Triple threat: neutrophil ER stress, NETosis, airway inflammation escalation.

This report aims to propose the novel term 'neutrophil endoplasmic reticulum (ER) stress' (NERS). NERS explores the influence of neutrophil extracellular trap (NET) formation and exacerbation of respiratory ailments. This inquiry aims to advance comprehension in neutrophil biology and respiratory health.

Clinical manifestations and outcomes of COVID-19 in maintenance hemodialysis patients of a high infectious epidemic country: a prospective cross-sectional study.

Introduction: The outbreak of COVID-19 poses great challenges for patients on maintenance haemodialysis. Here, we reported the clinical characteristics and laboratory features of maintenance haemodialysis (MHD) patients with COVID-19 in Bangladesh. Methods: Altogether, 67 MHD patients were enroled in the study from two dedicated tertiary-level hospitals for COVID-19 after the prospective cross-sectional execution of selection criteria. Data were collected from medical records and interviews. Different statistical analysis was carried out in the data analysis. Results: The mean age was 55.0±9.9 years, with 40 males (59.7%). The mean dialysis duration was 23.4±11.5 months. The most common symptoms were fever (82.1%), cough (53.7%), and shortness of breath (55.2%), while the common comorbid condition was hypertension (98.5%), followed by diabetes (56.7%). Among MHD patients, 52.2% to 79.1% suffered from severe to critical COVID-19, 48 patients (71.6%) had 26-75% lung involvement on high resolution computed tomography of the chest, 23 patients (34.3%) did not survive, 20 patients (29.9%) were admitted to ICU, and nine patients (13.4%) needed mechanical ventilation. Patients who did not survive were significantly older (mean age: 63.0 vs. 50.86 years, P=0.0001), had significantly higher cardiovascular risk factors (69.6% vs. 43.2%, P=0.04), severe shortness of breath (82.6% vs. 40.9%, P=0.0001), and longer hospital stays (mean days: 17.9 vs. 13.0, P=0,0001) compared to the survivor group. The white blood cell count, C-reactive protein, lactate dehydrogenase, pro-calcitonin, and thrombocytopenia were significantly (P<0.0001) higher, while the albumin level was significantly lower (P=0.0001) in non-survivor compared to patients who survived. Conclusion: Maintenance haemodialysis patients had severe to critical COVID-19 and had a higher risk of non-survival if they were older and had comorbidities such as hypertension and diabetes. Therefore, MHD patients with COVID-19 need close monitoring to improve their outcomes.

Multidrug Resistance Urinary Tract Infection in Chronic Kidney Disease Patients: An Observational Study.

OBJECTIVE: To determine the presence of multidrug-resistant (MDR) urinary tract infections (UTI) and the MDR pattern of the bacterial isolates causing MDR UTI in chronic kidney disease (CKD) patients. METHODS: This cross-sectional study was conducted among 326 diagnosed CKD patients in the Department of Nephrology at Bangabandhu Sheikh Mujib Medical University (BSMMU). Purposive sampling technique was used, and data were collected from the respondents using a semi-structured questionnaire. From duly collected urine samples, identification of organisms and antibiotic susceptibility tests were done, maintaining proper procedure in the microbiology laboratory. RESULTS: The study population was predominantly female (60.1%). The outpatient department provided the majority of the respondents (75.2%). A history of UTI within the last six months was present among 74.2% of the respondents, and 59.2% had a history of taking antibiotics. Bacterial isolates were predominantly gram-negative (79.4%). Escherichia coli was the most prevalent bacterial isolate, present in 55.5% of the study population. Among the respondents, 64.7% were found to have MDR UTI, and among them, 81.5% were gram-negative, and 18.5% were gram-positive isolates. Among all the antibiotics tested, Colistin Sulphate, Polymyxin B, Cefoxitin, Vancomycin, and Linezolid had the highest (100%) sensitivity, followed by Meropenem, with 94.9% sensitivity. Among the gram-negative isolates, Acinetobacter and Enterobacter were most resistant to aminoglycoside, at 70% and 91.7%, respectively. E. coli, Klebsiella, Proteus, and Pseudomonas were most resistant to quinolone at 76.8%, 76.9%, 83.3%, and 66.7%, respectively. Among the gram-positive isolates, Enterococci and Staphylococcus aureus were most resistant to aminoglycoside, 81.5% and 88.9%, respectively. Streptococcus was found to be most resistant to cephalosporin (75.0%). There was a statistically significant (p < 0.05) relationship between MDR UTI, history of UTI, and previous antibiotic intake, and diabetic CKD. CONCLUSIONS: The prevalence of MDR UTI among CKD patients is considerably high. When treating UTI, choosing an appropriate antibiotic by urine culture and implementing a guideline on the rational use of antibiotics are essential to managing and preventing the development of MDR UTI.

Comparative Study of Frequency of Alveolar Osteitis, with and without using Platelet-Rich Fibrin in Mandibular Third Molar Surgery.

Introduction: Alveolar ostitis (AO) is the dissolution of blood clot due to enhanced local fibrinolysis and is caused by trauma to the jaw (direct) or because of bacterial involvement (indirect), which result in the activation of plasminogen pathway. Platelet-rich fibrin (PRF) is a platelet concentrate that comprises numerous autologous growth factors, and immune cells hence has the potential to expedite the healing process. The objective of the study was to determine the efficacy of PRF in the surgically extracted third molar in the context of its potential progress to AO. Materials and Methods: A total of 180 patients of 18-65 years with unilateral painful mandibular third molars due to caries, failed endodontics treatment, and pericoronitis were included in the study. Exclusion criteria were patients who were medically compromised, smokers, alcoholic, poor oral hygiene, third molar having associated periapical pathology, and receiving antibiotic regime in the last 2 weeks. Before starting surgical procedure, patients were randomly divided into two groups using lottery method. Group I received PRF in the extraction socket, while in Group II, the extraction site was left for normal healing as practiced in a standard procedure. Pain was assessed in terms of pain score, and it was recorded on a 10 mm visual analog scale on the first and third postoperative days. Results: Mean age of the patients was 41.35 ± 9.87 years. The mean age in Group I was 42.84 ± 10.52 years, and in Group II, it was 40.54 ± 9.52 years. Out of 180 patients, 90 (50.0%) were male and 90 (50.0%) were female, with a male-to-female ratio of 1 : 1. Frequency of AO following mandibular third molar surgery in Group I receiving PRF was 2.22% and in non-PRF group 12.22% (p-value = 0.010). Conclusion: The incidence of AO following mandibular third molar surgery was lower when PRF was used.

Comparison Of Efficacy Of Steroids Alone And Combination Of Steroids With Hyaluronidase On Mouth Opening In Oral Submucous Fibrosis Patients.

BACKGROUND: Eventually Oral submucous fibrosis causes pronounced stiffness and failure to open the mouth. Objectives are to determine compare the efficacy of intralesional steroids alone and combination of steroids with hyaluronidase on mouth opening in oral submucous fibrosis. METHODS: It was a prospective comparative cohort study. Total of 74 patients both male and female having history of pan chewing and limited mouth opening and burning sensations were included in the study. Informed consent was taken and divided into two groups. Patients of group 1 were managed with mixture of betamethasone 1 ml and hyaluronidase 1500 IU and patients of group 2 were treated with only steroid injection of betamethasone 1 ml given intralesional, both injections were given intralesional, by multiple puncture technique and once a week and continued for twelve weeks (3 months). And data compiled and analyzed in SPSS-20. RESULTS: The mean age of group 1 was 40.027±6.97 years, and mean age of Group 2 was 37.351±5.48 years. In both groups, the greatest number of cases aged from 31-59 years. Compared to females in both groups, the majority of patients were males. In 32 (86.4)% patients of group 1 showed efficacy compared with 18[43.2] patients in group 2 [p-0.000]. Conclusion: In this study Intralesional steroids with hyaluronidase injections are more efficient for opening the mouth in patients with oral sub-mucus fibrosis.

Chemical, Pharmacological and Computerized Molecular Analysis of Stem's Extracts of Bauhinia scandens L. Provide Insights into the Management of Diarrheal and Microbial Infections.

Bauhinia scandens L. (Family: Fabaceae) is commonly used to treat cholera, diarrhea, asthma, and diabetes disorder in integrative medicine. This study aimed to screen the presence of phytochemicals (preliminary and UPLC-QTOF-M.S. analysis) and to examine the pharmacological activities of Bauhinia scandens L. stems (MEBS) stem extracts. Besides, in silico study was also implemented to elucidate the binding affinity and drug capability of the selected phytochemicals. In vivo anti diarrheal activity was investigated in mice models. In vitro, antibacterial and antifungal properties of MEBS against several pathogenic strains were evaluated using the disc diffusion method. In addition, in silico study has been employed using Discovery studio 2020, UCFS Chimera, PyRx autodock vina, and online tools. In the anti-diarrheal investigation, MEBS showed a significant dose-dependent inhibition rate in all three methods. The antibacterial and antifungal screening showed a remarkable zone of inhibition, of the diameter 14-26 mm and 12-28 mm, by MEBS. The present study revealed that MEBS has remarkable anti-diarrheal potential and is highly effective in wide-spectrum bacterial and fungal strains. Moreover, the in silico study validated the results of biological screenings. To conclude, MEBS is presumed to be a good source in treating diarrhea, bacterial and fungal infections.

Chiral Magnetism and High-Temperature Skyrmions in B20-Ordered Co-Si.

Magnets with chiral crystal structures and helical spin structures have recently attracted much attention as potential spin-electronics materials, but their relatively low magnetic-ordering temperatures are a disadvantage. While cobalt has long been recognized as an element that promotes high-temperature magnetic ordering, most Co-rich alloys are achiral and exhibit collinear rather than helimagnetic order. Crystallographically, the B20-ordered compound CoSi is an exception due to its chiral structure, but it does not exhibit any kind of magnetic order. Here, we use nonequilibrium processing to produce B20-ordered Co_{1+x}Si_{1-x} with a maximum Co solubility of x=0.043. Above a critical excess-Co content (x_{c}=0.028), the alloys are magnetically ordered, and for x=0.043, a critical temperature T_{c}=328 K is obtained, the highest among all B20-type magnets. The crystal structure of the alloy supports spin spirals caused by Dzyaloshinskii-Moriya interactions, and from magnetic measurements we estimate that the spirals have a periodicity of about 17 nm. Our density-functional calculations explain the combination of high magnetic-ordering temperature and short periodicity in terms of a quantum phase transition where excess-cobalt spins are coupled through the host matrix.

Magneto-optical properties of topological insulator thin films with broken inversion symmetry.

We determine the optical response of ultrathin film topological insulators in the presence of a quantizing external magnetic field taking into account both hybridization between surface states, broken inversion symmetry and explicit time reversal symmetry breaking by the magnetic field. We find that breaking of inversion symmetry in the system, which can be due to interaction with a substrate or electrical gating, results in Landau level crossings and opening of additional optical transition channels that were previously forbidden. We show that by tuning the hybridization and symmetry breaking parameters, a transition from the normal to a topological insulator phase occurs with measureable signatures in both static (dc) and dynamic (optical) conductivity. Moreover, we find that these signatures in the optical Hall conductivity remain robust against a significant range of disorder strength.

Investigation of antinociceptive activity of methanolic extract of Persicaria orientalis leaves in rodents.

BACKGROUND: This study aims to evaluate the scientific basis of traditional application of Persicaria orientalis for reducing pain and inflammation. METHODS: An in vitro method was performed to investigate the presence of the anti-inflammatory activity of methanolic crude extract of P. orientalis. In addition, an in vivo study was conducted in which the hot-plate and tail immersion methods were applied to explore the acute effect of P. orientalis on analgesia. The potency to inhibit chronic inflammation in mice was justified by the carrageenan-induced paw edema and formalin-induced edema methods. For all in vivo testing in animal models (albino mice and rats), plant extract was given via the oral route at doses of 250 mg/kg and 500 mg/kg. RESULTS: The methanolic extract of P. orientalis produced a significant (p<0.001) inhibition of analgesia with a prolongation of pain response time by 61.80% at 500 mg/kg. The extract also exhibited a potential anti-inflammatory (56.99%) effect, which was also statistically significant (p<0.001). The present study suggests that the methanolic extract of P. orientalis has potential anti-inflammatory as well as analgesic activity and this extract is effective in the treatment of both acute and chronic pain. CONCLUSIONS: Our current study revealed pharmacological properties of the methanolic extract of P. orientalis and also gave a solid scientific platform against its traditional use. The protecting ability of P. orientalis against inflammatory stimuli may be due to phenolic or flavonoid compounds which we have found through phytochemical analysis.

Oral Manifestations of Osteopetrosis.

Osteopetrosis is a hereditary disorder of bone characterized by sclerosis of bone and decreased marrow spaces. Due to depressed marrow function, this disorder can cause anemia, hepatosplenomegaly, recurrent infections and osteomyelitis of jaw. Excessive bone deposition in skull base leads to narrowing of foramina and cranial nerve compression. Bone marrow transplantation is the only curative treatment. Other treatments, like interferon gamma, corticosteroids, parathormone and erythropoietin are also used for management. Transfusion of blood, debridement of wound and antibiotics is used to manage complications. Due to its rarity, it is always difficult to diagnose osteopetrosis. Proper diagnosis and treatment decreases the long-term sequelae of the disease.

Richness and cover of nontimber economic plants along altitude in temperate Himalayan forest-use types.

Pakistani Himalaya stretches over a wide range of altitudinal gradients and supports high diversity of medicinal plants that are an important source for rural livelihood. Altitudinal effects on ground vegetation have already been indicated but ground vegetation is also under severe threat of grazing and over collection. The present study investigated the effect of altitude on medicinal plants abundance in both old-growth and derived woodland forests. Each of the five line transects was selected in old-growth and derived woodland forests. Each line transect consisted of four plots distributed at four altitudinal levels (2200, 2300, 2400, and 2500 m asl). Species richness under derived woodland had shown strong negative correlation (r = -0.95) with altitude while it was found to be nonsignificant under old-growth. Cover of most of the species such as Veronica laxa (r = -0.95, P ≤ 0.05) had shown significant negative correlation with altitude under derived woodland. Cover abundance of some species like Valeriana jatamansi and Viola canescens has also shown significant negative correlation under old-growth forest. Derived woodland can decrease the cover abundance of valuable medicinal plants towards extension at higher altitudes. Thus, protection of the derived woodland could serve as a tool for the improvement of rural livelihood and ecological restoration.

Decreased cumulative access survival in arteriovenous fistulas requiring interventions to promote maturation.

BACKGROUND AND OBJECTIVES: New arteriovenous fistulas (AVF) are frequently unsuitable for hemodialysis because of AVF nonmaturation. Aggressive endovascular or surgical interventions are often undertaken to salvage nonmaturing AVFs. The effect of early interventions to promote AVF maturation on subsequent long-term AVF outcomes is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We evaluated 173 hemodialysis patients from two academic centers who received a new AVF. Of these, 96 (56%) required no further intervention, 54 (31%) required one intervention, and 23 (13%) required two or more interventions to achieve suitability for dialysis. We calculated AVF survival and frequency of postmaturation interventions in each group. RESULTS: Cumulative AVF survival (access cannulation to permanent failure) in patients with two or more versus one versus zero interventions before maturation was 68% versus 78% versus 92% at 1 year, 57% versus 71% versus 85% at 2 years, and 42% versus 57% versus 75% at 3 years. Using Cox regression analysis with interventions before maturation, age, sex, race, diabetes, peripheral vascular disease, access site, and obesity in the model, intervention before maturation (two or more) was the only factor associated with cumulative AVF survival. The number of interventions required to maintain patency after maturation was 3.51 ± 2.20 versus 1.37 ± 0.31 versus 0.76 ± 0.10 per year in patients with two or more versus one versus zero interventions before maturation. CONCLUSIONS: Compared with AVF that mature without interventions, AVF that require interventions have decreased cumulative survival and require more interventions to maintain their patency for hemodialysis.

Acute renal artery thrombosis treated with t-PA power-pulse spray rheolytic thrombectomy.

PURPOSE: To describe a new application of tissue plasminogen activator (t-PA) power-pulse spray rheolytic (pharmacomechanical) thrombectomy in the treatment of acute renal artery thrombosis. CASE REPORT: Acute renal artery thrombosis is a relatively rare, but serious condition in which it is imperative to restore perfusion as quickly as possible. Percutaneous pharmacomechanical thrombectomy technique was utilized to provide an effective means of restoring renal flow and function. We therefore present two unique cases of spontaneous and iatrogenic renal artery thromboses that were treated successfully with t-PA power-pulse spray rheolytic thrombectomy. CONCLUSION: t-PA Power-pulse spray rheolytic (pharmacomechanical) thrombectomy has the potential to be a useful means to restore perfusion and function in the setting of acute renal artery thrombosis.

In silico studies of urease inhibitors to explore ligand-enzyme interactions.

In continuation of our previous study on the urease inhibition by a number of chalcones, 2,3-dihydro-1,5-benzothiazepines and 2,3,4,5-tetrahydro-1,5-benzothiazepines, FlexX docking has been exploited to get a deeper insight into the mechanism of their inhibitory action. A comparison of the IC(50) values of the active compounds reveals that, of the three classes of compounds studied, 2,3-dihydro-1,5-benzothiazepines were the most potent urease inhibitors. An in silico examination of these compounds showed that the activity is related to the interaction of ligand with the nickel metallocentre, its interaction with two amino acid residues, Asp224 and Cys322, in addition to the orientation of rings A and B in the catalytic core of the enzyme. The most active compound 2,3-dihydro-1,5-benzothiazepine (4) anchor tightly through a network of interactions with Ni701 and Ni702. This includes a number of hydrogen bonds and hydrophobic contacts with the amino acid residues in its vicinity. For their reduced analogs, the difference in the activity of different diastereomers has been observed to be configuration-dependent. This may be ascribed mainly to the difference in the orientation of ring B of the two stereoisomers and the extent of their interaction with Asp224 and Cys322 present in the catalytic core of the enzyme.

Combinatorial synthesis, lead identification, and antitumor study of a chalcone-based positional-scanning library.

A 175-member chalcone library was designed and synthesized from seven differently substituted acetophenones (A(1)-A(7)) and 25 differently substituted aryl or heteroaryl aldehydes (B(1)-B(25)). Potential lead compounds were identified by deconvolution of a two-dimensional library matrix via positional scanning, and the members of the most-active sub-libraries were synthesized and screened against crown-gall tumors with the aid of the potato-disc assay. The resulting hits gave rise to significant antitumor activities, with no antibacterial effect on the tumor-producing bacterium Agrobacterium tumefaciens. Two identified lead structures, (2E)-3-(2-chlorophenyl)-1-phenylprop-2-en-1-one (A(1)B(9)) and the hydroxy analogue (2E)-3-(2-chlorophenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one (A(2)B(9)), are promising candidates to be developed into highly effective anticancer chemotherapeutics.