2-Staged Surgical Protocol for Management of Large Odontogenic Keratocyst.

The World Health Organisation classification and the treatment protocol for the odontogenic keratocyst (OKC), previously referred to as the keratocystic odontogenic tumour, were examined based on a study of the literature. Because not all OKCs have an identifiable protein patched homolog mutation, the idea of changing the management protocol for OKC in response to this shift in tumour category was met with scepticism and was not widely adopted. This study's objective was to outline a successful management plan for an odontogenic keratocyst in a patient who was 23 years old. The procedure for therapy involved marsupialisation, which was followed by enucleation, peripheral osteotomy, and the injection of 5 FFU. Following a 2-year observation period (clinical and radiological monitoring), it was found that bone regeneration was normal and there was no sign of a recurrence.

Asymptomatic COVID-19-Associated Acquired Hemophilia A and Disseminated Intravascular Coagulation From a Bypassing Agent.

Acquired hemophilia A (AHA) is a clotting disorder characterized by the presence of neutralizing antibodies that inhibit factor VIII, resulting in increased bleeding risk. Known etiologies include malignancy, autoimmune conditions, graft-vs-host disease, and more recently coronavirus disease 2019 (COVID-19) infection. In this case report, we describe an 86-year-old female who was found to have AHA incidentally during preoperative workup for meningioma resection. She was subsequently found to have COVID-19 infection which was the likely cause of her development of AHA. She was treated with factor eight inhibitor bypassing agent (FEIBA) and recombinant factor VII (rVII) for a small hematoma on her right arm along with prednisone and cyclophosphamide. She then developed disseminated intravascular coagulation (DIC) initially secondary to FEIBA and subsequently rFVII. DIC resolved after these factor concentrates were withheld. The aim of this case report was to emphasize the importance of monitoring partial thromboplastin time (PTT) in patients with COVID-19 and proceeding with AHA workup if indicated. It is also imperative to know and understand the potentially life-threatening, albeit rare, adverse effects of DIC associated with the administration of factor concentrates, especially in the elderly population and withholding these factor concentrates once DIC is suspected.

Anti-PF4 ELISA-Negative, SRA-Positive Heparin-Induced Thrombocytopenia.

Heparin products are frequently used in the inpatient setting to prevent and treat venous thromboembolism, but they simultaneously put patients at risk of developing heparin-induced thrombocytopenia (HIT). The 4Ts score determines the pretest probability of HIT. Diagnosis is made with a screening antiplatelet factor (PF4) immunoassay and the serotonin-release assay (SRA) as a confirmatory test. Anti-PF4 assays have high sensitivity (98%) but lower specificity (50%) and result in frequent false-positive tests. We present a rare case from our institution of a patient with anti-PF4-Polyanion ELISA-negative, SRA-positive HIT and describe the challenges in making a timely diagnosis in this case.

Investigating the Role of 17-Beta Estradiol in the Regulation of the Unfolded Protein Response (UPR) in Pancreatic Beta Cells.

Diabetes mellitus is clinically defined by chronic hyperglycemia. Sex differences in the presentation and outcome of diabetes exist with premenopausal women having a reduced risk of developing diabetes, relative to men, or women after menopause. Accumulating evidence shows a protective role of estrogens, specifically 17-beta estradiol, in the maintenance of pancreatic beta cell health; however, the mechanisms underlying this protection are still unknown. To elucidate these potential mechanisms, we used a pancreatic beta cell line (BTC6) and a mouse model of hyperglycemia-induced atherosclerosis, the ApoE-/-:Ins2+/Akita mouse, exhibiting sexual dimorphism in glucose regulation. In this study we hypothesize that 17-beta estradiol protects pancreatic beta cells by modulating the unfolded protein response (UPR) in response to endoplasmic reticulum (ER) stress. We observed that ovariectomized female and male ApoE-/-:Ins2+/Akita mice show significantly increased expression of apoptotic UPR markers. Sham operated female and ovariectomized female ApoE-/-:Ins2+/Akita mice supplemented with exogenous 17-beta estradiol increased the expression of adaptive UPR markers compared to non-supplemented ovariectomized female ApoE-/-:Ins2+/Akita mice. These findings were consistent to what was observed in cultured BTC6 cells, suggesting that 17-beta estradiol may protect pancreatic beta cells by repressing the apoptotic UPR and enhancing the adaptive UPR activation in response to pancreatic ER stress.

Transitioning from MODIS to VIIRS Global Water Reservoir Product.

Reservoirs play a crucial role in regulating water availability and enhancing water security. Here, we develop NASA's Visible Infrared Imaging Radiometer Suite (VIIRS) based Global Water Reservoir (GWR) product, consisting of measurements of reservoir area, elevation, storage, evaporation rate, and evaporation loss for 164 large global reservoirs. The dataset is available at 8-day and monthly temporal resolutions. Since the Moderate Resolution Imaging Spectroradiometer (MODIS) is close to the end of its life, we further evaluated the consistency between MODIS and VIIRS-based GWR to ensure continuity to the 20+ year MODIS GWR product. Independent assessment of VIIRS reservoir storage (8-day) retrievals against in-situ measurements shows an average of R2 = 0.84, RMSE = 0.47 km3, and NRMSE = 16.45%. The evaporation rate has an average of R2 = 0.56, RMSE = 1.32 mm/day, and NRMSE = 28.14%. Furthermore, results show good consistency (R2 ≥ 0.90) between the VIIRS and MODIS-based product components, confirming that long-term data continuity can be achieved. This dataset can provide valuable insights for long-term trend analysis, hydrological modeling, and understanding hydroclimatic extremes in the context of reservoirs.

Cyclic Thrombocytopenia in the Setting of Intracranial Hemorrhage: A Diagnostic and Therapeutic Challenge.

Cyclic thrombocytopenia (CTP) as the name suggests presents with cyclic episodes of thrombocytopenia and is frequently initially misdiagnosed as immune thrombocytopenia. Following a lack of sustained response or abnormally increased response to common treatments used for immune thrombocytopenia, a proper diagnosis of CTP can then be made. Prior reports have shown a subset of patients who respond to cyclosporin A. Here, we present a case of CTP that was initially at another facility presumed to have and treated for immune thrombocytopenic purpura. However, after multiple attempts to treat with steroids, intravenous immunoglobulin (IVIG), rituximab, and eltrombopag, episodes of severe thrombocytopenia followed by thrombocytosis continued. The patient ultimately developed intracerebral hemorrhage (ICH) in the setting of one of the episodes of severe thrombocytopenia and developed multiple subsequent complications from which the patient unfortunately did not recover. It was only after developing ICH that the patient had been evaluated at a center with hematology consultation capabilities, at which time after a detailed review of his case and pattern recognition the proper diagnosis of CTP was made with initiation of cyclosporine. This case was further complicated by need to maintain an adequate platelet threshold post-ventriculoperitoneal shunt placement which was necessary due to his ICH and was placed before diagnosis of CTP could be made. While CTP is a rare diagnosis, this case reinforces a greater need to properly diagnose and consider cyclosporine treatment for CTP, as it has been effective in some patients and may help to prevent patient morbidity and especially catastrophic bleeding complications.

Cytokine release syndrome and cancer immunotherapies - historical challenges and promising futures.

Cancer is the leading cause of death worldwide. Cancer immunotherapy involves reinvigorating the patient's own immune system to fight against cancer. While novel approaches like Chimeric Antigen Receptor (CAR) T cells, bispecific T cell engagers, and immune checkpoint inhibitors have shown promising efficacy, Cytokine Release Syndrome (CRS) is a serious adverse effect and remains a major concern. CRS is a phenomenon of immune hyperactivation that results in excessive cytokine secretion, and if left unchecked, it may lead to multi-organ failure and death. Here we review the pathophysiology of CRS, its occurrence and management in the context of cancer immunotherapy, and the screening approaches that can be used to assess CRS and de-risk drug discovery earlier in the clinical setting with more predictive pre-clinical data. Furthermore, the review also sheds light on the potential immunotherapeutic approaches that can be used to overcome CRS associated with T cell activation.

A Case of Vancomycin-Induced Severe Immune Thrombocytopenia.

A male in his 60s presented with left lower extremity fractures following a vehicle accident. Hemoglobin, initially, was 12.4 mmol/L, and platelet count was 235 k/mcl. On day 11 of admission, his platelet count initially dropped to 99 k/mcl, and after recovery it rapidly decreased to 11 k/mcl on day 16 when the INR was 1.3 and aPTT was 32 s, and he continued to have a stable anemia throughout admission. There was no response in platelet count post-transfusion of four units of platelets. Hematology initially evaluated the patient for disseminated intravascular coagulation, heparin-induced thrombocytopenia (anti-PF4 antibody was 0.19), and thrombotic thrombocytopenic purpura (PLASMIC score of 4). Vancomycin was administered on days 1-7 for broad spectrum antimicrobial coverage and day 10, again, for concerns of sepsis. Given the temporal association of thrombocytopenia and vancomycin administration, a diagnosis of vancomycin-induced immune thrombocytopenia was established. Vancomycin was discontinued, and 2 doses of 1000 mg/kg of intravenous immunoglobulin 24 h apart were administered with the subsequent resolution of thrombocytopenia.

Three Class Classification of Alzheimer's Disease Using Deep Neural Networks.

Alzheimer's disease (AD) is a prevalent type of dementia that can cause neurological brain disorders, poor decision making, impaired memory, mood swings, unstable emotions, and personality change. Deep neural networks are proficient in classifying Alzheimer's disease based on MRI images. This classification assists human experts in diagnosing AD and predicts its future progression. The paper proposes various Deep Neural Networks (DNN) for early AD detection to save cost and time for doctors, radiologists, and caregivers. A 3330-image-based Kaggle dataset is used to train the DNN, including 52 images of AD, 717 images of Mild Cognitive Impairment (MCI), and the remaining images of Cognitive Normal (CN). Stratified partitioning splits the dataset into 80% and 20% proportions for training and validation datasets. Proposed models include DenseNet169, DenseNet201, and Res- Net152 DNNs with additional three fully-connected layers and softmax and Kullback Leibler Divergence (KLD) loss function. These models are trained considering pre-trained, partially pre-trained, and fully re-trained extended base models. The KLD loss function reduces the error and increases accuracy for all models. The partially pre-trained DenseNet201 model outperformed all the other models. DenseNet201 gives the highest accuracy of 99.98% for training, 99.07% for validation, and 95.66% for test datasets. The DenseNet201 model has the highest accuracy in comparison to other state-of-artmethods.

Fish and macroinvertebrate assemblages reveal extensive degradation of the world's rivers.

Rivers suffer from multiple stressors acting simultaneously on their biota, but the consequences are poorly quantified at the global scale. We evaluated the biological condition of rivers globally, including the largest proportion of countries from the Global South published to date. We gathered macroinvertebrate- and fish-based assessments from 72,275 and 37,676 sites, respectively, from 64 study regions across six continents and 45 nations. Because assessments were based on differing methods, different systems were consolidated into a 3-class system: Good, Impaired, or Severely Impaired, following common guidelines. The proportion of sites in each class by study area was calculated and each region was assigned a Köppen-Geiger climate type, Human Footprint score (addressing landscape alterations), Human Development Index (HDI) score (addressing social welfare), % rivers with good ambient water quality, % protected freshwater key biodiversity areas; and % of forest area net change rate. We found that 50% of macroinvertebrate sites and 42% of fish sites were in Good condition, whereas 21% and 29% were Severely Impaired, respectively. The poorest biological conditions occurred in Arid and Equatorial climates and the best conditions occurred in Snow climates. Severely Impaired conditions were associated (Pearson correlation coefficient) with higher HDI scores, poorer physico-chemical water quality, and lower proportions of protected freshwater areas. Good biological conditions were associated with good water quality and increased forested areas. It is essential to implement statutory bioassessment programs in Asian, African, and South American countries, and continue them in Oceania, Europe, and North America. There is a need to invest in assessments based on fish, as there is less information globally and fish were strong indicators of degradation. Our study highlights a need to increase the extent and number of protected river catchments, preserve and restore natural forested areas in the catchments, treat wastewater discharges, and improve river connectivity.

The impact of sequencing depth and relatedness of the reference genome in population genomic studies: A case study with two caddisfly species (Trichoptera, Rhyacophilidae, Himalopsyche).

Whole genome sequencing for generating SNP data is increasingly used in population genetic studies. However, obtaining genomes for massive numbers of samples is still not within the budgets of many researchers. It is thus imperative to select an appropriate reference genome and sequencing depth to ensure the accuracy of the results for a specific research question, while balancing cost and feasibility. To evaluate the effect of the choice of the reference genome and sequencing depth on downstream analyses, we used five confamilial reference genomes of variable relatedness and three levels of sequencing depth (3.5×, 7.5× and 12×) in a population genomic study on two caddisfly species: Himalopsyche digitata and H. tibetana. Using these 30 datasets (five reference genomes × three depths × two target species), we estimated population genetic indices (inbreeding coefficient, nucleotide diversity, pairwise F ST, and genome-wide distribution of F ST) based on variants and population structure (PCA and admixture) based on genotype likelihood estimates. The results showed that both distantly related reference genomes and lower sequencing depth lead to degradation of resolution. In addition, choosing a more closely related reference genome may significantly remedy the defects caused by low depth. Therefore, we conclude that population genetic studies would benefit from closely related reference genomes, especially as the costs of obtaining a high-quality reference genome continue to decrease. However, to determine a cost-efficient strategy for a specific population genomic study, a trade-off between reference genome relatedness and sequencing depth can be considered.

A comparative analysis of surgical outcome in uveitic and non-uveitic steroid-induced glaucoma in children.

Purpose: To compare outcomes of surgical management of uveitic glaucoma (UG) and steroid-induced glaucoma (SIG) in children in terms of intraocular pressure (IOP) control, visual acuity, and associations for failure. Methods: This was a retrospective case-control study of consecutive UG (cases) and non-uveitic SIG (controls) in children <18 years of age who underwent surgery between January 2005 and December 2017. Results: Primary trabeculectomy with mitomycin C (MMC) was performed in 12 cases (mean age: 9.2 ± 4.3 years) and 40 controls (mean age: 10.4 ± 3.7 years) (P = 0.33). Primary phaco-trabeculectomy with MMC was performed in 11 cases (mean age: 11.4 ± 4.7 years) and 16 controls (mean age: 10.4 ± 3.4 years) (P = 0.57). IOP control (P = 0.26), visual acuity (P = 0.97), number of glaucoma medications (P = 0.06), and survival rates (49% cases vs. 68% controls at 5 years; P = 0.22) were similar between the two groups following trabeculectomy. Survival rates in the phaco-trabeculectomy group at 5 years were 68% cases vs. 69% controls (P = 0.71). IOP was higher (P = 0.008) and visual acuity was worse (P = 0.02) in cases at the last visit. Associations for failure (univariate analysis) were younger age (OR: 6.29, 95% CL: 1.43, 27.67; P = 0.03) and male gender (OR: 4.79, 95% CL: 1.09, 20.97; P = 0.04). On multivariate analysis, younger age (OR: 11.985, 95% CL: 1.071, 134.153; P = 0.04) remained significant. Preoperative number of uveitic attacks was protective on univariate (OR: 0.75, 95% CL: 0.48, 1.15; P = 0.1) and multivariate analyses (OR: 0.49, 95% CL: 0.24, 0.09; P = 0.04). Conclusion: Outcomes of trabeculectomy between cases and controls were similar in our series. However, phaco-trabeculectomy in pediatric uveitic eye group fared worse than eyes with SIG.

Bilateral adrenal haemorrhage in antiphospholipid syndrome and a short review of the literature.

Antiphospholipid syndrome (APS) is an uncommon autoantibody-mediated condition characterised by acquired thrombophilia resulting in recurrent arterial and venous thrombosis. An inciting factor allows for the exposure of endothelial phospholipids, causing antigen formation and subsequent creation of antibodies. A woman in her 70s presented after vehicular trauma, suffering broken ribs, pneumothorax and incidentally discovered left adrenal haemorrhage. Two weeks later she presented with acute-onset abdominal pain and was found to have a right adrenal gland haemorrhage on CT imaging without interval trauma occurring. The patient had antiphospholipid antibody laboratory studies drawn and was given intravenous heparin with a bridge to warfarin at discharge. Laboratory results returned positive for lupus anticoagulant, beta-2 glycoprotein and anticardiolipin antibodies indicating triple positivity, with repeated laboratory tests positive in 12 weeks' time, confirming the diagnosis. Bilateral adrenal haemorrhage, rather than traditional venous thromboembolism, was the presenting pathology in this patient's diagnosis of APS.

Outcomes from a tertiary care center using a catheter thrombectomy system for managing acute iliofemoral deep vein thrombosis.

OBJECTIVE: The aim of the present study was to report a large, single-center experience using the ClotTriever thrombectomy system (Inari Medical, Irvine, CA) for the management of acute iliofemoral (IF) deep vein thrombosis (DVT). One limitation of all endovascular devices for the treatment of acute IF-DVT has been the inability to completely remove all acute thrombus and the need for adjunctive thrombolysis with its attendant risk of bleeding complications. METHODS: A single-center retrospective review of consecutive patients with acute IF-DVT treated with the ClotTriever thrombectomy system (Inari Medical) is reported. Procedural efficacy was evaluated by an independent core imaging laboratory (Syntactx, New York, NY). Both procedural and in-hospital safety were assessed during the index hospitalization. The treated vein patency was assessed using duplex ultrasound at 30 days after the procedure. RESULTS: A total of 96 patients were included in the present retrospective review, 40 of whom (40%) had contraindications to thrombolytic therapy. In terms of efficacy, 93 patients (97%) had ≥75% thrombus removal. During the index hospitalization, two patients (2%) had experienced a symptomatic pulmonary embolus. However, no mortality, major bleeding, or device-related complications had occurred in the study population. Of the 96 patients, 64 had undergone duplex ultrasound at 30 days after the procedure. Of the 64 patients, 62 had normal flow (97%), 53 (83%) had normal compressibility, and 11 (17%) had partial compressibility. CONCLUSIONS: The ClotTriever thrombectomy catheter was both safe and effective in our cohort of patients with acute IF-DVT outside a randomized clinical trial.

Practices of Procedural Pain Management in Neonates through Continuous Quality Improvement Measures.

OBJECTIVE: Although the benefits of pain control measures in neonates are well known, the actual usage was not optimal in our unit. Therefore, we implemented a quality improvement project to improve pain management practices through multiple Plan-Do-Study-Act (PDSA) cycles. METHOD: Our project included hemodynamically stable newborns weighing ≥1300 g. We identified four common procedures: intravenous cannulation, venous sampling, heel prick, and nasogastric tube insertion. The selected pain control measures were skin-to-skin contact, breastfeeding, expressed breast milk orally, and oral sucrose. Between April 2019 and September 2019, we intervened multiple times and reassessed shortcomings. We encouraged evidence-based practices and gave solutions for shortcomings. Data were interpreted weekly to assess the compliance to pain control interventions. RESULTS: Minimal pain control measures (3-4%) were utilized for identified procedures before the project began. We could improve the use of pain control measures steadily and achieve the target of 80% of procedures after seven different interventions over five months. There was a retention of the effect on reassessing twice at second and fourth months of stopping further intervention once the target got achieved. CONCLUSION: Quality Improvement science can identify the shortcomings and help to improve the compliance for pain control practices in neonates, as demonstrated in this neonatal unit.

Management of congenital dysfibrinogenemia in pregnancy: A challenging patient case.

Afibrinogenemia and congenital dysfibrinogenemia (CD) are rare conditions with limited information available for appropriate management. Previous case reports have demonstrated the safe and efficacious use of fibrinogen replacement therapy (FRT) as a therapeutic approach to prevent hemorrhage and fetal loss in pregnant women with CD. In this case report, we present a 28-year-old pregnant woman who sought testing for CD given her family history. She denied any current or previous bleeding symptoms. Laboratory testing confirmed the diagnosis of CD. She was treated with FRT and prophylactic anticoagulation starting in her third trimester. She had preterm labor that prompted an urgent cesarean section with FRT support. This case adds to the sparse literature about fibrinogen disorders in pregnancy, and highlights the benefits, safety, and tolerability of FRT and prophylactic anticoagulation in pregnant women with CD. Finally, it emphasizes the importance of a multidisciplinary team approach for an uneventful delivery.

Establishing the relationship between benthic macroinvertebrates and water level fluctuation in subtropical shallow wetlands.

Wetland water level fluctuations often influence benthic macroinvertebrate communities through changes in water quality, substrate, and macrophytes and, hence, affect the structure and function of aquatic ecosystems. However, there is lack of understanding on how water level fluctuations affect the structure and composition of benthic macroinvertebrates in subtropical shallow wetlands in Nepal. Here, we assessed the changes in benthic macroinvertebrate community composition in response to water level fluctuations and identified indicator taxa sensitive to such fluctuations. A study was conducted over 4 seasons covering one annual cycle of water level fluctuation in 4 wetlands of Koshi Tappu Wildlife Reserve, Nepal. The study revealed that benthic macroinvertebrate composition significantly differed across water levels. Dissimilarities in macroinvertebrate community composition were mainly attributed by families Atyidae, Dytiscidae, Baetidae, Planorbidae, Chironomidae, Bithyniidae, Sphaeriidae, and Thiaridae. Taxon specific richness, densities, and biomass varied across the water levels while no difference was documented for overall family richness, density, and biomass. Ephemeroptera and Trichoptera richness decreased when water levels were low while Coleoptera and Diptera richness increased. Medium water level supported high benthic macroinvertebrate diversity. Indicator taxa analysis identified Coleoptera: Hydrophilidae and Dytiscidae, Hemiptera: Pleidae, Diptera: Muscidae and Mollusca: Sphaeriidae, Viviparidae, and Thiaridae, as indicators of low water level. Similarly, Coleoptera: Scirtidae, Hemiptera: Micronectidae and Oligochaeta: Tubificidae as indicators of medium water level, and Trichoptera: Polycentropodidae and Ephemeroptera: Caenidae as indicators of high water level. Redundancy analysis identified water level as one of the most influencing factors in benthic macroinvertebrate community variation. Considering the significant response of benthic macroinvertebrates to water level fluctuations, they are important as ecological indicators in research aimed at developing environmental flow frameworks. Indicator species are likely to be a vital tool in environmental impact assessment and monitoring in relation to hydrological development. The outcomes of this research have important implications to conservation and management of wetlands to preserve the valuable ecosystem functions provided by wetlands.

Hyperhemolysis Syndrome in a Patient With Sickle Cell Disease and Acute Chest Syndrome.

Sickle cell anemia patients often present to the hospital with acute vaso-occlusive pain crisis. Symptoms can include, but are not limited to, chest pain, abdominal pain, and musculoskeletal pain. These symptoms are brought about due to the pathology of the disease. Abnormal hemoglobin S causes red blood cells to band together, otherwise known as "sickling." These patients also often present with very low hemoglobin levels on initial evaluation. In most cases, packed red blood cell transfusions are needed in order to replenish these patient's functional hemoglobin supply. Unfortunately, transfusing sickle cell patients can lead to an unwanted consequence, that of hyperhemolysis syndrome, in which blood transfusions prompt further hemolysis of the already sickled red blood cells. When this complication arises, caution must be exercised in deciding the next steps of treatment.

Evaluation of effect of low level laser therapy with intracanal medicament on periapical healing: A randomised control trial.

OBJECTIVE(S): Photobiomodulation, also commonly referred to as low level laser therapy (LLLT), uses light energy to elicit biological responses from the cell and normalise cell function. Using LLLT on bone has been demonstrated to be effective in modulating inflammation, accelerating bone cell proliferation and enhancing the healing process. The objectives of this study were to evaluate postoperative pain and periapical healing in two different groups. MATERIALS AND METHODS: 40 subjects with periapical lesion were selected and were assigned randomly into two groups. Group I: Conventional root canal therapy along with LLLT. Group II: Conventional root canal therapy only. Radiographs were obtained and assessed at baseline, 3, 6 and 9 months postoperatively. The VAS pain scale was assessed post operatively at 0, 7th and 14th day respectively. The Independent t-test was used for evaluation of the data. RESULTS: Significant differences were noted in reduction of periapicallesion at 3 and 9 months follow-up. The healing was better in Group I that received LLLT with the conventional Root Canal Treatment (RCT). Values for postoperative pain was lower in Group I than Group II, but were statistically non-significant. CONCLUSION(S): LLLT when used as an adjunct with conventional root canal treatment showed acceleration of the healing process of periapical lesions. LLLT has a positive effect on modulating the immune response for favourable healing.