Department of Medicine 2040: Implementing a Constrained Disorder Principle-Based Second-Generation Artificial Intelligence System for Improved Patient Outcomes in the Department of Internal Medicine.

Internal medicine departments must adapt their structures and methods of operation to accommodate changing healthcare systems. The present paper discusses some challenges departments of medicine face as healthcare providers and consumers continue to change. A co-pilot model is described in this article for augmenting physicians rather than replacing them.

Long-term green-Mediterranean diet may favor fasting morning cortisol stress hormone; the DIRECT-PLUS clinical trial.

Background: Fasting morning cortisol (FMC) stress hormone levels, are suggested to reflect increased cardiometabolic risk. Acute response to weight loss diet could elevate FMC. Richer Polyphenols and lower carbohydrates diets could favor FMC levels.

Systematic identification of gene combinations to target in innate immune cells to enhance T cell activation.

Genetic engineering of immune cells has opened new avenues for improving their functionality but it remains a challenge to pinpoint which genes or combination of genes are the most beneficial to target. Here, we conduct High Multiplicity of Perturbations and Cellular Indexing of Transcriptomes and Epitopes (HMPCITE-seq) to find combinations of genes whose joint targeting improves antigen-presenting cell activity and enhances their ability to activate T cells. Specifically, we perform two genome-wide CRISPR screens in bone marrow dendritic cells and identify negative regulators of CD86, that participate in the co-stimulation programs, including Chd4, Stat5b, Egr2, Med12, and positive regulators of PD-L1, that participate in the co-inhibitory programs, including Sptlc2, Nckap1l, and Pi4kb.

Sinus floor augmentation using crestal approach in conjunction with hydroxyapatite/cross-linked collagen sponge: A pilot study.

Background: Different biomaterials were suggested for sinus floor augmentation (SFA). Recently, new materials were launched showing true bone formation without remnants.

Purpose: The aim of this prospective study was to evaluate an hydroxyapatite-based, sugar cross-linked collagen sponge (OSSIX™ Bone) in transcrestal SFA (t-SFA).

Muscle injury causes long-term changes in stem-cell DNA methylation.

Injury to muscle brings about the activation of stem cells, which then generate new myocytes to replace damaged tissue. We demonstrate that this activation is accompanied by a dramatic change in the stem-cell methylation pattern that prepares them epigenetically for terminal myocyte differentiation. These de- and de novo methylation events occur at regulatory elements associated with genes involved in myogenesis and are necessary for activation and regeneration.

Modeling sex differences in humans using isogenic induced pluripotent stem cells.

Biological sex is a fundamental trait influencing development, reproduction, pathogenesis, and medical treatment outcomes. Modeling sex differences is challenging because of the masking effect of genetic variability and the hurdle of differentiating chromosomal versus hormonal effects. In this work we developed a cellular model to study sex differences in humans.

and genome editing to explore GNE functions.

GNE myopathy is an adult onset neuromuscular disorder characterized by slowly progressive distal and proximal muscle weakness, caused by missense recessive mutations in the gene. Although the encoded bifunctional enzyme is well known as the limiting factor in the biosynthesis of sialic acid, no clear mechanisms have been recognized to account for the muscle atrophic pathology, and novel functions for GNE have been hypothesized. Two major issues impair studies on this protein.

The role of bacterial translocation in sepsis: a new target for therapy.

Sepsis is a leading cause of death in critically ill patients, primarily due to multiple organ failures. It is associated with a systemic inflammatory response that plays a role in the pathogenesis of the disease. Intestinal barrier dysfunction and bacterial translocation (BT) play pivotal roles in the pathogenesis of sepsis and associated organ failure.

Hepatic adropin is regulated by estrogen and contributes to adverse metabolic phenotypes in ovariectomized mice.

Objective: Menopause is associated with visceral adiposity, hepatic steatosis and increased risk for cardiovascular disease. As estrogen replacement therapy is not suitable for all postmenopausal women, a need for alternative therapeutics and biomarkers has emerged.

Methods: 9-week-old C57BL/6 J female mice were subjected to ovariectomy (OVX) or SHAM surgery (n = 10 per group), fed a standard diet and sacrificed 6- & 12 weeks post-surgery.

Misleading Positive Serology for Cat Scratch Disease following Administration of Intravenous Immunoglobulin.

Cat scratch disease (CSD), caused by , usually presents as regional lymphadenopathy/lymphadenitis, known as typical CSD or as atypical CSD, which includes, among others, neurological manifestations. Serology for anti- IgG antibodies is the most commonly used diagnostic tests for CSD. Intravenous immunoglobulin (IVIG) is given for an increasing number of medical conditions and may cause interference with serological testing.

Overcoming resistance to EGFR monotherapy in HNSCC by identification and inhibition of individualized cancer processes.

Therapeutic strategies for advanced head and neck squamous carcinoma (HNSCC) consist of multimodal treatment, including Epidermal Growth Factor Receptor (EGFR) inhibition, immune-checkpoint inhibition, and radio (chemo) therapy. Although over 90% of HNSCC tumors overexpress EGFR, attempts to replace cytotoxic treatments with anti-EGFR agents have failed due to alternative signaling pathways and inter-tumor heterogeneity. Using protein expression data obtained from hundreds of HNSCC tissues and cell lines we compute individualized signaling signatures using an information-theoretic approach.

Results of using the AssiAnchor capsule device for subluxated crystalline lenses.

Purpose: To describe our results with the AssiAnchor capsule device in cases of subluxated crystalline lenses.

Methods: This was a retrospective consecutive case series. Seven eyes of four patients with subluxated crystalline lenses underwent lensectomy/phacoemulsification with intraocular lens (IOL) implantation using the AssiAnchor capsule device in the Kaplan medical center, ophthalmology department.

Immune Changes Induced by Orthodontic Forces: A Critical Review.

Orthodontic tooth movement (OTM) is generated by a mechanical force that induces an aseptic inflammatory response in the periodontal tissues and a subsequent coordinated process of bone resorption and apposition. In this review, we critically summarize the current knowledge on the immune processes involved in OTM inflammation and provide a novel insight into the relationship between classical inflammation and clinical OTM phases. We found that most studies focused on the acute inflammatory process, which ignites the initial alveolar bone resorption.

The Prevalence of Gingival Dendritic Cell Subsets in Periodontal Patients.

As the most potent cells activating and polarizing naive T cells, dendritic cells (DCs) are of major importance in the induction of immunity and tolerance. DCs are a heterogeneous population of antigen-presenting cells that are widely distributed in lymphoid and nonlymphoid tissues. Murine studies have highlighted the important role of oral DCs and Langerhans cells (LCs) in orchestrating the physiological homeostasis of the oral mucosa.

Contamination rates of different methods of urine culture collection in children: A retrospective cohort study.

Aim: Urinary tract infection is a common cause of paediatric morbidity. However, there is no consensus on the default method for urine culture collection in children. This study aimed to examine the contamination rates of different urine collection methods.

Senolytic elimination of Cox2-expressing senescent cells inhibits the growth of premalignant pancreatic lesions.

Objective: Cellular senescence limits tumourigenesis by blocking the proliferation of premalignant cells. Additionally, however, senescent cells can exert paracrine effects influencing tumour growth. Senescent cells are present in premalignant pancreatic intraepithelial neoplasia (PanIN) lesions, yet their effects on the disease are poorly characterised.

The efficacy of a protective protocol for oral and maxillofacial surgery procedures in a COVID-19 pandemic area-results from 1471 patients.

Objective: To examine the effectiveness of an empiric protection protocol during oral surgical treatments in a COVID-19 pandemic area and to evaluate the potential effect of postponed dental procedures on the frequency of facial infections during a lockdown period.

Methods: We performed a retrospective analysis of a case series of a broad-spectrum of oral surgeries in a COVID-19 pandemic area. Data collection included patient age, type of procedure performed, and COVID-19 status of staff and patients.

Immunorthodontics: in vivo gene expression of orthodontic tooth movement.

Orthodontic tooth movement (OTM) is a "sterile" inflammatory process. The present study aimed to reveal the underlying biological mechanisms, by studying the force associated-gene expression changes, in a time-dependent manner. Ni-Ti springs were set to move the upper 1-molar in C57BL/6 mice.

Empty SV40 capsids increase survival of septic rats by eliciting numerous host signaling networks that participate in a number of systemic functions.

Sepsis is an excessive, dysregulated immune response to infection that activates inflammatory and coagulation cascades, which may lead to tissue injury, multiple organ dysfunction syndrome and death. Millions of individuals die annually of sepsis. To date, the only treatment available is antibiotics, drainage of the infection source when possible, and organ support in intensive care units.

Triangular correlation (TrC) between cancer aggressiveness, cell uptake capability, and cell deformability.

The malignancy potential is correlated with the mechanical deformability of the cancer cells. However, mechanical tests for clinical applications are limited. We present here a Triangular Correlation (TrC) between cell deformability, phagocytic capacity, and cancer aggressiveness, suggesting that phagocytic measurements can be a mechanical surrogate marker of malignancy.

Upregulation of Hallmark Muscle Genes Protects GneM743T/M743T Mutated Knock-In Mice From Kidney and Muscle Phenotype.

Background: Mutations in GNE cause a recessive, adult onset myopathy characterized by slowly progressive distal and proximal muscle weakness. Knock-in mice carrying the most frequent mutation in GNE myopathy patients, GneM743T/M743T, usually die few days after birth from severe renal failure, with no muscle phenotype. However, a spontaneous sub-colony remains healthy throughout a normal lifespan without any kidney or muscle pathology.

Risk factors for third-generation cephalosporin resistant Enterobacteriaceae in gestational urine cultures: A retrospective cohort study based on centralized electronic health records.

Third-generation-cephalosporin resistant Enterobacteriaceae (3GCR-EB) carriage in pregnant women poses challenges for infection control and therapeutic decisions. The factors associated with multidrug resistant Enterobacteriaceae carriage in the gestational period are not well documented. The aim of our study was to identify risk factors associated with 3GCR-EB isolation in gestational urine cultures.