Follicular regulatory T cells control humoral and allergic immunity by restraining early B cell responses.

Follicular regulatory T (TFR) cells have specialized roles in modulating follicular helper T (TFH) cell activation of B cells. However, the precise role of TFR cells in controlling antibody responses to foreign antigens and autoantigens in vivo is still unclear due to a lack of specific tools. A TFR cell-deleter mouse was developed that selectively deletes TFR cells, facilitating temporal studies. TFR cells were found to regulate early, but not late, germinal center (GC) responses to control antigen-specific antibody and B cell memory. Deletion of TFR cells also resulted in increased self-reactive immunoglobulin (Ig) G and IgE. The increased IgE levels led us to interrogate the role of TFR cells in house dust mite models. TFR cells were found to control TFH13 cell-induced IgE. In vivo, loss of TFR cells increased house-dust-mite-specific IgE and lung inflammation. Thus, TFR cells control IgG and IgE responses to vaccines, allergens and autoantigens, and exert critical immunoregulatory functions before GC formation.

Insight into antiphospholipid syndrome: the role and clinical utility of neutrophils extracellular traps formation.

Antiphospholipid syndrome (APLS) is a systemic immune dysregulation distinguished by repetitive complications and pregnancy loss in the absence of definite etiology. Most research focuses on the laboratory detection and clinical features of APLS, but its precise etiology remains to be deeply explored. NETosis is a newly developed theory in the pathophysiology of APLS which may serve as the missing bridge between coagulation and inflammation reaching the disease progression and severity. We aimed in this study to navigate the prognostic role of NETosis in thrombotic APLS. Our study included 49 newly diagnosed APLS patients (both 1ry and 2ry) who met clinical and laboratory criteria as per the international consensus statement on the update of the classification criteria for definite APLS and were sub-classified according to the occurrence of thrombotic events in thrombotic and non-thrombotic types. In addition, 20 sex and age-matched reactive subjects and 20 sex and age-matched healthy volunteer controls were enrolled. NETosis formation was assessed by measuring serum Myeloperoxidase (MPO) and Histones level using the enzyme-linked immunosorbent assay (ELISA) technique. Both MPO and Histones levels were able to discriminate among APLS cases from normal controls, showing significant cutoffs of > 2.09 ng/ml for MPO and > 1.45 ng/ml for Histones (AUC values were 0.987and 1.000, respectively). These values can be used as predictors for NETosis pathophysiology in APLS patients. Additionally, these markers demonstrated a significant association with several prognostic indicators, including thrombosis, higher PT and INR, and lower hemoglobin (Hb) levels which are supposed to be ameliorated by using NETs inhibitors. In conclusion, we suggest that measuring NETosis markers, MPO, and Histones, in the early course of APLS using proposed cutoff values will facilitate the timely initiation of anti-NETosis therapy and improve the overall prognosis, particularly for patients with thrombotic APLS.

Curcumin protects against lamotrigine-induced chronic ovarian and uterine toxicity in rats by regulating PPAR-γ and ROS production.

Lamotrigine (LTG) is an antiepileptic drug with possible adverse effects on the female reproductive system. Curcumin was declared to improve ovarian performance. Therefore, this study aimed to clarify ovulatory dysfunction (OD) associated with LTG and the role of curcumin in ameliorating this dysfunction. Adult female Wister albino rats were assigned into four groups: negative control (received saline), positive control (received curcumin only), LTG, and LTG with curcumin groups. Drugs were administered for 90 days. The hormonal profile, including testosterone, estrogen, progesterone, luteinizing hormone, and follicle-stimulating hormone, in addition to the lipid profile and glycemic analysis, were tested. Oxidative stress biomarkers analysis in the ovaries and uterus and peroxisome proliferator-activated receptor-γ (PPAR-γ) gene expression were also included. Histopathological examination of ovarian and uterine tissues and immunohistochemical studies were also performed. Curcumin could improve the OD related to chronic LTG intake. That was proved by the normalization of the hormonal profile, glycemic control, lipidemic status, oxidative stress markers, and PPAR-γ gene expression. The histopathological and immunohistochemical examination of ovarian and uterine tissues revealed an improvement after curcumin administration. The results describe an obvious deterioration in ovarian performance with LTG through the effect on lipidemic status, PPAR-γ gene, and creating an oxidative stress condition in the ovaries of chronic users, with a prominent improvement with curcumin addition to the treatment protocol.

Targeting PI3K/p-Akt/eNOS, Nrf2/HO-1, and NF-κB/p53 signaling pathways by angiotensin 1-7 protects against liver injury induced by ischemia-reperfusion in rats.

The liver is an important organ, and hepatic ischemia-reperfusion (IR) injury is a frequent pathophysiological process that can cause significant morbidity and mortality. Thus, our study aimed to investigate the effect of targeting PI3K/p-Akt/eNOS (phosphoinositide 3-kinase/phospho-protein kinase B/endothelial nitric oxide synthase), Nrf2/HO-1 (nuclear factor-erythroid 2-related factor-2/heme oxygenase-1), and NF-κB/p53 (nuclear factor-κB/tumor protein 53) signaling pathways by using angiotensin (1-7) [ang-(1-7)] against hepatic injury induced by IR. Thirty-two male rats were included in sham group, ang-(1-7)-treated group, hepatic IR group, and hepatic IR group treated with ang-(1-7). The levels of hepatic ang-(1-7), angiotensin II (Ang II), angiotensin-converting enzyme 2 (ACE2), HO-1, malondialdehyde (MDA), PI3K, and p-Akt were assessed. The expressions of eNOS and B-cell leukemia/lymphoma-2 (BCL-2) in the liver were determined. Histological assessment and immunohistochemical expression of NF-κB, p53, and Nrf2 were carried out. The levels of reduced glutathione (GSH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in serum were estimated. Results showed that administration of ang-(1-7) to hepatic IR rats led to significant amelioration of hepatic damage through a histological evaluation that was associated with significant upregulation of the expressions of PI3K/p-Akt/eNOS and Nrf2/HO-1 with downregulation of NF-κB/p53 signaling pathways. In conclusion, PI3K/p-Akt/eNOS and Nrf2/HO-1 signaling pathways are involved in the protective effects of ang-(1-7) against hepatic damage induced by IR. Therefore, ang-(1-7) can be used to prevent hepatic IR, which occurs in certain conditions such as liver transplantation, hemorrhagic shock, and severe infection.

Theoretical and Experimental Determination of Thermomechanical Properties of Epoxy-SiO2 Nanocomposites.

Improvements in the thermomechanical properties of epoxy upon inclusion of well-dispersed SiO2 nanoparticles have been demonstrated both experimentally and through molecular dynamics simulations. The SiO2 was represented by two different dispersion models: dispersed individual molecules and as spherical nanoparticles. The calculated thermodynamic and thermomechanical properties were consistent with experimental results. Radial distribution functions highlight the interactions of different parts of the polymer chains with the SiO2 between 3 and 5 nm into the epoxy, depending on the particle size. The findings from both models were verified against experimental results, such as the glass transition temperature and tensile elastic mechanical properties, and proved suitable for predicting thermomechanical and physicochemical properties of epoxy-SiO2 nanocomposites.

Evaluation of the Antimicrobial Activity of Phytochemicals from Tea and Agarwood Leaf Extracts against Isolated Bacteria from Poultry and Curd.

Antibiotic-resistant bacteria are becoming increasingly common, leading to a global health crisis. The effects of abusing antibiotics not only increase pathogenic resistance but also cause various diseases and syndromes. Gut microbiota contains many beneficial roles for health, while antibiotics kill both pathogens and gut microbiota which is considered one of the major side effects of antibiotics. In fact, new antibiotic compounds are needed in this urgent scenario; phytoremediation is the oldest but most effective method, and research on the antibacterial properties of several types of medicinal plants has already been conducted. Tea and agarwood plants are well known for their economic contribution in both beverage and cosmetic production, as well as for their medicinal value. In this study, tea and agarwood leaf extracts were analyzed for their antimicrobial activity against both pathogenic and beneficial bacteria. Fresh tea (Camellia sinensis) leaves were collected in three varieties, namely, BT-6 from Sylhet, BT-7 from Moulvibazar, and BT-8 from Habiganj; also, green tea (nonfermented tea), black tea (fully fermented tea), and agarwood (Aquilaria malaccensis) were collected from Sylhet region of Bangladesh. Unlike commercial antibiotics, which have side effects on probiotics (beneficiary bacteria), leaf extract activities were analyzed to check if they had positive effects on probiotics that can be found in the gastrointestinal tract as well as dairy products. Potential beneficiary bacteria, Lysinibacillus macroides strain SRU-001 (NCBI accession no. MW665108), and pathogenic bacteria, Aeromonas caviae strain YPLS-62 (NCBI accession no. MW666783), were isolated from the small intestine of poultry and curd, respectively. Tea and agarwood leaves (5 g powder/80 mL methanol) with solvents were kept for seven days at room temperature, and extracts were applied for antimicrobial assays by the disc diffusion assay against the isolated bacteria. 50 µL of each leaf extract was examined against 50 µL of each bacterial culture, where gentamicin was a control. After 24 hours of incubation, tea and agarwood leaf extracts showed an 11-15 mm zone of inhibition against pathogenic A. caviae, while only BT-8 showed 7 mm (disc diameter 6 mm) against probiotic L. macroides. However, compared to leaf extracts, gentamicin showed a 27 mm zone of inhibition against both L. macroides strain SRU-001 and A. caviae strain YPLS-62 bacteria. This research clearly indicates that gentamicin kills both pathogenic and beneficiary bacteria, while leaf extracts from tea and agarwood plants contain antimicrobial activity against only pathogenic A. caviae but no effects on probiotic L. macroides. This outcome indicates not only the potential therapeutic values of tea and agarwood leaves as antibiotics over commercial antibiotics but also the chance of having pathogens in curd and potential beneficial bacteria from the poultry small intestine.

The Impact of Optical Coherence Tomography in the Early Identification of Children with Sickle Cell Retinopathy.

Introduction: Sickle cell disease is characterized by the production of abnormal hemoglobin, which affects hemoglobin molecule stability during hypoxia and leads to the formation of sickle cells, resulting in increased hematic viscosity, hemolysis, and microvascular blockage. Vasoocclusion is assumed to be the primary cause of vision-threatening retinopathy in sickle cell disease. The aim of this study was to improve the early detection of sickle cell retinopathy (SCR) in children with sickle cell disease (SCD) and investigate the link between systemic and ocular symptoms. Methods: This cross-sectional study comprised children with SCD. The patient files provided a detailed medical history. The laboratory tests included a blood count, reticulocyte count, and Hb electrophoresis. The slit lamp, fundus, optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA) were all part of the ophthalmological examination. Results: The study comprised 15 children with sickle cell disease who met the inclusion and exclusion criteria, with a mean age of 11.15 ± 1.29 years. Nine of the children were males (60%) and six were females (40%). 8 (53.3%) of the children had Hb SS, three (20%) had Hb SC, three (20%) had Hb SB+, and one (6.7%) had Hb SB0. Four children (26.7%) had poor visual acuity. A fundus examination revealed significant abnormal findings in 12 of the 7 children's eyes (40 percent). Macular thinning was detected by OCT in 10 eyes of 7 children (33.3%). Flow voids at the deep retinal capillary plexus were detected by OCTA in 10 eyes of 7 children (33.3%). Longer disease duration, higher reticulocytic percent, more painful crises, and noncompliance with hydroxyurea medication were all linked to the existence of eye abnormalities on fundus examination and OCT. Conclusion: OCTA can show early retinal damage in sickle cell patients with macular changes. Sickle cell retinopathy is usually associated with more severe disease.

Detection of hypokalemia disorder and its relation with hypercalcemia in blood serum using LIBS technique for patients of colorectal cancer grade I and grade II.

Cancer continues to be the most dangerous disease around the world; it causes electrolyte imbalance as well as metabolic changes. There is a complicated relationship between electrolyte disorder and cancer. Cancer patients commonly pass with abnormalities in serum electrolyte levels such as hypokalemia, hyperkalemia, hyponatremia, and hypercalcemia. So, these electrolyte imbalances indicate the existence of paraneoplastic processes and help come to a more informed prognosis. Hypokalemia is defined as a serum potassium concentration below 3.5 mmol/L and it is the second common electrolyte imbalance seen in patients with malignant diseases. In this paper, the contribution of serum potassium concentration to tumor progression was studied by applying a promising and non-invasive technique called laser-induced breakdown spectroscopy (LIBS). It was found that there is a correlation between hypokalemia and the colorectal cancer problem. Also, significant serum potassium concentration differences were detected among two different stages of the same cancer and also between two groups of the same stage of a cancer held in common but one of them suffers from hypercalcemia. In addition, the optimum conditions of LIBS setup were arranged such that it will be suitable to work with serum samples on glass substrate.

Follicular T cells mediate donor-specific antibody and rejection after solid organ transplantation.

Following solid organ transplantation, a substantial proportion of chronic allograft loss is attributed to the formation of donor-specific antibodies (DSAs) and antibody-mediated rejection (AbMR). The frequency and phenotype of T follicular helper (Tfh) and T follicular regulatory (Tfr) cells is altered in the setting of kidney transplantation, particularly in patients who develop AbMR. However, the roles of Tfh and Tfr cells in AbMR after solid organ transplantation is unclear. We developed mouse models to inducibly and potently perturb Tfh and Tfr cells to assess the roles of these cells in the development of DSA and AbMR. We found that Tfh cells are required for both de novo DSA responses as well as augmentation of DSA following presensitization. Using orthotopic allogeneic kidney transplantation models, we found that deletion of Tfh cells at the time of transplantation resulted in less severe transplant rejection. Furthermore, using inducible Tfr cell deletion strategies we found that Tfr cells inhibit de novo DSA formation but only have a minor role in controlling kidney transplant rejection. These studies demonstrate that Tfh cells promote, whereas Tfr cells inhibit, DSA to control rejection after kidney transplantation. Therefore, targeting these cells represent a new therapeutic strategy to prevent and treat AbMR.

Development and Validation of a Chiral Liquid Chromatographic Assay for Enantiomeric Separation and Quantification of Verapamil in Rat Plasma: Stereoselective Pharmacokinetic Application.

A novel, fast and sensitive enantioselective HPLC assay with a new core-shell isopropyl carbamate cyclofructan 6 (superficially porous particle, SPP) chiral column (LarihcShell-P, LSP) was developed and validated for the enantiomeric separation and quantification of verapamil (VER) in rat plasma. The polar organic mobile phase composed of acetonitrile/methanol/trifluoroacetic acid/triethylamine (98:2:0.05: 0.025, v/v/v/v) and a flow rate of 0.5 mL/min was applied. Fluorescence detection set at excitation/emission wavelengths 280/313 nm was used and the whole analysis process was within 3.5 min, which is 10-fold lower than the previous reported HPLC methods in the literature. Propranolol was selected as the internal standard. The S-(-)- and R-(+)-VER enantiomers with the IS were extracted from rat plasma by utilizing Waters Oasis HLB C18 solid phase extraction cartridges without interference from endogenous compounds. The developed assay was validated following the US-FDA guidelines over the concentration range of 1-450 ng/mL (r2 ≥ 0.997) for each enantiomer (plasma) and the lower limit of quantification was 1 ng/mL for both isomers. The intra- and inter-day precisions were not more than 11.6% and the recoveries of S-(-)- and R-(+)-VER at all quality control levels ranged from 92.3% to 98.2%. The developed approach was successfully applied to the stereoselective pharmacokinetic study of VER enantiomers after oral administration of 10 mg/kg racemic VER to Wistar rats. It was found that S-(-)-VER established higher Cmax and area under the concentration-time curve (AUC) values than the R-(+)-enantiomer. The newly developed approach is the first chiral HPLC for the enantiomeric separation and quantification of verapamil utilizing a core-shell isopropyl carbamate cyclofructan 6 chiral column in rat plasma within 3.5 min after solid phase extraction (SPE).

Reliability of propeller flaps in post-traumatic reconstruction of wrist and hand defects.

PURPOSE: This is a purely observational study with a literature comparison to assess the effectiveness of radial and ulnar arteries propeller perforator-based flaps in post-traumatic soft tissue reconstruction and identify the risk factors for complications. METHODS: Sixteen patients were involved with post-traumatic wrist and hand soft tissue defects not exceeding 5 × 20 cm. Defects were covered with propeller radial and ulnar arteries perforator-based flaps. Patient demographics, soft tissue defects, complications and clinical outcomes were recorded. Assessment of patients' satisfaction for donor site morbidity and aesthetic outcome of the flap were performed. RESULTS: Radial artery propeller perforator flap was performed in seven cases, and ulnar artery propeller perforator flap was done in nine cases. The size of the skin paddle ranged from 2.5 × 5 cm to 4.5 × 10.5 cm. Primary closure of the donor site was performed in all cases. One flap was lost, while superficial epidermolysis occurred in seven cases (45%). Edge necrosis ranging between 3 and 7 mm occurred in nine cases (60%). Patients' factors, mode of injury, associated injuries and interval between trauma and coverage were all correlated with complication incidence. The patients' satisfaction for donor site morbidity was very good and good in 80% of patients, while satisfaction for aesthetic outcome of the flap was very good and good in only 40%. CONCLUSION: Radial and ulnar arteries have reliable perforators for flap elevation, which produce reliable outcome for small- and medium-sized soft tissue reconstruction. Effectiveness decreases in post-traumatic reconstructions. Complications are more frequent in crushing injuries especially if associated with bony fractures. Most complications in trauma cases were attributed to venous congestion, for which supercharging with a vein if accessible to the surgeon is recommended.

Follicular T-cell regulation of alloantibody formation.

PURPOSE OF REVIEW: To summarize recent studies elucidating the roles of follicular T cells in controlling allospecific antibody responses and antibody-mediated rejection (AbMR). RECENT FINDINGS: The field of antibody regulation has provided an in depth identification of the T-cell subsets involved in regulation of antibody responses. In addition, tools have been developed to study these cells during disease. Over the past few years, these strategies have been implemented in the field of transplantation to study the roles of T cells in mediating pathogenic antibody responses. SUMMARY: AbMR is largely responsible for long-term graft failure after solid organ transplantation and is induced by allospecific antibodies. In vaccination and infection, antiboody responses are controlled by humoral immunoregulation in which T follicular helper (Tfh) cells promote, and T follicular regulatory (Tfr) cells inhibit, antibody responses. Recent studies have suggested multifaceted roles for follicular T-cell subsets in regulating allospecific antibody responses and AbMR during organ transplantation. In addition, we discuss research priorities for the field to help elucidate mechanisms used by these cells so that new targeted therapeutics can be developed to prevent AbMR in human organ transplantation.

Lipid profile and hepatic steatosis in hepatitis C infected egyptian survivors of childhood cancer.

BACKGOUND/AIM: Studies associating chronic hepatitis C virus (HCV) infection with lipid profile and hepatic steatosis in children and adolescents are scarce. This study investigated lipid profile abnormalities and hepatic steatosis among HCV-infected Egyptian children and adolescents who survived leukemia and lymphoma and evaluated impact on response to antiviral therapy. SUBJECTS AND METHODS: Thirty-six leukemia/lymphoma cured children and adolescents (mean age: 12.47 ± 3.56 years) with chronic HCV infection and 30 healthy controls (mean age: 11.64 ± 3.96 years) were enrolled in this prospective study. Serum lipid profile and abdominal ultrasonography were done for all patients and controls. Guided liver biopsy with histopathological examination was done for 32 (88.9%) patients eligible for antiviral therapy. RESULTS: Total cholesterol, LDL-cholesterol, and apolipoprotein B (apo-B) in patients were significantly lower than in the control group (P ≤ .01, ≤ .01, and ≤ .05, respectively). Among those who underwent liver biopsy (n = 32), macrovesicular hepatic steatosis associated with chronic hepatitis C was documented in 10 children (31.3%). Body mass index was significantly higher (P ≤ .05) and apo-B was significantly lower in steatotic (P ≤ .05) than non-steatotic HCV-infected children. Liver span by ultrasound, alanine aminotransferase (ALT), and apo-B were independent predictors for hepatic steatosis (P < .001, <.001, and <.05, respectively). A significantly worse response to interferon alpha 2-b plus ribavrin treatment for HCV was reported among children with steatosis (P < .001). CONCLUSIONS: The study showed low serum lipids in HCV-infected children with cured leukemia/lymphoma. Hepatic steatosis was found in a significant proportion of patients and was associated with a poor response to antiviral treatment.

Morphology of the Sella Turcica in Individuals With Different Skeletal Malocclusions in Upper Egypt Assessed Using Lateral Cephalometric Radiographs.

OBJECTIVE: To evaluate the morphology of sella turcica (ST) in individuals with different skeletal malocclusions in upper Egypt. MATERIALS AND METHODS: 300 lateral cephalometric radiographs of adult patients of both sexes, varying ages from 18 to 30 years, were selected and divided into three equal groups, group (1): skeletal class I (control group), group (2): skeletal class II, and group (3): skeletal class III. Pre-treatment lateral cephalograms were taken from the archives of the Department of Orthodontics, Faculty of Dentistry, Minia University. The tuberculum and dorsum sella, the floor of ST, and posterior and anterior clinoid processes (ACPs) were drawn. The direct measurements such as diameter (APD), depth (D), and length(L) of sella were measured using Silverman and Kisling methods. RESULTS: A significant difference was found in depth (D) between class I and class II, with class II having a greater depth. Also, the largest diameter (APD) was found in the class III group. A significant difference was found in diameter (APD) between the two age groups (from 18 to 24 years and from 25 to 30 years) Conclusion: The larger diameter values were seen in the skeletal class III subjects, while the larger depth values were observed in the class II subjects. The older age group (25-30 years) has a greater diameter than the younger one. Highly significant differences were found in length and depth between the sexes.

Modulating tumoral exosomes and fibroblast phenotype using nanoliposomes augments cancer immunotherapy.

Cancer cells program fibroblasts into cancer associated fibroblasts (CAFs) in a two-step manner. First, cancer cells secrete exosomes to program quiescent fibroblasts into activated CAFs. Second, cancer cells maintain the CAF phenotype via activation of signal transduction pathways. We rationalized that inhibiting this two-step process can normalize CAFs into quiescent fibroblasts and augment the efficacy of immunotherapy. We show that cancer cell-targeted nanoliposomes that inhibit sequential steps of exosome biogenesis and release from lung cancer cells block the differentiation of lung fibroblasts into CAFs. In parallel, we demonstrate that CAF-targeted nanoliposomes that block two distinct nodes in fibroblast growth factor receptor (FGFR)-Wnt/ß-catenin signaling pathway can reverse activate CAFs into quiescent fibroblasts. Co-administration of both nanoliposomes significantly improves the infiltration of cytotoxic T cells and enhances the antitumor efficacy of αPD-L1 in immunocompetent lung cancer-bearing mice. Simultaneously blocking the tumoral exosome-mediated activation of fibroblasts and FGFR-Wnt/ß-catenin signaling constitutes a promising approach to augment immunotherapy.

Circularized Nanodiscs for Multivalent Mosaic Display of SARS-CoV-2 Spike Protein Antigens.

The emergence of vaccine-evading SARS-CoV-2 variants urges the need for vaccines that elicit broadly neutralizing antibodies (bnAbs). Here, we assess covalently circularized nanodiscs decorated with recombinant SARS-CoV-2 spike glycoproteins from several variants for eliciting bnAbs with vaccination. Cobalt porphyrin-phospholipid (CoPoP) was incorporated into the nanodisc to allow for anchoring and functional orientation of spike trimers on the nanodisc surface through their His-tag. Monophosphoryl-lipid (MPLA) and QS-21 were incorporated as immunostimulatory adjuvants to enhance vaccine responses. Following optimization of nanodisc assembly, spike proteins were effectively displayed on the surface of the nanodiscs and maintained their conformational capacity for binding with human angiotensin-converting enzyme 2 (hACE2) as verified using electron microscopy and slot blot assay, respectively. Six different formulations were prepared where they contained mono antigens; four from the year 2020 (WT, Beta, Lambda, and Delta) and two from the year 2021 (Omicron BA.1 and BA.2). Additionally, we prepared a mosaic nanodisc displaying the four spike proteins from year 2020. Intramuscular vaccination of CD-1 female mice with the mosaic nanodisc induced antibody responses that not only neutralized matched pseudo-typed viruses, but also neutralized mismatched pseudo-typed viruses corresponding to later variants from year 2021 (Omicron BA.1 and BA.2). Interestingly, sera from mosaic-immunized mice did not effectively inhibit Omicron spike binding to human ACE-2, suggesting that some of the elicited antibodies were directed towards conserved neutralizing epitopes outside the receptor binding domain. Our results show that mosaic nanodisc vaccine displaying spike proteins from 2020 can elicit broadly neutralizing antibodies that can neutralize mismatched viruses from a following year, thus decreasing immune evasion of new emerging variants and enhancing healthcare preparedness.

Living with Fibrodysplasia Ossificans Progressiva: Radiological Images of a Patient with Extensive Heterotopic Ossification.

Fibrodysplasia ossificans progressiva (FOP) is an exceptionally rare genetic disorder characterized by the progressive formation of heterotopic bone in soft tissues. Here, we present the radiological findings of an 18-year-old female diagnosed with FOP who had severe spinal and right-upper-limb abnormalities. Her SF-36 scores suggested significant impairment in physical function, affecting work and other regular daily activities. Radiographic evaluation with X-rays and CT scans revealed scoliosis and total fusion of almost all levels of the spine, with only a few disc spaces spared. A large mass of heterotopic bone was observed, corresponding to the location of the paraspinal muscles in the lumbar region, branching upwards and fusing with the scapulae on both sides. On the right side, this exuberant heterotopic bone mass fused with the humerus, resulting in a fixed right shoulder, while the rest of the upper and lower limbs are spared and have a range of motion. Our report highlights the extensive ossification that can manifest in patients with FOP, resulting in restricted mobility and a poor quality of life. While there is no definite treatment that can reverse the effects of the disease, preventing injuries and minimizing iatrogenic harm is of critical importance in this patient as inflammation is known to play a key role in triggering heterotopic bone. Meanwhile, ongoing research into therapeutic strategies holds the key to unlocking a potential cure for FOP in the future.

Modifiable fall risk factors among older adults with advanced cancer: Secondary analysis of a cluster-randomized clinical trial.

INTRODUCTION: Older adults with cancer have unique fall risk factors related to their disease and treatment such as polypharmacy and neurotoxic treatments. In this secondary analysis, we identified modifiable risk factors associated with future falls among older adults with advanced cancers. MATERIALS AND METHODS: Data were from the COACH study (ClinicalTrials.gov: NCT02107443; PI: Mohile). Patients were age ≥ 70, had stage III/IV solid tumor or lymphoma, ≥1 geriatric assessment impairment, and were receiving palliative intent treatment. Falls were self-reported at baseline (in the past six months), four to six weeks, three months, and six months. We generated inverse probability weights to account for mortality-related loss to follow-up and applied these in generalized linear mixed models to estimate incidence rate ratios. RESULTS: Of 541 patients (mean age: 77, standard deviation [SD]: 5.27), 140 (26%) reported prior falls at baseline, and 467 (86%) had falls data for ≥1 follow-up timepoint. Of those, 103 (22%) reported at least one fall during the follow-up period, and 112 (24%) had incomplete follow-up due to death. In fully adjusted models, prior falls and impaired Timed Up and Go score were associated with higher incidence of falls over 6 months. DISCUSSION: We identified several potentially modifiable fall risk factors in older adults with advanced cancers. Future studies should consider ways to integrate fall risk assessment into ongoing cancer care and intervene to reduce falls in this population.

Modified Anterior Lamellar Recession for All Grades of Upper Eyelid Trachomatous Cicatricial Entropion.

Purpose: This study aims to assess the combination of anterior lamellar recession (ALR) with blepharoplasty, suprasternal fixation, and internal eyelash bulb extirpation of aberrant lashes posteriorly located in patients with any grade of upper eyelid trachomatous cicatricial entropion. Patients and Methods: We reviewed the clinical data of eighty-six patients (143 eyelids) including age, gender, systemic medical illnesses, and comprehensive ophthalmological assessment. Eyelid evaluation was recorded, including laterality, previous surgical technique used, possible trichiasis etiology, abnormality of the lid margin, tarsal plate consistency (shrinkage or loosening), skin fold overhanging, laxity of the pretarsal skin, margin reflex distance 1 (MRD1), lagophthalmos, and lid retraction. The success rate was assessed at 3, 6, 9, and 12 months postoperative. Results: The success rate was 97.2% in the third month, which decreased significantly to 92.3% in the 6th month and 90.2% in the 9th month (P = 0.01, and 0.001 respectively). In the 9th month, we had fourteen failed cases. All of them were submitted for a second intervention. Three underwent electrolysis, four cases underwent re-internal bulb extirpation, four cases underwent the same procedure, and three cases underwent epilation. The success of the failed cases after the second intervention was significantly associated with the type of reintervention (P = 0.03), in which all of them succeed except two cases that underwent epilation. Kaplan-Meier analysis showed that the mean recurrence time in our study was 6.8 months (95% CI = 5.8-7.7 months). Conclusion: This study showed the combination of ALR with blepharoplasty, suprasternal fixation, and cauterization or internal bulb extirpation of posteriorly located lashes procedure resulted in a high success rate in patients with any form of UCE with no increase in incidence or degree of lagophthalmos associated with UCE.

Uncovering a novel role of focal adhesion and interferon-gamma in cellular rejection of kidney allografts at single cell resolution.

Background: Kidney transplant recipients are currently treated with nonspecific immunosuppressants that cause severe systemic side effects. Current immunosuppressants were developed based on their effect on T-cell activation rather than the underlying mechanisms driving alloimmune responses. Thus, understanding the role of the intragraft microenvironment will help us identify more directed therapies with lower side effects. Methods: To understand the role of the alloimmune response and the intragraft microenvironment in cellular rejection progression, we conducted a Single nucleus RNA sequencing (snRNA-seq) on one human non-rejecting kidney allograft sample, one borderline sample, and T-cell mediated rejection (TCMR) sample (Banff IIa). We studied the differential gene expression and enriched pathways in different conditions, in addition to ligand-receptor (L-R) interactions. Results: Pathway analysis of T-cells in borderline sample showed enrichment for allograft rejection pathway, suggesting that the borderline sample reflects an early rejection. Hence, this allows for studying the early stages of cellular rejection. Moreover, we showed that focal adhesion (FA), IFNg pathways, and endomucin (EMCN) were significantly upregulated in endothelial cell clusters (ECs) of borderline compared to ECs TCMR. Furthermore, we found that pericytes in TCMR seem to favor endothelial permeability compared to borderline. Similarly, T-cells interaction with ECs in borderline differs from TCMR by involving DAMPS-TLRs interactions. Conclusion: Our data revealed novel roles of T-cells, ECs, and pericytes in cellular rejection progression, providing new clues on the pathophysiology of allograft rejection.