Infant Salmonella enterica Meningitis: A Rare Case Report and Review of Literature.

Meningitis caused by Salmonella enterica can be a fatal condition that is more common in low- and middle-income countries and uncommon in infants. This case of a 2-month-old male infant reported Salmonella meningitis symptoms, such as fever, irritability, altered sensorium, and diarrhoea. Clinical examination revealed bulging anterior fontanelles, dehydration, and sunken eyes. Screening for normal hearing, cranial ultrasound, and magnetic resonance imaging (MRI) revealed no brain abnormalities. A cerebrospinal fluid (CSF) culture revealed gram-negative Salmonella enterica bacilli. Treatment with meropenem and ampicillin was initiated after antibiotic susceptibility testing showed sensitivity. The patient's cerebrospinal fluid parameters and bacterial growth improved after antibiotic therapy. Two weeks later, the baby was neurologically healthy and discharged. Paediatricians should be aware that Salmonella enterica can cause meningitis in children with non-specific symptoms.

Challenges University Students Face while Studying away from Hometown: A Cross-Sectional Study.

This study aims to highlight the challenges that undergraduates face when traveling a significant distance from home to study. These challenges are psychological, financial, and nutritional. The study was descriptive and based on a survey conducted to investigate the challenges faced by university students while studying away from their hometown. A questionnaire was used to collect data from 214 undergraduates between February and April 2021. The collected data were analyzed using the computer program SPSS version 24. Pearson's Chi-square and Fisher's exact tests were applied to observe associations between qualitative variables. A total of 214 undergraduates participated in the study, with a median age of 22 years. The study found significant relationships between weight change and housing (P < 0.001), weight change and distance (P < 0.001), level of homesickness and housing (P < 0.001), level of homesickness and college distance (P < 0.001), and financial status with housing (P = 0.025). The study revealed that a significant number of undergraduate participants face psychological, financial, and nutritional challenges. These challenges include psychosocial issues, such as homesickness financial difficulties, such as money issues, and nutritional concerns, such as weight changes.

Genome-wide CRISPR screens identify novel regulators of wild-type and mutant p53 stability.

Tumor suppressor p53 (TP53) is frequently mutated in cancer, often resulting not only in loss of its tumor-suppressive function but also acquisition of dominant-negative and even oncogenic gain-of-function traits. While wild-type p53 levels are tightly regulated, mutants are typically stabilized in tumors, which is crucial for their oncogenic properties. Here, we systematically profiled the factors that regulate protein stability of wild-type and mutant p53 using marker-based genome-wide CRISPR screens. Most regulators of wild-type p53 also regulate p53 mutants, except for p53 R337H regulators, which are largely private to this mutant. Mechanistically, FBXO42 emerged as a positive regulator for a subset of p53 mutants, working with CCDC6 to control USP28-mediated mutant p53 stabilization. Additionally, C16orf72/HAPSTR1 negatively regulates both wild-type p53 and all tested mutants. C16orf72/HAPSTR1 is commonly amplified in breast cancer, and its overexpression reduces p53 levels in mouse mammary epithelium leading to accelerated breast cancer. This study offers a network perspective on p53 stability regulation, potentially guiding strategies to reinforce wild-type p53 or target mutant p53 in cancer.

IL7 in combination with radiotherapy stimulates a memory T-cell response to improve outcomes in HNSCC models.

Clinically approved head and neck squamous cell carcinoma (HNSCC) immunotherapies manipulate the immune checkpoint blockade (ICB) axis but have had limited success outside of recurrent/metastatic disease. Interleukin-7 (IL7) has been shown to be essential for effector T-cell survival, activation, and proliferation. Here, we show that IL7 in combination with radiotherapy (RT) is effective in activating CD8 + T-cells for reducing tumor growth. Our studies were conducted using both human papillomavirus related and unrelated orthotopic HNSCC murine models. Immune populations from the tumor, draining lymph nodes, and blood were compared between treatment groups and controls using flow cytometry, proteomics, immunofluorescence staining, and RNA sequencing. Treatment with RT and IL7 (RT + IL7) resulted in significant tumor growth reduction, high CD8 T-cell tumor infiltration, and increased proliferation of T-cell progenitors in the bone marrow. IL7 also expanded a memory-like subpopulation of CD8 T-cells. These results indicate that IL7 in combination with RT can serve as an effective immunotherapy strategy outside of the conventional ICB axis to drive the antitumor activity of CD8 T-cells.

Practical applications of robots in prosthodontics for tooth preparation and denture tooth arrangement: A scoping review.

STATEMENT OF PROBLEM: With the increasing interest in using robots in dentistry and the widespread dissemination of information on this topic and its applications, a comprehensive review of robot applications in prosthodontics is needed. PURPOSE: The purpose of this scoping review was to assess the current status of prosthodontic robotic applications, their achievements to date, and the barriers hindering their broader adoption and further advancement. MATERIAL AND METHODS: The checklist for Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) was used to conduct this review. A comprehensive search methodology was developed to identify relevant studies on the use of robots in prosthodontic procedures in the PubMed, Scopus, Web of Science, and Google Scholar databases. The inclusion criteria were studies that specifically outlined the application of robots in the field of prosthodontics. RESULTS: Eighteen relevant studies were found. Of these, 10 studies focused on assessing the effectiveness of robotic systems through in vitro testing using phantom models for tooth preparation. These studies specifically explored the processes involved in creating complete crowns and veneers. The remaining 8 studies investigated the use of robotics in tooth alignment, with a specific focus on complete dentures. CONCLUSIONS: Robots have the potential to improve precision and accuracy in prosthetic dentistry. However, clinical studies are needed to confirm the widespread use of robots in prosthodontics, as their clinical application is still in its early stages.

Sensory nerve release of CGRP increases tumor growth in HNSCC by suppressing TILs.

BACKGROUND: Perineural invasion (PNI) and nerve density within the tumor microenvironment (TME) have long been associated with worse outcomes in head and neck squamous cell carcinoma (HNSCC). This prompted an investigation into how nerves within the tumor microenvironment affect the adaptive immune system and tumor growth. METHODS: We used RNA sequencing analysis of human tumor tissue from a recent HNSCC clinical trial, proteomics of human nerves from HNSCC patients, and syngeneic orthotopic murine models of HPV-unrelated HNSCC to investigate how sensory nerves modulate the adaptive immune system. FINDINGS: Calcitonin gene-related peptide (CGRP) directly inhibited CD8 T cell activity in vitro, and blocking sensory nerve function surgically, pharmacologically, or genetically increased CD8 and CD4 T cell activity in vivo. CONCLUSIONS: Our data support sensory nerves playing a role in accelerating tumor growth by directly acting on the adaptive immune system to decrease Th1 CD4 T cells and activated CD8 T cells in the TME. These data support further investigation into the role of sensory nerves in the TME of HNSCC and points toward the possible treatment efficacy of blocking sensory nerve function or specifically inhibiting CGRP release or activity within the TME to improve outcomes. FUNDING: 1R01DE028282-01, 1R01DE028529-01, 1P50CA261605-01 (to S.D.K.), 1R01CA284651-01 (to S.D.K.), and F31 DE029997 (to L.B.D.).

Cleft Lip and Palate Research Trends in Saudi Arabia: A Bibliometric Analysis.

As Saudi Arabia advances in medical education and patient care, assessing its contribution to cleft lip and palate (CLP) research is vital. This bibliometric analysis aims to map the trends, collaborations, and impact of Saudi research in CLP. Utilizing the Web of Science database, this study conducted a comprehensive bibliometric analysis of CLP research related to Saudi Arabian publications. The analysis included data extraction and assessment of publications, citations, H-index, and international collaborations using advanced bibliometric tools and software. A total of 89 CLP-related articles in Saudi Arabia were retrieved. The findings indicated a steady increase in publications and citations over the years, reflecting growing interest and recognition of CLP's challenges in the Saudi healthcare context. King Abdulaziz University and King Saud University emerged as leading contributors. International collaboration was evident, with significant partnerships with countries like the USA, Canada, the UK, and others. The Cleft Palate-Craniofacial Journal and the Saudi Dental Journal were identified as the most influential journals in disseminating Saudi CLP research. The study highlights a positive growth trajectory in Saudi CLP research, marked by increased publications, citations, and international collaborations. It underscores the importance of continuous research and the need for enhanced efforts to further the understanding and treatment of CLP. Future studies should consider including a broader range of databases to provide a more comprehensive global view of CLP research trends.

PPARα Agonism Enhances Immune Response to Radiotherapy while Dietary Oleic Acid Results in Counteraction.

INTRODUCTION: Head and neck cancer (HNC) improvements are stagnant, even with advances in immunotherapy. Our previous clinical trial data show altered fatty acid (FA) metabolism correlates with outcome. We hypothesized that pharmacologic and dietary modulation of FA catabolism will impact therapeutic efficacy. METHODS: We performed in vivo and in vitro experiments employing PPARα agonism with fenofibrate (FF) or high oleic acid diets (OAD) with radiotherapy, generating metabolomic, proteomic, stable isotope tracing, extracellular flux analysis, and flow cytometric data to investigate these alterations. RESULTS: FF improved anti-tumor efficacy of high dose per fraction radiotherapy in HNC murine models, while the OAD reversed this effect. FF treated mice on the control diet had evidence of increased FA catabolism. Stable isotope tracing showed less glycolytic utilization by ex vivo CD8+ T cells. Improved efficacy correlated with intratumoral alterations in eicosanoid metabolism and downregulated mTOR and CD36. CONCLUSION: Metabolic intervention with increased FA catabolism improves efficacy of HNC therapy and enhance anti-tumoral immune response.

Heated and humidified high flow therapy (HHHFT) in extreme and very preterm neonates with respiratory distress syndrome (RDS): a retrospective cohort from a tertiary care setting in Pakistan.

OBJECTIVE: To determine the role of heated humidified high flow therapy (HHHFT) as primary respiratory support in spontaneously breathing moderate-late, very and extreme preterm neonates with respiratory distress syndrome (RDS) at a tertiary care hospital from a developing country. DESIGN: Retrospective cohort study. SETTING: Neonatal intensive care unit of Indus Hospital and Health Network, Karachi, Pakistan. PATIENTS: All preterm neonates with RDS and who received HHHFT as primary respiratory support were included retrospectively, while neonates with orofacial anomalies, congenital heart and lung diseases other than RDS, abdominal wall defects, encephalopathy, congenital pneumonia and received continuous positive airway pressure or invasive ventilation were excluded. INTERVENTIONS: HHHFT as primary respiratory support for RDS. MAIN OUTCOME MEASURES: Effectiveness, duration, failure rate and complications of HHHFT as a primary respiratory support in moderate-late, very and extremely preterm neonates were evaluated. RESULTS: The cohort included 138 neonates during a period of 12 months. The median gestational age was 32 weeks, and the median birth weight was 1607 g. Grade 1-2 RDS was seen in 97%, surfactant instillation was done in 10.8% and HHHFT was provided in all the neonates as primary respiratory support. The total duration of HHHFT support was <1 week in 94% of neonates. Bronchopulmonary dysplasia and pneumothorax until discharge or death were observed in one neonate, haemodynamically significant Patent Ductus Artriosus (HsPDA) in two neonates and intraventricular haemorrhage Grade ≥2 in five neonates, while only one neonate died. CONCLUSION: This study appears to show that HHHFT is a simple, safe, efficient and cheap mode of primary respiratory support that can be given to spontaneously breathing moderate-late, very and extremely preterm neonates with RDS, especially in low- or middle-income countries.

Awareness of Preeclampsia and Its Associated Factors Among Women in Al Baha Region, Saudi Arabia.

BACKGROUND: Preeclampsia is associated with the incidence of common fetal problems including intra-uterine growth restriction (IUGR), premature delivery oligohydramnios, placental abruption, fetal discomfort, and intrauterine fetal death. Pregnant women are not well-informed about preeclampsia, including its symptoms, risk factors, and consequences. The aim of the current study is to evaluate the awareness of preeclampsia and its associated factors among women in the Al Baha region, Saudi Arabia. METHODOLOGY: An observational cross-sectional design was employed to assess the awareness of preeclampsia and its associated factors among women in the Al Baha region of Saudi Arabia. Data was collected from April 2023 to September 2023. A questionnaire was designed to gather information on participants' sociodemographic characteristics (such as age, educational level, and residency) and their awareness of preeclampsia, including knowledge about signs/symptoms, risk factors, and complications. RESULTS: In the current study, we included 485 pregnant women. The majority of participants were aged 40 years or older (37.5%), followed by those aged 35-39 (20.4%). Among the participants, 70.9% confirmed that they had heard about pre-eclampsia before. The most common signs and symptoms were high blood pressure (47.4%), increased protein in urine (40.2%), continuous headache (39.2%), and vomiting/nausea (40.0%). Participants demonstrated awareness of obesity (29.7%), diabetes mellitus (35.5%), chronic hypertension (47.0%), and chronic kidney disease (31.3%) as major risk factors. Participants were aware of potential risks such as kidney disorders (34.6%), heart disorders (23.7%), and preterm delivery (50.9%). The analysis reveals that younger participants below 20 years old (3.3%) and lower educational levels (5.6%) had lower awareness of preeclampsia compared to older age groups. CONCLUSION: The findings of this study highlight a reasonable level of preeclampsia awareness and knowledge among Saudi Arabian women residing in the Al Baha region. While the majority of participants were familiar with preeclampsia, there were significant knowledge gaps regarding the precise symptoms, risk factors, and consequences of the condition.

Mutational processes of tobacco smoking and APOBEC activity generate protein-truncating mutations in cancer genomes.

Mutational signatures represent a genomic footprint of endogenous and exogenous mutational processes through tumor evolution. However, their functional impact on the proteome remains incompletely understood. We analyzed the protein-coding impact of single-base substitution (SBS) signatures in 12,341 cancer genomes from 18 cancer types. Stop-gain mutations (SGMs) (i.e., nonsense mutations) were strongly enriched in SBS signatures of tobacco smoking, APOBEC cytidine deaminases, and reactive oxygen species. These mutational processes alter specific trinucleotide contexts and thereby substitute serines and glutamic acids with stop codons. SGMs frequently affect cancer hallmark pathways and tumor suppressors such as TP53, FAT1, and APC. Tobacco-driven SGMs in lung cancer correlate with smoking history and highlight a preventable determinant of these harmful mutations. APOBEC-driven SGMs are enriched in YTCA motifs and associate with APOBEC3A expression. Our study exposes SGM expansion as a genetic mechanism by which endogenous and carcinogenic mutational processes directly contribute to protein loss of function, oncogenesis, and tumor heterogeneity.

Epidemiology and Management of Poisoning Cases in the Emergency Room: A Cross-Sectional Study in Saudi Arabia.

Introduction Acute poisoning, arising from exposure to toxic substances, is a critical healthcare challenge. In the United States, it's one of the primary causes of morbidity and mortality. European institutions report that about 1% of all emergency department admissions relate to poisoning, a statistic that becomes alarming given the life-threatening implications. While there's an underreporting of these cases, the actual figure could be much higher. Acute poisoning has resulted in over a million morbidity cases with a 20% mortality rate. Most concerning is the World Health Organization's data indicating that over 90% of accidental poisoning deaths occur in low to middle-income countries. Methods This was a cross-sectional study conducted over a 12-month period in three major hospitals in Saudi Arabia. The study population comprised of 1470 patients who presented to emergency departments with suspected acute poisoning. Medical records were retrospectively reviewed, capturing data on patient demographics, nature and type of poisoning, initial management, and outcomes. Data were analyzed using SPSS software version 28.0 (IBM Corp., Armok, NY). Descriptive statistics were used to summarize the data, while Chi-square tests were employed to determine associations between demographic factors and the nature of poisoning. Furthermore, the Pearson correlation was used to evaluate the link between referrals to specialized centers and patient outcomes. Results Out of the 1470 participants, a significant majority were males, constituting 77.1%. The dominant age group was between 18-24 years, representing 71.4% of the sample. A substantial 88.6% had visited the emergency room due to medical complications stemming from poisoning. When queried about their understanding of acute poisoning, 60.0% were able to correctly define the term. However, a concerning 54.3% reported they had never received any formal training or been part of awareness programs regarding poisoning. There was a marked association (p < 0.001) between demographics and the nature of toxin exposure. Delving deeper into the specifics of poisoning incidents, medications were identified as the primary culprits in 8.6% of the cases, followed by household chemicals at 5.7%. Crucially, a vast majority, 82.9%, were of the opinion that with the right education and precautions in place, the incidence of poisoning cases could be substantially reduced. Conclusion Acute poisoning is a pressing concern in Saudi Arabia, with a significant proportion of the population unaware or inadequately trained to handle such emergencies. This study underscores the importance of awareness campaigns, formal education, and specialized training to prevent and effectively manage poisoning cases in emergency settings. Moreover, the strong association between certain demographics and toxin exposures suggests that targeted interventions might be necessary for specific groups.

Predictors and Outcomes of Falls in Older Adults Presenting to the Emergency Room in Saudi Arabia: A Cross-Sectional Analysis.

INTRODUCTION: Saudi Arabia is witnessing a demographic shift characterized by a rising elderly population. Cases of fall in this demographic have emerged as a significant health concern, especially in emergency room (ER) settings. Despite this, there is limited research on the causes and outcomes of such incidents. This study intends to bridge the gap in understanding the factors leading to falls in elderly patients presenting to ERs and the subsequent outcomes. Such understanding is pivotal for the formulation of effective prevention strategies and enhanced healthcare services for the elderly. METHODS: To achieve the study's objectives, we employed SPSS software for Windows, version 28.0 (IBM Corp., Armonk, NY) for data analysis. We collected demographic information, including age, gender, education, employment status, and location, to measure patient satisfaction with the quality and responsiveness of emergency care, using Likert scale responses via electronic survey conducted as a cross-sectional study from January 2023 to August 2023, summarizing it using descriptive statistics. We analyzed categorical variables by frequencies and percentages. Chi-square tests were utilized to examine differences in distribution across categories for fall factors, and a p-value below 0.05 was deemed significant. Through logistic regression, we pinpointed the predictors of falls among older adults, showcasing the strength and direction of these relationships. Adjusted odds ratios with 95% confidence intervals were documented. A perception survey was also conducted to evaluate ER patient satisfaction. RESULTS: Our results shed light on various aspects of fall prevention and emergency care. There was a pronounced representation in age groups of 18-24 and 25-34 years, indicating the need for interventions tailored to different age groups. Patterns were identified where subjects engaged in limited physical activity and consumed alcohol infrequently. Mobility and balance problems were commonly found, stressing the need to address these issues. Chronic conditions such as hypertension and diabetes correlated with fall incidents. Additionally, sociodemographic factors like gender, education, and employment status played a role in influencing the risk of falls. Although age and location seemed to have a less pronounced effect, there exists an opportunity to enhance communication and patient participation in emergency care for improved experiences. CONCLUSION: The findings from our study provide crucial insights into the prevention of falls and enhancement of emergency care for Saudi Arabia's elderly population. By revealing the intricate relationships between sociodemographic attributes, health indicators, chronic ailments, and incidents of falls, we emphasize the need for well-rounded interventions. There is a pressing requirement for comprehensive fall prevention initiatives tailored to specific risk groups. Additionally, improving ER services is integral to ensuring the safety and well-being of older adults. This research can serve as a foundational resource for healthcare professionals and policymakers to devise robust strategies to reduce fall-related injuries and elevate the quality of emergency care outcomes.

Differential DNA damage repair and PARP inhibitor vulnerability of the mammary epithelial lineages.

It is widely assumed that all normal somatic cells can equally perform homologous recombination (HR) and non-homologous end joining in the DNA damage response (DDR). Here, we show that the DDR in normal mammary gland inherently depends on the epithelial cell lineage identity. Bioinformatics, post-irradiation DNA damage repair kinetics, and clonogenic assays demonstrated luminal lineage exhibiting a more pronounced DDR and HR repair compared to the basal lineage. Consequently, basal progenitors were far more sensitive to poly(ADP-ribose) polymerase inhibitors (PARPis) in both mouse and human mammary epithelium. Furthermore, PARPi sensitivity of murine and human breast cancer cell lines as well as patient-derived xenografts correlated with their molecular resemblance to the mammary progenitor lineages. Thus, mammary epithelial cells are intrinsically divergent in their DNA damage repair capacity and PARPi vulnerability, potentially influencing the clinical utility of this targeted therapy.

Assessment of Arabic Web-Based Knowledge About Clear Aligners: An Infodemiologic Study.

BACKGROUND: Orthodontic treatments aim to enhance dental aesthetics, functionality, and long-term oral health. Clear aligners have gained popularity as an aesthetic and convenient option for patients seeking orthodontic correction. However, the quality and readability of online Arabic patient-centered information regarding clear aligners has not been studied yet. The aim of our study is to investigate the quality and readability of Arabic patient-centered information about clear aligners. METHODS: We conducted an extensive evaluation of Arabic web-based content pertaining to clear aligners using three prominent search engines. Eligible websites were categorized based on specialization, organizational affiliation, material type, and presentation style. We assessed website quality and reliability using the DISCERN instrument, Journal of American Medical Association (JAMA) benchmarks, and Health on the Net (HON) code. In addition, we measured readability using the Flesch Reading Ease Score (FRES), Simplified Measure of Gobbledygook (SMOG), and Flesch-Kincaid Grade Level (FKGL). RESULTS: Out of 600 search results, 195 websites met the inclusion criteria. None of the websites were HON-code accredited. DISCERN assessments revealed low content quality, with none of the websites achieving high-quality status. The JAMA benchmarks showed limited compliance with the four items, with currency being the most frequently achieved. Readability assessments indicated generally high readability, with FKGL scores suggesting easy comprehension for the average readers. CONCLUSION: While Arabic web-based information on clear aligners is highly readable, its credibility and quality require significant improvement. Websites should adhere to medical information standards, subject content to rigorous assessments, and seek accreditation to ensure reliability. Enhancing the accessibility and comprehensibility of health-related content will empower individuals to make informed health decisions. Addressing limitations, such as social media and video content evaluation, and conducting comparisons with English websites in future research will provide a more comprehensive understanding of the landscape of online orthodontic information.

Pentoxifylline for treatment of sepsis and necrotising enterocolitis in neonates.

BACKGROUND: Mortality and morbidity due to neonatal sepsis and necrotising enterocolitis (NEC) remain high despite the use of potent antimicrobial agents. Agents that modulate inflammation may improve outcomes. Pentoxifylline (PTX), a phosphodiesterase inhibitor, is one such agent. This is an update of a review first published in 2003 and updated in 2011 and 2015. OBJECTIVES: To assess the effectiveness and safety of intravenous PTX as an adjunct to antibiotic therapy on mortality and morbidity in neonates with suspected or confirmed sepsis and neonates with NEC. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and trial registries in July 2022. We also searched the reference lists of identified clinical trials and handsearched conference abstracts.   SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs assessing the efficacy of PTX with antibiotics (any dose or duration) for treatment of suspected or confirmed sepsis or NEC in neonates. We included three comparisons: (1) PTX with antibiotics compared to placebo or no intervention with antibiotics; (2) PTX with antibiotics compared to PTX with antibiotics and adjunct treatments such as immunoglobulin M-enriched intravenous immunoglobulin (IgM-enriched IVIG); (3) PTX with antibiotics compared to adjunct treatments such as IgM-enriched IVIG with antibiotics. DATA COLLECTION AND ANALYSIS: We reported typical risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) for continuous outcomes derived from a fixed-effect model of meta-analysis. We calculated the number needed to treat for an additional beneficial outcome (NNTB) if there was a statistically significant reduction in RD. MAIN RESULTS: We identified no new studies for this update. We included six RCTs (416 neonates). All of the included studies examined neonates with sepsis; we identified no studies on neonates with NEC. Four of the six trials had high risk of bias for at least one risk of bias domain. Comparison 1: PTX with antibiotics compared to placebo with antibiotics, or antibiotics alone, in neonates with sepsis may reduce all-cause mortality during hospital stay (typical RR 0.57, 95% CI 0.35 to 0.93; typical RD -0.08, 95% CI -0.14 to -0.01; NNTB 13, 95% CI 7 to 100; 6 studies, 416 participants, low-certainty evidence) and may decrease length of hospital stay (LOS) (MD -7.74, 95% CI -11.72 to -3.76; 2 studies, 157 participants, low-certainty evidence). The evidence is very uncertain that PTX with antibiotics compared to placebo or no intervention results in any change in chronic lung disease (CLD) (RR 1.50, 95% CI 0.45 to 5.05; 1 study, 120 participants, very low-certainty evidence), severe intraventricular haemorrhage (sIVH) (RR 0.75, 95% CI 0.28 to 2.03; 1 study, 120 participants, very low-certainty evidence), periventricular leukomalacia (PVL) (RR 0.50, 95% CI 0.10 to 2.63; 1 study, 120 participants, very low-certainty evidence), NEC (RR 0.56, 95% CI 0.29 to 1.06; 6 studies, 405 participants, very low-certainty evidence), or retinopathy of prematurity (ROP) (RR 0.40, 95% CI 0.08 to 1.98; 1 study, 120 participants, very low-certainty evidence) in neonates with sepsis. Comparison 2: the evidence is very uncertain that PTX with antibiotics compared to PTX with antibiotics and IgM-enriched IVIG has any effect on mortality (RR 0.71, 95% CI 0.24 to 2.10; 102 participants, 1 study, very low-certainty evidence) or development of NEC in neonates with sepsis (RR 1.33, 95% CI 0.31 to 5.66; 1 study, 102 participants, very low-certainty evidence). The outcomes of CLD, sIVH, PVL, LOS, and ROP were not reported. Comparison 3: the evidence is very uncertain that PTX with antibiotics compared to IgM-enriched IVIG with antibiotics has any effect on mortality (RR 1.25, 95% CI 0.36 to 4.39; 102 participants, 1 study, very low-certainty evidence) or development of NEC (RR 1.33, 95% CI 0.31 to 5.66; 102 participants, 1 study, very low-certainty evidence) in neonates with sepsis. The outcomes of CLD, sIVH, PVL, LOS, and ROP were not reported. All of the included studies evaluated adverse effects due to PTX, but none were reported in the intervention group in any of the comparisons. AUTHORS' CONCLUSIONS: Low-certainty evidence suggests that adjunct PTX therapy in neonatal sepsis may decrease mortality and length of hospital stay without any adverse effects. The evidence is very uncertain if PTX with antibiotics compared to PTX with antibiotics and IgM-enriched IVIG, or PTX with antibiotics compared to IgM-enriched IVIG with antibiotics, has any effect on mortality or development of NEC. We encourage researchers to undertake well-designed multicentre trials to confirm or refute the effectiveness and safety of pentoxifylline in reducing mortality and morbidity in neonates with sepsis or NEC.

Simultaneous targeting of PD-1 and IL-2Rßγ with radiation therapy inhibits pancreatic cancer growth and metastasis.

In pancreatic ductal adenocarcinoma (PDAC) patients, we show that response to radiation therapy (RT) is characterized by increased IL-2Rß and IL-2Rγ along with decreased IL-2Rα expression. The bispecific PD1-IL2v is a PD-1-targeted IL-2 variant (IL-2v) immunocytokine with engineered IL-2 cis targeted to PD-1 and abolished IL-2Rα binding, which enhances tumor-antigen-specific T cell activation while reducing regulatory T cell (Treg) suppression. Using PD1-IL2v in orthotopic PDAC KPC-driven tumor models, we show marked improvement in local and metastatic survival, along with a profound increase in tumor-infiltrating CD8+ T cell subsets with a transcriptionally and metabolically active phenotype and preferential activation of antigen-specific CD8+ T cells. In combination with single-dose RT, PD1-IL2v treatment results in a robust, durable expansion of polyfunctional CD8+ T cells, T cell stemness, tumor-specific memory immune response, natural killer (NK) cell activation, and decreased Tregs. These data show that PD1-IL2v leads to profound local and distant response in PDAC.

Management of pediatric blunt abdominal trauma with split liver or spleen injuries: a retrospective study.

BACKGROUND: Blunt abdominal trauma is a prevailing cause of pediatric morbidity and mortality. It constitutes the most frequent type of pediatric injuries. Contrast-enhanced sonography (CEUS) and contrast-enhanced computed tomography (CECT) are considered pivotal diagnostic modalities in hemodynamically stable patients. AIM: To report the experience in management of pediatric split liver and spleen injuries using CEUS and CECT. PATIENTS AND METHODS: This study included 246 children who sustained blunt abdominal trauma, and admitted and treated at three tertiary hospitals in the period of 5 years. Primary resuscitation was offered to all children based on the advanced trauma and life support (ATLS) protocol. A special algorithm for decision-making was followed. It incorporated the FAST, baseline ultrasound (US), CEUS, and CECT. Patients were treated according to the imaging findings and hemodynamic stability. RESULTS: All 246 children who sustained a blunt abdominal were studied. Patients' age was 10.5 ± 2.1. Road traffic accidents were the most common cause of trauma; 155 patients (63%). CECT showed the extent of injury in 153 patients' spleen (62%) and 78 patients' liver (32%), while the remaining 15 (6%) patients had both injuries. CEUS detected 142 (57.7%) spleen injury, and 67 (27.2%) liver injury. CONCLUSIONS: CEUS may be a useful diagnostic tool among hemodynamically stable children who sustained low-to-moderate energy isolated blunt abdominal trauma. It may be also helpful for further evaluation of uncertain CECT findings and follow-up of conservatively managed traumatic injuries.

Corrosion Behavior of Aluminium-Coated Cans.

Hundreds of billions of aluminium-based cans are manufactured and used every year worldwide including those containing soft drinks. This study investigates and evaluates the performance and quality of two well-known energy and soft drinks brands, Green Cola and Red Bull. Recent health hazards and concerns have been associated with aluminium leakage and bisphenol A (BPA) dissociation from the can's internal protective coating. The cans were examined under four conditions, including coated and uncoated samples, the soft drink's main solution, and 0.1 M acetic acid solution. Electrochemical measurements such as potentiodynamic polarization and impedance spectroscopy (EIS), element analyses using inductively coupled plasma optical emission spectrometry (ICP-OES), and energy dispersive X-ray spectroscopy (EDS) were performed. In addition, sample characterization by scanning electron microscopy (SEM) and X-ray diffraction spectroscopy (XRD) were employed to comprehensively study and analyze the effect of corrosion on the samples. Even though the internal coating provided superior corrosion protection concerning main or acetic acid solutions, it failed to prevent aluminium from dissolving in the electrolyte. Green Cola's primary solution appears to be extremely corrosive, as the corrosion rate increased by approximately 333% relative to the acetic acid solution. Uncoated samples resulted in increases in the percentage of oxygen, the appearance of more corrosion spots, and decreases in crystallinity. The ICP-OES test detected dangerous levels of aluminium in the Green Cola solution, which increased significantly after increasing the conductivity of the solution.