The Impact of a Pediatric Continuity Care Intensivist Program on Patient and Parent Outcomes: An Unblinded Randomized Controlled Trial.

Objectives We studied the impact of a standardized continuity care intensivists (CCIs) program on patient and family outcomes for long-stay patients in the pediatric intensive care unit (PICU), also assessing the intervention's acceptability and feasibility. Methods A patient-level, unblinded randomized-controlled trial in a PICU at a large children's hospital. Participants included: (1) patients with ≥ 7 days PICU admission and likely to stay another 7 days; (2) their parents; (3) PICU attendings participating as continuity attendings; and (4) PICU attendings providing usual care (UC). We examined a bundled intervention: (1) standardized continuity attending role, (2) communication training course for CCI, and (3) standardized timing of contact between CCI and patient/family. Results Primary outcome was patient PICU length of stay. Secondary outcomes included patient, parental, and clinician outcomes. We enrolled 115 parent-patient dyads (231 subjects), 58 patients were randomized into treatment arm and 56 into the UC arm. Thirteen attendings volunteered to serve as CCI, 10 as UC. No association was found between the intervention and patient PICU length of stay ( p = 0.5), other clinical factors, or parental outcomes. The intervention met a threshold for feasibility of enrollment, retention, and implementation while the majority of providers agreed the intervention was acceptable with more efficient decision making. Thirty percent CCIs felt the role took too much time, and 20% felt time was not worth the benefits. Conclusion CCI intervention did not impact patient or family outcomes. PICU attendings believed that the implementation of the CCI program was feasible and acceptable with potential benefits for efficiency of decision making.

Effects of aflatoxin B1 on metabolism- and immunity-related gene expression in Hermetia illucens L. (Diptera: Stratiomyidae).

Contamination of food products with mycotoxins such as aflatoxin B1 (AFB1) poses a severe risk to human health. Larvae of the black soldier fly (BSFL), Hermetia illucens (Diptera: Stratiomyidae), can successfully metabolize AFB1 without any negative consequences on their survival or growth. Organic waste streams contaminated with mycotoxins can be upcycled into protein-rich BSFL as an alternative feed for livestock and the left-over feed residue into nutrient-rich crop fertilizers. However, the underlying mechanisms that allow BSFL to metabolize AFB1 are unknown. In this study, five-day-old BSFL were fed with either a control or an AFB1-spiked (20 µg/kg) diet to elucidate the underlying mechanisms. Larval samples were collected at three timepoints (6 h, 24 h and 72 h) and subjected to RNA-Seq analysis to determine gene expression patterns. Provision of an AFB1-spiked diet resulted in an up-regulation of 357 and a down-regulation of 929 unique genes. Upregulated genes include multiple genes involved in AFB1 metabolism in other (insect) species. Downregulated genes were generally involved in the insects' growth, development, and immunity. BSFL possesses a diverse genetic arsenal that encodes for enzymes capable of metabolizing AFB1 without trade-offs on larval survival. In conclusion, the adverse impact of AFB1 exposure on immunity-related processes is observed in the transcriptomic response, and is indicative of a trade-off between detoxification and immune responses.

Incentives and individualized coaching improves completion rates of supervised exercise therapy for claudication.

OBJECTIVE: Supervised exercise therapy (SET) provides clinical benefit for patients suffering from intermittent claudication and has been widely recommended as first-line therapy before endovascular or surgical intervention. However, published rates of SET program completion range from 5% to 55%, with historic completion of 54% at our own institution. As such, we sought to identify if targeted patient-supportive interventions improve SET completion rates while still maintaining efficacious SET programming. METHODS: Patients who were diagnosed with intermittent claudication, as defined by ankle-brachial index (ABI) <0.9 without rest pain, were offered enrollment in a prospective quality improvement protocol for our 12-week SET for peripheral artery disease program. Program completion was defined as ≥24 of 36 offered sessions over 12 weeks. A three-pronged approach was utilized to improve completion during the study, including financial incentives up to $180, scheduled coaching with our advanced practitioner staff, and informational materials on the importance of SET programming and lifestyle modification. Patient-reported improvements in walking symptoms were tracked via regularly administered questionnaires. Functional measures of SET programming including total walking duration and distance, metabolic equivalent of task, and ABIs; vascular intervention within 12-months after enrollment was also collected and compared using univariate paired analysis. RESULTS: In total, seventy-three patients were enrolled in SET for peripheral artery disease programming over the study period. Utilizing our three-pronged coaching approach, 56 patients completed SET programming, increasing our SET completion rate to 76.7% over a 2-year study period. Compared with pre-SET baseline, patients who completed SET noted less pain, aching, cramps in calves when walking (P = .004), and less difficulty walking 1 block (P = .038). Additionally, patients significantly increased their metabolic equivalent of task (3.1 vs 2.6; P < .001), total walking duration (30 mins vs 13.5 mins; P < .001), and total walking distance (0.7 vs 0.3 miles; P < .001) from their pre-SET baseline. There were no changes in participant ABIs from enrollment to completion in participants. Patients who completed SET programming also delayed vascular intervention compared with those who did not complete SET or declined participation (213.5 vs 122.5 days from enrollment; P = .041). CONCLUSIONS: Targeted incentives, including cost-coverage vouchers and personalized coaching with instructional materials, successfully improved patient completion of a prescribed SET program. Patients who completed SET programming reported subjective improvement in walking symptoms and objective walking benefits. In addition, these patients had delayed time to vascular intervention, supporting current vascular guidelines advocating for effective SET therapy prior to offering vascular intervention for intermittent claudication.

Genomic sequencing for newborn screening: current perspectives and challenges.

Traditional newborn screening (NBS) serves as a critical tool in identifying conditions that may impact a child's health from an early stage. Newborn sequencing (NBSeq), the comprehensive analysis of an infant's genome, holds immense promise for revolutionizing health care throughout the lifespan. NBSeq allows for early detection of genetic disease risk and precision personalized medicine. The rapid evolution of DNA sequencing technologies and increasing affordability have spurred numerous endeavors to explore the potential of whole-genome sequencing in newborn screening. However, this transformative potential cannot be realized without challenges. Ethical aspects must be carefully navigated to safeguard individual rights and maintain public trust. Moreover, genomic data interpretation poses complex challenges due to its amount, the presence of variants of uncertain significance, and the dynamic nature of our understanding of genetics. Implementation hurdles, including cost, infrastructure, and specialized expertise, also present barriers to the widespread adoption of NBSeq. Addressing these challenges requires collaboration among clinicians, researchers, policymakers, ethicists, and stakeholders across various sectors. Robust frameworks for informed consent, data protection, and governance are essential. Advances in bioinformatics, machine learning, and genomic interpretation are crucial for translation into actionable clinical insights. Scalability and improving downstream health care access are vital for equitability, particularly in underserved communities. By fostering interdisciplinary collaboration, advancing technology and infrastructure, and upholding ethical principles, we can unlock the full potential of NBSeq as a tool for precision medicine and pave the way toward a future where every child has the opportunity for a healthier, genomics-informed start to life.

How pharmacists would design and implement a community pharmacy-based colorectal cancer screening program.

Background: Distributing CRC screening through pharmacies, a highly accessible health service, may create opportunities for more equitable access to CRC screening. However, providing CRC screening in a new context introduces a substantial implementation challenge. Methods: We conducted 23 semi-structured interviews with community pharmacists practicing in Washington state and North Carolina about distributing fecal immunochemical tests (FIT) to patients in the pharmacy. The Consolidated Framework for Implementation Research (CFIR) was used to guide analysis. Results: Pharmacists believed that delivering FITs was highly compatible with their environment, workflow, and scope of practice. While knowledge about FIT eligibility criteria varied, pharmacists felt comfortable screening patients. They identified standardized eligibility criteria, patient-facing educational materials, and continuing education as essential design features. Pharmacists proposed adapting existing pharmacy electronic health record systems for patient reminders/prompts to facilitate FIT completion. While pharmacists felt confident that they could discuss test results with patients, they also expressed a need for stronger communication and care coordination with primary care providers. Discussion: When designing a pharmacy-based CRC screening program, pharmacists desired programmatic procedures to fit their current knowledge and context. Findings indicate that if proper attention is given to multi-level factors, FIT delivery can be extended to pharmacies.

Colorectal cancer screening knowledge among community pharmacists: A national survey.

BACKGROUND: Colorectal cancer (CRC) screening can reduce CRC morbidity and mortality. Community pharmacies could be a viable option for delivering home-based CRC screening tests such as fecal immunochemical tests (FITs). However, little is known about community pharmacists' knowledge about CRC screening guidelines. OBJECTIVE: We assessed community pharmacists' knowledge about CRC screening to identify education and training needs for a pharmacy-based CRC screening program. METHODS: Between September 2022 and January 2023, we conducted an online national survey of community pharmacists practicing in the United States. Responders were eligible if they were currently-licensed community pharmacists and currently practiced in the United States. The survey assessed knowledge of national CRC screening guidelines, including recommended starting age, frequency of screening, different screening modalities, and follow-up care. Using multiple linear regression, we evaluated correlates of community pharmacists' level of CRC screening knowledge, defined as the total number of knowledge questions answered correctly from "0" (no questions correct) to "5" (all questions correct). RESULTS: A total of 578 eligible community pharmacists completed the survey, with a response rate of 59%. Most community pharmacists correctly answered the question about the next steps following a positive FIT (87%) and the question about where a FIT can be done (84%). A minority of community pharmacists responded correctly to questions about the age to start screening with FIT (34%) and how often a FIT should be repeated (28%). Only 5% of pharmacists answered all knowledge questions correctly. Community pharmacists answered more CRC screening knowledge questions correctly as their years in practice increased. Board-certified community pharmacists answered more CRC screening knowledge questions correctly compared to those who were not board-certified. CONCLUSION: To ensure the successful implementation of a pharmacy-based CRC screening program, community pharmacists need to be educated about CRC screening and trained to ensure comprehensive patient counseling and preventive service delivery.

Fabrication of a wearable and foldable photodetector based on a WSe2-MXene 2D-2D heterostructure using a scalable handprint technique.

Several studies on semiconductor material-based single-band, high-performance photosensitive, and chemically stable photodetectors are available; however, the lack of broad spectral response, device flexibility, and biodegradability prevents them from being used in wearable and flexible electronics. Apart from that, the selection of the device fabrication technique is a very crucial factor nowadays in terms of equipment utilization and environmental friendliness. This report presents a study demonstrating a straightforward solvent- and equipment-free handprint technique for the fabrication of WSe2-Ti3C2TX flexible, biodegradable, robust, and broadband (Vis-NIR) photodetectors. X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), energy dispersive X-ray spectroscopy (EDX), UV-visible spectroscopy, and X-ray photoelectron spectroscopy (XPS) confirm the formation of a WSe2-Ti3C2TX film. The WSe2-Ti3C2TX van der Waals heterostructure plays a key role in enhancing the optoelectrical properties. The as-prepared photodetector exhibits efficient broadband response with a photoresponsivity and a detectivity of 0.3 mA W-1 and 6.8 × 1010 Jones, respectively, under NIR (780 nm) irradiation (1.0 V bias). Under various pressure and temperature conditions, the device's flexibility and durability were tested. The biodegradable photodetector prepared through the solvent- and equipment-free handprint technique has the potential to attract significant interest in wearable and flexible electronics in the future.

Patient Reported Barriers for Participation in Supervised Exercise Therapy for Symptomatic Peripheral Artery Disease.

BACKGROUND: Supervised exercise therapy (SET) provides clinical benefit for patients suffering from intermittent claudication due to peripheral artery disease (PAD). However, enrollment in programs when offered remains low. We sought to identify patient-reported barriers to enrollment in SET as part of a prospective quality improvement program. METHODS: Patients who presented to clinic and were diagnosed with claudication were offered enrollment in a prospective quality improvement protocol, offered at 9 regional offices throughout our health system. Both patients who enrolled and declined enrollment were offered a 12-question questionnaire to identify potential barriers to enrollment. Additional data including gender, smoking status, ankle-brachial index (ABI), proximity to the nearest regional office, and disadvantage levels of neighborhoods (low: 1-3, medium: 4-7, and high: 8-10 area deprivation index [ADI]) was collected and compared by program participation using univariate analysis. RESULTS: Patients enrolled in the SET program (n = 66 patients) versus those who declined (n = 84 patients) were of similar age (medium age: 71.4 vs. 69.7 years, P = 0.694), baseline ABI (0.6 vs. 0.6, P = 0.944), smoking status (former 56.1% vs. 53.6%, P = 0.668), distance away from outpatient center (8.2 mi vs. 8.4 mi, P = 0.249), and had similar Connecticut state ADIs (2021 high-disadvantage: 35.4% vs. 33.3%, P = 0.549). Patients participating in the SET program were more likely to be male (78.8% vs. 56.0%, P = 0.003). Top self-reported barriers for patients who declined participation included transportation/distance (39.3%), preference for independent walking (56.0%), inability to commit to 3 sessions per week (52.4%), and lack of interest (20.2%). In addition, a higher proportion of patients who declined participation identified severe barriers of preference for independent walking (39.3% vs. 1.5%, P < 0.001), inability to commit to 3 sessions per week (26.2% vs. 3.0% P < 0.001), transportation/distance issues (23.8% vs. 7.6% P = 0.008), and cost (27.4% vs. 9.1%, P = 0.005) as significant barriers for participation in SET. CONCLUSIONS: Patients who declined participation in SET for PAD had similar disease status and access to care than participating counterparts. Top reported barriers to enrollment include a preference for independent walking, transportation/distance, commitment to 3x/week program, and cost, which highlight areas of focus for equitable access to these limb-saving services.

Findings From a National Survey of Older US Adults on Patient Willingness to Use Telehealth Services: Cross-Sectional Survey.

BACKGROUND: Telehealth (telemedicine and telepharmacy) services increase access to patient services and ensure continuity of care. However, few studies have assessed factors that influence patients' willingness to use telehealth services, and we sought to investigate this. OBJECTIVE: This study aims to examine respondents' (aged between 45 and 75 years) willingness to use telehealth services (telepharmacy and telemedicine) and the correlates of the willingness to use telehealth services. METHODS: We administered a cross-sectional national survey of 1045 noninstitutionalized US adults aged between 45 and 75 years in March and April 2021. Multiple logistic regression analyses were used to identify demographic and health service use correlates of self-reported willingness to use telehealth services. RESULTS: Overall willingness to use telemedicine was high (674/1045, 64.5%). Adults aged 55 years and older were less willing to use telemedicine (aged between 55 and 64 years: odds ratio [OR] 0.61, 95% CI 0.42-0.86; aged 65 years or older: OR 0.33, 95% CI 0.22-0.49) than those younger than 55 years. Those with a regular provider (OR 1.01, 95% CI 1-1.02) and long travel times (OR 1.75, 95% CI 1.03-2.98) were more willing to use telemedicine compared to those without a regular provider and had shorter travel times, respectively. Willingness to use telemedicine services increased from 64.5% (674/1045) to 83% (867/1045) if the service was low-cost or insurance-covered, was with their existing health care provider, or was easy-to-use. Overall willingness to use telepharmacy was 76.7% (801/1045). Adults aged older than 55 years were less willing to use telepharmacy (aged between 55 and 64 years: OR 0.57, 95% CI 0.38-0.86; aged 65 years or older: OR 0.24, 95% CI 0.15-0.37) than those younger than 55 years. Those who rated pharmacy service quality higher were more willing to use telepharmacy (OR 1.06, 95% CI 1.03-1.09) than those who did not. CONCLUSIONS: Respondents were generally willing to use telehealth (telemedicine and telepharmacy) services, but the likelihood of their being willing to use telehealth decreased as they were older. For those initially unwilling (aged 55 years or older) to use telemedicine services, inexpensive or insurance-covered services were acceptable.

A Green Light-Activated Insulin Depot with Ultrafast In Vivo Efficiency in the Subcutaneous Space.

In this work, for the first time, we demonstrate light control of a therapeutic protein's release from a depot in the subcutaneous layer of the skin. The subcutaneous layer is a standard location for therapeutic protein depots due to its large size and ease of access, but prior attempts to utilize this space failed because insufficient light can reach this deeper layer. An analysis of existing biophysical literature suggested that an increase of photoactivation wavelength from 365 to 500 nm could allow an increase of depot irradiation in the subcutaneous by >100-fold. We therefore used a green light-activated thio-coumarin-based material and demonstrated robust release of a therapeutic, insulin, in response to skin illumination with an LED light source. We further demonstrated that this release is ultrafast, as fast or faster than any commercially used insulin, while maintaining the native insulin sequence. This release of insulin was then accompanied by a robust reduction in blood glucose, demonstrating the retention of bioactivity despite the synthetic processing required to generate the material. In addition, we observed that the material exhibits slow basal release of insulin, even in the absence of light, potentially through biochemical or photochemical unmasking of insulin. Thus, these materials can act much like the healthy pancreas does: releasing insulin at a slow basal rate and then, upon skin irradiation, releasing an ultrafast bolus of native insulin to reduce postprandial blood glucose excursions.

Locations and characteristics of pharmacy deserts in the United States: a geospatial study.

Pharmacies are important health care access points, but no national map currently exists of where pharmacy deserts are located. This cross-sectional study used pharmacy address data and Census Bureau surveys to define pharmacy deserts at the census tract level in all 50 US states and the District of Columbia. We also compared sociodemographic characteristics of pharmacy desert vs non-pharmacy desert communities. Nationally, 15.8 million (4.7%) of all people in the United States live in pharmacy deserts, spanning urban and rural settings in all 50 states. On average, communities that are pharmacy deserts have a higher proportion of people who have a high school education or less, have no health insurance, have low self-reported English ability, have an ambulatory disability, and identify as a racial or ethnic minority. While, on average, pharmacies are the most accessible health care setting in the United States, many people still do not have access to them. Further, the people living in pharmacy deserts are often marginalized groups who have historically faced structural barriers to health care. This study demonstrates a need to improve access to pharmacies and pharmacy services to advance health equity.

Implementing Whole Genome Sequencing (WGS) in Clinical Practice: Advantages, Challenges, and Future Perspectives.

The integration of whole genome sequencing (WGS) into all aspects of modern medicine represents the next step in the evolution of healthcare. Using this technology, scientists and physicians can observe the entire human genome comprehensively, generating a plethora of new sequencing data. Modern computational analysis entails advanced algorithms for variant detection, as well as complex models for classification. Data science and machine learning play a crucial role in the processing and interpretation of results, using enormous databases and statistics to discover new and support current genotype-phenotype correlations. In clinical practice, this technology has greatly enabled the development of personalized medicine, approaching each patient individually and in accordance with their genetic and biochemical profile. The most propulsive areas include rare disease genomics, oncogenomics, pharmacogenomics, neonatal screening, and infectious disease genomics. Another crucial application of WGS lies in the field of multi-omics, working towards the complete integration of human biomolecular data. Further technological development of sequencing technologies has led to the birth of third and fourth-generation sequencing, which include long-read sequencing, single-cell genomics, and nanopore sequencing. These technologies, alongside their continued implementation into medical research and practice, show great promise for the future of the field of medicine.

Unlocking Infertility: Enhancing Pregnancy Rates With Personalized Embryo Transfers Using Optimal Time for Endometrial Receptivity Analysis in Recurrent Implantation Failure Patients Undergoing In Vitro Fertilization.

Background Infertility remains a significant global challenge, and recurrent implantation failure (RIF) poses a considerable concern in assisted reproductive technology. Understanding the factors contributing to implantation failure is essential for developing accurate diagnostic tools and treatment strategies. Endometrial receptivity (ER) during the window of implantation is crucial for successful embryo implantation in in vitro fertilization (IVF) procedures. Molecular-based endometrial receptivity analysis and next-generation sequencing provide insights into ER, but there is a lack of research on these in the Indian population, particularly in patients with RIF. This retrospective cohort study evaluates the effectiveness of Optimal Timing for Endometrial Receptivity Analysis (OpERA)-guided personalized embryo transfer (pET) in Indian patients with a history of RIF. Methodology The study includes 158 female patients with a history of failed embryo transfers who underwent OpERA testing before frozen embryo transfer. Patients were categorized based on the number of previous failed transfers. OpERA outcomes were assessed, and clinical outcomes were compared between groups undergoing preimplantation genetic testing for aneuploidy (PGT-A) with and without OpERA. Endometrial preparation involved hormone replacement therapy, and OpERA testing was performed at the Neuberg Centre for Genomic Medicine using RNA extraction, cDNA conversion, and sequencing. Results OpERA outcomes showed no significant differences in receptive rates among patient groups. Group 3, with three or more failed transfers, exhibited significantly higher biochemical pregnancy rates (BPRs), clinical pregnancy rates (CPRs), and abortion rates (ARs) compared to Groups 1 and 2. OpERA with PGT-A showed significantly higher BPR, implantation rate, CPR, and lower AR compared to OpERA without PGT-A. Conclusions OpERA-guided pET, especially with PGT-A, demonstrated improved pregnancy outcomes, particularly in patients with a history of RIF. The study emphasizes the importance of OpERA in determining optimal transfer timing, moving beyond the traditional reliance on embryo quality alone. OpERA presents promise in predicting pregnancy outcomes for Indian patients with previous IVF failures. The integration of OpERA and PGT-A represents a significant advancement in personalized reproductive medicine, offering new hope for individuals grappling with infertility complexities.

Semaglutide improves metabolic dysfunction-associated steatohepatitis: A 10-year retrospective study.

Background and Aims: Semaglutide has been studied in patients with metabolic dysfunction-associated steatohepatitis (MASH) due to potential benefit from weight loss on liver inflammation. However, preclinical studies suggest that MASH improvement may be independent of weight loss. We aim to assess the impact of semaglutide on MASH in relation to weight loss. Methods: This retrospective study included 420 patients with diabetes on semaglutide for at least 12 months between 2011 and 2022. Exclusion criteria were liver disease other than MASH, decompensated cirrhosis, malignancy, and bariatric surgery. Primary endpoints were clinically significant improvements in AST or ALT (mean difference > 6.3 U/L and > 10.6 U/L respectively). Statistical analysis included Student's t-test/ANOVA, Wilcoxon signed-rank test/Friedman test as appropriate, and binary logistic regression. Results: Median duration of semaglutide was 22.5 months and 80% of patients received 1 mg/week. BMI improved by a mean (SD) of 1.9 points (2.8), weight by 13.3 lbs. (19.1), AST by 4.1 U/L (11.5), and ALT by 5.3 U/L (14.2). In 28% and 22% of patients respectively, AST and ALT had a clinically significant improvement. MASH scores (NFS, FIB4, APRI) improved after semaglutide (p < 0.001). No statistically significant differences in AST or ALT improvement were found when patients were stratified by BMI prior to semaglutide or when stratified by percentage of weight loss. On logistic regression, the duration of semaglutide and pretreatment APRI score increased the odds of clinically significant improvements of AST and ALT. Conclusion: Semaglutide treatment was associated with improvement in transaminases and MASH scores. Higher odds of positive semaglutide effects were observed with longer treatment duration and were independent of weight loss.

Reopening schools safely and educating youth (ROSSEY) study: Protocol for a community-based, cluster randomized controlled trial.

INTRODUCTION: ROSSEY is a community-academic partnership aiming to develop and test a COVID-19 risk communication intervention for elementary school students and families in Yakima County, Washington. We describe the ROSSEY study protocol that will be implemented in the Yakima School District. METHODS: Aim 1 is to identify the community's social, ethical, and behavioral needs and resources for students to return to school and maintain onsite learning. We will conduct semi-structured interviews with students and school employees and focus groups with parents. Aim 2 is to evaluate the effectiveness of risk communication on students' school attendance. We will conduct a cluster randomized control trial. We will enroll 14 Yakima School District elementary schools with 900 student participants and randomize the schools into the COVID-19 risk communication intervention or control group. Aim 3 will assess implementation of the risk communication intervention and schools' COVID-19 mitigation strategies. We will use the RE-AIM framework to guide this work, which will entail conducting semi-structured interviews with students and school employees and focus groups with parents. DISCUSSION: Implementation of science-based risk communication can educate the community on the benefits and safety of COVID-19 testing and vaccination. Risk communication may also inform families about the role of COVID-19 testing and vaccines as part of mitigation strategies to allow for safe in-person learning. Schools have extraordinary influence to promote children's health through policy and practice change. Study findings will provide evidence to facilitate policy decisions and best practices at schools that facilitate adoption of COVID-19 risk communication. TRIAL REGISTRATION: ClinicalTrials.govNCT04859699. Registered on April 26, 2021.

Severe Spontaneous Tilt of Scleral-Fixated Intraocular Lenses.

PURPOSE: To report and evaluate a multicenter series of 18 cases of severe, spontaneous IOL tilt involving the flanged intrascleral haptic fixation technique (FISHF). DESIGN: Clinical study with historical controls. METHODS: We report a cross-sectional study of 46 FISHF cases using the CT Lucia 602 IOL at a single academic center over a period of 24 weeks to determine the incidence of severe rotisserie-style rotational tilt. These rates were then compared with the same time-frame the prior year to help determine if this is a new phenomenon. Additional cases of severe tilt were solicited from another 4 academic centers. RESULTS: Among 46 FISHF cases at a single center, 5 developed severe tilt. No clear pattern in surgical technique, ocular history, or ocular anatomy was evident in these cases compared with controls, although the involved IOLs clustered within a narrow diopter range, indicative of a batch effect. In the same 24-week interval the year before, 33 FISHF cases were performed, none of which exhibited severe rotational tilt. In our multicenter dataset, 18 cases of tilt were identified. Surgeons included fellow and early-career physicians as well as surgeons with multiple years of experience with the Yamane technique. A variety of surgical approaches for FISHF were represented. In at least 8 of the cases, haptic rotation and/or dehiscence at the optic-haptic junction were documented. CONCLUSIONS: The identification of haptic rotation and dehiscence intraoperatively in several cases may reflect a new stability issue involving the optic-haptic junction.

Green Chemistry and In silico Techniques for Synthesis of Novel Pyranopyrazole and Pyrazolo-pyrano-pyrimidine Derivatives as Promising Antifungal Agents.

BACKGROUND: Every year Invasive Fungal Infections (IFI) are globally affecting millions of people. Candida albicans and Aspergillus niger have been reported as the most infectious and mortality-inducing fungal strains among all pathogenic fungi. AIMS & OBJECTIVES: To tackle this problem in the current study Pyranopyrazoles and Pyrazolopyrano- pyrimidine derivatives were developed using molecular hybridization, green chemistry and one-pot multicomponent reaction. MATERIALS AND METHODS: In the present work, New Chemical entities (NCE's) were developed on the basis of Structure activity relationship. All designed NCE's were screened for ADMET studies using the QikProp module of Schrodinger software. NCE's with zero violations were further docked on the crystal structure of 14α demethylase, cytochrome P450 and thymidine synthase (PDB ID: 5V5Z, 7SHI, 1BID). Selected molecules were synthesized using green chemistry techniques and evaluated for in vitro antifungal activity against Candida albicans and Aspergillus niger. RESULTS AND DISCUSSION: Designed NCE's (B1-12 and C1-11) showed favorable results in ADMET studies. In the docking study six compounds from series-B and five molecules from series- C showed good dock score and binding interaction when compared with the standard drugs. Compounds B-3 and C-4 showed the highest zone of inhibition activity against Candida albicans, where as B-1 and C-3 had shown highest zone of inhibition activity against Aspergillus niger. CONCLUSION: Bicyclic ring (series B) showed better activity as compare to fused tricyclic ring (series C).

Chondrolipoma of the Breast: A Myofibroblastoma Variant or a Distinct Lesion?

The entity commonly referred to as chondrolipoma is a rare and enigmatic breast lesion with unclear histogenesis and a complete lack of molecular characterization. It is uncertain whether it represents a hamartoma, choristoma, or a distinct neoplasm, including possibly a variant of mammary-type myofibroblastoma. We report two additional chondrolipomatous lesions of the breast. The lesions had varying histologic and immunohistochemical features similar to myofibroblastoma, including the loss of retinoblastoma (Rb) protein expression in one lesion. Molecular analysis by chromosomal microarray analysis performed on a second lesion did not demonstrate a loss of 13q14 or 16q typical of myofibroblastoma. Our findings further support the concept that at least a subset of breast lesions that historically have been classified as chondrolipoma are related to myofibroblastoma. However, the lack of myofibroblastoma-specific molecular alterations in one lesion suggests chondrolipomas may also have varying origins.