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Phakomatoses are a group of congenital disorders characterised by hamartomatous lesions of the skin as well as the central and peripheral nervous systems. The presence of naevus flammeus or port-wine stain is a characteristic feature of many such disorders including Sturge-Weber syndrome (SWS), Klippel-Trenaunay syndrome (KTS) and Phakomatosis pigmentovascularis (PPV).We describe the ocular findings in a patient with coexisting PPV, SWS and KTS

We formalize a notion of a privacy wrapper, defined as an algorithm that can take an arbitrary and untrusted script and produce an output with differential privacy guarantees. Our novel privacy wrapper, named TAHOE, incorporates two design ideas: a type of stability under subsetting, and randomization over subset size. We show that TAHOE imposes differential privacy for every possible script. When the data alphabet is finite and small enough, TAHOE can be practically run on a single computer. Performance simulations show that TAHOE has greater accuracy than a benchmark algorithm based on a subsample-and-aggregate approach for certain scenarios and parameter values.

Purpose: Men with metastatic castration-resistant prostate cancer (mCRPC) frequently develop resistance to androgen receptor signaling inhibitor (ARSI) treatment; therefore, new therapies are needed. Trophoblastic cell-surface antigen (TROP-2) is a transmembrane protein identified in prostate cancer and overexpressed in multiple malignancies. TROP-2 is a therapeutic target for antibody–drug conjugates (ADC). Experimental Design: TROP-2 gene (TACSTD2) expression and markers of treatment resistance from prostate biopsies were analyzed using data from four previously curated cohorts of mCRPC (n = 634) and the PROMOTE study (dbGaP accession phs001141.v1.p1, n = 88). EPCAM or TROP-2–positive circulating tumor cells (CTC) were captured from peripheral blood for comparison of protein (n = 15) and gene expression signatures of treatment resistance (n = 40). We assessed the efficacy of TROP-2–targeting agents in a mouse xenograft model generated from prostate cancer cell lines. Results: We demonstrated that TACSTD2 is expressed in mCRPC from luminal and basal tumors but at lower levels in patients with neuroendocrine prostate cancer. Patients previously treated with ARSI showed no significant difference in TACSTD2 expression, whereas patients with detectable AR-V7 expression showed increased expression. We observed that TROP-2 can serve as a cell surface target for isolating CTCs, which may serve as a predictive biomarker for ADCs. We also demonstrated that prostate cancer cell line xenografts can be targeted specifically by labeled anti–TROP-2 agents in vivo. Conclusions: These results support further studies on TROP-2 as a therapeutic and diagnostic target for mCRPC.

Factors influencing the clinical outcomes after periacetabular osteotomy (PAO) have not been well explored. This study evaluated the influence of symptom duration in developmental dysplasia of the hip on short-term patient-reported outcomes after PAO. A retrospective review of prospectively collected data identified PAOs performed on 139 patients. Sixty-five patients were then stratified into two groups based on preoperative symptom duration: 2 years or less (n=22) vs more than 2 years (n=43). We compared the results of hip-specific patient-reported outcome surveys collected preoperatively and postoperatively. When comparing the two groups, we found no significant differences in clinical outcome scores except for the UCLA Activity Scale. The shorter duration group achieved improvement 6 months postoperatively on the visual analog scale average pain score (from 4.5 to 2.167; P =.0017), International Hip Outcome Tool-12 (from 42.95 to 59.19; P =.0176), and Harris Hip Score (from 53.88 to 69.88; P =.049). The longer duration group also achieved postoperative improvement across multiple surveys. Nevertheless, a multivariate analysis controlling for age, sex, and body mass index and found that symptom duration did not independently affect the change in clinical outcomes. Although PAO leads to improvements in functional status and pain, preoperative symptom duration does not significantly affect these clinical outcomes. [ Orthopedics . 202x;4x(x):xx–xx.]

A new Vierordt’s Method or simultaneous equation method was developed and validated for the simultaneous estimation of raloxifene hydrochloride (RAL) and naringin (NAR) in their pure binary mixture and nanoformulation dosage form. The method was based on measuring absorbance at two wavelengths 289nm and 284nm (λmax of RAL and NAR) respectively in methanol. Absorptivities of RAL at 289 and 284nm were (689.5 and 683.13), and those of NAR was (282.45 and 316.75). The % recovery values for accuracy studies were found to be in the range (102% and 96.45%) for RAL and NAR, respectively. The % recovery values for precision studies were found to be in the range (Intraday precision; 102.78% and 96.13%), ( Interday precision; 102.58% and 96.02%) for RAL and NAR, respectively were found to be satisfactory. The linearity of the calibration plots was confirmed by the high value of the correlation coefficients (R2 = 0.9994 for RAL and 0.995 for NAR). The limit of detection and limit of quantification were theoretically calculated which were found to be (0.57µg/ml and 0.613µg/ml) and (4.25µg/ml and 4.55µg/ml) for RAL and NAR, respectively. Robustness was also carried out and %RSD was found to be less than 2.0%. The proposed method was successfully used to estimate RAL and NAR in the pure binary mixture and their nanoformulation dosage forms.

Background: Pre-clinical removable prosthodontic training is an integral part of undergraduate curriculum. The objectives of the study were to evaluate the application of pre-clinical removable prosthodontic laboratory training in general dental practice and relevance of its teaching in undergraduate curriculum. Methods: A descriptive questionnaire was developed to assess the extent of practice of pre-clinical removable prosthodontic lab skills in their dental practice. The responses were evaluated and statistically analyzed with a significance value of p

Background: High degree atrioventricular block (HDAVB) is an uncommon complication of non-ST-segment elevation myocardial infarction (NSTEMI) that frequently necessitates pacemaker implantation. This contemporary analysis compares need for pacemaker implantation based on the timing of intervention in acute NSTEMI complicated by HDAVB. Methods: We used 2016-2017 National Inpatient Sample database to identify admissions with NSTEMI and HDAVB. Time to coronary intervention from initial admission was used to segregate the admissions into two groups: early invasive strategy (EIS) (24 hours). Multivariable linear and logistic regression analysis was performed to compare in-hospital outcomes among the two groups. Results: Out of 949,984 NSTEMI related admissions, coexistent HDAVB was present in 0.7% (n=6725) patients. Amongst those, 55.61% (n=3740) hospitalizations included invasive intervention (EIS=1320, DIS=2420). Patients treated with EIS were younger (69.95 years vs. 72.38 years, P

In 2021 an estimated 74 million individuals had diabetes in India, almost all type 2 diabetes. More than half of patients with diabetes are estimated to be undiagnosed and more 90% have dyslipidemia that is associated with accelerated development of atherosclerotic cardiovascular disease (ASCVD). Patients of Indian descent with diabetes have multiple features that distinguish them from patients with diabetes in Western populations. These include characteristics such as earlier age of onset, higher frequency of features of the metabolic syndrome, more prevalent risk factors for ASCVD, and more aggressive course of ASCVD complications. In light of the unique features of diabetes and diabetic dyslipidemia in individuals of Indian descent, the Lipid Association of India developed this expert consensus statement to provide guidance for management of diabetic dyslipidemia in this very high risk population. The recommendations contained herein are the outgrowth of a series of 165 webinars conducted by the Lipid Association of India across the country from May 2020 to July 2021, involving 155 experts in endocrinology and cardiology and an additional 2880 physicians.

Background: Breast cancer related lymphedema (BCRL) represents a dreaded complication of breast cancer treatment that can lead to morbidity, diminished quality of life, and psychosocial harm and is associated with increased costs. Increasingly, data has supported the concept of prospective BCRL surveillance coupled with early intervention to mitigate these effects. Methods: We performed a systematic review of the literature searching for published randomized and prospective data evaluating prospective BCRL surveillance with early intervention. Results: We identified 12 studies (2,907 patients) including 4 randomized trials (1,203 patients) and 8 prospective studies (1,704 patients). Randomized data consistently demonstrate that early intervention reduces rates of progression to chronic BCRL with multiple paradigms and diagnostic modalities utilized; the strongest data in the review comes from the randomized PREVENT trial which demonstrated early detection with bioimpedance spectroscopy (BIS), coupled with a compression garment applied for 12 hours a day over 4 weeks, significantly reduced the rate of chronic BCRL compared to tape measurement. Conclusions: Current data support the role of prospective BCRL surveillance with early detection and intervention to reduce rates of chronic BCRL. Breast cancer patients at risk for BCRL should undergo prospective surveillance as part of survivorship. Given the level 1 data demonstrating that BIS is superior to conventional tape measure, it should be included as the standard BCRL diagnostic modality unless an equally effective modality is employed. Citation Format: Pat Whitworth, Frank Vicini, Stephanie Valente, Kirstyn Brownson, Beth Dupree, Manpreet Kohli, Laura Lawson, Chirag Shah. Reducing Rates of Chronic Breast Cancer Related Lymphedema with Screening & Early Intervention: An Update of Recent Data [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-08-15.

Background Anodyspareunia may be an adverse outcome of prostate cancer (PCa) treatment for gay, bisexual, and other men who have sex with men (GBM). Aim The aims of this study were to (1) describe the clinical symptoms of painful receptive anal intercourse (RAI) in GBM following PCa treatment, (2) estimate the prevalence of anodyspareunia, and (3) identify clinical and psychosocial correlates. Methods This was a secondary analysis of baseline and 24-month follow-up data from the Restore-2 randomized clinical trial of 401 GBM treated for PCa. The analytic sample included only those participants who attempted RAI during or since their PCa treatment (N = 195). Outcomes Anodyspareunia was operationalized as moderate to severe pain during RAI for ≥6 months that resulted in mild to severe distress. Additional quality-of-life outcomes included the Expanded Prostate Cancer Index Composite (bowel function and bother subscales), the Brief Symptom Inventory–18, and the Functional Assessment of Cancer Therapy–Prostate. Results Overall 82 (42.1%) participants reported pain during RAI since completing PCa treatment. Of these, 45.1% experienced painful RAI sometimes or frequently, and 63.0% indicated that the pain was persistent. The pain at its worst was moderate to very severe for 79.0%. The experience of pain was at least mildly distressing for 63.5%. Painful RAI worsened for a third (33.4%) of participants after completing PCa treatment. Of the 82 GBM, 15.4% were classified as meeting criteria for anodyspareunia. Antecedents of anodyspareunia included a lifelong history of painful RAI and bowel dysfunction following PCa treatment. Those reporting symptoms of anodyspareunia were more likely to avoid RAI due to pain (adjusted odds ratio, 4.37), which was negatively associated with sexual satisfaction (mean difference, −2.77) and self-esteem (mean difference, −3.33). The model explained 37.2% of the variance in overall quality of life. Clinical Implications Culturally responsive PCa care should include the assessment of anodyspareunia among GBM and explore treatment options. Strengths and Limitations This is the largest study to date focused on anodyspareunia among GBM treated for PCa. Anodyspareunia was assessed with multiple items characterizing the intensity, duration, and distress related to painful RAI. The external validity of the findings is limited by the nonprobability sample. Furthermore, the cause-and-effect relationships between the reported associations cannot be established by the research design. Conclusions Anodyspareunia should be considered a sexual dysfunction in GBM and investigated as an adverse outcome of PCa treatment.

If you and your spouse have been trying to conceive for a year and neither of you has been successful, there is a possibility that you are one of the 50–80 million people throughout the world who struggle with infertility. There is a male component present in approximately 20%-30% of these instances. It is common knowledge that low-quality sperm and oxidative stress (OS) both have a role in the aetiology of male infertility. Because of the oxidation of DNA, proteins, and lipids, excessive levels of reactive oxygen species (ROS) have the potential to disrupt the viability, motility, and morphology of sperm cells. ROS are responsible for these changes. Methods: Through the use of the PubMed interface, we searched the MEDLINE database for studies that had been completed and published during the past ten years that analysed the effect that antioxidants had on sperm in infertile guys (2012–2022). A number of different phrases, including infertility, alpha-lipoic acid, zinc, folate, coenzyme Q10, selenium, and vitamin, were utilised during the search. The study's findings indicate that inositol serves a purpose in a number of different mechanisms that foster contacts between sperm and oocytes, and that it also affects OS levels in sperm cells by way of its engagement in mitochondrial events. Alpha-lipoic acid (ALA) lessens the damage caused by reactive oxygen species (ROS) and improves the quality of sperm in a number of ways, including motility, morphology, and count. There might be a connection between not getting enough zinc in your diet and having low-quality sperm. Zinc and folate are two nutrients that can boost the quantity and quality of sperm. When taken orally, coenzyme Q10 increases the number of sperm as well as their overall motility and forward movement. A therapy with selenium (Se) results in an improvement in the sperm's overall quality, and this improvement is connected with an increase in ejaculatory production. Only vitamin B12 has been found to improve the quality of sperm; it does this by boosting sperm count and motility and by decreasing sperm DNA damage. Vitamin B12 is the only vitamin that has been proved to do this. Conclusions: Dietary supplementation with antioxidants may improve sperm quality in men with low-quality semen by reducing OS-induced sperm damage and increasing hormone synthesis and spermatozoa concentration, motility, and morphology. This may be achieved in men who also have low levels of antioxidants in their semen. Antioxidants can exert their effects in a variety of ways; hence, it is important for researchers conducting future clinical trials to study the possibility of combining a number of antioxidants.

Purpose of Review Metabolic liver diseases encompass several different inherited conditions that affect metabolism and can lead to hepatic dysfunction. Understanding the role of dietary interventions is critical, as nutrition continues to play a large role in management of these diseases and at times can even be lifesaving. Recent Findings Despite novel genetic and enzymatic therapies, dietary management remains fundamental in inherited metabolic diseases of the liver. Appropriate restriction, supplementation, and overall nutrition must be taken into consideration for optimal growth and hepatoprotection. Summary Understanding the pathophysiology of diseases, as well as how nutritional approaches fit into treatment paradigms, allows for optimal care of patients with metabolic liver disease. Treatment should be multidisciplinary and include a dietician with expertise in metabolic disease.

OBJECTIVE The authors sought to determine if postoperative disc height loss is associated with pseudarthrosis following anterior cervical discectomy and fusion (ACDF). They also sought to determine if the amount of postoperative disc height loss is predictive of need for revision for pseudarthrosis, as well as the impact of postoperative disc height loss on patient-reported outcome measures (PROMs) following surgery. METHODS The authors retrospectively identified patients aged > 18 years who underwent primary one- to three-level ACDF with allograft at a single institution with 1-year postoperative lateral and flexion-extension cervical spine radiographs. Logistic regression models and receiver operating characteristic curves were used for analysis. Alpha was set at p < 0.05. RESULTS Anterior or posterior disc height loss ≥ 2 mm was found in 52.5% of patients. Patients with a loss ≥ 2 mm were more likely to develop pseudarthrosis (p = 0.021) but not to undergo revision surgery due to pseudarthrosis (p = 0.459). Multivariable analysis identified male sex (OR 1.66, p = 0.013), the number of levels fused (OR 2.09, p < 0.001), and fusion at C6–7 (OR 1.52, p = 0.043) as predictors of disc height loss. The analysis also revealed that levels at the top (OR 0.383, 95% CI 0.170–0.854, p = 0.020) and middle (OR 0.174, 95% CI 0.053–0.548, p = 0.003) of fusion constructs were significant independent predictors of lower pseudarthrosis rates while disc height loss was not. Patients with disc height loss had significantly less improvement in scores for the Neck Disability Index (p = 0.002), visual analog scale (VAS) for arm pain (p = 0.018), and VAS for neck pain (p = 0.011) at 1 year following surgery. CONCLUSIONS This study is, to the authors’ knowledge, the largest study to date to assess the impact of postoperative disc height loss after ACDF. Disc height loss following ACDF was not predictive of revision surgery for pseudarthrosis or overall pseudarthrosis rates. However, pseudarthrosis was less likely to occur at the top and middle of fusion constructs. Loss in disc height postoperatively was significantly associated with less improvement in PROMs.

Dominant missense pathogenic variants in cardiac myosin heavy chain cause hypertrophic cardiomyopathy (HCM), a currently incurable disorder that increases risk for stroke, heart failure and sudden cardiac death. In this study, we assessed two different genetic therapies—an adenine base editor (ABE8e) and a potent Cas9 nuclease delivered by AAV9—to prevent disease in mice carrying the heterozygous HCM pathogenic variant myosin R403Q. One dose of dual-AAV9 vectors, each carrying one half of RNA-guided ABE8e, corrected the pathogenic variant in ≥70% of ventricular cardiomyocytes and maintained durable, normal cardiac structure and function. An additional dose provided more editing in the atria but also increased bystander editing. AAV9 delivery of RNA-guided Cas9 nuclease effectively inactivated the pathogenic allele, albeit with dose-dependent toxicities, necessitating a narrow therapeutic window to maintain health. These preclinical studies demonstrate considerable potential for single-dose genetic therapies to correct or silence pathogenic variants and prevent the development of HCM.

Zinc oxide nanoparticles (ZnO NP) are commonly used engineered NPs with extensive usage in consumer products, thus leading to direct exposure to humans. The direct route of exposure is through inhalation. Once inhaled, these particles accumulate in the lungs, increasing the chances of respiratory tract illness through cellular organelle damage. Zinc oxide nanoparticle-treated lung cells are reported to display cytotoxicity, increase DNA damage, and induce oxidative stress. The current study focused on the effects of ZnO NPs on mitochondrial dynamics (fission and fusion) in human lung epithelial cells (A549). The lung cells were exposed to ZnO NPs at 50 and 100 μg/ml concentrations, and their mitochondrial dynamics were assessed to understand the effects of the NPs. Treatment with ZnO NPs reduced the activity of mitochondrial complex I and complex III and altered mitochondrial structural and functional characteristics in a concentration-dependent manner. Zinc oxide nanoparticles exposure showed an increase in small and round-shaped mitochondria. The expression of various fission proteins (Drp1 and Fis1) and fusion proteins (Mfn1, Mfn2, and OPA1) was altered upon exposure to ZnO NPs. Our studies showed dysfunction of the mitochondria induced by ZnO NPs. In fibroblast mitochondrial dynamics, fission symbolizes threshold damage. In this paper, we have shown that the mitochondrial fission phenotype increased upon exposure to ZnO NPs. The paper emphasizes that these particles enter mitochondria, triggering a stress response that results in the removal of mitochondria via fission. It provides relevant data for safety guidelines to ensure the safer use of these particles.

Rice (Oryza sativa) is an important staple crop to address the Hidden Hunger problem not only in Asia but also in Africa where rice is fast becoming an important source of calories. The brown rice (whole grain with bran) is known to be more nutritious due to elevated mineral composition. The genetics underlying brown rice ionome (sum-total of such mineral composition) remains largely unexplored. Hence, we conducted a comprehensive study to dissect the genetic architecture of the brown rice ionome. We used genome-wide association studies (GWAS), gene-set analysis, and targeted association analysis for 12 micronutrients in the brown rice grains. A diverse panel of 300 resequenced indica accessions, with more than 1.02 million single nucleotide polymorphisms (SNPs), was used. We identified 109 candidate genes with 5 to 20% phenotypic variation explained (PVE) for the 12 micronutrients and identified epistatic interactions with multiple micronutrients. Pooling all candidate genes per micronutrient exhibited PVE values ranging from 11% to almost 40%. The key donor lines with larger concentrations for most of the micronutrients possessed superior alleles which were absent in the breeding lines. Through gene regulatory networks we identified enriched functional pathways for central regulators that were detected as key candidate genes through GWAS. This study provided important insights on the ionome variations in rice, on the genetic basis of the genome-ionome relationships and on the molecular mechanisms underlying micronutrient signatures.

Hepatopulmonary syndrome (HPS) is associated with increased waitlist mortality in liver transplantation (LT) candidates. Children with HPS are granted Model for End-Stage Liver Disease (MELD)/Pediatric End-Stage Liver Disease (PELD) exception points for waitlist prioritization in the United States based on criterion developed for adults. In this study, the impact of this MELD/PELD exception policy on post-LT survival in children was examined. A retrospective cohort of patients aged younger than 18 years with a MELD/PELD exception request who underwent LT between 2007 and 2018 were identified in the Scientific Registry of Transplant Recipients. Patients were stratified by waitlist partial pressure of arterial oxygen (PaO

The fabricated catalyst ZnO/CuI/PPy facilitates the synthesis of 2,4,5-trisubstituted imidazole under solvent free conditions with ideal values of green metrics.