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Respiratory syncytial virus (RSV) is the major cause of bronchiolitis among children under 5 years of age worldwide, accounting for a prevalence of 25%–88% in Saudi Arabia. Although no effective treatment for the virus exists, passive immunoprophylaxis reduced RSV hospitalizations in high-risk children. With recent advances in immunization, the Saudi Initiative of Bronchiolitis Diagnosis, Management, and Prevention panel screened recent relevant international guidelines, locally published data, and expert consensus to update guidelines for RSV prevention, taking into consideration the resources, timing, varying health profiles, and RSV burden in Saudi Arabia. The panel updated its recommendations to include immunization of infants, mothers, and older adults. Practical guidelines were prepared to facilitate the administration of the short-acting and newly developed long-acting RSV monoclonal antibodies (mAb) during the regular follow-ups of high-risk infants in specialized clinics. In addition, long-acting mAb was highlighted as all-infant protection in the routine immunization calendar.

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions. Here, the Nomenclature Committee on Cell Death (NCCD) gathered to critically summarize an abundant pre-clinical literature mechanistically linking the core apoptotic apparatus to organismal homeostasis in the context of disease.

Mosquito-borne diseases (MBDs), like malaria and mosquito-borne viruses (MBVs), have caused the deaths of millions of people. Their threat resides in the variety of transmission modes that they possess, along with the wide selection of favorable hosts, such as humans, cattle, and rodents. MBDs are increasingly gaining a reputation as one of the most dangerous threats to public health in recent years. Mosquito numbers have been increasing in recent years as a result of multiple factors such as climate change and deforestation. This situation highlights the urgent need for actions to mitigate mosquito and MBD pathogen distributions. In the Middle East, many outbreaks of MBDs have been reported in the region. However, there are no reports of any endemic episodes of MBDs. The Middle East has faced many challenges over the years; however, the Syrian refugee crisis may be strongly related to the spread of infectious diseases. As mass gatherings and high-density populations are common features in the region, it is possible to understand why MBDs can spread easily. This review summarizes the state of MBDs in the Middle East, highlighting the different types of MBDs that have been reported in the region and discussing how to move forward with controlling their spread and limiting the risks they pose. According to the data reported by the electronic State Parties Self-Assessment Annual Reporting Tool (e-SPAR), the capacity to anticipate MBVs varies among Middle East countries. Therefore, the Middle East is on the frontline in the challenge to control a potential public health crisis. Consequently, the countries of the Middle East should be encouraged to improve their health and research capacities to mitigate the threat posed by MBDs.

Abstract Objectives Certain low‐level immune‐related adverse events (irAEs) have been associated with survival benefits in patients with various solid tumors on immune checkpoint inhibitors (ICIs). We aimed to investigate the association between irAEs and response to neoadjuvant ICIs in patients with head and neck squamous cell carcinoma (HNSCC) and to identify differences in circulating cytokine levels based on irAE status. Methods This was a retrospective cohort study including three neoadjuvant clinical trials from July 2017 to January 2022: NCT03238365 (nivolumab ± tadalafil), NCT03854032 (nivolumab ± BMS986205), NCT03618654 (durvalumab ± metformin). The presence and type of irAEs, pathologic treatment response, and survival were compared. Canonical linear discriminant analysis (LDA) was performed to identify combinations of circulating cytokines predictive of irAEs using plasma sample multiplex assay. Results Of 113 participants meeting inclusion criteria, 32 (28.3%) developed irAEs during treatment or follow‐up. Positive p16 status was associated with irAEs (odds ratio [OR] 2.489; 95% CI 1.069–6.119; p = 0.043). irAEs were associated with pathologic treatment response (OR 3.73; 95% CI 1.34–10.35; p = 0.011) and with higher OS in the combined cohort (HR 0.319; 95% CI 0.113–0.906; p = 0.032). Patients with irAEs within the nivolumab cohort had significant elevations of select cytokines pre‐treatment. Canonical LDA identified key drivers of irAEs among all trials, which were highly predictive of future irAE status. Conclusions irAEs are associated with response to neoadjuvant ICI therapy in HNSCC and can serve as clinical indicators for improved clinical outcomes. irAEs can be predicted by concentrations of several circulating cytokines prior to treatment.

Age-related macular degeneration (AMD), the leading cause of irreversible blindness among Americans over 50, is characterized by dysfunction and death of retinal pigment epithelial (RPE) cells. The RPE accumulates iron in AMD, and iron overload triggers RPE cell death in vitro and in vivo. However, the mechanism of RPE iron accumulation in AMD is unknown. We show that high-fat-diet-induced obesity, a risk factor for AMD, drives systemic and local inflammatory circuits upregulating interleukin-1β (IL-1β). IL-1β upregulates RPE iron importers and downregulates iron exporters, causing iron accumulation, oxidative stress, and dysfunction. We term this maladaptive, chronic activation of a nutritional immunity pathway the cellular iron sequestration response (CISR). RNA sequencing (RNA-seq) analysis of choroid and retina from human donors revealed that hallmarks of this pathway are present in AMD microglia and macrophages. Together, these data suggest that inflamed adipose tissue, through the CISR, can lead to RPE pathology in AMD.

Glioblastomas (GBM) are highly invasive, malignant primary brain tumors. The overall prognosis is poor, and management of GBMs remains a formidable challenge, necessitating novel therapeutic strategies such as dendritic cell vaccinations (DCVs). While many early clinical trials demonstrate an induction of an antitumoral immune response, outcomes are mixed and dependent on numerous factors that vary between trials. Optimization of DCVs is essential; the selection of GBM-specific antigens and the utilization of 18F-fludeoxyglucose Positron Emission Tomography (FDG-PET) may add significant value and ultimately improve outcomes for patients undergoing treatment for glioblastoma. This review provides an overview of the mechanism of DCV, assesses previous clinical trials, and discusses future strategies for the integration of DCV into glioblastoma treatment protocols. To conclude, the review discusses challenges associated with the use of DCVs and highlights the potential of integrating DCV with standard therapies.

Background: The One Health concept (OHC) seeks to improve the health of plants, animals, and humans because improving animal and plant health will increase the capacity for improving human health. Many risks such as plant and animal biotechnology applications have the potential to generate new diseases that can be transmitted to humans. In this way, the health of humans, animals, and plants is interrelated and depends on one another. However, it has been difficult to apply the OHC in some countries, such as those in the Middle East. The absence of financial support in the region is a major hindrance to applying this concept in the region. The application of the OHC requires the support of specialists who can advocate the government for support in launching OHC-related projects. Here, we discuss the OHC in the context of antimicrobial resistance, zoonotic diseases, and biosafety/biosecurity, which are important public health issues. Furthermore, we describe the current status of the OHC in the Middle East and recent research conducted related to this concept. There has been recent international solidarity in the application of the OHC to reduce risks that threaten the health of organisms. Several countries jointly launched the Global Health Security Agenda in 2014 with the aim of realizing a world that is free of infectious disease-related health risks. However, no previous review articles have examined the applications of the OHC in the Middle East region. This article discusses the OHC in terms of its needs and current applications in the Middle East. Methodology: The following keywords were used in the search: “One Health,” “Middle East,” “medicinal plants,” “viruses,” “rabies,” “MERS,” and “antimicrobial resistance.” Related papers were obtained by searching for these keywords using available search engines, such as PubMed, Google Scholar, and Google search, as well as international organization websites. Conclusion: The concept of One Health is relatively new and has not been applied in most countries, possibly because the value of this concept for improving human health is not well understood. The key principle defining this concept and its importance is the interdependency of plants, animals, and human health. By applying the OHC, humans can benefit from healthy plants and animals by enhancing their growing conditions, medications, and environments. This would in turn improve general human health by allowing the safe extraction of therapeutics and food resources.

Biotechnology became a paradigm-shifting science among all subfields of biology. The benefits of biotechnology have reached many practical fields, whether human health, animal, and/or agricultural. However, wherever there is a biotechnology practice, there is an associated biohazard with it, and its negative impact may reach all living entities including humans. Therefore, the cooperation of the leading institutions in this field has culminated in creating the concepts and applications of biosafety and biosecurity. The countries of the Middle East are considered biotechnology-practicing and have shown a clear acceptance to this field. But unfortunately, the Middle East region is one that is facing the most multi-challenges, which would constitute real and noticeable concern at the local and international levels. Such challenges represented by wars and armed conflicts, deteriorating economic conditions, the large number of refugees, and the spread of many epidemics. Thus, limiting the region's ability to deal with the surrounding biological hazards and struggling the way to the one health concept. Therefore, this article aims to shed light on the activities of the Middle East countries in the field of biotechnology and to address potential biological threats, whether natural such as the spread of viruses, or intentional such as biological attacks and bioterrorism. The article also shows the capacity of the countries of the region in the field of biosafety and biosecurity based on available information. Accordingly, some countries are lacking the required level of preparedness to face potential biological threats. Multi-institutional and international cooperation between the concerned countries will significantly enhance the capacity of the region in biosafety and biosecurity to meet the level of biological risk.Search methodology: wide range of related keywords (based on the section) combined with the name of the region, or one country individually have been searched using available search engines and databases such as google scholar and PubMed. After scanning the content of the found results, irrelevant articles have been excluded. Figures 2, 3, 4, 6, and 7 were created by biorender.com.

The serine/threonine kinase WNK1 is an inhibitor of chloride efflux. Here the authors show that this inhibition is a means of negatively regulating the activation of the NLRP3 inflammasome in macrophages, leading to reduced inflammatory responses.

Background: Free flap (FF) reconstruction of traumatic injuries to the head and neck is uncommon. Methods: Multi‐institutional retrospective case series of patients undergoing FF reconstruction for a traumatic injury (n = 103). Results: Majority were gunshot wounds (GSW; 85%, n = 88) and motor vehicle accidents (11%, n = 11). Majority underwent osseous reconstruction (82%, n = 84). FF failures (9%, n = 9/103) occurred in GSW patients (100%, n = 9/9) and when multiple subsites were injured (89%, n = 8/9). Preoperative antibiotics correlated with lower rates of a neck washouts (4% vs. 19%) (p = 0.01) and 30‐day readmissions (4% vs. 17%) (p = 0.02). Conclusions: All FF failures occurred in the setting of a GSW and the majority involved multiple subsites. Preoperative antibiotics correlated with lower rates of postoperative washout procedures and 30‐day readmission. [ABSTRACT FROM AUTHOR]

Apolipoprotein E (APOE) is a component of lipid-transporting particles and a recognition ligand for receptors, which bind these particles. The APOE isoform ε2 is a risk factor for age-related macular degeneration; nevertheless, APOE absence in humans and mice does not significantly affect the retina. We found that retinal cholesterol biosynthesis and the levels of retinal cholesterol were increased in Apoe-/- mice, whereas cholesterol elimination by metabolism was decreased. No focal cholesterol deposits were observed in the Apoe-/- retina. Retinal proteomics identified the most abundant cholesterol-related proteins in WT mice and revealed that, of these cholesterol-related proteins, only APOA4 had increased expression in the Apoe-/- retina. In addition, there were changes in retinal abundance of proteins involved in proinflammatory and antiinflammatory responses, cellular cytoskeleton maintenance, vesicular traffic, and retinal iron homeostasis. The data obtained indicate that when APOE is absent, particles containing APOA1, APOA4, and APOJ still transport cholesterol in the intraretinal space, but these particles are not taken up by retinal cells. Therefore, cholesterol biosynthesis inside retinal cells increase, whereas metabolism to oxysterols decreases to prevent cells from cholesterol depletion. These and other compensatory changes underlie only a minor retinal phenotype in Apoe-/- mice.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.

Background and objectiveNeonatal sepsis (NS) continues to be a critical healthcare priority for the coming decades worldwide. The aim of this study was to critically appraise the quality of recent clinical practice guidelines (CPGs) for neonatal sepsis and to summarize and compare their recommendations.MethodsThis study involves a systematic review of CPGs. We identified clinical questions and eligibility criteria and searched and screened for CPGs using bibliographic and CPG databases and professional societies. Each included CPG was assessed by four independent appraisers using the Appraisal of Guidelines for REsearch & Evaluation II (AGREE II) instrument. We summarized the recommendations in a comparison practical table. The systematic review was drafted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. Its protocol was registered in the PROSPERO International Prospective Register of Systematic Reviews (ID: CRD42021258732).ResultsOur search retrieved 4,432 citations; of which five CPGs were eligible and appraised: American Academy of Pediatrics (AAP 2018) (35 and 34 weeks); Canadian Pediatric Society (CPS 2017); National Institute for Health and Care Excellence (NICE 2021); and Queensland Maternity and Neonatal Services (QH 2020). Among these, the overall assessment of two evidence-based CPGs scored > 70% (NICE and QH), which was consistent with their higher scores in the six domains of the AGREE II instrument. In domain 3 (rigor of development), NICE and QH scored 99 and 60%, respectively. In domain 5 (applicability), they scored 96 and 74%, respectively, and in domain 6 (editorial independence), they scored 90 and 71%, respectively.ConclusionThe methodological quality of the NICE CPG was superior followed by the QH CPG with relevant recommendations for use in practice.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021258732, PROSPERO (CRD42021258732).

Respiratory syncytial virus (RSV) is the major cause of bronchiolitis among children under 5 years of age worldwide, accounting for a prevalence of 25%--88% in Saudi Arabia. Although no effective treatment for the virus exists, passive immunoprophylaxis reduced RSV hospitalizations in high-risk children. With recent advances in immunization, the Saudi Initiative of Bronchiolitis Diagnosis, Management, and Prevention panel screened recent relevant international guidelines, locally published data, and expert consensus to update guidelines for RSV prevention, taking into consideration the resources, timing, varying health profiles, and RSV burden in Saudi Arabia. The panel updated its recommendations to include immunization of infants, mothers, and older adults. Practical guidelines were prepared to facilitate the administration of the short-acting and newly developed long-acting RSV monoclonal antibodies (mAb) during the regular follow-ups of high-risk infants in specialized clinics. In addition, long-acting mAb was highlighted as all-infant protection in the routine immunization calendar. [ABSTRACT FROM AUTHOR]

Summary: Age-related macular degeneration (AMD), the leading cause of irreversible blindness among Americans over 50, is characterized by dysfunction and death of retinal pigment epithelial (RPE) cells. The RPE accumulates iron in AMD, and iron overload triggers RPE cell death in vitro and in vivo. However, the mechanism of RPE iron accumulation in AMD is unknown. We show that high-fat-diet-induced obesity, a risk factor for AMD, drives systemic and local inflammatory circuits upregulating interleukin-1β (IL-1β). IL-1β upregulates RPE iron importers and downregulates iron exporters, causing iron accumulation, oxidative stress, and dysfunction. We term this maladaptive, chronic activation of a nutritional immunity pathway the cellular iron sequestration response (CISR). RNA sequencing (RNA-seq) analysis of choroid and retina from human donors revealed that hallmarks of this pathway are present in AMD microglia and macrophages. Together, these data suggest that inflamed adipose tissue, through the CISR, can lead to RPE pathology in AMD.

Gasdermins mediate lytic cell death by forming pores in the plasma membrane. Here the authors show that gasdermins also permeabilize mitochondrial membrane, thereby facilitating intrinsic apoptosis pathway, downstream of apoptotic (Gasdermin E) and inflammatory (Gasdermin D) caspase activation.

The ketone bodies β-hydroxybutyrate (BHB) and acetoacetate (AcAc) support mammalian survival during states of energy deficit by serving as alternative sources of ATP. BHB levels are elevated by starvation, caloric restriction, high-intensity exercise, or the low-carbohydrate ketogenic diet. Prolonged fasting reduces inflammation; however, the impact that ketones and other alternative metabolic fuels produced during energy deficits have on the innate immune response is unknown. We report that BHB, but neither AcAc nor the structurally related short-chain fatty acids butyrate and acetate, suppresses activation of the NLRP3 inflammasome in response to urate crystals, ATP and lipotoxic fatty acids. BHB did not inhibit caspase-1 activation in response to pathogens that activate the NLR family, CARD domain containing 4 (NLRC4) or absent in melanoma 2 (AIM2) inflammasome and did not affect non-canonical caspase-11, inflammasome activation. Mechanistically, BHB inhibits the NLRP3 inflammasome by preventing K(+) efflux and reducing ASC oligomerization and speck formation. The inhibitory effects of BHB on NLRP3 are not dependent on chirality or starvation-regulated mechanisms like AMP-activated protein kinase (AMPK), reactive oxygen species (ROS), autophagy or glycolytic inhibition. BHB blocks the NLRP3 inflammasome without undergoing oxidation in the TCA cycle, and independently of uncoupling protein-2 (UCP2), sirtuin-2 (SIRT2), the G protein-coupled receptor GPR109A or hydrocaboxylic acid receptor 2 (HCAR2). BHB reduces NLRP3 inflammasome-mediated interleukin (IL)-1β and IL-18 production in human monocytes. In vivo, BHB or a ketogenic diet attenuates caspase-1 activation and IL-1β secretion in mouse models of NLRP3-mediated diseases such as Muckle-Wells syndrome, familial cold autoinflammatory syndrome and urate crystal-induced peritonitis. Our findings suggest that the anti-inflammatory effects of caloric restriction or ketogenic diets may be linked to BHB-mediated inhibition of the NLRP3 inflammasome.

The NLRP3 inflammasome is an important component of inflammatory responses, but how it is negatively regulated is still unclear. Here the authors show that post-translational modification of NLRP3 by sumoylation suppresses inflammasome activity, and that desumoylation of NLRP3 by the SENP6 and SENP7 proteases promotes NLRP3 activation.

Francisella tularensis, the causative agent of tularemia, infects host macrophages, which triggers production of the proinflammatory cytokines interleukin 1beta (IL-1beta) and IL-18. We elucidate here how host macrophages recognize F. tularensis and elicit this proinflammatory response. Using mice deficient in the DNA-sensing inflammasome component AIM2, we demonstrate here that AIM2 is required for sensing F. tularensis. AIM2-deficient mice were extremely susceptible to F. tularensis infection, with greater mortality and bacterial burden than that of wild-type mice. Caspase-1 activation, IL-1beta secretion and cell death were absent in Aim2(-/-) macrophages in response to F. tularensis infection or the presence of cytoplasmic DNA. Our study identifies AIM2 as a crucial sensor of F. tularensis infection and provides genetic proof of its critical role in host innate immunity to intracellular pathogens.

The inflammasomes are multiprotein complexes that activate caspase-1 in response to infections and stress, resulting in the secretion of pro-inflammatory cytokines. Here we report that IκB kinase α (IKKα) is a critical negative regulator of apoptosis-associated specklike protein containing a C-terminal caspase-activation-andrecruitment (CARD) domain (ASC)-dependent inflammasomes. IKKα controls the inflammasome at the level of the adaptor ASC, which interacts with IKKα in the nucleus of resting macrophages in an IKKα kinase-dependent manner. Loss of IKKα kinase activity results in inflammasome hyperactivation. Mechanistically, the downstream nuclear effector IKK-related kinase (IKKi) facilitates translocation of ASC from the nucleus to the perinuclear area during inflammasome activation. ASC remains under the control of IKKα in the perinuclear area following translocation of the ASC/IKKα complex. Signal 2 of NLRP3 activation leads to inhibition of IKKα kinase activity through the recruitment of PP2A, allowing ASC to participate in NLRP3 inflammasome assembly. Taken together, these findings reveal a IKKi-IKKα-ASC axis that serves as a common regulatory mechanism for ASC-dependent inflammasomes.

Background: Since the outbreak of Covid-19, several studies have demonstrated that healthcare workers (HCWs) are at risk of developing mental health disorders. Objective: To survey Saudi healthcare workers exposed to Covid-19 patients for most commonly reported mental health disorders. Study type, settings & duration: A descriptive cross-sectional study carried out at King Fahd Armed Forces Hospital Jeddah, Kingdom of Saudi Arabia (KSA) during June 2020. Methodology: The population comprised of healthcare workers (physicians, nurses and paramedical staff). The mental health disorders explored were depression, anxiety, insomnia and post traumatic stress disorder (PTSD). Data analysis was performed using SPSS statistical software version 22.0 (IBM Corp). Results: The most frequent mental health disorder reported in the present study was anxiety (68.6%) followed by insomnia (30.3%), PTSD (15.7%) and clinically significant depression (11.1%). Frontline healthcare workers demonstrated significantly higher risk of developing anxiety and PTSD after adjustment for other factors (OR of 1.9, 95% CI: 1.13-3.15, p =0.015), and (OR of 2.7, 95% CI: 1.22-6.01, p =0.014) respectively. Conclusion: Frontline HCWs demonstrated approximately two-fold increased risk of developing anxiety and approximately three-fold risk of developing post-traumatic stress disorders after adjustment for other variables. We suggest launching a large scale health education program and screening for Saudi HCWs engaged in the management of Covid-19 patients.

Background: Vertical transmission of SARS-CoV-2 is under investigation. A few reports suggest the possibility of SARS-CoV-2 transmission from mothers to their neonates. Most neonates have mild symptoms, but some develop multisystem involvement and shock.Case Presentation: We report two cases of possible SARS-CoV-2 vertical transmission from mothers to their neonates. The first case shows maternal infection with SARS-CoV-2 in the second trimester followed by recurrent infection in the third trimester right before the delivery. The infant demonstrated respiratory distress soon after delivery along with myocardial dysfunction and multi-organ system involvement. The second case shows maternal infection with SARS-COV-2 at the time of delivery with preterm labor secondary to placental abruption, with that delivery resulting in the preterm neonate requiring non-invasive ventilation with multisystem involvement in the context of persistently positive SARS-COV-2 PCR in the neonate. Both neonates were treated with IVIG along with steroids. Both neonates recovered fully and were discharged and allowed to go home.Conclusion: In neonates, COVID-19 usually presents as an asymptomatic or mild illness; some may develop a more severe course. Our two cases, however, demonstrate that multisystem involvement, although rare, is possible. This report also supports the current evidence of possible vertical transmission from mothers to their neonates. This multisystem involvement might be underreported and should be considered in neonates with respiratory distress when born to mothers suffering of COVID-19.Clinical Trial Registration: [KSUMC], identifier [No#98763298].

DFNA5 is related to the caspase-dependent pyroptosis inducer gasdermin D. Here the authors find that DFNA5 is cleaved by caspase 3 and show this cleavage skews cells away from apoptosis into secondary necrosis, a form of cell death characterized by membrane ballooning similar to pyroptosis.

Apolipoprotein E (APOE) is a component of lipid-transporting particles and a recognition ligand for receptors, which bind these particles. The APOE isoform ε2 is a risk factor for age-related macular degeneration; nevertheless, APOE absence in humans and mice does not significantly affect the retina. We found that retinal cholesterol biosynthesis and the levels of retinal cholesterol were increased in Apoe−/− mice, whereas cholesterol elimination by metabolism was decreased. No focal cholesterol deposits were observed in the Apoe−/− retina. Retinal proteomics identified the most abundant cholesterol-related proteins in WT mice and revealed that, of these cholesterol-related proteins, only APOA4 had increased expression in the Apoe−/− retina. In addition, there were changes in retinal abundance of proteins involved in proinflammatory and antiinflammatory responses, cellular cytoskeleton maintenance, vesicular traffic, and retinal iron homeostasis. The data obtained indicate that when APOE is absent, particles containing APOA1, APOA4, and APOJ still transport cholesterol in the intraretinal space, but these particles are not taken up by retinal cells. Therefore, cholesterol biosynthesis inside retinal cells increase, whereas metabolism to oxysterols decreases to prevent cells from cholesterol depletion. These and other compensatory changes underlie only a minor retinal phenotype in Apoe−/− mice.

Bronchiolitis is the leading cause of admissions in children less than two years of age. It has been recognized as highly debated for many decades. Despite the abundance of literature and the well-recognized importance of palivizumab in the high risk groups, and despite the existence of numerous, high-quality, recent guidelines on bronchiolitis, the number of admissions continues to increase. Only supportive therapy and few therapeutic interventions are evidence based and proved to be effective. Since Respiratory Syncytial Virus (RSV) is the major cause of bronchiolitis, we will focus on this virus mostly in high risk groups like the premature babies and children with chronic lung disease and cardiac abnormalities. Further, the prevention of RSV with palivizumab in the high risk groups is effective and well known since 1998; we will discuss the updated criteria for allocating infants to this treatment, as this medication is expensive and should be utilized in the best condition. Usually, diagnosis of bronchiolitis is not challenging, however there has been historically no universally accepted and validated scoring system to assess the severity of the condition. Severe RSV, especially in high risk children, is unique because it can cause serious respiratory sequelae. Currently there is no effective curative treatment for bronchiolitis. The utility of different therapeutic interventions is worth a discussion.

Background: There is sparse literature on the effect of preoperative immunotherapy on complications after surgery for primary head and neck squamous cell carcinoma (HNSCC). The objectives are to compare complication rates in patients receiving surgery with and without neoadjuvant immune checkpoint inhibitors (nICI) for primary HNSCC and to evaluate factors associated with increased odds of surgical complications. Methods: A retrospective review of patients who underwent ablation and free flap reconstruction or transoral robotic surgery (TORS) for primary HNSCC between 2017–2021 was conducted. Complications were compared between patients who underwent surgery with or without nICI before and after propensity score matching. Regression analysis to estimate odds ratios was performed. Results: A total of 463 patients met inclusion criteria. Free flap reconstruction constituted 28.9% of patients and TORS constituted 71.1% of patients. nICI was administered in 83 of 463 (17.9%) patients. There was no statistically significant difference in surgical, medical, or overall complications between patients receiving surgery with or without nICI. In the unmatched cohort, multivariable model identified non‐White race, former/current smoking history, free flap surgery, and perineural invasion as factors significantly associated with increased complications. In the matched cohort, multivariable model identified advanced age and free flap surgery as factors significantly associated with increased complications. Plain Language Summary: It is safe to give immunotherapy before major surgery in patients who have head and neck cancer.Advanced age, non‐White race, current/former smoking, free flap surgery, and perineural invasion may be associated with increased the odds of surgical complications. In this study, neoadjuvant immune checkpoint inhibitors (nICI) did not increase the risk of overall complications after adjusting for important confounders. Definitive surgery can be conducted safely after nICI. [ABSTRACT FROM AUTHOR]