Lecanemab blocks the effects of the Aß/fibrinogen complex on blood clots and synapse toxicity in organotypic culture.

Proteinaceous brain inclusions, neuroinflammation, and vascular dysfunction are common pathologies in Alzheimer's disease (AD). Vascular deficits include a compromised blood-brain barrier, which can lead to extravasation of blood proteins like fibrinogen into the brain. Fibrinogen's interaction with the amyloid-beta (Aß) peptide is known to worsen thrombotic and cerebrovascular pathways in AD. Lecanemab, an FDA-approved antibody therapy for AD, clears Aß plaque from the brain and slows cognitive decline. Here, we show that lecanemab blocks fibrinogen's binding to Aß protofibrils, preventing Aß/fibrinogen-mediated delayed fibrinolysis and clot abnormalities in vitro and in human plasma. Additionally, we show that lecanemab dissociates the Aß/fibrinogen complex and prevents fibrinogen from exacerbating Aß-induced synaptotoxicity in mouse organotypic hippocampal cultures. These findings reveal a possible protective mechanism by which lecanemab may slow disease progression in AD.

The ß2-adrenergic receptor associates with CXCR4 multimers in human cancer cells.

While the existence and functional role of class C G-protein-coupled receptors (GPCR) dimers is well established, there is still a lack of consensus regarding class A and B GPCR multimerization. This lack of consensus is largely due to the inherent challenges of demonstrating the presence of multimeric receptor complexes in a physiologically relevant cellular context. The C-X-C motif chemokine receptor 4 (CXCR4) is a class A GPCR that is a promising target of anticancer therapy. Here, we investigated the potential of CXCR4 to form multimeric complexes with other GPCRs and characterized the relative size of the complexes in a live-cell environment. Using a bimolecular fluorescence complementation (BiFC) assay, we identified the ß2 adrenergic receptor (ß2AR) as an interaction partner. To investigate the molecular scale details of CXCR4-ß2AR interactions, we used a time-resolved fluorescence spectroscopy method called pulsed-interleaved excitation fluorescence cross-correlation spectroscopy (PIE-FCCS). PIE-FCCS can resolve membrane protein density, diffusion, and multimerization state in live cells at physiological expression levels. We probed CXCR4 and ß2AR homo- and heteromultimerization in model cell lines and found that CXCR4 assembles into multimeric complexes larger than dimers in MDA-MB-231 human breast cancer cells and in HCC4006 human lung cancer cells. We also found that ß2AR associates with CXCR4 multimers in MDA-MB-231 and HCC4006 cells to a higher degree than in COS-7 and CHO cells and in a ligand-dependent manner. These results suggest that CXCR4-ß2AR heteromers are present in human cancer cells and that GPCR multimerization is significantly affected by the plasma membrane environment.

A possible mechanism for the enhanced toxicity of beta-amyloid protofibrils in Alzheimer's disease.

The amyloid-beta peptide (Aß) is a driver of Alzheimer's disease (AD). Aß monomers can aggregate and form larger soluble (oligomers/protofibrils) and insoluble (fibrils) forms. There is evidence that Aß protofibrils are the most toxic form, but the reasons are not known. Consistent with a critical role for this form of Aß in AD, a recently FDA-approved therapeutic antibody targeted against protofibrils, lecanemab, slows the progression of AD in patients. The plasma contact system, which can promote coagulation and inflammation, has been implicated in AD pathogenesis. This system is activated by Aß which could lead to vascular and inflammatory pathologies associated with AD. We show here that the contact system is preferentially activated by protofibrils of Aß. Aß protofibrils bind to coagulation factor XII and high molecular weight kininogen and accelerate the activation of the system. Furthermore, lecanemab blocks Aß protofibril activation of the contact system. This work provides a possible mechanism for Aß protofibril toxicity in AD and why lecanemab is therapeutically effective.

Establishment of the mid-sagittal reference plane for three-dimensional assessment of facial asymmetry: a systematic review : Establishment of the mid-sagittal reference plane: a systematic review.

OBJECTIVE: To systematically review the literature for mid-sagittal plane establishment approaches to identify the most effective method for constructing the mid-sagittal plane for the evaluation of facial asymmetry. MATERIALS AND METHODS: Six electronic databases (PubMed, Medline (via Ovid), EMBASE (via Ovid), Cochrane Library, Web of Science, and Scopus) and grey literature were searched for the studies that computed the mid-sagittal reference plane three-dimensionally, using a combination of MeSH terms and keywords. The methodological quality and the level of evidence for the included studies were analyzed using QUADAS-2 and GRADE, respectively. RESULTS: The preliminary search yielded 6746 records, of which 42 articles that met the predefined inclusion criteria were included in the final analysis. All the included articles reported the construction of the mid-sagittal reference plane (MSP) using varied methods. The risk of bias and concerns regarding the applicability of the included studies were judged to be 'low'. The level of evidence was determined to be 'low' for the effectiveness of the technique and 'moderate' for the ease of clinical applicability. CONCLUSION: Despite methodological heterogeneity, this review substantiates the comparable efficacy of cephalometric and morphometric MSP construction methods. A fully automated morphometric MSP holds promise as a viable option for routine clinical use. Nevertheless, future prospective studies with an emphasis on the impact, accuracy, and clinical applicability of MSP construction techniques in cases of facial asymmetry are required. CLINICAL RELEVANCE: The present review will assist clinicians in selecting the most suitable method for MSP construction, leading to improved treatment planning and ultimately more favorable treatment outcomes.

Bark thickness and related parameters of tree species along an elevation transect leading to treeline in Central Himalaya.

Since treelines are generally fire-free, the trees growing there are expected to have thin bark, unless adaptation to other factors than fire results in the selection of a thick bark. Related to this is also higher proportional investment in inner bark in such an environment of infrequent fire. This study has considered stem bark thickness both in absolute and relative terms and also in the frame of the composition of outer and inner bark components of 20 tree species along an elevation transect (2100-3300 m) in high ranges of the Central Himalaya leading to treelines. The study species varied from 2.1 to 16.2 mm for total bark thickness and from 1.2 to 18.85% for relative bark thickness. The average absolute total bark thickness across the tree species decreased with elevation from forest to treeline, both when trees of all diameters (10.2 ± 0.84 mm for forest and 6.9 ± 1.79 mm for treeline) and those of the same stem diameter range (18-20 m) were compared (9.10 ± 1.30 mm for forest species and 6.38 ± 1.31 mm for treeline species). Nevertheless, the treeline bark thickness was similar to those of several forest communities considered to have comparatively thick bark. Like many other biological structures, bark carries out multiple functions; therefore, its thickness could be affected by more than one environmental factor. We suggest that the requirement of mechanical resistance to the snowfall, rainstorms, wind and adaptation to a high sunlight and UV radiations or storage of water, and non-structural carbohydrates could affect total, outer and inner bark thickness. Studies on these aspects in similar ecosystems may help understand the multi-functional attributes of the bark. For trees of comparable sizes (trees with 18-20 cm diameter at breast height) treeline species also had lower relative bark thickness (< 6%) than trees of forest below it (> 7%). The median proportion of inner bark of the total bark (70.5%) for our 20 species was more than that for savannas (~ 50%), exposed to frequent fire regime and similar to those of in cool sclerophyllous forests and temperate rain forests where fire return time is > 100 years. However, it was lower than the inner bark proportion reported for tropical rain forests. To conclude, in spite of a fire-free environment, the Himalayan treeline and adjoining forest species show mixed bark characters.

Comparison of laparoscopic port site skin closure techniques (CLOSA): transcutaneous suturing versus subcuticular sutures versus adhesive strips: a prospective single-blinded randomized control trial.

BACKGROUND: Cosmesis is an essential aspect of laparoscopic surgery. Various methods of skin closure techniques have been described. We conducted a study to evaluate the cosmesis and patient satisfaction with the scars three months after laparoscopic surgery using transcutaneous suture (TS) vs. adhesive strips (AS) and subcuticular suturing (SS). METHODS: A randomized, controlled, prospective study was conducted at AIIMS, Bhubaneswar. The included patients were randomly assigned among the three arms. The time for skin closure was measured. Wounds were assessed till discharge, at 14 days, one month, and three months. Cosmesis was measured by the Hollander Wound evaluation scale (HWES) for each incision separately, and patient satisfaction by a 10- point Visual analog scale (VAS). RESULTS: One hundred six patients were assessed for eligibility, and 90 patients were randomized. Three-month follow-up data was obtained from 83 patients (92.22%). Baseline characteristics were similar among the groups. Cosmetic outcome was assessed in 312 incisions across 83 patients, and 206 (66.03%) incisions had an HWE Score of 0, but there was no significant difference (p = 0.86). Patient satisfaction was highest in the TS group (TS = 1.29, SS = 1.79, AS = 2.04, p = 0.03). Time for skin closure was the least in the AS arm (41.4 secs, p = 0.00). Skin dehiscence was significantly more in the AS arm. Four (4.44%) patients had port site infections. CONCLUSION: This study demonstrates that skin closure by transcutaneous, subcuticular, or adhesive strip methods had comparable cosmetic outcomes at three months. However, the transcutaneous closure method showed better patient satisfaction and minimal post-operative complications.

On-demand (SOS) analgesia through Transversus Abdominis Plane (TAP) catheter route for post-operative pain relief in Emergency Laparotomies-a non-randomised interventional study (STAPLE trial).

INTRODUCTION: This study aimed to compare the efficacy and safety of on-demand bupivacaine infusion via transversus abdominis plane (TAP) catheter in emergency laparotomy patients. METHODS: A non-randomised interventional study was conducted on patients undergoing emergency midline laparotomy. The intervention group received an on-demand infusion of 10 ml 0.5% bupivacaine through TAP catheters, whilst the control group received standard analgesic care. The primary outcome was the amount of rescue analgesic consumption. Secondary outcomes included the post-operative, measured by visual analogue scores (VAS), side effects, time to first flatus, post-operative nausea and vomiting, and pulmonary complications. RESULTS: One-hundred-twenty patients (58 in the TAP-SOS group, 62 in the control group) were included in the final analysis. The TAP-SOS group showed significantly reduced rescue analgesic requirement by 91% (p < 0.001) and lower VAS scores at 3, 6, 12, and 24 h (adjusted p < 0.00). Time to out-of-bed mobilisation was significantly shorter in the TAP-SOS group by 12.47 h (p < 0.001), and post-operative pulmonary complications were lower by 75% (p < 0.05). There were no significant differences in bowel recovery, catheter-related complications, or post-operative morbidity. No incidences of catheter-site infection were reported on follow-up; however, the catheter tip-culture was positive in 3 (5.17%) patients. CONCLUSION: On-demand bupivacaine infusion through a TAP catheter effectively reduced post-operative pain and opioid requirements in emergency laparotomy patients without complications. If an epidural is not an option, the TAP-SOS approach can be a helpful adjunct in implementing the ERAS protocol in an emergency since it allows for early ambulation and better pain management.

Comparison of surgical site infection (SSI) between negative pressure wound therapy (NPWT) assisted delayed primary closure and conventional delayed primary closure in grossly contaminated emergency abdominal surgeries: a randomized controlled trial.

PURPOSE: NPWT has been tried in many surgical fields, including colorectal, thoracic, vascular, and non-healing wounds, for the prevention of SSI. However, its efficacy in the prevention of SSI-grade IV closed abdominal wounds is yet to be explored. METHODS: All patients with grade IV abdominal wounds were included in the study. They were randomized into the conventional arm and the VAC arm after confirming the diagnosis intra-operatively. The sheath was closed, and the skin was laid open in the postoperative period. In the VAC arm, the NPWT dressing was applied on postoperative day (POD)-1 and removed on POD-5. In the conventional arm, only regular dressing was done postoperatively. The skin was closed with a delayed primary intention on POD-5 in both arms. The sutures were removed after 7 to 10 days of skin closure. RESULTS: The rate of SSI (10% in the VAC arm vs. 37.5% in the conventional arm, p-value = 0.004) was significantly lower in the VAC arm, as were the rates of seroma formation (2.4% in the VAC arm vs. 20% in the conventional arm, p = 0.014) and wound dehiscence (7.3% vs. 30%, p = 0.011). The conventional arm had a significant delay in skin closure beyond POD5 due to an increased rate of SSI, which also led to a prolonged hospital stay (5 days in the VAC arm vs. 6.5 days in the conventional arm, p-value = 0.005). CONCLUSION: The VAC dressing can be used routinely in grade IV closed abdominal wounds to reduce the risk of SSI and wound dehiscence.

Clinical Effectiveness of Elexacaftor/Tezacaftor/Ivacaftor in People with Cystic Fibrosis: A Clinical Trial.

Rationale: The cystic fibrosis (CF) modulator drug, elexacaftor/tezacaftor/ivacaftor (ETI), proved highly effective in controlled clinical trials for individuals with at least one F508del allele, which occurs in at least 85% of people with CF. Objectives: PROMISE is a postapproval study to understand the broad effects of ETI through 30 months' clinical use in a more diverse U.S. patient population with planned analyses after 6 months. Methods: Prospective, observational study in 487 people with CF age 12 years or older with at least one F508del allele starting ETI for the first time. Assessments occurred before and 1, 3, and 6 months into ETI therapy. Outcomes included change in percent predicted FEV1 (ppFEV1), sweat chloride concentration, body mass index (BMI), and self-reported respiratory symptoms. Measurements and Main Results: Average age was 25.1 years, and 44.1% entered the study using tezacaftor/ivacaftor or lumacaftor/ivacaftor, whereas 6.7% were using ivacaftor, consistent with F508del homozygosity and G551D allele, respectively. At 6 months into ETI therapy, ppFEV1 improved 9.76 percentage points (95% confidence interval [CI], 8.76 to 10.76) from baseline, cystic fibrosis questionnaire-revised respiratory domain score improved 20.4 points (95% CI, 18.3 to 22.5), and sweat chloride decreased -41.7 mmol/L (95% CI, -43.8 to -39.6). BMI also significantly increased. Changes were larger in those naive to modulators but substantial in all groups, including those treated with ivacaftor at baseline. Conclusions: ETI by clinical prescription provided large improvements in lung function, respiratory symptoms, and BMI in a diverse population naive to modulator drug therapy, using existing two-drug combinations, or using ivacaftor alone. Each group also experienced significant reductions in sweat chloride concentration, which correlated with improved ppFEV1 in the overall study population. Clinical trial registered with www.clinicaltrials.gov (NCT NCT04038047).

Defending the Defender: Adversarial Learning Based Defending Strategy for Learning Based Security Methods in Cyber-Physical Systems (CPS).

Cyber-Physical Systems (CPS) are prone to many security exploitations due to a greater attack surface being introduced by their cyber component by the nature of their remote accessibility or non-isolated capability. Security exploitations, on the other hand, rise in complexities, aiming for more powerful attacks and evasion from detections. The real-world applicability of CPS thus poses a question mark due to security infringements. Researchers have been developing new and robust techniques to enhance the security of these systems. Many techniques and security aspects are being considered to build robust security systems; these include attack prevention, attack detection, and attack mitigation as security development techniques with consideration of confidentiality, integrity, and availability as some of the important security aspects. In this paper, we have proposed machine learning-based intelligent attack detection strategies which have evolved as a result of failures in traditional signature-based techniques to detect zero-day attacks and attacks of a complex nature. Many researchers have evaluated the feasibility of learning models in the security domain and pointed out their capability to detect known as well as unknown attacks (zero-day attacks). However, these learning models are also vulnerable to adversarial attacks like poisoning attacks, evasion attacks, and exploration attacks. To make use of a robust-cum-intelligent security mechanism, we have proposed an adversarial learning-based defense strategy for the security of CPS to ensure CPS security and invoke resilience against adversarial attacks. We have evaluated the proposed strategy through the implementation of Random Forest (RF), Artificial Neural Network (ANN), and Long Short-Term Memory (LSTM) on the ToN_IoT Network dataset and an adversarial dataset generated through the Generative Adversarial Network (GAN) model.

The reliability of analytical reference lines for determining esthetically pleasing lip position: An assessment of consistency, sensitivity, and specificity.

INTRODUCTION: This study aimed to identify a simple yet reliable soft-tissue parameter for the clinical determination of esthetic lip position by investigating the most consistent reference lines and assessing their sensitivity and specificity. METHODS: A total of 5745 records from Chinese patients aged >18 years were screened. In part I of the study, lateral view photographs of 96 subjects (33 males, 63 females) with esthetic facial profiles were selected. The profile esthetics of each photograph was first scored by 52 dental students, followed by 97 laypeople on a 5-point attractiveness scale. For the top 25% of photographs with the highest score for each sex (8 males, 16 females), the consistency of 6 commonly used reference lines were assessed to determine the esthetic lip position. In part II of the study, lip positions relative to Steiner's (S) and Ricketts' (E) lines in the profile photographs of 86 patients (43 males, 43 females) deemed to have an esthetically unpleasing profile were compared with those in 86 Chinese movie star idols (43 males, 43 females). RESULTS: In part I of the study, the S, E, and Burstone's (B) lines exhibited the lowest standard deviations for the upper and lower lips. B line was excluded from further analysis because of its higher mean absolute values, and S and E lines were used for the subjective assessment in part II of the study. In part II, the S line showed a sensitivity of 86.0% and 86.0% and a specificity of 81.4% and 83.7% for males and females, respectively. In contrast, the E line presented a sensitivity of 88.4% and 93.0% and a specificity of 79.1% and 74.4% for males and females, respectively. CONCLUSIONS: S, E, and B lines were the most consistent soft-tissue parameters among both sexes; however, because of the smaller absolute values, the S line would be more convenient among the 3 for a quick clinical assessment of lip position. Moreover, the performance of both S and E lines was similar among both sexes, which supports using these lines in assessing the esthetic lip position.

131I dose coefficients for a reference population using age-specific models.

Age-specific dose coefficients are required to assess internal exposure to the general public. This study utilizes reference age-specific biokinetic models of iodine to estimate the total number of nuclear disintegrations ã(rS,τ) occurring in source regions (rS) during the commitment time (τ). Age-specific S values are estimated for 35 target regions due to131I present in 22rSusing data from 10 paediatric reference computational phantoms (representing five ages for both sexes) published recently by the International Commission of Radiation Protection (ICRP). Monte Carlo transport simulations are performed in FLUKA code. The estimated ã(rS,τ) and S values are then used to compute the committed tissue equivalent dose HT(τ) for 27 radiosensitive tissues and dose coefficients e(τ) for all five ages due to inhalation and ingestion of131I. The derived ã(rS,τ) values in the thyroid source are observed to increase with age due to the increased retention of iodine in the thyroid. S values are found to decrease with age, mainly due to an increase in target masses. Generally, HT(τ) values are observed to decrease with age, indicating the predominant behaviour of S values over ã(rS,τ). On average, ingestion dose coefficients are 63% higher than for inhalation in all ages. The maximum contribution to dose coefficients is from the thyroid, accounting for 96% in the case of newborns and 98%-99% for all other ages. Furthermore, the estimated e(τ) values for the reference population are observed to be lower than previously published reference values from the ICRP. The estimated S, HT(τ) and e(τ) values can be used to improve estimations of internal doses to organs/whole body for members of the public in cases of131I exposure. The estimated dose coefficients can also be interpolated for other ages to accurately evaluate the doses received by the general public during131I therapy or during a radiological emergency.

Testing the effects of combining azithromycin with inhaled tobramycin for P. aeruginosa in cystic fibrosis: a randomised, controlled clinical trial.

RATIONALE: Inhaled tobramycin and oral azithromycin are common chronic therapies in people with cystic fibrosis and Pseudomonas aeruginosa airway infection. Some studies have shown that azithromycin can reduce the ability of tobramycin to kill P. aeruginosa. This trial was done to test the effects of combining azithromycin with inhaled tobramycin on clinical and microbiological outcomes in people already using inhaled tobramycin. We theorised that those randomised to placebo (no azithromycin) would have greater improvement in forced expiratory volume in one second (FEV1) and greater reduction in P. aeruginosa sputum in response to tobramycin. METHODS: A 6-week prospective, randomised, placebo-controlled, double-blind trial testing oral azithromycin versus placebo combined with clinically prescribed inhaled tobramycin in individuals with cystic fibrosis and P. aeruginosa airway infection. RESULTS: Over a 6-week period, including 4 weeks of inhaled tobramycin, the relative change in FEV1 did not statistically significantly differ between groups (azithromycin (n=56) minus placebo (n=52) difference: 3.44%; 95% CI: -0.48 to 7.35; p=0.085). Differences in secondary clinical outcomes, including patient-reported symptom scores, weight and need for additional antibiotics, did not significantly differ. Among the 29 azithromycin and 35 placebo participants providing paired sputum samples, the 6-week change in P. aeruginosa density differed in favour of the placebo group (difference: 0.75 log10 CFU/mL; 95% CI: 0.03 to 1.47; p=0.043). CONCLUSIONS: Despite having greater reduction in P. aeruginosa density in participants able to provide sputum samples, participants randomised to placebo with inhaled tobramycin did not experience significantly greater improvements in lung function or other clinical outcomes compared with those randomised to azithromycin with tobramycin.

Identification and validation of a key genomic region on chromosome 6 for resistance to Fusarium stalk rot in tropical maize.

KEY MESSAGE: A key genomic region was identified for resistance to FSR at 168 Mb on chromosome 6 in GWAS and haplotype regression analysis, which was validated by QTL mapping in two populations. Fusarium stalk rot (FSR) of maize is an economically important post-flowering stalk rot (PFSR) disease caused by Fusarium verticillioides. The pathogen invades the plant individually, or in combination with other stalk rot pathogens or secondary colonizers, thereby making it difficult to make accurate selection for resistance. For identification and validation of genomic regions associated with FSR resistance, a genome-wide association study (GWAS) was conducted with 342 maize lines. The panel was screened for FSR in three environments using standard artificial inoculation methodology. GWAS using the mixed linear model corrected for population structure and kinship was done, in which 290,626 SNPs from genotyping-by-sequencing were used. A total of 7 SNPs, five on chromosome 6 showing strong LD at 168 Mb, were identified to be associated with FSR. Haplotype regression analysis identified 32 haplotypes with a significant effect on the trait. In a QTL mapping experiment in two populations for validating the identified variants, QTLs were identified with confidence intervals having overlapped physical coordinates in both the populations on chromosome 6, which was closely located to the GWAS-identified variants on chromosome 6. It makes this genomic region a crucial one to further investigate the possibility of developing trait markers for deployment in breeding pipelines. It was noted that previously reported QTLs for other stalk rots in maize mapped within the same physical intervals of several haplotypes identified for FSR resistance in this study. The possibility of QTLs controlling broad-spectrum resistance for PFSR in general requires further investigation.

Non-invasive diagnostic potential of microRNA-203 in liquid biopsy of urothelial carcinoma of bladder.

Increased CD44 antigen activity has been reported in recurrent cases of UBC. To date, no reliable biomarker is available with high significance and specificity for non-invasive detection of UBC. This study aimed to identify a CD44-linked microRNAs (miRNAs) (miR-9, miR-34a, miR-203) for non-invasive diagnosis of bladder cancer from other urinary tract malignancies. The expression of CD44-linked miRNAs was examined in serum, urine, and tissue specimens of Indian UBC patients (N = 25). For this purpose, healthy subjects (N = 25) and benign prostatic hyperplasia (BPH) (N = 10) patients were taken as controls. The relative expression of miRNAs was analyzed in serum, urine, and tissue samples using real-time quantitative reverse transcription PCR (qRT-PCR). The diagnostic potential of these miRNAs was accessed by plotting ROC curve. Increased miR-9 expression was observed in serum of UBC patients than healthy and BPH controls. In UBC patients, miR-34a expression was lower than healthy controls but non-significant as compared to BPH. miR-203 expression was considerably higher in serum of UBC patients but non-significant as compared to BPH controls. miR-203 was found to be considerably higher in urine samples from UBC patients as compared to BPH and healthy controls. The diagnostic potential of these miRNAs was evaluated using the ROC curve. Higher miR-203 levels in the urine of Indian UBC patients demonstrate its non-invasive diagnostic ability out of the three miRNAs studied. Our results characterize the non-invasive diagnostic potential of CD44-linked miR-203 in the urine of Indian UBC patients, which could be utilized in clinical settings in future after validation in larger patient cohort.

Sulphur in Jharia and Raniganj coalfields: Chemical fractionation and its environmental implications.

In coal, total sulphur content is not the only important factor for the industry, but also the forms of sulphur and their distributions should be considered before utilizing any coal for a particular use. In Jharia and Raniganj coalfields, sulphur is present in the forms of organic sulphur (OS), pyritic sulphur (PS), and sulphate sulphur (SS). In this perspective, the present study aims to know the different forms of sulphur in coking and non-coking coals of Jharia and Raniganj coalfields. Twenty samples were collected from both the mining areas. The total sulphur content in coking coals varied from 0.28% to 0.55% and in non-coking coals it varied from 0.33% to 0.54%. The distribution pattern of sulphur showed that PS and OS are dominating in both the coalfields. The OS in Jharia field varied from 0.13% to 0.47%, and in Raniganj coalfield it varied from 0.19% to 0.41%. This depicts that both the coalfields were formed under freshwater condition. Similarly, PS varied from 0.01% to 0.21% and from 0.06% to 0.29%, and SS varied from 0.0052% to 0.01% and 0.005%-0.02% in the above fields, respectively. It is noticed that the content of sulphate sulphur is less than 0.1 wt%, which is lower than other forms of sulphur. In the past two decades, sulphur emission has increased with the increase of thermal power plants due to more demand for power, which is one of the causes of global warming. During coal combustion, H2S and SOx, are produced and that can react with O2 and H2O to form H2SO3, H2SO4 or H2S. Thus, sulphur release can respond within the ecosystem in the form of acidic precipitation that may acidify and affect lakes and streams, sub-surface water and historical monuments. In India, coal consumption and ecological contaminations are increasing day by day due to the rapid energy consumption. Therefore, special attention should be given to adopt clean coal technologies though the coal contains less sulphur.

An antibody against HK blocks Alzheimer's disease peptide ß-amyloid-induced bradykinin release in human plasma.

Bradykinin is a proinflammatory factor that mediates angioedema and inflammation in many diseases. It is a key player in some types of hereditary angioedema and is involved in septic shock, traumatic injury, Alzheimer's disease (AD), and stroke, among others. Activation of the plasma contact system leads to elevated levels of plasma kallikrein, which cleaves high molecular weight kininogen (HK) to release bradykinin. Drug development for bradykinin-meditated pathologies has focused on designing inhibitors to the enzymes that cleave HK (to prevent bradykinin release) or antagonists of endothelial bradykinin receptors (to prevent downstream bradykinin action). Here we show a strategy to block bradykinin generation by using an HK antibody that binds to HK, preventing its cleavage and subsequent bradykinin release. We show that this antibody blocks dextran sodium sulfate-induced HK cleavage and bradykinin production. Moreover, while the pathogenic AD peptide ß-amyloid (Aß)42 cleaves HK and induces a dramatic increase in bradykinin production, our HK antibody blocked these events from occurring. These results may provide strategies for developing treatments for bradykinin-driven pathologies.

Three-dimensional assessment of facial asymmetry in Class III subjects. Part 1: a retrospective study evaluating postsurgical outcomes.

OBJECTIVE: The present study aimed to determine the site and severity of maxillomandibular asymmetry before and after orthognathic surgery in asymmetric patients. MATERIALS AND METHODS: Presurgery and postsurgery cone beam computed tomography (CBCT) data of 21 facial asymmetry patients (7 males and 14 females, mean age: 23.0 ± 3.36 years) with soft tissue chin deviation ≥ 3 mm who had undergone bimaxillary surgery were evaluated. Seven midline and twenty bilateral hard tissue landmarks were identified for the evaluation of facial asymmetry and outcomes were assessed against age- and gender-matched control subjects. RESULTS: In the asymmetry group, bilateral landmarks exhibited significant deviation in the mandible and midface regions. Before surgery, asymmetry was more severe at the mandibular midline and sites close to it, in the asymmetry group. Bimaxillary surgery proved to be highly effective, with a significant correction of the menton to a clinically normal value (2.90 mm, p < 0.001). After surgery, significant residual asymmetry was observed at the mental foramen (p = 0.001) in the R-L direction. Moreover, significant asymmetry persisted at the sigmoid notch (p = 0.001) in the S-I direction. CONCLUSIONS: Mandibular midline landmarks and chin peripheral regions contribute significantly to overall facial asymmetry characteristics. Despite significant correction after bimaxillary surgery, asymmetry persisted at several sites, thereby requiring secondary correction. Comprehensive 3D presurgical planning is central for asymmetry correction in a single surgery. CLINICAL RELEVANCE: The present study specifies the location of residual asymmetry sites and advocates the correction of those sites during initial surgery.

A Novel Decentralized Blockchain Architecture for the Preservation of Privacy and Data Security against Cyberattacks in Healthcare.

Nowadays, in a world full of uncertainties and the threat of digital and cyber-attacks, blockchain technology is one of the major critical developments playing a vital role in the creative professional world. Along with energy, finance, governance, etc., the healthcare sector is one of the most prominent areas where blockchain technology is being used. We all are aware that data constitute our wealth and our currency; vulnerability and security become even more significant and a vital point of concern for healthcare. Recent cyberattacks have raised the questions of planning, requirement, and implementation to develop more cyber-secure models. This paper is based on a blockchain that classifies network participants into clusters and preserves a single copy of the blockchain for every cluster. The paper introduces a novel blockchain mechanism for secure healthcare sector data management, which reduces the communicational and computational overhead costs compared to the existing bitcoin network and the lightweight blockchain architecture. The paper also discusses how the proposed design can be utilized to address the recognized threats. The experimental results show that, as the number of nodes rises, the suggested architecture speeds up ledger updates by 63% and reduces network traffic by 10 times.

Clinical Profile and Prevalence of H Pylori, Iga-Ttg, and Spectrum of Duodenal Abnormalities in Non Ulcer Dyspepsia.

The Rome IV criterion for a diagnosis of NUD is chronic or recurrent epigastric pain within the last 3 months and an onset of symptoms at least 6 months prior to presentation. The term functional Dyspepsia and idiopathic dyspepsia are often used as well. Symptoms include ulcer-like dyspepsia; gastroparetic-like (nausea, early satiety, and post-prandial pain), and undifferentiated. Pathogenesis of NUD is not completely known yet. Several mechanisms have been proposed to be responsible for these symptoms. Although there is strong evidence of an association between H. pylori infection and NUD, Celiac Disease and NUD. Being a tropical country, the prevalence of infections is parasitic cause. Dyspepsia is likely to be more in India. However, the present data from India as scares in literature. Hence the present study was planned to decipher the clinical profile, prevalence of H. pylori, IgA tTG, spectrum of duodenal biopsy abnormalities in NUD patients. MATERIAL: This Descriptive Observational study was carried out in the Gastro Enterology center in GOI research institute from August 2020 to March 2021. Initially, 200 dyspepsia patients were selected. 50 patients were excluded due to various reasons. Finally, 150 patients who met the Rome 4 criteria for NUD/Functional Dyspepsia were recruited. The inclusion criteria were patients above 18 years of age, dyspepsia for >/- 6 months, and no evidence of underlying malignancy, pan gastritis, previous gastric ulcers, and pancreatitis. The patients underwent routine blood investigations like haemogram and biochemistry, Rapid Urease Test (RUT), Upper Gastro-Intestinal Endoscopy, Duodenal Biopsy, and Serum IgA-tTG antibody. OBSERVATION: The mean age was 46.3 yrs. +/- 14.12 yrs, of which 49.3% were females and 50.70% were males. The prevalence of Epigastric Pain Syndrome (EPS) was found in 37.3%, Post Prandial Distress Syndrome (PDS) in 30.7%, and 32% had both EPS+PDS. 38% of the NUD patients were positive on Rapid Urease Test (RUT) suggesting H. pylori infection. 88.7% of NUD patients were IgA-tTG antibody negative and 11.3% serologically positive. The Duodenal biopsy was normal in 48% of patients, 21.3% had mild inflammation/duodenitis, 8% chronic duodenitis and 22.7% had various grades of Celiac Disease (as per Marsh Grading). These 22.7% showing evidence of Celiac Disease on histopathological examination showed Marsh Grade 1 in 12.7%, Grade-2 in 2%, Grade 3A in 6.7%, and Grade 3B in 1.3%. Only 17.6% of biopsy positive had IgA-tTG antibody positivity but only 4% of total cases were positive for both biopsy and IgA-tTG antibody (p-value 0.05). Eosinophilic infiltration in duodenum common in NUD patients. It was observed that 17.33% (26/150) NUD patients had duodenal eosinophilia. Further, look for the association of duodenal eosinophilia with various diseases. 33.33% (19/57) H. pylori patients had duodenal eosinophilia with p-value < 0.001. It was also observed that 7.52% (7/93) others like normal individual, Chronic duodenitis, mild inflammation/ duodenitis had Duodenal eosinophilia. CONCLUSION: The prevalence of H. pylori and IgA-tTG antibodies in non-ulcer dyspepsia patients was 38% and 11.3% respectively. The spectrum of Duodenum biopsy abnormalities in NUD patients included mild inflammation/ duodenitis, Chronic duodenitis, and Celiac Disease. 22.7% of NUD patients had various degrees of celiac disease morphology on D2 biopsy and only 17.6% of these biopsy positive patients were positive for IgA-tTG. Only 4% of total NUD patients were positive for both biopsy and IgA-tTG antibody labeled as Celiac Disease (CeD). There is a significant association between H. pylori and duodenal eosinophilia.