1α and its receptor CXCR4 in primary and metastatic PCa tissue samples. In vitro analyses using PCa cells revealed an important role of CXCR4 in cell invasion but not radiotolerance. Pharmacologic inhibition of CXCR4 using AMD3100 showed no efficacy in orthotopic primary and bone metastatic PCa models. However, when combined with RT, AMD3100 potentiated the effect of local single-dose RT (12 Gy) in both models. Moreover, CXCR4 inhibition also reduced lymph node metastasis from primary PCa. Notably, CXCR4 inhibition promoted the normalization of bone metastatic PCa vasculature and reduced tissue hypoxia. In conclusion, the SDF1α/CXCR4 axis is a potential therapeutic target in metastatic PCa patients treated with RT.

Molecular engineering of a cryptic epitope in Spike RBD improves manufacturability and neutralizing breadth against SARS-CoV-2 variants.

There is a continued need for sarbecovirus vaccines that can be manufactured and distributed in low- and middle-income countries (LMICs). Subunit protein vaccines are manufactured at large scales at low costs, have less stringent temperature requirements for distribution in LMICs, and several candidates have shown protection against SARS-CoV-2. We previously reported an engineered variant of the SARS-CoV-2 Spike protein receptor binding domain antigen (RBD-L452K-F490W; RBD-J) with enhanced manufacturability and immunogenicity compared to the ancestral RBD. Here, we report a second-generation engineered RBD antigen (RBD-J6) with two additional mutations to a hydrophobic cryptic epitope in the RBD core, S383D and L518D, that further improved expression titers and biophysical stability. RBD-J6 retained binding affinity to human convalescent sera and to all tested neutralizing antibodies except antibodies that target the class IV epitope on the RBD core. K18-hACE2 transgenic mice immunized with three doses of a Beta variant of RBD-J6 displayed on a virus-like particle (VLP) generated neutralizing antibodies (nAb) to nine SARS-CoV-2 variants of concern at similar levels as two doses of Comirnaty. The vaccinated mice were also protected from challenge with Alpha or Beta SARS-CoV-2. This engineered antigen could be useful for modular RBD-based subunit vaccines to enhance manufacturability and global access, or for further development of variant-specific or broadly acting booster vaccines.

Azide-Alkyne Cycloaddition Catalyzed by Copper(I) Coordination Polymers in PPM Levels Using Deep Eutectic Solvents as Reusable Reaction Media: A Waste-Minimized Sustainable Approach.

Two air-stable copper(I)-halide coordination polymers 1 and 2 with NNS and NNO ligand frameworks were synthesized and successfully utilized as efficient catalysts in an important organic reaction, namely, copper-catalyzed azide-alkyne cycloaddition, which is generally conducted in a mixture of water and organic solvents. The azide-alkyne "click" reaction was successfully conducted in pure water at r.t. under aerobic conditions. Other green solvents, including ethanol and glycerol, were also effectively used. Finally, deep eutectic solvents as green and sustainable reaction media were successfully utilized. In deep eutectic solvents, complete conversion with excellent isolated yield was achieved in a short period of time (1 h) with low catalyst loading (1 mol %) at r.t. Full conversion could also be achieved within 24 h with ppm-level (50 ppm) catalyst loading at 70 °C. Optimized reaction conditions were used for the syntheses of a large number of 1,4-disubstituted 1,2,3-triazoles with various functionalities. Triazole products were easily isolated by simple filtration. The reaction media, such as water and deep eutectic solvents, were recovered and recycled in three consecutive runs. The limited waste production is reflected in a very low E-factor (0.3-2.8). Finally, the CHEM21 green metrics toolkit was employed to evaluate the sustainability credentials of different optimized protocols in various green solvents such as water, ethanol, glycerol, and deep eutectic solvents.

Clinicopathological predictors of repeated recurrence in sinonasal inverted papilloma.

PURPOSE: To evaluate association between clinical and pathological findings and repeated recurrence in sinonasal inverted papilloma. METHODS: Retrospective cohort study conducted at a tertiary care teaching hospital included all patients operated for inverted papilloma from January 2010 to December 2019. Patients were categorized as primary and recurrent cases. Based on disease status at follow-up, they were subcategorized into 'primary with no recurrence' (PnR), 'primary with recurrence' (PwR), 'recurrent with no further recurrence' (RnR), and 'recurrent with further recurrence' (RwR) groups. Data including demography, clinical, endoscopic and pathological findings were collected and analyzed. RESULTS: Increased incidence of pale appearance of lesion in RnR group (p = 0.017), polypoidal appearance in primary group (p = 0.002) and fibrous appearance in the recurrent group (p = 0.002) were statistically significant. Predominant epithelium was combined respiratory and squamous epithelium in primary and recurrent groups and also in RnR group (p = 0.019), while it was squamous (p = 0.024) in RwR group. Epithelial hyperplasia was more common in primary and RnR groups. Oncocytic change, cystic dilatation, microabscess and squamous metaplasia were seen more in recurrent and RnR groups. Cytoplasmic glycogenation was more in recurrent and RwR groups. Stroma was predominantly edematous in all the groups. CONCLUSIONS: Patients with recurrence are younger and present earlier than those with primary disease. Fleshy appearance and pink/red colour of tumour, lining epithelium being squamous and cytoplasmic glycogenation could be considered as features predicting recurrence. Negative predictors of recurrence of IP include pale appearance of tumour, combined respiratory and squamous epithelium lining and squamous metaplasia.

The Impact of Exogenous Testosterone on Breast Cancer Risk in Transmasculine Individuals.

BACKGROUND: Exogenous testosterone is vital to gender-affirming therapy for transmasculine individuals. Testosterone may be implicated in breast cancer (BCa) because it can activate androgen and estrogen receptors. To further explore this risk, we performed a systematic review to investigate the impact of exogenous testosterone on BCa risk in transmasculine individuals. METHODS: We searched PubMed/MEDLINE and Ovid/Embase for clinical and preclinical studies assessing BCa and testosterone therapy and screened 6125 articles independently. We ascertained level of evidence using a modified tool from Cook et al (Chest. 1992;102:305S-311S) and risk of bias using a modified Joanna Briggs Institute's Critical Appraisal Tool. RESULTS: Seventy-six studies were included. Epidemiological data suggested that BCa incidence was higher in transmasculine individuals compared with cisgender men but lower compared with cisgender women. Histological studies of transmasculine breast tissue samples also demonstrated a low incidence of precancerous lesions. Interestingly, cases demonstrated that BCa occurred at a younger average age in transmasculine individuals and was predominantly hormone receptor positive. The mechanism for BCa in transmasculine individuals may be related to androgen receptor stimulation or conversion to estradiol. Serum studies reported varied estradiol levels associated with exogenous testosterone. Animal and in vitro studies demonstrated that testosterone was growth inhibitory but may induce proliferation at higher doses or with low estradiol levels. CONCLUSIONS: Plastic surgeons play a critical role in providing gender-affirming care for transmasculine patients. The limited studies available suggest that this patient population has decreased risk for BCa when compared with cisgender women; however, any BCa that does occur may have different clinical presentations and underlying mechanisms compared with cisgender women and men. Overall, the limitations for clinical studies and discrepancies among preclinical studies warrant further investigation.

Chronic total occlusion rotational atherectomy (CTO RA) versus non-CTO RA in coronary artery disease: A meta-analysis of clinical outcomes and complications.

Background: Chronic total occlusion rotational atherectomy (CTO RA) is an emerging intervention in coronary artery disease (CAD), although data comparing its outcomes and complications with non-CTO RA are scarce. We sought to evaluate the outcomes of RA in CTO lesions compared to those in non-CTO lesions by performing a meta-analysis. Methods: We conducted a systematic review and meta-analysis of studies comparing the clinical outcomes and complications between CTO RA and non-CTO RA in patients with CAD. We searched PUBMED, CINAHL, EMBASE and Cochrane Central Register of Clinical Trials for any studies that compared the outcomes of RA in CTO and non-CTO lesions. The outcomes analyzed included in-hospital major adverse cardiovascular events (MACE), target vessel revascularization (TVR), angiographic success, procedural success, periprocedural complications, coronary perforation, and all-cause mortality. Results: Four studies with a total of 1868 patients were included, spanning from 2018 to 2022, from Germany, Taiwan, and Korea. The median age of included patients was 71. The rate of the pooled results indicated a moderate, non-significant increase in in-hospital MACE and TVR for CTO RA compared to non-CTO RA. There was a small, non-significant decrease in angiographic and procedural success in CTO RA compared to non-CTO RA. CTO RA was associated with a non-significant increase in periprocedural complications and a significant increase in coronary perforation compared to non-CTO RA. All-cause mortality showed a non-significant increase in the CTO RA group. Conclusion: This meta-analysis provides evidence that while CTO RA may be associated with a higher risk of coronary perforation, the risk of other outcomes including MACE, TVR, and all-cause mortality is not significantly different compared to non-CTO RA. More research is needed to further understand these relationships and to optimize treatment strategies in patients with CAD undergoing CTO RA.

Construct and Validation of a Three-Dimensional Physical Model for Training in Transnasal Office Procedures.

Most simulation models in rhinology are costly and are primarily meant to enhance endoscopic surgical skills. The present study aimed to construct a 3-dimensional model of the nose which is easily constructible with commonly available low cost plaster of Paris (POP) and assess its usefulness in training residents in basic transnasal procedures. A nose model was created using plaster of Paris and assessed for face and content validity by experts in rhinology while a construct validation was performed on five specified tasks by residents. All experts agreed with the resemblance of 10 of the 13 anatomical landmarks in the POP model and its utility in teaching basic transnasal procedures. There was a statistically significant difference in the time taken by I and III year residents in performing a diagnostic nasal endoscopy (p = 0.007), anterior nasal packing with polyvinyl alcohol tampon (p = 0.007), posterior nasal packing with Foley's catheter (p = 0) and nasopharyngeal swabbing (p = 0.025). This study demonstrates the construct of a low cost 3-dimensional POP model and validates its utility in training residents in routine transnasal rhinological procedures. Face and content validation showed a high degree of resemblance to human anatomy with good agreement that this model could increase resident competency. The significant difference in time taken by residents at various levels of experience in performing rhinological procedures also confirmed a reliable construct validity. The described model could be an affordable and easily constructible alternative tool to other simulation models in otorhinolaryngology residency programs especially in developing countries.

Sodium Dodecyl Sulfate-Mediated Graphene Sensor for Electrochemical Detection of the Antibiotic Drug: Ciprofloxacin.

The present study involves detecting and determining CIP by a new electrochemical sensor based on graphene (Gr) in the presence of sodium dodecyl sulfate (SDS) employing voltammetric techniques. Surface morphology studies of the sensing material were analyzed using a scanning electron microscope (SEM) and atomic force microscope (AFM). In the electroanalysis of CIP at the developed electrode, an enhanced anodic peak response was recorded, suggesting the electro-oxidation of CIP at the electrode surface. Furthermore, we evaluated the impact of the electrolytic solution, scan rate, accumulation time, and concentration variation on the electrochemical behavior of CIP. The possible electrode mechanism was proposed based on the acquired experimental information. A concentration variation study was performed using differential pulse voltammetry (DPV) in the lower concentration range, and the fabricated electrode achieved a detection limit of 2.9 × 10-8 M. The proposed sensor detected CIP in pharmaceutical and biological samples. The findings displayed good recovery, with 93.8% for tablet analysis and 93.3% to 98.7% for urine analysis. The stability of a developed electrode was tested by inter- and intraday analysis.