Laboratory Investigations Research Articles

Correlation of simple hematological parameters with disease activity and damage indices among Egyptian patients with systemic lupus erythematosus

ObjectiveTo evaluate the correlation of different hematological parameters in lupus patients with SLE disease activity index (SLEDAI), the Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI), and some laboratory data related to kidney functions in active patients with nephritis. Material and methods80 inactive SLE patients (SLEDAI score<10 points), and 80 active patients (SLEDAI≥10 points) were enrolled in this study. All patients underwent full medical history taking, clinical evaluation including calculation of SLEDAI and SLICC/ACR DI scores, and laboratory investigations including complete blood count. The two groups were compared regarding different disease parameters. Correlations of some hematological parameters with SLEDAI, SLICC/ACR DI scores and some laboratory data related to kidney function in patients with nephritis were made. ResultsThe active group showed statistically significantly higher mean NLR (P=0.000), NC3R (P=0.000), MLR (P=0.000), PLR (P=0.000), and RDW (P=0.001), and statistically significantly lower mean MPV (P=0.002). The mean MLR (P=0.018) and PLR (P=0.005) were statistically significantly higher in the active patients with nephritis. For both groups, there were no significant correlations between studied parameters and SLEDAI or SLICC/ACR DI, except with NC3R values in the active group which were associated with SLEDAI (r=.221, P=0.049). ConclusionThe hematological parameters in SLE have promising potential clinical application as a novel activity marker, especially in patients with nephritis.

Laboratory Investigation of Energy Dissipation and Turbulent Mixing During Internal Solitary Wave Breaking on the Rough Shelf Slope

AbstractWhen internal solitary waves (ISW) propagate to the continental shelf, they typically runup and break on the forereef. This process might lead to periodic temperature drops at the reef slope, which has potential to protect coral reefs from bleaching threats. A series of laboratory experiments were conducted to investigate turbulence characteristics and energy dissipation during the ISW breaking events on the shelf slope with different bottom roughness to mimic the forereef environment. Particle image velocimetry (PIV) and planar laser‐induced fluorescence (PLIF) were coupled to obtain simultaneous high‐resolution velocity and density fields, based on which we then calculate the energy budget and turbulent dissipation rate. We found that the ISW breaking can be divided into two turbulent processes, the production of shear instability and coherent structures. Ratio of energy loss is weakened with the increase of bottom roughness and the collapse height, while the rough structure substantially enhanced the turbulent dissipation rate. The mixing efficiency is between 0.1 and 0.3, close to its maximal rate at 0.25. Our results reveal that the bottom roughness has impact on the mixing efficiency and turbulent process during the ISW breaking events. We found that rough structures at the shelf slope inhibit the mixing efficiency, especially in cases with small amplitude incline ISW. This finding may help us to better understand the reef damage and coral reef decline and support the management of coral protection strategy.

Laboratory investigation of the effect of using metakaolin and clay on the behaviour of recycled glass powder-based geopolymer mortars

Civil infrastructure relies on cement, a common building material. However, Portland cement production pollutes the world by consuming mineral resources and emitting carbon dioxide. Using modern, cost-effective, and eco-friendly cement materials seems necessary. One such material is geopolymer cement, also known as green cement, composed of aluminosilicate base materials and alkaline-silicate activators. In the present study, waste glass powder was utilised to provide a rich aluminosilicate base material by substituting 10%, 20%, and 30% of the metakaolin or clay with calcium carbide residue as an alkaline activator. The samples were processed under two distinct temperature conditions: natural environment and thermal processing at 80 °C in an autoclave. The mechanical and microstructural properties of the mortars were evaluated regarding compressive strength, bending strength, setting time, volume control, and Scanning Electron Microscope (SEM). The results indicate that the type and amount of glass powder alternatives significantly determine the final sample strength. Substituting 10% metakaolin and 20% clay for glass powder maximises compressive strength. The optimal bending strength of geopolymer samples was obtained by substituting 10% clay with 10% metakaolin. SEM images validate this discovery by exhibiting a more compact and cohesive arrangement. Additionally, the processing conditions of geopolymer samples significantly influence the mechanical properties of geopolymer mortars. The results of the V-cut test indicate that geopolymeric mortars are sluggish and require additional time to reach their primary and secondary strength. This study suggests that geopolymers could produce environmentally friendly concrete by reducing cement use and advancing economic and environmental goals.

Potential of Ilhéus virus to emerge

Ilhéus virus (ILHV)(Flaviviridae:Orthoflavivirus) is an arthropod-borne virus (arbovirus) endemic to Central and South America and the Caribbean. First isolated in 1944, most of our knowledge derives from surveillance and seroprevalence studies. These efforts have detected ILHV in a broad range of mosquito and vertebrate species, including humans, but laboratory investigations of pathogenesis and vector competence have been lacking. Here, we develop an immune intact murine model with several ages and routes of administration. Our model closely recapitulates human neuroinvasive disease with ILHV strain- and mouse age-specific virulence, as well as a uniformly lethal Ifnar−/− A129 immunocompromised model. Replication kinetics in several vertebrate and invertebrate cell lines demonstrate that ILHV is capable of replicating to high titers in a wide variety of potential host and vector species. Lastly, vector competence studies provide strong evidence for efficient infection of and potential transmission by Aedes species mosquitoes, despite ILHV's phylogenetically clustering with Culex vectored flaviviruses, suggesting ILHV is poised for emergence in the neotropics.

Role of ultrasonography (USG) and color Doppler in the evaluation of thyroid nodules and its association with USG-guided FNAC - A cross-sectional study.

Thyroid diseases affect approximately 42 million people in India. The majority (15%-40%) of these cases remain asymptomatic and benign and warrant special investigations such as ultrasonography (USG) and fine-needle aspiration cytology (FNAC) for diagnosis. Early diagnosis and management of thyroid disorders determine the disease course in many patients. To determine the role of USG and color Doppler in the evaluation of thyroid nodules and its association with USG-guided FNAC. We did a cross-sectional analytical study over 2 years, where we recruited 108 patients with thyroid swelling attending the OPD. We used a semi-structured data collection proforma that captured information on sociodemographic details, clinical symptoms, physical examination, and all ne cessary laboratory investigations. All patients underwent USG, color Doppler, and FNAC as a part of the investigation of thyroid nodules. The diagnostic value of ultrasound and Doppler parameters was assessed in terms of sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for detection of malignancy in comparison to FNAC. Approximately 155 nodules were identified from the selected 108 cases, and the prevalence of malignancy among the selected thyroid nodule patients was found to be 9.1%. We observed that malignant tumors were likely to be solitary with lobulated margins, >2 cm in size with <50% peripheral halo, with markedly hypoechoic, predominantly solid, with nodal involvement and extrathyroidal extension, microcalcifications, and central vascularity. We also observed that tumors that had USG characteristics of being taller than wide (91%), poorly defined margins (92%), marked hypoechoic (95%), and microcalcifications (96%) had the highest diagnostic accuracy in detecting malignancy when compared to FNAC. Thus, through our study findings, we conclude that USG and color Doppler can serve as vital tools for the evaluation of thyroid nodules with high sensitivity and specificity.

A Unique Clinical Appearance of Upper Maxillary Premolar associated with Dentigerous Cyst: Case Report

During dental development, a variety of hereditary and environmental variables interact to cause dental abnormalities. The etiology may involve multi-tiered, multi-directional, and multi-factorial processes. Fusion is a dental anomaly that happens during tooth development, where two separated teeth bud fuse together to form a single tooth. The morpho-differentiation or histo-differentiation stages of tooth development, genetic and environmental variables can induce developmental dental abnormalities. A clinical resemblance of a "double-headed" maxillary second upper left premolar with two crowns, formed on the both coronal and apical root end or whether it is just a hypercementosis of apical root discovered after surgical extraction and enucleation of cyst. Investigations to confirm such unique findings were performed. This case report discusses the importance of clinical, radiographic and laboratory investigations to confirm the unique appearance of the maxillary second premolar.

Factors Associated with the Nutritional Status of Mechanically Ventilated Patients in Intensive Care Unit: A Cross Sectional Study

Background: Nutritional status significantly impacts the outcomes of critically ill patients in intensive care units (ICU), with malnutrition being a common complication that can exacerbate morbidity and mortality rates. The Nutrition Risk in the Critically ill (NUTRIC) score is a valuable tool for identifying patients at risk of malnutrition and guiding nutritional interventions. Objective: This study aimed to evaluate the factors influencing the nutritional status, as assessed by the NUTRIC score, of mechanically ventilated patients in ICUs across tertiary care hospitals, and to explore the association between nutritional risk and patient outcomes. Methods: A cross-sectional descriptive study was conducted in five tertiary care hospitals in Khyber Pakhtunkhwa, Pakistan, from August to December 2023. The study included patients aged 18 and above, who were mechanically ventilated for more than 48 hours. The NUTRIC score was calculated based on data collected on demographics, clinical characteristics, and laboratory investigations. Multiple linear regression analysis was performed to identify factors affecting the NUTRIC score using SPSS version 25. Results: Out of 335 patients, 75.2% were male, and 51.3% were aged between 50-75 years. A high NUTRIC score (indicating higher risk of malnutrition) was found in 25% of patients, while 74.9% had a low NUTRIC score. Factors significantly affecting the NUTRIC score included ventilation status (invasive/non-invasive), number of comorbidities, age, status of life (alive/deceased), and length of stay in ICU. The mortality rate was 3.9%, with a higher prevalence in older age groups. Conclusion: The study highlights the prevalence of nutritional risk among mechanically ventilated ICU patients and underscores the importance of early nutritional assessment and intervention. Targeted nutritional support, especially for patients with higher risk profiles, is crucial for improving outcomes and reducing mortality rates in this vulnerable population.

CLINICAL OBSERVATION OF TREATMENT EFFICACY IN SEPSIS: A PROSPECTIVE STUDY

Objective: To examine the safety and efficacy associated with various treatment approaches and to identify trends and variations in the management of severe sepsis, including the usage of antibiotics, and supportive care. To examine factors associated with improved or worsened outcomes in severe sepsis cases, such as patient demographics, comorbidities, or timing of treatment. Design: A hospital-based prospective study was done on all inpatients and outpatients in Princess DurruShehvar Childrens &amp; General Hospital, Hyderabad, Telangana for 6 months. Methods: The data collection form and patient consent form were designed for this study. It comprises information regarding the study subjects data such as demographics, medical and medication history, laboratory investigations, diagnosis, present prescribed medication, and progress chart. Investigators collected the relevant data and recorded it in data collection form. The prescription will be selected based on inclusion criteria and exclusion criteria. The data obtained was compiled and analysed using appropriate statistical tests. Quantitative variables were summarized using descriptive studies (percentages, mean, standard deviation, number of observations). The data was statistically analyzed using spss and pair t test, graphs, pie diagrams, and bar graphs. Results A total of 115 patients were included in this prospective study and 60% of them show culture sensitivity. Meropenem was found to be the most potent antibiotic. The analysis of the treatments impact reveals noteworthy outcomes across multiple parameters. The intervention demonstrates a significant effect in reducing systolic blood pressure, although no major influence on diastolic blood pressure is observed. Regarding erythrocyte sedimentation rate (ESR), a substantial and statistically significant decrease is indicated post-treatment. Notably, arterial blood gas (ABG) levels exhibit a considerable difference pre- and post-treatment, with a p-value below 0.05, suggesting a rejection of the null hypothesis. Additionally, the treatment is associated with a significant increase in total leukocyte counts, as evidenced by the positive mean difference and a 95% confidence interval entirely above zero. These findings underscore the diverse impacts of the treatment on various physiological markers. Conclusion Prospective sepsis treatment studies offer a nuanced grasp of real-world effectiveness, linking controlled experiments to clinical reality. Despite biases, they contribute to evidence-based strategies, acknowledging clinical complexities. This practical approach guides healthcare professionals with adaptable, patient-centered methods. Emphasis on rigorous statistical methodologies enhances comprehension. Integrating observational and experimental data enriches our understanding of sepsis management. Overall, these studies shape holistic approaches for effective treatment.

Flow characteristics and energy dissipation over stepped spillway with various step geometries: case study (steps with curve end sill)

Stepped weirs are used in a wide range of applications, designed to increase energy dissipation. In this study, laboratory experiments were conducted in a flume on six stepped weir models, with a downstream angle of θ = 26.6°. The physical models used were on a scale of 10:1, and tests of discharges up to 0.055 m3/s were carried out. Several step geometries including traditional step, sill and curve geometries were used to study flow behavior and overall energy dissipation. The laboratory investigations were augmented by modelling numerically the within step flow and energy behavior using a 2-D CFD model, incorporating the k-ε model for turbulence closure. The results showed that energy dissipation was greatest for the curved steps by about 10.5%, where it was observed that the skimming flow regime was shifted to a higher discharge range. Numerical modelling results showed good agreement with the experimental results. An inspection of the modelled streamlines highlighted the increase in vortex intensity for the curve model, reflecting the strong circulation observed. The predicted stepwise energy dissipation showed the energy dissipation increase when the step number Ns increases. For the range of step height hs, tested, our results showed that energy dissipation increased with step height. The results from this study can be used to inform engineering design for steps with θ = 26.6° and provide estimates of the expected energy dissipation and residual energy.

Independent clinic-based evaluation of dual POCTs for screening for HIV and syphilis in men who have sex with men in Italy, Malta, Peru, and the United Kingdom

IntroductionGlobally, the incidence of HIV and syphilis can be reduced by the use of validated point of care tests (POCTs). As part of the WHO PRoSPeRo Network, we aimed to evaluate the performance, acceptability, and operational characteristics of two dual HIV/syphilis POCTs (Bioline HIV/Syphilis Duo (Abbott) and DPP® HIV-Syphilis assay (Chembio) for the screening of HIV and syphilis amongst men who have sex with men (MSM).Method and analysesA cross sectional study of 2,577 MSM in Italy, Malta, Peru, and the United Kingdom (UK) presenting to seven clinic sites, were enrolled. Finger prick blood was collected to perform POCTs and results compared with standard laboratory investigations on venepuncture blood. Acceptability and operational characteristics were assessed using questionnaires. Diagnostic meta-analysis was used to combine data from the evaluation sites.ResultsBased on laboratory tests, 23.46% (n = 598/2549) of participants were confirmed HIV positive, and 35.88% of participants (n = 901/2511) were positive on treponemal reference testing. Of all participants showing evidence of antibodies to Treponema pallidum, 50.56% (n = 455/900) were Rapid Plasma Reagin (RPR) test reactive. Of HIV positive individuals, 60.62% (n = 354/584) had evidence of antibodies to T. pallidum, and of these 60.45% (n = 214/354) exhibited reactive RPR tests indicating probable (co)infection. For Bioline POCT, pooled sensitivities and specificities for HIV were 98.95% and 99.89% respectively, and for syphilis were 73.79% and 99.57%. For Chembio pooled sensitivities and specificities for HIV were 98.66% and 99.55%, and for syphilis were 78.60% and 99.48%. Both tests can detect greater than 90% of probable active syphilis cases, as defined by reactive RPR and treponemal test results. These dual POCTs were preferred by 74.77% (n = 1,926) of participants, due to their convenience, and the operational characteristics made them acceptable to health care providers (HCPs).ConclusionsBoth the Bioline and the Chembio dual POCT for syphilis and HIV had acceptable performance, acceptability and operational characteristics amongst MSM in the PRoSPeRo network. These dual POCTs could serve as a strategic, more cost effective, patient and healthcare provider (HCP) friendly alternative to conventional testing; in clinical and other field settings, especially those in resource-limited settings.

Coexistence of Sickle Cell Thalassaemia with Overlapping Syndrome: A Case Report of Systemic Lupus Erythematosus and Autoimmune Hepatitis

This case report highlights a rare and unique occurrence: the simultaneous presence of sickle cell thalassaemia and overlapping syndrome, which involves systemic lupus erythematosus and autoimmune hepatitis. The coexistence of sickle cell disease with overlapping syndrome is exceptionally rare, with only a few documented cases in the literature, one of which involves sickle cell β-thalassaemia. Significantly, this case enhances understanding of the intricate relationship among these conditions, and offers valuable perspectives on how to clinically manage them. The authors present the case of a young male in his early 20s, who presented with haemolytic anaemia, jaundice, joint pain, and hepatomegaly. Extensive laboratory investigations, including serological markers, haemoglobin electrophoresis, and liver function tests, confirmed the coexistence of sickle cell thalassaemia, systemic lupus erythematosus, and autoimmune hepatitis. The treatment included O2 therapy, hydration, hydroxyurea, and antibiotics. After 4–5 days, the patient showed improvement, and at discharge, hydroxyurea and folic acid were continued. Significantly, considering the complex medical history of the patient, a decision was made to include a carefully considered, low-dose steroid regimen. The choice of a maintenance dose over an induction therapy was specifically made to mitigate potential complications, particularly the risk of vaso-occlusive crises in patients with sickle cell disease. This case report contributes to the understanding of concurrent manifestation of these complex conditions, and emphasises the importance of a comprehensive approach, early diagnosis, and timely management, to optimise patient outcomes in such intricate overlapping syndromes.

Bearing capacity and the settlement of foundation on biomodified coastal soil

Construction of the foundation on the marine the soil deposit is susceptible to excessive settlement and the construction of foundation is difficult. Although, the most common practice is to construct the raft foundation in these regions even for the low-rise building, excessive settlement can be observed in several building. So, in the present study, laboratory investigations have been done on the marine soil by modifying it with two different type of biopolymer such as Guar gum and Xanthan gum. The geotechnical properties of the soil modified with 1% and 1.5% biopolymer has been evaluated and the obtained properties has been used for settlement analysis. During the settlement analysis, the foundation soil model has been created as layered soil because the top layer has been replaced by biomodified soil. Several combi-nations have been created by varying the thickness of modified soil layer and the type and percentage of modifying agent. The settlement analysis has been performed in the settle 3D software and the biopolymer modification of soil has been found effective in controlling the foundation settlement.

Aetiology and Clinical Profile of Acute Pancreatitis in a Tertiary Care Hospital

Background: Acute Pancreatitis is a potentially serious condition with an overall mortality of 10%. Early diagnosis is important for its management. So clinician must carefully evaluate the patient with history, physical examination, laboratory tests and imaging studies before arriving a correct diagnosis. Death is more likely in certain subgroups of patients including elderly, co-morbidity, severe coexisting hospital acquired infection and organ dysfunction. Objectives: To assess aetiology and clinical profile of acute pancreatitis in a tertiary care hospital. Methods: A six-month Cross sectional study carried out at the department of Medicine, Comilla Medical College. Ethical approval from the institutional review board was obtained to ensure patient privacy and confidentiality. Results: The majority of patients are within the age group of 21-60 years (88.4%), with a higher proportion of males (71.2%) than females (28.8%). The most common clinical presentations were abdominal pain (95.6%) and nausea/vomiting (89.6%). Idiopathic (38%) and gallstone-related (38.4%) causes were the most common etiologies, while necrotizing pancreatitis (9.6%) and pancreatic pseudocysts (4.8%) were the most frequent complications. Regarding outcomes, a majority of patients experienced a favorable prognosis, with 64.4% recovering and being discharged. However, the complexity and severity of some cases were evident, as 17.6% of patients required referral to higher levels of care for further management. Additionally, a small percentage of patients left against medical advice (14.8%), and mortality was observed in 3.2% of cases. Laboratory investigations played a crucial role in diagnosing acute pancreatitis, and elevated levels of serum amylase (64.4%) and lipase (95.2%) were prominent diagnostic markers. Other abnormal laboratory parameters, such as elevated transaminase (90.8%) and C-reactive protein (86.4%), provided valuable insights for diagnosis and management. Conclusion: The study found acute pancreatitis with a wide range of clinical presentations and aetiologies. Abdominal pain is the most common symptom and gallstones are the most common causes. The study has evaluated the outcomes and complications of acute pancreatitis indicating that a significant proportion of cases had a favorable prognosis. A notable proportion required referral to higher levels of care, suggesting the complexity and severity of some instances of acute pancreatitis. A smaller percentage left against medical advice, and a few cases resulted in mortality. J Com Med Col Teachers’ Asso July 2023; 27(2): 67-74

Needs assessment of a pythiosis continuing professional development program.

Pythiosis is a rare disease with high mortality, with over 94% of cases reported from Thailand and India. Prompt diagnosis and surgery improves patient outcomes. Therefore, continuing professional development (CPD) is essential for early recognition. However, a needs assessment related to a pythiosis CPD program has not been performed. We conducted a needs assessment to develop a pythiosis CPD program. We conducted a survey study with 267 King Chulalongkorn Memorial Hospital residents (141 internal medicine (IM) residents and 126 surgery residents). A 30-item survey consisting of a knowledge assessment, demographic section, and an attitudes portion was distributed both electronically and via paper. The data was analyzed with descriptive and inferential statistics. Sixty-seven percent completed the survey (110/141 IM residents, 70/126 surgery residents). The mean score [95% confidence interval] on the knowledge assessment was 41.67% [39.64%-43.69%] across all objectives. The three domains with the highest scores were pythiosis risk factors (67.22% correct), microbiologic characteristics (50.83%), and radiographic interpretation (50.56%). The three domains with the lowest scores were laboratory investigation (15.00%), epidemiology (29.17%), and symptomatology (30.83%). Most participants noted that the program should be online with both synchronous and asynchronous sessions, with a preferred length of 60-90 minutes per session. The pythiosis CPD program should emphasize education regarding symptomatology, laboratory investigation, and epidemiology, all of which are critical for the early detection of pythiosis to decrease mortality from this devastating disease. Most respondents felt this program was necessary and should be implemented in a virtual blended format.

Role of ortho-pantho-graphic X-ray in the diagnosis of osteoporosis

Background: Osteoporosis affects people, especially old age, as postmenopausal women and remains unnoticeable until the patient presents with a fracture. Osteoporosis in human begins started with the loss of bone mass that increases with age, this is related to the decrease in bone density and an increase in porosity that will cause fractures in this osteoporotic bone. Objective was to assess the usefulness of orthopanthographic (OPG) in the early detection of osteoporosis. Methods: This is an analytic across-sectional test validation study, was done in Hawari Hospital-Benghazi, Libya which considered a referral General Hospital affiliated with University of Benghazi. This study was done during a period from March 2022 to July 2023. Sixty women were selected, divided into osteoporotic and non osteoporotic groups depending on the clinical and laboratory investigations under the supervision of an orthopedic consultant in the outpatient clinic. Panoramic radiographic X-rays were taken for evaluation and estimation of the mandibular cortex on the basis of (Mental index, Klemetti index, and Panoramic mandibular index) as a diagnostic tool to differentiate normal from osteoporotic patient, all three indices correlated significantly with bone mineral density and used as useful indicators for detected the osteopenia and osteoporosis. Results: We calculated values of the three indices (Mental index, Klemetti index, and Panoramic mandibular index) values were low especially in the osteoporotic group, as well the values of mental index and panoramic mandibular index were low compared with low bone mineral density of the patient and klemetti index with: C2, C3 categories (moderate and severe erosion) most common observed in the osteoporotic patient. Conclusions: Orthopanthographic X-rays provide a valuable tool for early detection and assessment of osteoporosis (preclinical stage) especially when characterized by a decrease in bone mineral density.

Nanoparticulate bioceramic putty suppresses osteoclastogenesis and inflammatory bone loss in mice via inhibition of TRAF6-mediated signalling pathways: A laboratory investigation.

This study aimed to determine the effects of iRoot BP Plus on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis invitro and inflammation-mediated bone resorption invivo and investigated the underlying molecular mechanisms. CCK-8 was performed to test cell viability in RANKL-induced RAW 264.7 cells and BMDMs in response to iRoot BP Plus. The effect of iRoot BP Plus on osteoclastogenesis was determined using TRAP staining and phalloidin staining, respectively. Pit formation assay was conducted to measure osteoclast resorptive capacity. Western blot and qPCR were performed to examine osteoclast-related proteins and gene expression, respectively. Western blot was also used to investigate the signalling pathways involved. For invivo experiments, an LPS-induced mouse calvarial bone resorption model was established to analyse the effect of iRoot BP Plus on bone resorption (n = 6 per group). At 7 days, mouse calvaria were collected and prepared for histological analysis. We identified that iRoot BP Plus extracts significantly attenuated RANKL-induced osteoclastogenesis, reduced sealing zone formation, restrained osteolytic capacity and decreased osteoclast-specific gene expression (p < .01). Mechanistically, iRoot BP Plus extracts reduced TRAF6 via proteasomal degradation, then suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs), blocked the nuclear translocation of c-Fos and diminished nuclear factor-κB (NF-κB) p65 and NFATc1 accumulation. Consistent with the invitro results, iRoot BP Plus extracts attenuated osteoclast activity thus protecting against inflammatory bone resorption invivo (p < .05), which was accompanied by a suppression of TRAF6, c-Fos, NFATc1 and cathepsin K expression. These findings provide valuable insights into the signalling mechanisms underlying nanoparticulate bioceramic putty-mediated bone homeostasis.

Association of Inflammatory Markers With Disease Progression and the Severity of COVID-19.

Introduction InDecember 2019, there was a massive outbreak of viral pneumonia, which had a high case fatality rate. Genetic sequencing of the virus showed similarity with severe acute respiratory syndrome coronavirus (SARS-CoV). It was later named novel coronavirus 2019 while the disease it caused was given the nomenclature of COVID-19. This deadly pneumonia outbreak was declared a pandemic by the World Health Organization (WHO). Aim To derive the strength of the correlation between blood levels of various inflammatory markers with the severity of COVID-19 pneumonia in patients affected with novel coronavirus 2019. Materials and methodology A prospective study was conducted on 300 confirmed cases of COVID-19 infection from August 2020 to July 2021 in SSG Hospital, Vadodara. Diagnosis of patients as confirmed cases of COVID-19 infection was done according to the WHO interim guidance for COVID-19. Their inflammatory markers were done for this study. All COVID-19-positive patients who had given negative consent for enrollment were excluded from the study. Patients were classified based on the severity of acute respiratory distress syndrome (ARDS). Comprehensive medical record information, encompassing biodata, clinical symptoms, comorbidities, and laboratory investigations, was systematically collected. Patients were given the standard treatment protocol as per guidelines. Patients were subjected to detailed investigations comprising complete blood counts and inflammatory markers like C-reactive protein (CRP), lactate dehydrogenase (LDH), serum ferritin, and D-dimer. Patients were further investigated by chest X-ray (posteroanterior view) or high-resolution computed tomography of the thorax. Results A total of 300 confirmed cases of COVID-19 infection were included in this study. Most of them were males (52%) with a mean age of 51 years and 48% were females with a mean age of 55 years. The majority of patients(40%) did not have ARDS, 23.3% of patients had mild, 16.7% of patients had moderate, and 20% of patients had severe ARDS. Higher CRP levels, serum ferritin, and serum D-dimer were significantly associated with the severity of COVID-19 infection as compared to those having no symptoms (p < 0.05). Increased levels were associated with severe clinical manifestations of COVID-19. The sensitivity of CRP is 69% and specificity is 100% as a diagnostic marker for COVID-19 pneumonia in terms of ARDS. The sensitivity of ferritin is 88% and specificity is 81% as a diagnostic marker for COVID-19 pneumonia in terms of ARDS. The sensitivity of D-dimer is 94% and specificity is 89% as a diagnostic marker for COVID-19 pneumonia in terms of ARDS. The sensitivity of LDH is 93% and specificity is 84% as a diagnostic marker for COVID-19 pneumonia in terms of ARDS. Conclusions Current evidence from our study showed that higher levels of inflammatory markers such as CRP, LDH, D-dimer, and ferritin are associated with the severity of COVID-19 in terms of ARDS and thus could be used as significant prognostic factors of the disease.These indicators might support clinical decisions to identify highfatality casesand poor diagnosis in the initial admission phase.

Resistance of a mixed bacterial culture isolated from bee dysbiosis to disinfectant in laboratory conditions

Disinfection is one of the components of preventive actions to prevent disease in animals by infectious agents. Through the elimination of agents of infectious diseases in the environment, it is able to interrupt the mechanisms of the epizootic process. For the development of beekeeping and obtaining quality and products, it is necessary to carry out activities in apiaries, which include disinfection. The introduction of new disinfectants in the field is possible after preliminary laboratory tests. The aim of our research objective to investigate the resistance of a mixed bacterial culture isolated from bees with the symptoms of dysbiosis to disinfectant under laboratory conditions. Bacteriological investigations carried out in Petri dishes using meat-peptone agar and Mueller-Hinton agar. The disinfectant diluted with distilled water at concentrations of 0.25 %, 0.5 %, 1,25 % and 2,5 %. On the Mueller Hinton agar, the bacterial elimination zones recorded at 1.25 % (11,6 ± 0,45 mm) and 2.5 % (12,4 ± 0,27 mm) concentration of disinfectant at 1 day of investigation, and 7,4 ± 0,27 mm (1,25 %), 11,2 ± 0,42 mm (2.5 %) at 72 hours of the experiment, respectively. In addition, the bacterial growth inhibition effect increased with experimental time and ranged from 24.0 ± 0.35 mm (0.5 %) to 28.2 ± 0.22 mm (2.5 %) on day 3 of the study. Bacteriostatic and bactericidal effects appeared to be less pronounced on meat-peptone agar. The highest diameters of inhibition of the processes of reproduction and development of microorganisms from mixed microbial association on this medium were recorded at 1.25 % and 2.5 % concentrations of the disinfectant at the 3rd day of the investigation with diameters of the zones of inhibition of growth 15.6 ± 0.45 mm and 26.4 ± 0.27 mm, respectively. The specificity of diffusion of the investigated active substance from the discs into the agar medium thickness was also noted. This effect has a varying effect on infectious agents in in vitro experiments. Thus bacteriological laboratory experiments should be performed on several culture media in purpose of obtaining accurate results. The analysis of the obtained results indicates the demonstration of antimicrobial effect of the investigated disinfectant against mixed bacterial culture in the form of bactericidal and bacteriostatic actions. Therefore, a promising direction of research for veterinary doctors and apiary business owners is the search for effective and efficient disinfectants. Laboratory investigation of the activity of a remedy are the first step before it is approbation.

Boolean modeling of breast cancer signaling pathways uncovers mechanisms of drug synergy.

Breast cancer is one of the most common types of cancer in females. While drug combinations have shown potential in breast cancer treatments, identifying new effective drug pairs is challenging due to the vast number of possible combinations among available compounds. Efforts have been made to accelerate the process with in silico predictions. Here, we developed a Boolean model of signaling pathways in breast cancer. The model was tailored to represent five breast cancer cell lines by integrating information about cell-line specific mutations, gene expression, and drug treatments. The models reproduced cell-line specific protein activities and drug-response behaviors in agreement with experimental data. Next, we proposed a calculation of protein synergy scores (PSSs), determining the effect of drug combinations on individual proteins' activities. The PSSs of selected proteins were used to investigate the synergistic effects of 150 drug combinations across five cancer cell lines. The comparison of the highest single agent (HSA) synergy scores between experiments and model predictions from the MDA-MB-231 cell line achieved the highest Pearson's correlation coefficient of 0.58 with a great balance among the classification metrics (AUC = 0.74, sensitivity = 0.63, and specificity = 0.64). Finally, we clustered drug pairs into groups based on the selected PSSs to gain further insights into the mechanisms underlying the observed synergistic effects of drug pairs. Clustering analysis allowed us to identify distinct patterns in the protein activities that correspond to five different modes of synergy: 1) synergistic activation of FADD and BID (extrinsic apoptosis pathway), 2) synergistic inhibition of BCL2 (intrinsic apoptosis pathway), 3) synergistic inhibition of MTORC1, 4) synergistic inhibition of ESR1, and 5) synergistic inhibition of CYCLIN D. Our approach offers a mechanistic understanding of the efficacy of drug combinations and provides direction for selecting potential drug pairs worthy of further laboratory investigation.

On the generality of the finite element modeling physical fields in biological systems by the multiscale smeared concept (Kojic transport model)

The biomechanical and biochemical processes in the biological systems of living organisms are extremely complex. Advances in understanding these processes are mainly achieved by laboratory and clinical investigations, but in recent decades they are supported by computational modeling. Besides enormous efforts and achievements in this modeling, there still is a need for new methods that can be used in everyday research and medical practice. In this report, we give a view of the generality of the finite element methodology introduced by the first author and supported by his collaborators. It is based on the multiscale smeared physical fields, termed as Kojic Transport Model (KTM), published in several journal papers and summarized in a recent book (Kojic et al., 2022) [1]. We review relevant literature to demonstrate the distinctions and advantages of our methodology and indicate possible further applications. We refer to our published results by a selection of a few examples which include modeling of partitioning, blood flow, molecular transport within the pancreas, multiscale-multiphysics model of coupling electrical field and ion concentration, and a model of convective-diffusive transport within the lung parenchyma. Two new examples include a model of convective-diffusive transport within a growing tumor, and drug release from nanofibers with fiber degradation.