UNASSIGNED: Cancer, the second leading cause of mortality worldwide, represents a global health challenge, primarily due to drug resistance. Vinorelbine is a chemotherapeutic agent that disrupts cancer cell growth by targeting microtubules and inducing apoptosis. However, drug resistance remains a formidable obstacle. This resistance is caused by various factors including genetic mutations, drug efflux mechanisms, and DNA repair systems. Resolution of this challenge requires an innovative approach. This study investigated the potential of small interfering RNA (siRNA) to target and downregulate a vinorelbine-resistant MCF-7/ADR breast cancer cell line.
UNASSIGNED: Cells were cultured in Dulbecco\'s modified Eagle\'s medium (DMEM) 10% fetal bovine serum/penicillin/streptomycin. An siRNA targeting ABCB1 was designed and synthesized, and the cells were transfected with siRNA at final concentrations of 10, 20, and 30 nM. The3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to assess cell viability. ABCB1 mRNA expression levels were determined by real-time polymerase chain reaction (PCR).
UNASSIGNED: MCF-7 cells exhibited a higher sensitivity to vinorelbine than MCF-7/ADR cells. MCF-7/ADR cells exhibited resistance to vinorelbine at concentrations, 12.50 and 25.00 μM. Treatment with siRNA significantly reduced ABCB1 expression by 2.93-fold (P=0.0001). Similarly, co-treatment with siRNA and vinorelbine produced a substantial 2.89-fold decrease in ABCB1 gene expression in MCF-7 cells compared to that in MCF-7/ADR cells (P=0.0001).
UNASSIGNED: The results of the present study indicate that the concurrent use of siRNA and vinorelbine holds substantial promise as a therapeutic approach to overcome ABCB1-mediated multidrug resistance (MDR) in breast cancer. It is necessary to conduct comprehensive clinical trials to determine the true effectiveness of this combination therapy.

The versatility of cytochrome P450 reductase (CPR) in transferring electrons to P450s from other closely related species has been extensively exploited, e.g., by using An. gambiae CPR (AgCPR), as a homologous surrogate, to validate the role of An. funestus P450s in insecticide resistance. However, genomic variation between the AgCPR and An. funestus CPR (AfCPR) suggests that the full metabolism spectrum of An. funestus P450s might be missed when using AgCPR. To test this hypothesis, we expressed AgCPR and AfCPR side-by-side with CYP6P9a and CYP6P9b and functionally validated their role in the detoxification of insecticides from five different classes. Major variations were observed within the FAD- and NADP-binding domains of AgCPR and AfCPR, e.g., the coordinates of the second FAD stacking residue AfCPR-Y456 differ from that of AgCPR-His456. While no significant differences were observed in the cytochrome c reductase activities, when co-expressed with their endogenous AfCPR, the P450s significantly metabolized higher amounts of permethrin and deltamethrin, with CYP6P9b-AfCPR membrane metabolizing α-cypermethrin as well. Only the CYP6P9a-AfCPR membrane significantly metabolized DDT (producing dicofol), bendiocarb, clothianidin, and chlorfenapyr (bioactivation into tralopyril). This demonstrates the broad substrate specificity of An. funestus CYP6P9a/-b, capturing their role in conferring cross-resistance towards unrelated insecticide classes, which can complicate resistance management.

UNASSIGNED: Basal cell carcinoma (BCC) cases exhibit variations in tumour number, location, and growth patterns. While some patients develop only one BCC, approximately one-third of patients later develop one or more additional lesions.
UNASSIGNED: The aim of the study was to identify risk factors for further BCC lesions in patients with different phenotypic presentations.
UNASSIGNED: We retrospectively evaluated 1052 histopathologically diagnosed tumours of 861 patients, who were divided into four phenotypic presentation groups according to tumour number at initial diagnosis and during follow-up. Age, sex, tumour characteristics, surgical margins, re-excision and residual tumour rates were compared. Univariate and multivariate logistic regression analyses were performed to determine risk factors for multiple tumour development.
UNASSIGNED: There were 723 patients in the single presentation phenotype 1 (SPP1) group, 19 in the SPP-more group, 114 in the multiple presentation phenotype (MPP)-cluster initial group, and five patients in the MPP-cluster later group. Male sex was more common in the MPP-cluster later group (P = 0.028). The mean age was lower in the SPP1 and SPP-more groups (P = 0.002). Ear involvement was more common in the MPP-cluster later group (P < 0.05). Superficial and basosquamous subtypes were more common in the SPP-more and MPP-cluster later groups (P < 0.05). Re-excision and residual tumour rates were lowest in the SPP1 group (P < 0.05). Age over 69 years, male sex, and periorbital or upper extremity location were significant risk factors for multiple tumour development (P < 0.05).
UNASSIGNED: The limitations of our study include the inability to evaluate environmental risk factors, phenotypic and ethnic characteristics, and the short follow-up period for newly added patients.
UNASSIGNED: Predicting different phenotypic presentations by taking the age, gender, and tumour characteristics (localization, histopathological subtype) of the patients into account may allow new tumours to be detected at an early stage.

Castleman\'s disease is a rare lymphoproliferative disease that usually presents as a solitary mass in the mediastinal or cervical region. Castleman\'s disease can be usually of two types: unicentric type (which involves only one site of lymph nodes) and multicentric type (which involves multiple sites of lymph nodes). We report the case of a 26-year-old female with multiple sclerotic bone lesions in unicentric Castleman\'s disease. The definitive diagnosis was made by excisional biopsy with immunohistochemistry, 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) study, and MRI scan. This case report emphasizes the need for proper workup for systemic manifestations in unicentric Castleman\'s disease.

Burst fractures of vertebrae are usually caused by high-energy axial compression force, mostly caused by fall from height or road traffic accidents. They frequently occur at the thoracolumbar junction mostly requiring surgery. Contiguous burst fractures involving multiple lumbar vertebrae are uncommon. This case is a male in his early 40s presented with low back pain and weakness of lower limbs following an injury sustained during a road traffic accident. Clinically, the patient had a bilateral foot drop. On radiological evaluation, he was diagnosed to have L3 and L4 burst fractures with spinal canal occlusion. He underwent posterior stabilization from L2-L5 and decompression at the L3-L4 level. At one-year follow-up, the patient was pain-free with complete neurological recovery. Contiguous lumbar spine burst fractures are very rare in occurrence. Though burst fractures are managed surgically to provide stability, the surgical approaches depend on the individual fracture pattern, degree of spinal canal occlusion, and neurological status.

The species included in the ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and the genus Enterobacter) have a high capacity to develop antimicrobial resistance (AMR), a health problem that is already among the leading causes of death and could kill 10 million people a year by 2050. The generation of new potentially therapeutic molecules has been insufficient to combat the AMR \"crisis\", and the World Health Organization (WHO) has stated that it will seek to promote the development of rapid diagnostic strategies. The physicochemical properties of metallic nanoparticles (MNPs) have made it possible to design biosensors capable of identifying low concentrations of ESKAPE bacteria in the short term; other systems identify antimicrobial susceptibility, and some have been designed with dual activity in situ (bacterial detection and antimicrobial activity), which suggests that, in the near future, multifunctional biosensors could exist based on MNPs capable of quickly identifying bacterial pathogens in clinical niches might become commercially available. This review focuses on the use of MNP-based systems for the rapid and accurate identification of clinically important bacterial pathogens, exhibiting the necessity for exhaustive research to achieve these objectives. This review focuses on the use of metal nanoparticle-based systems for the rapid and accurate identification of clinically important bacterial pathogens.

BACKGROUND: Prediction models help to target patients at risk of multidrug-resistant organism (MDRO) colonization or infection and could serve as tools informing clinical practices to prevent MDRO transmission and inappropriate empiric antibiotic therapy. However, there is limited evidence to identify which among the available models are of low risk of bias and suitable for clinical application.
OBJECTIVE: To identify, describe, appraise, and summarise the performance of all prognostic and diagnostic models developed or validated for predicting MDRO colonization or infection.
METHODS: Six electronic literature databases and clinical registration databases were searched until April 2022.
METHODS: Development and validation studies of any multivariable prognostic and diagnostic models to predict MDRO colonization or infection in adults.
METHODS: Adults (≥ 18 years old) without MDRO colonization or infection (in prognostic models) or with unknown or suspected MDRO colonization or infection (in diagnostic models).
UNASSIGNED: The Prediction Model Risk of Bias Assessment Tool was used to assess the risk of bias. Evidence certainty was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach.
UNASSIGNED: Meta-analyses were conducted to summarize the discrimination and calibration of the models\' external validations conducted in at least two non-overlapping datasets.
RESULTS: We included 162 models (108 studies) developed for diagnosing (n = 135) and predicting (n = 27) MDRO colonization or infection. Models exhibited a high-risk of bias, especially in statistical analysis. High-frequency predictors were age, recent invasive procedures, antibiotic usage, and prior hospitalization. Less than 25% of the models underwent external validations, with only seven by independent teams. Meta-analyses for one diagnostic and two prognostic models only produced very low to low certainty of evidence.
CONCLUSIONS: The review comprehensively described the models for identifying patients at risk of MDRO colonization or infection. We cannot recommend which models are ready for application because of the high-risk of bias, limited validations, and low certainty of evidence from meta-analyses, indicating a clear need to improve the conducting and reporting of model development and external validation studies to facilitate clinical application.

OBJECTIVE: To identify current practices in the management of selective fetal growth restriction (sFGR) in monochorionic diamniotic (MCDA) twin pregnancies.
METHODS: Cross-sectional survey.
METHODS: International.
METHODS: Clinicians involved in the management of MCDA twin pregnancies with sFGR.
METHODS: A structured, self-administered survey.
METHODS: Clinical practices and attitudes to diagnostic criteria and management strategies.
RESULTS: Overall, 62.8% (113/180) of clinicians completed the survey; of which, 66.4% (75/113) of the respondents reported that they would use an estimated fetal weight (EFW) of <10th centile for the smaller twin and an inter-twin EFW discordance of >25% for the diagnosis of sFGR. For early-onset type I sFGR, 79.8% (75/94) of respondents expressed that expectant management would be their routine practice. On the other hand, for early-onset type II and type III sFGR, 19.3% (17/88) and 35.7% (30/84) of respondents would manage these pregnancies expectantly, whereas 71.6% (63/88) and 57.1% (48/84) would refer these pregnancies to a fetal intervention centre or would offer fetal intervention for type II and type III cases, respectively. Moreover, 39.0% (16/41) of the respondents would consider fetoscopic laser surgery (FLS) for early-onset type I sFGR, whereas 41.5% (17/41) would offer either FLS or selective feticide, and 12.2% (5/41) would exclusively offer selective feticide. For early-onset type II and type III sFGR cases, 25.9% (21/81) and 31.4% (22/70) would exclusively offer FLS, respectively, whereas 33.3% (27/81) and 32.9% (23/70) would exclusively offer selective feticide.
CONCLUSIONS: There is significant variation in clinician practices and attitudes towards the management of early-onset sFGR in MCDA twin pregnancies, especially for type II and type III cases, highlighting the need for high-level evidence to guide management.

BACKGROUND: Many patients suffer from osteoarthritis (OA) in multiple joints, possibly resulting in multiple joint arthroplasties (MJAs). Primarily, we determined the cumulative incidence (Cin) of MJA in hip and knee joints up to 10 years. Secondly, we calculated the mean time between the first and subsequent joint arthroplasty, and evaluated the different MJA trajectories. Lastly, we compared patient characteristics and outcomes (functionality and pain) after surgery between MJA patients and single hip arthroplasty or knee arthroplasty (HA and KA) patients.
METHODS: Primary index (first) HA or KA for OA were extracted from the Dutch Arthroplasty Register. The 1, 2, 5, and 10-year Cin (including competing risk death) of MJA, mean time intervals, and MJA-trajectories were calculated and stratified for primary index HA or KA. Sex, preoperative age, and body mass index were compared using ordinal logistic regression. Outcomes, measured preoperatively, 3, 6, and 12 months postoperatively (function: Hip Disability or Knee Injury and OA Outcome Score; Pain: Numerical Rating Scale), were compared using linear regression.
RESULTS: A total of 140,406 HA-patients and 140,268 KA-patients were included. One, 2, 5, and 10-year Cin for a second arthroplasty were respectively 8.9% [95% confidence interval (CI): 8.7 to 9.0], 14.3% [95% CI: 14.1 to 14.5], 24.0% [95% CI: 23.7 to 24.2], and 32.7% [95% CI: 32.2 to 33.1] after index HA, and 9.5% [95% CI: 9.4 to 9.7], 16.0% [95% CI: 15.9 to 16.2], 26.4% [95% CI: 26.1 to 26.6], and 35.8% [95% CI: 35.4 to 36.3] after index KA. The 10-year Cin for > 2 arthroplasties were small in both the index HA and KA groups. Time-intervals from first to second, third, and fourth arthroplasty were 26 [95% CI: 26.1 to 26.7], 47 [95% CI: 46.4 to 48.4], and 58 [95% CI: 55.4 to 61.1] months after index HA, and 26 [95% CI: 25.9 to 26.3], 52 [95% CI: 50.8 to 52.7], and 61 [95% CI: 58.3 to 63.4] months after index KA. There were 83% of the second arthroplasties placed in the contralateral cognate joint (ie, knee or hip). Differences in postoperative functionality and pain between MJAs and single HAs and KAs were small.
CONCLUSIONS: The 10-year Cin showed that about one-third of patients received a second arthroplasty after approximately 2 years, with the majority in the contralateral cognate joint. Few patients received > 2 arthroplasties within 10 years. Being a women, having a higher body mass index, and being younger increased the odds of MJA. Postoperative outcomes were slightly negatively affected by MJA.

Objectives  To describe the obstetric management and perinatal outcomes in multiple pregnancies with delayed-interval delivery (DID) of the cotwin in a tertiary hospital. Methods  This is a retrospective chart review of all cases of DID between December 2021 and 2022 at The Ottawa Hospital. Five cases of DID were identified and reviewed to obtain information on obstetric management and maternal-neonatal outcomes. We included eligible twins and triplets. No multiples were excluded. We obtained ethics approval for this case series. Results  Four sets of dichorionic diamniotic twins and one trichorionic triamniotic triplet were included. Our patients were admitted between 17 3/7 and 21 5/7 weeks of gestation. We achieved an interval delivery range between 1 and 36 days. Four out of six multiples did not survive in DID. The two surviving newborns were born at 23 0/7 and 23 2/7 , stayed in the neonatal intensive care unit (NICU) for 111 and 131 days, discharged with a weight of 3,594 and 2,743 g, respectively. All DID cases were delivered spontaneously except for two patients that required augmentation due to maternal sepsis. Conclusion  Despite the high risk of maternal, fetal, and neonatal morbidity and mortality, if delivery of the first twin occurs before 20 gestational weeks, DID could be considered in selected cases to improve outcomes for the cotwin.