Zika Virus Infection during Pregnancy in Mice Causes Placental Damage and Fetal Demise.

Zika virus (ZIKV) infection in pregnant women causes intrauterine growth restriction, spontaneous abortion, and microcephaly. Here, we describe two mouse models of placental and fetal disease associated with in utero transmission of ZIKV. Female mice lacking type I interferon signaling (Ifnar1(-/-)) crossed to wild-type (WT) males produced heterozygous fetuses resembling the immune status of human fetuses. Maternal inoculation at embryonic day 6.5 (E6.5) or E7.5 resulted in fetal demise that was associated with ZIKV infection of the placenta and fetal brain. We identified ZIKV within trophoblasts of the maternal and fetal placenta, consistent with a trans-placental infection route. Antibody blockade of Ifnar1 signaling in WT pregnant mice enhanced ZIKV trans-placental infection although it did not result in fetal death. These models will facilitate the study of ZIKV pathogenesis, in utero transmission, and testing of therapies and vaccines to prevent congenital malformations.

Predicting post-surgical functional status in high-grade glioma with resting state fMRI and machine learning.

PURPOSE: High-grade glioma (HGG) is the most common and deadly malignant glioma of the central nervous system. The current standard of care includes surgical resection of the tumor, which can lead to functional and cognitive deficits. The aim of this study is to develop models capable of predicting functional outcomes in HGG patients before surgery, facilitating improved disease management and informed patient care. METHODS: Adult HGG patients (N = 102) from the neurosurgery brain tumor service at Washington University Medical Center were retrospectively recruited. All patients completed structural neuroimaging and resting state functional MRI prior to surgery. Demographics, measures of resting state network connectivity (FC), tumor location, and tumor volume were used to train a random forest classifier to predict functional outcomes based on Karnofsky Performance Status (KPS < 70, KPS ≥ 70). RESULTS: The models achieved a nested cross-validation accuracy of 94.1% and an AUC of 0.97 in classifying KPS. The strongest predictors identified by the model included FC between somatomotor, visual, auditory, and reward networks. Based on location, the relation of the tumor to dorsal attention, cingulo-opercular, and basal ganglia networks were strong predictors of KPS. Age was also a strong predictor. However, tumor volume was only a moderate predictor. CONCLUSION: The current work demonstrates the ability of machine learning to classify postoperative functional outcomes in HGG patients prior to surgery accurately. Our results suggest that both FC and the tumor's location in relation to specific networks can serve as reliable predictors of functional outcomes, leading to personalized therapeutic approaches tailored to individual patients.

Evolving Barriers to Clinical Trial Enrollment and Clinical Care in Neuro-oncology in the Face of COVID-19.

The lack of treatments with durable response in neuro-oncology highlights the critical need for clinical trials to advance patient care. The intersection of relatively low incidence, evolving classification schema, and entrenched community, healthcare provider, and organizational factors have been historic challenges against successful trial enrollment and implementation. The additional need for multidisciplinary, often tertiary-level care, further magnifies latent national and international health inequities with rural and under-served populations. The COVID-19 pandemic both unveiled fundamental weaknesses in historical approaches and prompted the necessity of new approaches and systems for conducting clinical trials. Here, we provide an overview of traditional barriers to clinical trial enrollment in neuro-oncology, the effect of COVID-19 on these barriers, and the discovery of additional systemic weaknesses. Finally, we discuss future directions by reflecting on lessons learned with strategies to broaden access of care and streamline clinical trial integration into clinical practice.

Proteomic clusters underlie heterogeneity in preclinical Alzheimer's disease progression.

Heterogeneity in progression to Alzheimer's disease (AD) poses challenges for both clinical prognosis and clinical trial implementation. Multiple AD-related subtypes have previously been identified, suggesting differences in receptivity to drug interventions. We identified early differences in preclinical AD biomarkers, assessed patterns for developing preclinical AD across the amyloid-tau-(neurodegeneration) [AT(N)] framework, and considered potential sources of difference by analysing the CSF proteome. Participants (n = 10) enrolled in longitudinal studies at the Knight Alzheimer Disease Research Center completed four or more lumbar punctures. These individuals were cognitively normal at baseline. Cerebrospinal fluid measures of amyloid-ß (Aß)42, phosphorylated tau (pTau181), and neurofilament light chain (NfL) as well as proteomics values were evaluated. Imaging biomarkers, including PET amyloid and tau, and structural MRI, were repeatedly obtained when available. Individuals were staged according to the amyloid-tau-(neurodegeneration) framework. Growth mixture modelling, an unsupervised clustering technique, identified three patterns of biomarker progression as measured by CSF pTau181 and Aß42. Two groups (AD Biomarker Positive and Intermediate AD Biomarker) showed distinct progression from normal biomarker status to having biomarkers consistent with preclinical AD. A third group (AD Biomarker Negative) did not develop abnormal AD biomarkers over time. Participants grouped by CSF trajectories were re-classified using only proteomic profiles (AUCAD Biomarker Positive versus AD Biomarker Negative = 0.857, AUCAD Biomarker Positive versus Intermediate AD Biomarkers = 0.525, AUCIntermediate AD Biomarkers versus AD Biomarker Negative = 0.952). We highlight heterogeneity in the development of AD biomarkers in cognitively normal individuals. We identified some individuals who became amyloid positive before the age of 50 years. A second group, Intermediate AD Biomarkers, developed elevated CSF ptau181 significantly before becoming amyloid positive. A third group were AD Biomarker Negative over repeated testing. Our results could influence the selection of participants for specific treatments (e.g. amyloid-reducing versus other agents) in clinical trials. CSF proteome analysis highlighted additional non-AT(N) biomarkers for potential therapies, including blood-brain barrier-, vascular-, immune-, and neuroinflammatory-related targets.

Incorporating genetic testing into a routine kidney clinic.

Incorporating genetic testing in routine outpatient nephrology clinic can improve on chronic kidney disease (CKD) diagnosis and utilization of precision medicine. We sent a genetic test on patients with atypical presentation of common kidney diseases, electrolytes derangements, and cystic kidney diseases. We were able to identify a gene variant contributing to patients' kidney disease in more than half of our cohort. We then showed that patients with ApoL1 risk allele have likely worse kidney disease, and we were able to confirm genetic focal segmental glomerulosclerosis (FSGS) in 2 patients and avoid unnecessary immunosuppression. Genetic testing has also improved our operation to establish a polycystic kidney disease excellence center by confirming our diagnosis, especially in patients without a well-defined family history. In conclusion, utilizing genetic testing in a routine outpatient renal clinic did not cause any burden to either patients or nephrologists, with minimal administrative effort and no financial cost to our patients. We expect that genetic testing in the right setting should become routine in nephrology to achieve a patient-centered precision medicine with less invasive means of kidney disease diagnosis.

Racial disparities in the attainment of textbook oncologic outcomes following colectomy for colon cancer: a national cancer database cohort study.

INTRODUCTION: Textbook oncologic outcome (TOO) is attained when all desired short-term quality metrics are met following an oncologic operation. The objective of this study was to determine the impact of race on TOO attainment following colectomy for colon cancer. METHODS: The 2004-2017 National Cancer Database was queried for patients with non-metastatic colon cancer who underwent colectomy. TOO was defined as: negative margins (R0), adequate lymphadenectomy (LAD) (n ≥ 12), no prolonged length of stay (LOS), no 30-day readmission or mortality, and initiation of systemic therapy in ≤ 12 weeks. Racial groups were defined as White, Black, or Hispanic. RESULTS: 508,312 patients were identified of which 34% achieved TOO. Blacks attained the least TOO (31.4%) as well as the TOO criteria of adequate LAD (81.1%), no prolonged LOS (52.3%), and no 30-day readmission (89.7%). Hispanics were least likely to have met the criteria of R0 resection (94.3%), no 30-day mortality (87.3%), and initiation of systemic therapy in ≤ 12 weeks (81.8%). Patients who attained TOO had a higher median overall survival (OS) than those without TOO (148.2 vs. 84.2 months; P < 0.001). Hispanic TOO patients had the highest median OS (181.2 months), while White non-TOO patients experienced the lowest (80.2 months, P < 0.001). Multivariate logistic regression models suggest that Black and Hispanic patients are less likely to achieve TOO than their White counterparts. CONCLUSIONS: Racial disparities exist in the achievement of TOO, with Blacks and Hispanics being less likely to attain TOO compared to their White counterparts.

The attainment of a patient acceptable symptom state in patients undergoing revision spine fusion.

INTRODUCTION: Revision lumbar fusion is most commonly due to nonunion, adjacent segment disease (ASD), or recurrent stenosis, but it is unclear if diagnosis affects patient outcomes. The primary aim of this study was to assess whether patients achieved the patient acceptable symptom state (PASS) or minimal clinically important difference (MCID) after revision lumbar fusion and assess whether this was influenced by the indication for revision. METHODS: We retrospectively identified all 1-3 level revision lumbar fusions at a single institution. Oswestry Disability Index (ODI) was collected at preoperative, three-month postoperative, and one-year postoperative time points. The MCID was calculated using a distribution-based method at each postoperative time point. PASS was set at the threshold of ≤ 22. RESULTS: We identified 197 patients: 56% with ASD, 28% with recurrent stenosis, and 15% with pseudarthrosis. The MCID for ODI was 10.05 and 10.23 at three months and one year, respectively. In total, 61% of patients with ASD, 52% of patients with nonunion, and 65% of patients with recurrent stenosis achieved our cohort-specific MCID at one year postoperatively with ASD (p = 0.78). At one year postoperatively, 33.8% of ASD patients, 47.8% of nonunion patients, and 37% of patients with recurrent stenosis achieved PASS without any difference between indication (p = 0.47). CONCLUSIONS: The majority of patients undergoing revision spine fusion experience significant postoperative improvements regardless of the indication for revision. However, a large proportion of these patients do not achieve the patient acceptable symptom state. While revision spine surgery may offer substantial benefits, these results underscore the need to manage patient expectations.

Developmental delay and its demographic and social predictors among preschool-age children in Palestine.

PURPOSE: This study was designed to assess the developmental outcomes among preschool-aged children and its associated factors in Palestine. METHODS: A cross-sectional, descriptive-correlational design involved a representative sample of preschool-aged children from kindergarten in Ramallah governorate. Data were collected using the Ages and Stages Questionnaire, Arabic version-3. Associations between developmental delay (DD), parent, child and family characteristics were analyzed utilizing SPSS-25 version. RESULTS: A total of 249 preschoolers participated in the study. The overall rate of children with Global Developmental Delay (GDD) was 23.7%. The most prevalent DD were in gross motor, personal social, and fine motor skills (25.3%, 17.7%, and 16.5%, respectively). Binary logistic regression analysis revealed that the male gender of a child (OR = 2.66, 95% CI [1.37, 5.19]), the mother's part-time work (OR = 6.01, 95% CI [1.68, 21.52]), low family income (OR = 3.67, 95% CI [1.05, 12.73]), and families with three or more children (OR = 1.43, 95% CI [1.15, 1.781]) were statistically significant independent predictors of GDD. CONCLUSION: The study findings revealed higher rate of DD among preschoolers in Palestine than regional areas, especially in gross motor, fine motor, and personal social skills, which has consequences for both national and global health. According to the results, factors related to the child, the mother and the family are associated with the cumulative risk of preschoolers having DD. IMPLICATIONS: It is a crucial role for pediatric nurses to detect DD early and its related risk factors through screening programs to limit the burden of problems in childhood and later adulthood.

Assessment of idiopathic scoliosis among adolescents and associated factors in Palestine.

PURPOSE: This study aimed to investigate adolescent idiopathic scoliosis (AIS) and its related risk factors, including body mass index (BMI), physical activity (PA), gender, time of the first menstrual cycle, transportation, backpack weight and the way of carrying a backpack. DESIGN AND METHOD: a cross-sectional quantitative design was utilized. A convenient sample of adolescent students in grades seven through ten was included in the study. A self-reported questionnaire with three sections: demographic data; physical data including height, weight and PA; and Adam's forward bend test to determine each student's spine's Cobb angle by measuring the angle of trunk rotation using a scoliometer. The data were analyzed using SPSS version 25, with confidence intervals of 95%. RESULTS: A total of 820 schoolchildren participated in the study; 53.7% were female and 46.3% were male. Only 22% of these students engaged in vigorous exercise, compared to 36.7% who engaged in low PA; additionally, 10% of the adolescents had a low BMI. After the analysis, it was found that 5.4% of participants had AIS. Low PA (p = 0.001), being underweight (p = 0.038), and time of first menstrual period (p = 0.033) were significantly associated with AIS, while gender, backpack weight, and way of carrying were not statistically related to AIS. Binary logistic regression identified low PA as an independent predictor of AIS (OR = 7.22, 95%CI [1.64, 31.79]). CONCLUSIONS: The frequency of AIS in Palestine was significant, which highlighted the importance of this issue at a national and global level. There was an association between AIS and BMI, PA, and the time of the first menstrual cycle, which signifies the importance of early detection of the problem to limit its burden later in life. PRACTICE IMPLICATIONS: Teachers, teenagers, and their parents should be provided with programs that educate and clarify AIS, and a specific protocol should be established for scoliosis screening in schools.

Density Functional Theory Unveils the Secrets of SiAuF3 and SiCuF3: Exploring Their Striking Structural, Electronic, Elastic, and Optical Properties.

In the quest for advanced materials with diverse applications in optoelectronics and energy storage, we delve into the fascinating world of halide perovskites, focusing on SiAuF3 and SiCuF3. Employing density functional theory (DFT) as our guiding light, we conduct a comprehensive comparative study of these two compounds, unearthing their unique structural, electronic, elastic, and optical attributes. Structurally, SiAuF3 and SiCuF3 reveal their cubic nature, with SiCuF3 demonstrating superior stability and a higher bulk modulus. Electronic investigations shed light on their metallic behavior, with Fermi energy levels marking the boundary between valence and conduction bands. The band structures and density of states provide deeper insights into the contributions of electronic states in both compounds. Elastic properties unveil the mechanical stability of these materials, with SiCuF3 exhibiting increased anisotropy compared to SiAuF3. Our analysis of optical properties unravels distinct characteristics. SiCuF3 boasts a higher refractive index at lower energies, indicating enhanced transparency in specific ranges, while SiAuF3 exhibits heightened reflectivity in select energy intervals. Further, both compounds exhibit remarkable absorption coefficients, showcasing their ability to absorb light at defined energy thresholds. The energy loss function (ELF) analysis uncovers differential absorption behavior, with SiAuF3 absorbing maximum energy at 6.9 eV and SiCuF3 at 7.2 eV. Our study not only enriches the fundamental understanding of SiAuF3 and SiCuF3 but also illuminates their potential in optoelectronic applications. These findings open doors to innovative technologies harnessing the distinctive qualities of these halide perovskite materials. As researchers seek materials that push the boundaries of optoelectronics and energy storage, SiAuF3 and SiCuF3 stand out as promising candidates, ready to shape the future of these fields.

The impact of prior fragility fractures on long-term periprosthetic fracture risk following total knee arthroplasty.

The study found that patients undergoing total knee arthroplasty with prior fragility fracture had increased risk of subsequent fragility fracture and periprosthetic fracture within 8 years postoperatively when compared to those without a prior history. However, these patients were not at increased risk for all-cause revision within this period. PURPOSE: The aim of this study was to characterize the association of prior FFs on long-term risk of secondary fragility fracture (FF), periprosthetic fracture (PPF), and revision TKA. METHODS: Patients at least 50 years of age who underwent elective TKA were identified in the PearlDiver Database. Patients were stratified based on whether they sustained a FF within 3 years prior to TKA (7410 patients) or not (712,954 patients). Demographics and comorbidities were collected. Kaplan Meier analysis was used to observe the cumulative incidence of all-cause revision, PPF, and secondary FF within 8 years of TKA. Cox Proportional hazard ratio analysis was used to statistically compare the risk. RESULTS: In total, 1.0% of patients had a FF within three years of TKA. Of these patients, only 22.6% and 10.9% had a coded diagnosis of osteoporosis and osteopenia, respectively, at time of TKA. The 8-year cumulative incidence of secondary FF and periprosthetic fracture was significantly higher in those with a prior FF (27.5% secondary FF and 1.9% PPF) when compared to those without (9.1% secondary FF and 0.7% PPF). After adjusting for covariates, patients with a recent FF had significantly higher risks of secondary FF (HR 2.73; p < 0.001) and periprosthetic fracture (HR 1.86; p < 0.001) than those without a recent FF. CONCLUSIONS: Recent FF before TKA is associated with increased risk for additional FF and PPF within 8 years following TKA. Surgeons should ensure appropriate management of fragility fracture is undertaken prior to TKA to minimize fracture risk, and if not, be vigilant to identify patients with prior FF or other bone health risk factors who may have undocumented osteoporosis.

A microbiological identification and recovery actions of critical symptoms of anammox image bacteria.

Currently, the risks posed by bacteria are becoming increasingly important. It now appears that the cell wall of Anammox image bacteria is very different from what has been generally considered for many years. Not every textbook contains the peptidoglycan on the cell wall of Anammox image bacteria - the sugar-protein chain that strengthens the cells of most bacteria. Most researchers in this Anammox image bacteria diseased identification wanted to find out what gave the Anammox image cell its stability. It used powerful cryo-electron microscopes to examine the bacterial cell wall and find the exact structure of the peptidoglycan. A new algorithm is proposed to discover that Anammox image bacteria contain peptidoglycan, which completes a theory in microbiology. The identification of different diseases is listed, and the proposed model compares the exact results while comparing the parameters like accuracy, precision, recall, and F1-Score. Keywords: Anammox image bacteria, cell wall, cell stability, cryo-electron, microscope images, accuracy, precision, recall, F1-score.

Sex-specific hypnotic effects of the neuroactive steroid (3ß,5ß,17ß)-3-hydroxyandrostane-17-carbonitrile are mediated by peripheral metabolism into an active hypnotic steroid.

BACKGROUND: The novel synthetic neuroactive steroid (3ß,5ß,17ß)-3-hydroxyandrostane-17-carbonitrile (3ß-OH) blocks T-type calcium channels but does not directly modulate neuronal γ-aminobutyric acid type A (GABAA) currents like other anaesthetic neurosteroids. As 3ß-OH has sex-specific hypnotic effects in adult rats, we studied the mechanism contributing to sex differences in its effects. METHODS: We used a combination of behavioural loss of righting reflex, neuroendocrine, pharmacokinetic, in vitro patch-clamp electrophysiology, and in vivo electrophysiological approaches in wild-type mice and in genetic knockouts of the CaV3.1 T-type calcium channel isoform to study the mechanisms by which 3ß-OH and its metabolite produces sex-specific hypnotic effects. RESULTS: Adult male mice were less sensitive to the hypnotic effects of 3ß-OH compared with female mice, and these differences appeared during development. Adult males had higher 3ß-OH brain concentrations despite being less sensitive to its hypnotic effects. Females metabolised 3ß-OH into the active GABAA receptor positive allosteric modulator (3α,5ß,17ß)-3-hydroxyandrostane-17-carbonitrile (3α-OH) to a greater extent than males. The 3α-OH metabolite has T-channel blocking properties with sex-specific hypnotic and pharmacokinetic effects. Sex-dependent suppression of the cortical electroencephalogram is more pronounced with 3α-OH compared with 3ß-OH. CONCLUSIONS: The sex-specific differences in the hypnotic effect of 3ß-OH in mice are attributable to differences in its peripheral metabolism into the more potent hypnotic metabolite 3α-OH.

Seasonal influence on physicochemical properties of the sediments from Bay of Bengal coast with statistical approach.

The current study aims to investigate the influence of seasonal changes on the pollution loads of the sediment of a coastal area in terms of its physicochemical features. The research will focus on analyzing the nutrients, organic carbon and particle size of the sediment samples collected from 12 different sampling stations in 3 different seasons along the coastal area. Additionally, the study discusses about the impact of anthropogenic activities such as agriculture and urbanization and natural activities such as monsoon on the sediment quality of the coastal area. The nutrient changes in the sediment were found to be: pH (7.96-9.45), EC (2.89-5.23 dS/m), nitrogen (23.98-57.23 mg/kg), phosphorus (7.75-11.36 mg/kg), potassium (217-398 mg/kg), overall organic carbon (0.35-0.99%), and sediment proportions (8.91-9.3%). Several statistical methods were used to investigate changes in sediment quality. According to the three-way ANOVA test, the mean value of the sediments differs significantly with each season. It correlates significantly with principal factor analysis and cluster analysis across seasons, implying contamination from both natural and man-made sources. This study will contribute to developing effective management strategies for the protection and restoration of degraded coastal ecosystem.

Low-Dose Initiation of Buprenorphine: A Narrative Review.

PURPOSE OF REVIEW: Opioid use disorder (OUD) is a chronic disorder in which a person loses control over the use of opioids, develops a compulsive behavior, and defends the use despite knowing the negative consequences. There are numerous treatments for OUD, including buprenorphine. Since it is displacing a full agonist opioid, precipitated withdrawal can occur with standard inductions involving buprenorphine. RECENT FINDINGS: Case reports have noted success with a low-dose initiation of buprenorphine, which is different from typical protocols, relatively limited by adverse effects when patients were recently administered full agonists. A cohort investigation studied the use of a transdermal patch as part of the protocol, which was fairly well tolerated. While ongoing research is being conducted on this topic, recent case studies and smaller cohort studies have demonstrated the feasibility of a trial to treat OUD with low-dose initiation of buprenorphine.

Frailty as a Superior Predictor of Dysphagia and Surgically Placed Feeding Tube Requirement After Anterior Cervical Discectomy and Fusion Relative to Age.

Frailty is a measure of physiological reserve that has been demonstrated to be a discriminative predictor of worse outcomes across multiple surgical subspecialties. Anterior cervical discectomy and fusion (ACDF) is one of the most common neurosurgical procedures in the United States and has a high incidence of postoperative dysphagia. To determine the association between frailty and dysphagia after ACDF and compare the predictive value of frailty and age. 155,300 patients with cervical stenosis (CS) who received ACDF were selected from the 2016-2019 National Inpatient Sample (NIS) utilizing International Classification of Disease, tenth edition (ICD-10) codes. The 11-point modified frailty index (mFI-11) was used to stratify patients based on frailty: mFI-11 = 0 was robust, mFI-11 = 1 was prefrail, mFI-11 = 2 was frail, and mFI-11 = 3 + was characterized as severely frail. Demographics, complications, and outcomes were compared between frailty groups. A total of 155,300 patients undergoing ACDF for CS were identified, 33,475 (21.6%) of whom were frail. Dysphagia occurred in 11,065 (7.1%) of all patients, and its incidence was significantly higher for frail patients (OR 1.569, p < 0.001). Frailty was a risk factor for postoperative complications (OR 1.681, p < 0.001). Increasing frailty and undergoing multilevel ACDF were significant independent predictors of negative postoperative outcomes, including dysphagia, surgically placed feeding tube (SPFT), prolonged LOS, non-home discharge, inpatient death, and increased total charges (p < 0.001 for all). Increasing mFI-11 score has better prognostic value than patient age in predicting postoperative dysphagia and SPFT after ACDF.

Inflammatory response to epoxy resin and calcium silicate sealers preheated with different temperatures: an in vivo study.

OBJECTIVE: To determine the impact of heat exposure of different sealers on inflammatory cytokine secretions and tissue response in vivo. MATERIALS AND METHODS: Silicone tubes were prefilled with epoxy resin (ER) or calcium silicate (CS) sealers, preheated at 37, 60, or 120 °C, and implanted in rat subcutaneous site. Peri-implant exudate and tissue were analyzed after 1 and 4 weeks for cytokine secretions and tissue organization. RESULTS: At 1 week, 120 °C-preheated CS and ER induced higher secretions of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), respectively, as compared to sham/empty tube groups. At 4 weeks, whereas TNF-α secretion was reduced in CS, it increased in ER group, particularly for 120 °C. Both sealers revealed high IL-6 after 4 weeks as compared to sham/empty tube, and generally, higher IL-6 secretions were associated with ER. Histology at 1 week revealed lower degree of inflammatory infiltrate in the groups of the highest preheating temperature (120 °C). Nonetheless, at 4 weeks, whereas fibrous capsule area and inflammatory infiltrate remained low in the CS120 group, they were high in ER120. CONCLUSION: Preheating ER sealer to 120 °C induced high and prolonged secretion of proinflammatory cytokines (TNF-α and IL-6), whereas this effect was transient for the CS sealer. This was associated with increased fibrous capsule and inflammatory infiltrate in response to 120 °C-preheated ER. CLINICAL RELEVANCE: Heat-induced changes in sealer properties alter the inflammatory response in vivo, which may affect the clinical outcome. This will not only help appropriate selection of obturation technique for different sealers, but also for optimizing the properties of new generation of sealers.

Temporal and Spatial Variations of Potentially Toxic Elements in PM10 Collected in Jeddah City, Saudi Arabia.

Air pollution causes environmental and health problems around the world. In this study, ambient particulate matter with an aerodynamic diameter equal to or less than 10 microns (PM10) has been collected at three different locations in Jeddah city, Saudi Arabia. The locations are characterized by differences in terms of traffic, residential intensity, industrial, and non-road mobile machinery activities. The monthly and annual mass concentration of the PM10 exceeds the recommended annual limit of the World Health Organization (15 µg/m3) and the European air quality standard (40 µg/m3) at the three locations. The collected PM10 samples as well as a certified reference material of atmospheric particulates (NIST 1678a) were digested in aqua regia using microwave digestion. The quantitative elemental analysis was carried out using inductively coupled plasma mass spectrometry. The variations of the elemental concentration in terms of workdays, weekends, seasons, and annual were determined at the three locations. The spatial and temporal elemental variations were found to be different between the three sites, pointing to local influences that should be further evaluated. The concentration of Cd was found to be high and may cause health problems.

Clavicular reconstruction utilizing free fibula flap with periosteal extension.

Clavicular reconstruction is typically managed conservatively. Despite demonstrating improving outcomes, including range of motion and pain, there are currently no published reports of acute reconstruction with vascularized free fibula flaps (VFFF) or vascularized periosteal extensions in adult patients with clavicular defects. VFFFs have been utilized to correct critical bony defects of the clavicle and chronic nonunions; however, descriptions following acute trauma are rare. Bony union enhancement with periosteal extension has been described in both pediatric and adult populations, but never in the case of clavicular reconstruction. Herein, we seek to fill this gap in the literature by describing the acute reconstruction of a 6.5 cm bony gap in a 29-year-old male following a gunshot wound to the chest, utilizing a 6.5 cm VFFF with periosteal extension, and inset to the internal mammary vessels. The postoperative course was uncomplicated, with bony consolidation noted by 10 weeks, and full, pain-free range of motion at 8 months, showing this technique may be a viable option following acute trauma.

Homologous Recombination Deficiency (HRD) in Cutaneous Oncology.

Skin cancers, including basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (SCC), and melanoma, are the most common malignancies in the United States. Loss of DNA repair pathways in the skin plays a significant role in tumorigenesis. In recent years, targeting DNA repair pathways, particularly homologous recombination deficiency (HRD), has emerged as a potential therapeutic approach in cutaneous malignancies. This review provides an overview of DNA damage and repair pathways, with a focus on HRD, and discusses major advances in targeting these pathways in skin cancers. Poly(ADP-ribose) polymerase (PARP) inhibitors have been developed to exploit HRD in cancer cells. PARP inhibitors disrupt DNA repair mechanisms by inhibiting PARP enzymatic activity, leading to the accumulation of DNA damage and cell death. The concept of synthetic lethality has been demonstrated in HR-deficient cells, such as those with BRCA1/2 mutations, which exhibit increased sensitivity to PARP inhibitors. HRD assessment methods, including genomic scars, RAD51 foci formation, functional assays, and BRCA1/2 mutation analysis, are discussed as tools for identifying patients who may benefit from PARP inhibitor therapy. Furthermore, HRD has been implicated in the response to immunotherapy, and the combination of PARP inhibitors with immunotherapy has shown promising results. The frequency of HRD in melanoma ranges from 18% to 57%, and studies investigating the use of PARP inhibitors as monotherapy in melanoma are limited. Further research is warranted to explore the potential of PARP inhibition in melanoma treatment.