RuBisCO activity assays: a simplified biochemical redox approach for in vitro quantification and an RNA sensor approach for in vivo monitoring.

BACKGROUND: Ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) is the most abundant soluble protein in nature. Extensive studies have been conducted for improving its activity in photosynthesis through approaches like protein engineering. Concurrently, multiple biochemical and radiolabeling assays have been developed for determining its activity. Although these existing assays yield reliable results, they require addition of multiple external components, rendering them less convenient and expensive. Therefore, in this study, we have developed two relatively cheaper, convenient, and easily reproducible assays for quantitative and qualitative estimation of RuBisCO activity. RESULTS: We simplified a contemporary NADH based spectrophotometric RuBisCO assay by using cyanobacterial cell lysate as the source for Calvin cycle enzymes. We analyzed the influence of inorganic carbon substrates, CO2 and NaHCO3, and varying protein concentrations on RuBisCO activity. Ribulose-1,5-bisphosphate (RuBP) consumption rates for the cultures grown under 5% CO2 were 5-7 times higher than the ones grown with 20 mM NaHCO3, at different protein concentrations. The difference could be due to the impaired activity of carbonic anhydrase in the cell lysate, which is required for the conversion of HCO3- to CO2. The highest RuBisCO activity of 2.13 nmol of NAD+/ µg of Chl-a/ min was observed with 50 µg of protein and 5% CO2. Additionally, we developed a novel RNA-sensor based fluorescence assay that is based on the principle of tracking the kinetics of ATP hydrolysis to ADP during the conversion of 3-phosphoglycerate (3-PG) to 1,3-bisphosphoglycerate (1,3-BPG) in the Calvin cycle. Under in vitro conditions, the fluorometric assay exhibited  ~ 3.4-fold slower reaction rate (0.37 min-1) than the biochemical assay when using 5% CO2. We also confirmed the in vivo application of this assay, where increase in the fluorescence was observed with the recombinant strain of Synechocystis sp. PCC 6803 (SSL142) expressing the ADP-specific RNA sensor, compared to the WT. In addition, SSL142 exhibited three-fold higher fluorescence when supplemented with 20 mM NaHCO3 as compared to the cells that were grown without NaHCO3 supplementation. CONCLUSIONS: Overall, we have developed a simplified biochemical assay for monitoring RuBisCO activity and demonstrated that it can provide reliable results as compared to the prior literature. Furthermore, the biochemical assay using 5% CO2 (100% relative activity) provided faster RuBP consumption rate compared to the biochemical assay utilizing 20 mM NaHCO3 (30.70% relative activity) and the in vitro fluorometric assay using 5% CO2 (29.64% relative activity). Therefore, the absorbance-based biochemical assay using 5% CO2 or higher would be suitable for in vitro quantification of the RuBisCO activity. On the other hand, the RNA-sensor based in vivo fluorometric assay can be applied for qualitative analysis and be used for high-throughput screening of RuBisCO variants. As RuBisCO is an enzyme shared amongst all the photoautotrophs, the assays developed in this study can easily be extended for analyzing the RuBisCO activities even in microalgae and higher plants.

Assessment of antiarthritic potential of Asparagus dumosus using formaldehyde and CFA-induced arthritic models in rats via modulation of oxidative stress biomarkers and mRNA expression of IL-1b, IL-6, RANKL, OPG, TNF-α and COX-2.

Medicinal plants play a pivotal role in the prevention of chronic non-communicable diseases including arthritis. Despite the traditional use of Asparagus dumosus in arthritis, it has not been studied yet for its effectiveness in arthritis. This study was aimed to explore the antiarthritic potential of A. dumosus in formaldehyde and complete Freund's adjuvant (CFA)-induced arthritic rats. Body weight, arthritic index, hepatic oxidative stress, hematological, biochemical and inflammatory markers were assessed using ELISA, whilst qRT-PCR studies were carried out for the mRNA expression of IL-1b, IL-6, RANKL, OPG, TNF-α and COX-2 genes. GCMS and HPLC analysis were performed to identify the secondary metabolites of A. dumosus. From day 8 to 28 post-administration of formaldehyde and CFA, oral administration of A. dumosus (600, 300 and 150 mg/kg) showed a noteworthy improvement (p < 0.001) in the body weights, immune organ weights, serum levels of rheumatoid (RA) factor, C-reactive protein, TNF-α and IL-6 levels in arthritic rats similar to the effect of piroxicam and methotrexate. Subsequently, the administration of A. dumosus to formaldehyde and CFA-challenged rats, caused a marked decrease (p < 0.001) in the mRNA expression of IL-1b, IL-6, OPG, RANKL, TNF-α and COX-2 genes in treated rats. Likewise, when assessed for antioxidant potential, A. dumosus produced a pronounced (p < 0.001) reduction in malondialdehyde (MDA) levels and hydrogen peroxide (H2O2) production, whilst a dose-dependent (p < 0.001) increase in catalase (CAT) and superoxide dismutase (SOD) activities was recorded. GCMS profiling of A. dumosus presented benzaldehyde, 3-hydroxy-4-methoxy-, 1-decanol and undecane as plant compositions, whereas HPLC fingerprinting displayed quercetin, benzaldehyde, 3-hydroxy-4-methoxy-, gallic acid and cinnamic acid as plants constituents. These results depict that A. dumosus possesses anti-arthritic effect mediated possibly through attenuation of arthritic indices, chronic inflammatory and oxidative stress biomarkers along with down-regulation in the mRNA expression of arthritic candid genes.

Characteristics of Immune Checkpoint Inhibitor-Associated Gastritis: Report from a Major Tertiary Care Center.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have increased our ability to treat an ever-expanding number of cancers. We describe a case series of 25 patients who were diagnosed with gastritis following ICI therapy. MATERIALS AND METHODS: This was a retrospective study involving 1712 patients treated for malignancy with immunotherapy at Cleveland Clinic from January 2011 to June 2019 (IRB 18-1225). We searched electronic medical records using ICD-10 codes for gastritis diagnosis confirmed on endoscopy and histology within 3 months of ICI therapy. Patients with upper gastrointestinal tract malignancy or documented Helicobacter pylori-associated gastritis were excluded. RESULTS: Twenty-five patients were found to meet the criteria for diagnosis of gastritis. Of these 25 patients, most common malignancies were non-small cell lung cancer (52%) and melanoma (24%). Median number of infusions preceding symptoms was 4 (1-30) and time to symptom onset 2 (0.5-12) weeks after last infusion. Symptoms experienced were nausea (80%), vomiting (52%), abdominal pain (72%), and melena (44%). Common endoscopic findings were erythema (88%), edema (52%), and friability (48%). The most common diagnosis of pathology was chronic active gastritis in 24% of patients. Ninety-six percent received acid suppression treatment and 36% of patients also received steroids with an initial median dose of prednisone 75 (20-80) mg. Within 2 months, 64% had documented complete resolution of symptoms and 52% were able to resume immunotherapy. CONCLUSION: Patients presenting with nausea, vomiting, abdominal pain, or melena following immunotherapy should be assessed for gastritis and if other causes are excluded, may require treatment as consideration for complication of immunotherapy.

Lung Cancer Treatment Advances in 2022.

The therapeutic landscape of lung cancer treatment is changing rapidly, and new data was presented at the recently concluded American Society of Clinical Oncology 2022 (ASCO22) meeting. We highlight studies of clinical relevance that represent significant updates in the current management of non-small cell lung cancer (SCLC) and small cell lung cancer (NSCLC). We summarize the updates in early-stage NSCLC, mutated and non-mutated advanced NSCLC as well as small cell lung cancer (SCLC), and discuss these advances in the context of the current clinical standard of care.

The extent of anticholinergic burden across an older Welsh population living with frailty: cross-sectional analysis of general practice records.

BACKGROUND: Anticholinergic medicines are associated with adverse outcomes for older people. However, little is known about their use in frailty. The objectives were to (i) investigate the prevalence of anticholinergic prescribing for older patients, and (ii) examine anticholinergic burden according to frailty status. METHODS: Cross-sectional analysis of Welsh primary care data from the Secure Anonymised Information Linkage databank including patients aged ≥65 at their first GP consultation between 1 January and 31 December 2018. Frailty was identified using the electronic Frailty Index and anticholinergic burden using the Anticholinergic Cognitive Burden (ACB) scale. Descriptive analysis and logistic regression were conducted to (i) describe the type and frequency of anticholinergics prescribed; and (ii) to estimate the association between frailty and cumulative ACB score (ACB-Sum). RESULTS: In this study of 529,095 patients, 47.4% of patients receiving any prescription medications were prescribed at least one anticholinergic medicine. Adjusted regression analysis showed that patients with increasing frailty had higher odds of having an ACB-Sum of >3 compared with patients who were fit (mild frailty, adj OR 1.062 (95%CI 1.061-1.064), moderate frailty, adj OR 1.134 (95%CI 1.131-1.136), severe frailty, adj OR 1.208 (95%CI 1.203-1.213)). CONCLUSIONS: Anticholinergic prescribing was high in this older population. Older people with advancing frailty are exposed to the highest anticholinergic burden despite being the most vulnerable to the associated adverse effects. Older people with advancing frailty should be considered for medicines review to prevent overaccumulation of anticholinergic medications, given the risks of functional and cognitive decline that frailty presents.

Association of a high-fat diet with I-FABP as a biomarker of intestinal barrier dysfunction driven by metabolic changes in Wistar rats.

BACKGROUND: The epithelial lining of the gut expresses intestinal fatty-acid binding proteins (I-FABPs), which increase in circulation and in plasma concentration during intestinal damage. From the perspective of obesity, the consumption of a diet rich in fat causes a disruption in the integrity of the gut barrier and an increase in its permeability. HYPOTHESIS: There is an association between the expression of I-FABP in the gut and various metabolic changes induced by a high-fat (HF) diet. METHODS: Wistar albino rats (n = 90) were divided into three groups (n = 30 per group), viz. One control and two HF diet groups (15 and 30%, respectively) were maintained for 6 weeks. Blood samples were thus collected to evaluate the lipid profile, blood glucose level and other biochemical tests. Tissue sampling was conducted to perform fat staining and immunohistochemistry. RESULTS: HF diet-fed rats developed adiposity, insulin resistance, leptin resistance, dyslipidemia, and increased expression of I-FABP in the small intestine compared to the control group. Increased I-FABP expression in the ileal region of the intestine is correlated significantly with higher fat contents in the diet, indicating that higher I-FABP expression occurs due to increased demand of enterocytes to transport lipids, leading to metabolic alterations. CONCLUSION: In summary, there is an association between the expression of I-FABP and HF diet-induced metabolic alterations, indicating that I-FABP can be used as a biomarker for intestinal barrier dysfunction.

Fabrication and characterization of a rapid-response, ultrasensitive dual-head interferometric pressure sensor.

A novel, to the best of our knowledge, dual-head Michelson interferometer-based pressure sensor with ultrahigh sensitivity and rapid response has been fabricated and optimized. The sensor consists of two diaphragm-based sensing heads, which operate on the principle of path-length variations of the interferometers due to the effect of pressure variation within the pressure channel. Pressure has been measured independently by the heads in terms of the fringe counts across two photodetectors with different sensitivities and working ranges. Head 1 had a linear working range of 0-6 psi and a sensitivity, resolution, and response time of 1295.04 fringe counts/psi, 25.74 µpsi, and 0.86 ms, respectively, which were 2.46, 2.46, and 0.86 times better than those of head 2. However, head 2 had a larger working range of 0-15 psi. Heads 1 and 2 yielded repeatable responses with negligible hysteresis and an average absolute error of 0.55% and 0.58%, respectively, compared to the predicted results. The proposed sensor has great potential for use in laboratory and industrial nonintrusive precise and fast-response pressure sensing applications.

Assessment of semen quality and anti-oxidative enzyme activity between bovine sex-sorted and non-sex-sorted frozen-thawed semen.

In the current study, the difference between the sex-sorted and non-sex-sorted frozen semen of Holstein Friesian breed cattle was investigated. Significant variation (p < .05) was found in the semen quality parameters such as motility; vitality; acrosome integrity rate; the anti-oxidative enzyme activity including GSH (glutathione); SOD (superoxide dismutase); CAT (catalase); GSH-Px (glutathione peroxidase) and the rate of fertilization. The results showed that the sperm acrosome integrity and motility of the non-sorted sperm were higher compared to sex-sorted sperm (p < .05). The linearity index and mean coefficient analysis revealed that the percentage of 'grade a' in sex-sorted sperm were significantly (p < .05) lower than non-sorted sperm. Interestingly, low SOD level and high CAT level was found in the non-sexed semen than in the sexed semen (p < .05). Furthermore, the GSH and GSH-Px activity in the sexed semen was found lower than the non-sexed semen (p < .05). In conclusion, sperm motility characteristics were lower in sex-sorted semen than in non-sex-sorted semen. This might be related to the complex process of sexed semen production, which could reduce sperm motility and movement characteristics, acrosomal integrity, CAT, SOD, GSH and GSH-Px, and finally lead to the decline in the fertilization rate.

The role of elective neck dissection in T1 and T2 nasal cavity squamous cell carcinomas.

PURPOSE: To evaluate the role of elective neck dissection (END) on oncological outcome in early-stage nasal cavity squamous cell carcinomas (SCCs). METHODS: In total, 87 patients with T1 (n = 59; 67.8%) and T2 (n = 28; 32.2%) SCCs were evaluated regarding performance of END, regional recurrences (RR) and its impact on cancer-specific survival (CSS). We further created a risk score based on T-classification, tumor subsite and grading to identify patients whom may benefit from END and calculated the corresponding numbers needed to treat (NNT) to prevent RR. RESULTS: Nine (10.3%) patients experienced RR of whom 3 (5.1%) were T1 and 6 (21.4%) T2 tumors (p = 0.042). All RR originated from moderately or poorly differentiated (G2-G3) SCCs of the nasal septum or vestibule. END was done in 15 (17.2%) patients and none of those experienced RR (p = 0.121). Onset of RR represented the worst prognostic factor for CSS (HR 23.3; p = 0.007) with a 5y-CSS of 44.4% vs. 97.3% (p < 0.001). RR occurred in none of the patients with no or low risk scores compared to 31.6% (6/19) in patients with high-risk scores (p = 0.006). Accordingly, three high-risk patients would need to undergo END (NNT 2.63) to prevent RR compared to a NNT of 8 for the whole cohort. CONCLUSIONS: Although rare, occurrence of RR significantly deteriorates outcome in early stage nasal cavity SCCs, which could be effectively reduced by performance of END. The importance of END is currently underestimated and our proposed risk score helps identifying those patients who will benefit from END.

A new nomogram to predict oncological outcome in laryngeal and hypopharyngeal carcinoma patients after laryngopharyngectomy.

BACKGROUND: To create nomograms for better prediction of the oncological outcome in advanced laryngeal (LxCAs) or hypopharyngeal (HpxCAs) cancer after laryngopharyngectomy. MATERIALS: 239 patients who underwent total laryngectomy or laryngopharyngectomy due to LxCA (52.7%) or HpxCA (47.3%) were included in this study. Based on clinical risk factors (tumor site, lymph node involvement, salvage setting), we created nomograms for prediction of disease-specific survival (DSS) and disease-free survival (DFS). RESULTS: HpxCAs showed a higher rate of lymph node involvement (p < 0.001), a 2.47-fold higher risk of a 2nd head and neck cancer (p = 0.009) and significantly worse loco-regional control rates (p = 0.003) compared to LxCAs. Positive neck nodes and salvage procedures were associated with significantly worse outcome. Nomograms demonstrated that hypopharyngeal tumors with positive neck nodes in salvage situations had the worst oncological outcome with a 5-year DSS of 15-20%. CONCLUSIONS: The oncological outcome is worse in hypopharyngeal carcinomas and could be easily quantified by our nomograms that are based on tumor site, lymph node involvement and salvage situation.

A cancer disparities curriculum in a hematology/oncology fellowship program.

BACKGROUND: After George Floyd's murder in 2020, the Center for Disease Control and Prevention (CDC) called systemic racism a public health crisis. This health crisis is connected to the already-documented racial and socioeconomic disparities in cancer care. Ensuring hematologists and oncologists are aware of these disparities through their medical education can help to address these disparities. METHODS: The authors implemented a healthcare disparities-focused curriculum in a Hematology/Oncology fellowship program during the 2020-2021 academic year at The Ohio State University Hematology/Oncology Fellowship Program. They implemented a pre- and post- survey to evaluate the efficacy of the program. RESULTS: Fifteen fellows completed the pre-curriculum survey and 14 completed the post-survey. Before the curriculum, 12 fellows (80%) noted a "Fair" or "Good" understanding of healthcare disparities, and 6 (40%) had a "Fair" understanding of disparities in clinical trials and access to novel therapies. Fourteen fellows (93.3%) had not previously participated in a research project focused on identifying or overcoming healthcare disparities. After the curriculum, 12 (85%) fellows strongly agreed or agreed that the information presented in the curriculum was useful for training as a hematologist/oncologist. Twelve fellows (85%) noted "Agree" or "Strongly Agree" that the information presented was relevant to their practice. Eleven fellows (92%) noted that they plan to incorporate healthcare disparities into a future research or clinical project. The majority of fellows, 11 (79%) recommended that the fellowship program continue to have a formal health disparities curriculum in the future. DISCUSSION/CONCLUSION: There is utility in incorporating cancer disparities education into a hematology/oncology academic curriculum. We recommend further analysis of such curricula to improve fellowship education and patient outcomes with these interventions.

Hybrid Deep Learning and Discrete Wavelet Transform-Based ECG Biometric Recognition for Arrhythmic Patients and Healthy Controls.

The intrinsic and liveness detection behavior of electrocardiogram (ECG) signals has made it an emerging biometric modality for the researcher with several applications including forensic, surveillance and security. The main challenge is the low recognition performance with datasets of large populations, including healthy and heart-disease patients, with a short interval of an ECG signal. This research proposes a novel method with the feature-level fusion of the discrete wavelet transform and a one-dimensional convolutional recurrent neural network (1D-CRNN). ECG signals were preprocessed by removing high-frequency powerline interference, followed by a low-pass filter with a cutoff frequency of 1.5 Hz for physiological noises and by baseline drift removal. The preprocessed signal is segmented with PQRST peaks, while the segmented signals are passed through Coiflets' 5 Discrete Wavelet Transform for conventional feature extraction. The 1D-CRNN with two long short-term memory (LSTM) layers followed by three 1D convolutional layers was applied for deep learning-based feature extraction. These combinations of features result in biometric recognition accuracies of 80.64%, 98.81% and 99.62% for the ECG-ID, MIT-BIH and NSR-DB datasets, respectively. At the same time, 98.24% is achieved when combining all of these datasets. This research also compares conventional feature extraction, deep learning-based feature extraction and a combination of these for performance enhancement, compared to transfer learning approaches such as VGG-19, ResNet-152 and Inception-v3 with a small segment of ECG data.

Anti-arthritic effects of geranium essential oil loaded chitosan nanoparticles in Freund's complete adjuvant induced arthritic rats through down-regulation of inflammatory cytokines.

Geranium essential oil (GEO) has been widely used in aromatherapy and traditional medicines. Nanoencapsulation, a novel technique has emerged to overcome the environmental degradation and less oral bioavailability of essential oils. This work was undertaken to encapsulate geranium essential oil in chitosan nanoparticles (GEO-CNPs) by ionic gelation technique and to explore anti-arthritic and anti-inflammatory potential in FCA-induced arthritic model in rats. The GEO was characterized by gas chromatography flame ionization detector (GCFID) and the nanosuspension was characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and X-rays diffraction (XRD). The Wistar albino rats (n = 32) were separated into four groups; Group 1 and 2 were considered as normal and arthritic controls. Group 3 was positive control that received oral celecoxib for 21 days while Group 4 was treated with oral GEO-CNPs after the induction of arthritis. Hind paw ankle joints diameters were weekly measured throughout the study and significant decrease (5.5 ± 0.5 mm) was observed in GEO-CNPs treatment group in comparison to arthritic group (9.17 ± 0.52 mm). Blood samples were drawn at end for evaluation of hematological, biochemical and inflammatory biomarkers. A significant upregulation of red blood cells and hemoglobin while downregulation of white blood cells, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP) and rheumatoid factor (RF) was observed. Ankles were transected for the histopathological and radiographic examination after animals were sacrificed which confirmed the alleviation of necrosis along cellular infiltration. It was concluded that GEO-CNPs were found to possess excellent therapeutic potential and promising candidates to reduce FCA-induced arthritis.

Quantifying the influence of urban road surface roughness on heavy metals pollution in road-deposited sediment's accumulation and wash-off.

Surface roughness is an important factor to consider when evaluating the loads of surface runoff caused by road-deposited sediment (RDS) wash-off and creating management solutions for this occurrence in metropolitan areas. Nevertheless, the implications of surface roughness on RDS development and escape remain unclear due to a paucity of experimental evidence distinguishing the significance of surface roughness. This research aimed to differentiate the impact of surface roughness on RDS accumulation and wash-off by employing paired asphalt, rainfall simulation designs, and concrete road surfaces. Our findings indicated that normal asphalt surfaces are typically rougher than typical concrete surfaces because they frequently contain deeper depressions. Compared to concrete surfaces, asphalt surfaces typically retain more RDS, a higher proportion of coarse aggregates, more RDS wash-off loads, and a lower proportion of wash-off. Surface roughness has varying impacts on the RDS motilities of particulates of varying sizes during rainy runoff; nevertheless, the settleable particles (40-150 µm) were more noticeably impacted by it. The first flush effect also seemed to be more pronounced on surfaces with lower roughness. Hence, surface roughness has a significant impact on how RDS builds on and is washed off of various road aspects.

Incidence of surgical site infection following open hernioplasty and comparison of infection rate among ventral and groin hernia repairs at a THQ hospital Lahore: a single surgeon experience.

OBJECTIVE: To determine the incidence of surgical site infection following open hernioplasty, and to compare the infection rate among ventral and groin hernia repairs. Method: The retrospective study was conducted from April 2 to November 30, 2021, at the Government Tehsil Headquarter Hospital Sabzazar, Lahore, Pakistan, and comprised data form June 2018 to December 2020 of patients with ventral abdominal and groin hernia. All patients underwent hernioplasty by a single consultant surgeon and were discharged within 2 days of surgery. Surgical-site infections were recorded on follow-up visits up to 30 days of operation, and were compared between ventral and groin hernia cases. Data was analysed using SPSS 22. RESULTS: Of the 218 patients with mean age 37.07±4.94 years, 117(53.67%) were males, 108(49.54%) smokers and 127(58.25%) hypertensive, while 110(50.45%) had ventral abdominal hernia and 108(49.54%) had groin hernias. Mean operative time and mean hospital stay were 56.53±6.20 minutes and 3.06±1.31days, respectively. Mean wound drainage in abdominal hernia cases was 8.99±2.02 days. Surgical site infection incidence following open hernioplasty was 2(0.91%). Infection rate among ventral abdominal and groin hernioplasty were 1(0.90%) and 1(0.92%) (p=0.50). CONCLUSIONS: Incidence of surgical site infection following open hernioplasty showed no significant difference between ventral abdominal and groin hernia repairs.

Phytochemical analysis and gastroprotective effect of Stellaria media (L.) Vill. methanolic extract on piroxicam-induced gastric ulcer in Wistar rats.

Stellaria media L. has traditionally been used to treat inflammatory and gastrointestinal ailments. This study aimed to phytochemically characterize the S. media extract and explore its anti-ulcer efficacy against piroxicam-induced stomach lesions in Wistar rats. Phytochemical analysis was performed and antioxidant capacity of extract was determined using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. In vivo, piroxicam (30mg/kg) was administered to induce gastric ulceration. Gastro protective effect of S. media extract was observed at 150, 300 and 450mg/kg, respectively. While omeprazole (20mg/kg) was used as a conventional anti-ulcer drug. After oral treatment for 14 days, stomach acidic secretions, ulcerogenic indices, hematological markers and oxidative stress parameters were assessed along with histological examination. The existence of polyphenol contents in S. media extract was confirmed in correlation to a marked DPPH inhibition (IC50 27.94µg/mL). S. media extract resulted in a dose-dependent elevation in gastric pH while a decrease in acid volume, acidity and ulceration. Also, S. media extract administration restored the impaired hematological markers (RBCs, Hb, WBCs and PLTs) and decreased oxidative stress by reducing oxidants (TOS and MDA) while raising antioxidants (TAC and CAT). Furthermore, gastric histological results corroborated the aforementioned findings. Conclusively, S. media could provide a promising protective effect against drug-induced gastric ulceration.

Using a smartphone on the move: do visual constraints explain why we slow walking speed?

Viewing one's smartphone whilst walking commonly leads to a slowing of walking. Slowing walking speed may occur because of the visual constraints related to reading the hand-held phone whilst in motion. We determine how walking-induced phone motion affects the ability to read on-screen information. Phone-reading performance (PRP) was assessed whilst participants walked on a treadmill at various speeds (Slow, Customary, Fast). The fastest speed was repeated, wearing an elbow brace (Braced) or with the phone mounted stationary (Fixed). An audible cue ('text-alert') indicated participants had 2 s to lift/view the phone and read aloud a series of digits. PRP was the number of digits read correctly. Each condition was repeated 5 times. 3D-motion analyses determined phone motion relative to the head, from which the variability in acceleration in viewing distance, and in the point of gaze in space in the up-down and right-left directions were assessed. A main effect of condition indicated PRP decreased with walking speed; particularly so for the Braced and Fixed conditions (p = 0.022). Walking condition also affected the phone's relative motion (p < 0.001); post-hoc analysis indicated that acceleration variability for the Fast, Fixed and Braced conditions were increased compared to that for Slow and Customary speed walking (p ≤ 0.05). There was an inverse association between phone acceleration variability and PRP (p = 0.02). These findings may explain why walking speed slows when viewing a hand-held phone: at slower speeds, head motion is smoother/more regular, enabling the motion of the phone to be coupled with head motion, thus making fewer demands on the oculomotor system. Good coupling ensures that the retinal image is stable enough to allow legibility of the information presented on the screen.

Prediction of basic drug exposure in milk using a lactation model algorithm integrated within a physiologically based pharmacokinetic model.

Medication use during breastfeeding can be a matter of concern due to unintended infant exposure to drugs through breast milk. The available information relating to the safety of most medications is limited and may vary. More precise information is needed regarding the safety to the newborn or infants of the medications taken by the mother during breastfeeding. Physiologically based Pharmacokinetic Model (PBPK) approaches can be utilized to predict the drug exposure in the milk of breastfeeding women and can act as a supporting tool in the risk assessment of feeding infants. This study aims to assess the predictive performance of an integrated 'log transformed phase-distribution' lactation model within a PBPK platform. The model utilizes the physicochemical properties of four basic drugs, namely tramadol, venlafaxine, fluoxetine, and paroxetine, and analyses the milk compositions to predict the milk-to-plasma (M/P) ratio. The M/P prediction model was incorporated within the Simcyp Simulator V20 to predict the milk exposure and to estimate the likely infant dose for these drugs. The PBPK models adequately predicted the maternal plasma exposure, M/P ratio, and the infant daily dose to within two-fold of the clinically observed values for all four compounds. Integration of the lactation model within PBPK models facilitates the prediction of drug exposure in breast milk. The developed model can inform the design of lactation studies and assist with the neonatal risk assessment after maternal exposure to such environmental chemicals or basic drugs which diffuse passively into the milk.

Hematopoietic Stem and Progenitor Cells (HSPCs) and Hematopoietic Microenvironment: Molecular and Bioinformatic Studies of the Zebrafish Models.

Hematopoietic stem cells (HSCs) reside in a specialized microenvironment in a peculiar anatomic location which regulates the maintenance of stem cells and controls its functions. Recent scientific progress in experimental technologies have enabled the specific detection of epigenetic factors responsible for the maintenance and quiescence of the hematopoietic niche, which has improved our knowledge of regulatory mechanisms. The aberrant role of RNA-binding proteins and their impact on the disruption of stem cell biology have been reported by a number of recent studies. Despite recent modernization in hematopoietic microenvironment research avenues, our comprehension of the signaling mechanisms and interactive pathways responsible for integration of the hematopoietic niche is still limited. In the past few decades, zebrafish usage with regards to exploratory studies of the hematopoietic niche has expanded our knowledge for deeper understanding of novel cellular interactions. This review provides an update on the functional roles of different genetic and epigenetic factors and molecular signaling events at different sections of the hematopoietic microenvironment. The explorations of different molecular approaches and interventions of latest web-based tools being used are also outlined. This will help us to get more mechanistic insights and develop therapeutic options for the malignancies.

Development of an assessment framework for the proposed Multi-Scalar Seasonally Amalgamated Regional Standardized Precipitation Evapotranspiration Index (MSARSPEI) for regional drought classifications in global warming context.

Drought hazard is one of the main consequences of global warming and climate change. Unlike other natural disasters, drought has complex climatic features. Therefore, accurate drought monitoring is a challenging task. This paper proposes a framework for assessing drought classifications at the regional level. The proposed framework provides a new drought monitoring indicator called Multi-Scalar Seasonally Amalgamated Regional Standardized Precipitation Evapotranspiration Index (MSARSPEI). MSARSPEI is an amalgam of the Standardized Precipitation Evapotranspiration (SPEI) (Vicente-Serrano et al., 2010) and Regionally Improved Weighted Standardized Drought Index (RIWSDI) (Jiang et al., 2020). In the proposed framework, the Boruta algorithm of feature selection is configured to ensemble monthly time series data of evaporation in various meteorological stations located in specific regions. Further, the framework suggests the standardization of the Cumulative Distribution Function (CDF) of K-Component Gaussian (K-CG) mixture distribution function for obtaining MSARSPEI data. The application of the proposed framework is based on seven different regions of Pakistan. For comparative analysis, this paper compared the performance of MSARSPE with SPEI using Pearson correlation. Outcomes associated with this research show that the proposed regional drought index has a strong correlation with the competing indicator in various time scales. In addition, the study assessed the spatial extent of various drought classifications under MSARSPEI. In summation, this research concludes that the choice of the MSARSPEI is rationally valid and more appropriate for the regional assessment of drought under the global warming scenario.