[Double to avoid trouble? An experience of double Memokath(tm) 044TW stents insertion for multiple anterior urethral stricture in hospital universiti sains Malaysia].

For the past two decades urethral stenting became more popular for treatment of urethral stricture. However, urethral stents still not widely used in view of good outcome from urethroplasty surgery. The MemokathTM stent is the most popular in this field. It is manufactured from a biocompatible alloy of nickel and titanium. Most of the studies have been limited to single stent insertion, and no studies done for double stents insertion. An 81-year-old man with history of multiple anterior urethral strictures since 2013. He underwent internal urethrotomy in the same year but failed and was on urinary catheter since then. The MemokathTM 044TW was the option due to patient has multiple comorbidities. The micturating cystourethrogram (MCUG) and ascending urethrogram showed multiple anterior urethral strictures. He underwent direct visual internal urethrotomy and two MemokathTM stents inserted in the whole length of urethral. However, one year after procedure, he had recurrent lower urinary tract symptoms and ultimately developed acute urinary retention (AUR). Patients stents were removed endoscopically. During endoscopic removal, he had encrustation of both stents that causing obstructive symptoms. He is under our follow-up with no recurrent urinary retention or urosepsis with satisfactory uroflowmetry. Stent encrustation is known to be a common late complication of urethral stents. Stent encrustation should be suspected if patient comes with obstructive symptoms. Endoscopic is shown to be the best method to detect the cause of obstructed stent.

Kinetic Spinodal Instabilities in the Mott Transition in V_{2}O_{3}: Evidence from Hysteresis Scaling and Dissipative Phase Ordering.

We present the first systematic observation of scaling of thermal hysteresis with the temperature scanning rate around an abrupt thermodynamic transition in correlated electron systems. We show that the depth of supercooling and superheating in vanadium sesquioxide (V_{2}O_{3}) shifts with the temperature quench rates. The dynamic scaling exponent is close to the mean field prediction of 2/3. These observations, combined with the purely dissipative continuous ordering seen in "quench-and-hold" experiments, indicate departures from classical nucleation theory toward a barrier-free phase ordering associated with critical dynamics. Observation of critical-like features and scaling in a thermally induced abrupt phase transition suggests that the presence of a spinodal-like instability is not just an artifact of the mean field theories but can also exist in the transformation kinetics of real systems, surviving fluctuations.

Design and synthesis of cis-restricted benzimidazole and benzothiazole mimics of combretastatin A-4 as antimitotic agents with apoptosis inducing ability.

A series of colchicine site binding tubulin inhibitors were designed and synthesized by the modification of the combretastatin A-4 (CA4) pharmacophore. The ring B was replaced by the pharmacologically relevant benzimidazole or benzothiazole scaffolds, and the cis-configuration of the olefinic bond was restricted by the incorporation of a pyridine ring which is envisaged by the structural resemblance to a tubulin inhibitor like E7010. These compounds were evaluated for their antiproliferative activity on selected cancer cell lines and an insight in the structure activity relationship was developed. The most potent compounds (6c and 6l) demonstrated an antiproliferative effect comparable and superior to that of CA4 (GI50 up to 40nM). Mitotic cell cycle arrest in G2/M phase revealed the disruption of microtubule dynamics that was confirmed by tubulin polymerization assays and immunocytochemistry studies at the cellular level. The molecular docking studies suggested that the binding of these mimics at the colchicine site of the tubulin is similar to that of combretastatin A-4.

Design, synthesis and antiproliferative activity of the new conjugates of E7010 and resveratrol as tubulin polymerization inhibitors.

A new class of (E)-N-phenyl-3-styrylpyridin-2-amine conjugates were designed and synthesized on the basis of E7010 and resveratrol scaffolds. These conjugates were evaluated for their antiproliferative activity in four human cancer cell lines with GI50 values ranging from 2.1 µM to 20 µM. Two of the conjugates RSV-1 and RSV-11 were found to possess 13-fold higher GI50 values than resveratrol and 1 to 2 fold higher GI50 values than E7010 against the human cervical HepG2 cancer line. They displayed high potency and selectivity in a panel of NCI 60 human cancer cell lines. Based on the GI50 values against the panel of 60 NCI cancer cell lines and dock scores from the molecular modelling studies, we selected RSV-1 and RSV-11 for tubulin polymerization and mechanistic studies. Furthermore, RSV-1 and RSV-11 compounds inhibited the assembly of tubulin by strongly binding to the colchicine-binding site. The G2/M-phase is arrested in HepG2 cells as assessed by flow cytometry. Structure based studies, western blotting and immunofluorescence experiments demonstrated that RSV-1 and RSV-11 depolymerize microtubules in the HepG2 cell line, resulting in an accumulation of G2/M cells.

Interactome analyses of Salmonella pathogenicity islands reveal SicA indispensable for virulence.

BACKGROUND: Serovars of Salmonella enterica, namely Typhi and Typhimurium, reportedly, are the bacterial pathogens causing systemic infections like gastroenteritis and typhoid fever. To elucidate the role and importance in such infection, the proteins of the Type III secretion system of Salmonella pathogenicity islands and two component signal transduction systems, have been mainly focused. However, the most indispensable of these virulent ones and their hierarchical role has not yet been studied extensively. RESULTS: We have adopted a theoretical approach to build an interactome comprising the proteins from the Salmonella pathogeneicity islands (SPI) and two component signal transduction systems. This interactome was then analyzed by using network parameters like centrality and k-core measures. An initial step to capture the fingerprint of the core network resulted in a set of proteins which are involved in the process of invasion and colonization, thereby becoming more important in the process of infection. These proteins pertained to the Inv, Org, Prg, Sip, Spa, Ssa and Sse operons along with chaperone protein SicA. Amongst them, SicA was figured out to be the most indispensable protein from different network parametric analyses. Subsequently, the gene expression levels of all these theoretically identified important proteins were confirmed by microarray data analysis. Finally, we have proposed a hierarchy of the proteins involved in the total infection process. This theoretical approach is the first of its kind to figure out potential virulence determinants encoded by SPI for therapeutic targets for enteric infection. CONCLUSIONS: A set of responsible virulent proteins was identified and the expression level of their genes was validated by using independent, published microarray data. The result was a targeted set of proteins that could serve as sensitive predictors and form the foundation for a series of trials in the wet-lab setting. Understanding these regulatory and virulent proteins would provide insight into conditions which are encountered by this intracellular enteric pathogen during the course of infection. This would further contribute in identifying novel targets for antimicrobial agents.

Synthesis and anticancer potential of benzothiazole linked phenylpyridopyrimidinones and their diones as mitochondrial apoptotic inducers.

A series of benzothiazole linked phenylpyridopyrimidinones (8a-g) and their diones (9a-g) have been designed, synthesized and evaluated for their anticancer activity. Among the series one of the conjugate 8b showed significant cytotoxicity against human cervical cancer cell line ME-180 with IC50 value of 4.01µM. This compound was tested on the cell cycle perturbations and DNA damage. Flow cytometry analysis revealed that the compound 8b showed drastic cell cycle perturbations due to concentration dependent increase in the sub-G0 phase in ME-180 cell line. DNA fragmentation and Hoechst staining reveals that this compound induced cell death by apoptosis. Further caspase-3 and loss of mitochondrial membrane potential suggested that the compound induces cell death by apoptosis.

Synthesis of 2-anilinopyridine dimers as microtubule targeting and apoptosis inducing agents.

A series of 2-anilinopyridine dimers have been synthesized and evaluated for their anticancer potential. Most of the compounds have showed significant growth inhibition of the cell lines tested and compound 4d was most effective amongst the series displaying a GI50 of 0.99 µM specifically against the prostate cancer cell line (DU145). Studies to understand the mechanism of action of 4d indicates that it disrupts microtubule dynamics by inhibiting tubulin polymerization thereby arresting the cell cycle in G2/M phase. Competitive colchicine binding assay suggests that 4d binds into colchicine binding site of the tubulin. Further from some detailed biological studies like mitochondrial membrane potential, caspase-3 assay, DNA fragmentation analysis and Annexin V-FITC assay it is evident that 4d induces apoptosis.Molecular modeling studies provide an insight into the binding modes of 4d with colchicine binding site of tubulin and the data obtained correlates with the antiproliferative activity.

Perceptions of vulnerable roadway users on autonomous vehicle regulations.

INTRODUCTION: Development and implementation of autonomous vehicle (AV) related regulations are necessary to ensure safe AV deployment and wide acceptance among all roadway users. Assessment of vulnerable roadway users' perceptions on AV regulations could inform policymakers the development of appropriate AV regulations that facilitate the safety of diverse users in a multimodal transportation system. METHOD: This research evaluated pedestrians' and bicyclists' perceptions on six AV regulations (i.e., capping AV speed limit, operating AV in manual mode in the sensitive areas, having both pilot and co-pilot while operating AVs, and three data-sharing regulations). In addition, pedestrians' and bicyclists' perceptions of testing AVs in public streets were evaluated. Statistical testing and modeling techniques were applied to accomplish the research objectives. RESULTS: Compared to the other AV regulations assessed in this research, strong support for AV-related data sharing regulations was identified. Older respondents showed higher approval of AV testing on public roadways and less support for regulating AVs. AV technology familiarity and safe road sharing perceptions with AVs resulted in lower support for AV regulations. CONCLUSIONS: Policymakers and AV technology developers could develop effective educational tools/resources to inform pedestrians and bicyclists about AV technology reliability and soften their stance, especially on AV regulations, which could delay technology development. PRACTICAL APPLICATIONS: The findings of this research could be used to develop informed AV regulations and develop policies that could improve pedestrians' and bicyclists' attitudes/perceptions on regulating AVs and promoting AV technology deployments.

A systematic review of the real-world effectiveness and economic and humanistic outcomes of selected oral antipsychotics among patients with schizophrenia in the United States: Updating the evidence and gaps.

BACKGROUND: Schizophrenia is a chronic, relapsing, and burdensome psychiatric disorder affecting approximately 0.25%-0.6% of the US population. Oral antipsychotic treatment (OAT) remains the cornerstone for managing schizophrenia. However, nonadherence and high treatment failure lead to increased disease burden and medical spending. Cost-effective management of schizophrenia requires understanding the value of current therapies to facilitate better planning of management policies while addressing unmet needs. OBJECTIVE: To review existing evidence and gaps regarding real-world effectiveness and economic and humanistic outcomes of OATs, including asenapine, brexpiprazole, cariprazine, iloperidone, lumateperone, lurasidone, olanzapine/samidorphan, paliperidone, and quetiapine. METHODS: We conducted a literature search using PubMed, American Psychological Association PsycINFO (EBSCOhost), and the Cumulative Index of Nursing and Allied Health Literature from January 2010 to March 2022 as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. English-language articles describing adults with schizophrenia receiving at least 1 of the selected OATs and reporting real-world effectiveness, direct or indirect costs, humanistic outcomes, behavioral outcomes, adherence/persistence patterns, or product switching were identified. RESULTS: We identified 25 studies from a total of 24,190 articles. Real-world effectiveness, cost, and adherence/persistence outcomes were reported for most OATs that were selected. Humanistic outcomes and product switching were reported only for lurasidone. Behavioral outcomes (eg, interpersonal relations and suicide ideation) were not reported for any OAT. The key economic outcomes across studies were incremental cost-effectiveness ratios, cost per quality-adjusted life-years, and health care costs. In studies that compared long-acting injectables (LAIs) with OATs, LAIs had a higher pharmacy and lower medical costs, while total health care cost was similar between LAIs and OATs. Indirect costs associated with presenteeism, absenteeism, or work productivity were not reported for any of the selected OATs. Overall, patients had poor adherence to OATs, ranging between 20% and 61% across studies. Product switching did not impact the all-cause health care costs before and after treatment. CONCLUSIONS: Our findings showed considerable gaps exist for evidence on behavioral outcomes, humanistic outcomes, medication switching, and adherence/persistence across OATs. Our findings also suggest an unmet need regarding treatment nonadherence and lack of persistence among patients receiving OATs. We identified a need for research addressing OATs' behavioral and humanistic outcomes and evaluating the impact of product switching in adults with schizophrenia in the United States, which could assist clinicians in promoting patient-centered care and help payers understand the total value of new antipsychotic drugs.

Biofilm formation, agr typing and antibiotic resistance pattern in methicillin-resistant Staphylococcus aureus isolated from hospital environments.

Biofilm development significantly enhances the virulence of methicillin-resistant Staphylococcus aureus (MRSA), leading to severe infections and decreased susceptibility to antibiotics, especially in strains associated with hospital environments. This study examined the occurrence of MRSA, their ability to form biofilms, agr typing, and the antibiotic resistance profiles of biofilm-forming MRSA strains isolated from environmental surfaces at Mymensingh Medical College Hospital (MMCH). From 120 swab samples, 86 (71.67%) tested positive for S. aureus. MRSA was identified in 86 isolates using the disk diffusion technique, and by polymerase chain reaction (PCR), 56 (65.1%) isolates were confirmed to carry the mecA gene. The Crystal Violet Microtiter Plate (CVMP) test revealed that 80.35% (45 isolates) were biofilm-forming and 19.6% (11 isolates) were non-biofilm-forming. Out of 45 biofilm producer isolates 37.5% and 42.9% isolates exhibited strong and intermediate biofilm-forming characteristics, respectively. Molecular analysis revealed that 17.78% of MRSA isolates carried at least one gene related to biofilm formation, specifically icaA, icaB, and icaD genes were discovered in 13.33%, 8.89%, 6.67% of the MRSA isolates, respectively. In agr typing, the most prevalent group was agr I (71.11%), followed by group III (17.78%) and group II (11.11%). Group IV was not detected. The distribution of agr gene groups showed a significant difference among biofilm-forming isolates (p < 0.05). In agr group I, 18.75% of isolates carried the icaA gene, 12.5% carried the icaB gene, and 9.37% carried the icaD gene. Biofilm-forming genes were not detected in any of the isolates from agr groups II or III. There are no statistically significant differences between agr groups and the presence of these genes (p > 0.05). Antibiotic resistance varied significantly among agr groups, with agr group I displaying the highest resistance, agr group II, and agr group III exhibiting the least resistance (p < 0.05). Seventy-three (73.3%) of the isolates were multi-drug resistant, with agr group I displaying nineteen MDR patterns. The occurrence of MRSA in hospital environments and their capacity to form biofilm raises concerns for public health. These findings support the importance of further research focused on agr quorum sensing systems as a basis for developing novel antibacterial agents.

Prevalence and Associated Factors of Liver Enzyme Abnormalities Among Bangladeshi Women: A Cross-Sectional Study.

Background Liver enzyme abnormalities can indicate underlying liver health issues and are influenced by various factors. This study aimed to investigate the prevalence of liver enzyme abnormalities and their associated factors among nonpregnant and nonlactating (NPNL) women in Bangladesh. Methodology A cross-sectional study was conducted among 251 NPNL Bangladeshi women. Data on demographic, socioeconomic, and health-related variables were collected. Logistic regression analysis was used to determine the association between liver enzyme abnormalities and associated factors. Results The prevalence of liver enzyme abnormalities among participants was determined, with associated factors such as age, body mass index (BMI), monthly income, and food security status examined. Elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were observed in 54 (21.5%) and 47 (18.7%) of participants, respectively, with 116 (46.2%) exhibiting an AST/ALT ratio exceeding 1.00. Food insecurity was significantly associated with a higher prevalence of elevated ALT levels (24.4% vs. 8.7%, P = 0.02), as well as low monthly income (18.8%, 14.7% vs. 36.7%, P < 0.01) and higher BMI (11% vs. 27.7% and 25.6%, P = 0.02). Similar trends were observed for AST levels. Moreover, participants with a higher BMI exhibited significantly higher rates of at least one abnormal liver function enzyme (15.9% vs. 34.9%, P = 0.01). Logistic regression analysis revealed a significant association between abnormal liver enzyme levels and certain demographic and socioeconomic factors, specifically BMI and age. Conclusions This study provides insights into the prevalence of liver enzyme abnormalities and their associated factors among NPNL Bangladeshi women. The findings underscore the importance of addressing factors such as BMI and age in mitigating liver health issues in this population. Further research and targeted interventions are warranted to address these concerns effectively.

Commonly consumed processed packaged foods in Bangladesh are unhealthy and their nutrient contents are not in conformity with the label declaration.

The present study was undertaken to identify the major nutrient content in processed foods commonly consumed in Bangladesh, their label conformity healthiness, and percent daily nutrient contribution. Twenty-four nationally representative composite samples were analyzed using AOAC and other standard methods. Results were compared with label information using a restrictive approach and EU tolerance guidelines. The healthiness of the products was evaluated in terms of the Health Star Rating (HSR) scheme and the UK traffic light labeling system. Among the analyzed samples, fried pulse, chanachur, lozenge, and fried peas had the highest amount of protein, fat, carbohydrates, and dietary fiber, respectively. Biscuits and milk chocolate had high levels of trans fatty acids (TFA) and saturated fatty acids (SFA). It was observed that around half of the products lacked information about saturated fatty acid (46%), followed by total dietary fiber and trans-fat (38% each). Other information was missing in one-fifth of the products, namely protein (17%), total fat (17%), available carbohydrate (17%), energy (17%), sugar (21%), and salt (21%). Label compliance analysis according to the restrictive approach revealed that none of the products accurately reported the salt, sugar, saturated fat, and trans fat content on the label. According to the EU tolerance guideline, approximately half of the products had protein (58%), fat (54%), and carbohydrate (42%) levels that fell within the EU tolerance limit. However, only around one-third of the samples had sugar (21%), salt (38%), and saturated fat (33%) levels that met the EU tolerance limit. In terms of healthiness analysis, according to the HSR, the range of stars was between 0.5 and 2.5 of the foods where fried peas got the highest rating (2.5 stars), while in terms of the UK traffic light system, none of the samples got all green signals. The lozenge got green lights for fat, SFA, and salt contents. It was also found that consumption of 100 g of fried peas or pulse would exceed the acceptable daily limit of salt, sugar, and SFA compared to the daily maximum allowable intake for the 2000 kcal diet recommended by the WHO. However, according to the serving size, biscuits were major contributors of TFA, sugar, and SFA, whereas fried pulse was a key contributor of sodium/salt. Proper regulatory actions should be introduced to promote healthy processed foods with user-friendly front-of-the-pack labeling and monitor their quality to prevent non-communicable diseases (NCDs).

Synthesis and study of benzothiazole conjugates in the control of cell proliferation by modulating Ras/MEK/ERK-dependent pathway in MCF-7 cells.

By applying a methodology, a series of benzothiazole-pyrrole based conjugates (4a-r) were synthesized and evaluated for their antiproliferative activity. Compounds such as 4a, 4c, 4e, 4g-j, 4m, 4n, 4o and 4r exhibited significant cytotoxic effect in the MCF-7 cell line. Cell cycle effects were examined for these conjugates at 2 µM as well as 4 µM concentrations and FACS analysis show an increase of G2/M phase cells with concomitant decrease of G1 phase cells thereby indicating G2/M cell cycle arrest by them. Interestingly 4o and 4r are effective in causing apoptosis in MCF-7 cells. Moreover, 4o showed down regulation of oncogenic expression of Ras and its downstream effector molecules such as MEK1, ERK1/2, p38 MAPK and VEGF. The apoptotic aspect of this conjugate is further evidenced by increased expression of caspase-9 in MCF-7 cells. Hence these small molecules have the potential to control both the cell proliferation as well as the invasion process in the highly malignant breast cancers.

Identification of high-risk roadway segments for wrong-way driving crash using rare event modeling and data augmentation techniques.

Wrong-Way Driving (WWD) crashes are relatively rare but more likely to produce fatalities and severe injuries than other crashes. WWD crash segment prediction task is challenging due to its rare nature, and very few roadway segments experience WWD events. WWD crashes involve complex interactions among roadway geometry, vehicle, environment, and drivers, and the effect of these complex interactions is not always observable and measurable. This study applied two advanced Machine Learning (ML) models to overcome the imbalanced dataset problem and identified local and global factors contributing to WWD crash segments. Five years (2015-2019) of WWD crash data from Florida state were used in this study for WWD model development. The first modeling approach applied four different hybrid data augmentation techniques to the training dataset before applying the XGBoost classification algorithm. In the second model, a rare event modeling approach using the Autoencoder-based anomaly detection method was applied to the original data to identify WWD roadway segments. A third model was applied based on the statistical method to compare the performance of ML models in predicting the WWD segments. The performance comparison of the adopted models showed that the XGBoost model with the Adaptive Synthetic Sampling (ADASYN) method performed best in terms of precision and recall values compared to the autoencoder-based anomaly detection method. The best-performing model was used for the feature analysis with an interpretable machine-learning technique. The SHapley Additive exPlanations (SHAP) values showed that high-intensity developed land use, length of roadway, log of Annual Average Daily traffic (AADT), and lane width were positively associated with WWD roadway segments. The results of this study can be used to deploy WWD countermeasures effectively.

Understanding the convergence of social enterprise, digital health, and citizen engagement for co-producing integrated Person-Centred health services: A critical review and theoretical framework.

INTRODUCTION: To achieve Universal Health Coverage and the United Nations' (UN) Sustainable Development Goals (SDGs) agenda for 2030, the World Health Organisation (WHO) recommended the use of social enterprise, digital technology, and citizen engagement in the delivery of Integrated People-Centred Health Services (IPCHS) as part of its strategic vision for 21st century primary care. METHODS: We conducted a hermeneutic review of frameworks, models and theories on social enterprise, digital health, citizen engagement and IPCHS. This involved multiple iterative cycles of (i) searching and acquisition, followed by (ii) critical analysis and interpretation of literature to assemble arguments and evidence for conceptual relationships until information saturation was reached. This process identified a set of constructs which we synthesised into a testable framework. RESULTS: Several interdisciplinary frameworks, models and theories explain how social enterprises could use digital technology, and citizen engagement to enable the technical and social integration required to facilitate people-centred primary care. Innovative approaches can be used to maintain financial sustainability while delivering IPCHS at lower cost to vulnerable and marginalised populations in both developed and developing countries. CONCLUSION: This framework provides a theoretical grounding to guide empirical inquiry into how social enterprises use digital technology to engage citizens in co-producing IPCHS.

Dietary vitamin A intake and its major food sources among rural pregnant women of South-West Bangladesh.

The study aimed to estimate the dietary intake of vitamin A and its major food sources among rural pregnant women from the southwest region of Bangladesh. A multi-stage random cluster sampling method was used to select the respondents (N = 1012). A semi-structured questionnaire was used to collect the data, and statistical analysis was conducted using IBM SPSS 20.0. The mean age of the respondents was 23.27 ± 5.23 years, and the majority were in their second (48%) and third trimester (49%). The mean dietary intake of vitamin A was 392 ± 566 µg Retinol Activity Equivalent (RAE)/day (51% of Recommended Dietary Allowance). The contribution of ß-carotene (plant source) and retinol (animal source) in vitamin A intake was about 60% and 40%, respectively. The major ß-carotene contributing food groups were vegetables (dark and light) and tubers, and food items were colocasia, potato, beans, brinjal, and ripe tomatoes. On the other hand, the major retinol-contributing food groups were fish, eggs, and milk, and food items were small fish, Rui (carp) fish, and cow's milk. It was also observed that the consumption of food items from ß-carotene and retinol-contributing food groups did not differ significantly among the three groups of respondents, but the variations in the amount of the different food items consumed were significant. Dietary vitamin A intake is low among pregnant women in the South-West region of Bangladesh. Hence, they are at a greater risk of adverse materno-fetal health outcomes associated with vitamin A deficiency.

Draft genome sequence of multidrug-resistant Escherichia coli MAHK_SCM_BAU_30A strain isolated from a subclinical mastitis cow in Bangladesh.

This study announces the sequence of a multidrug-resistant Escherichia coli MAHK_SCM_BAU_30A strain isolated from bovine subclinical mastitis milk in 2022 in Bangladesh. Our assembled genome had a length of 4,884,948 bp, three plasmids, two CRISPR arrays, five prophages, 51 predicted antibiotic resistance, and 72 predicted virulence factor genes.

Synthesis, anticancer activity and apoptosis inducing ability of bisindole linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates.

A series of bisindole-pyrrolobenzodiazepine conjugates (5a-f) linked through different alkane spacers was prepared and evaluated for their anticancer activity. All compounds exhibited significant anticancer potency and the most potent compounds 5b and 5e were taken up for detailed studies on MCF-7 cell line. Cell cycle effects were examined apart from investigating the inhibition of tubulin polymerization for compounds 2a, 2b, 5b and 5e at 2µM. FACS analysis showed that at higher concentrations (4 and 8µM) there was an increase of sub-G1 phase cells and decrease of G2/M phase cells, thus indicating that compounds 5b and 5e are effective in causing apoptosis in MCF-7 cells. It was also observed that compounds 5b and 5e showed the down regulation of histone deacetylase protein levels such as HDAC1, 2, 3, 8 and increase in the levels of p21, followed by apoptotic cell death. The apoptotic nature of these compounds was further evidenced by increased expression of cleaved-PARP and active caspase-7 in MCF-7 cells.

Application of Bayesian Space-Time interaction models for Deer-Vehicle crash hotspot identification.

The objective of this research was to identify and prioritize deer-vehicle crash (DVC) hotspots using five years of crash data. This study applied Bayesian spatiotemporal models for the identification of the DVC hotspots. The Bayesian spatiotemporal model allows to observe area-specific trends in the DVC data and highlights specific locations where DVC occurrence is deteriorating or improving over time. Census Tracts (CTs) were used as the geographic units to aggregate DVC, land use, and transportation infrastructure related data of Minnesota (MN) for the year 2015 to 2019. Several tests were conducted to evaluate the performance of the hotspot identification methods. The result showed that Type-I spatiotemporal interaction model (Model-2) outperforms other four space-time models in terms of predicting DVC frequency in CTs and hotspot identification performance test measures. Results showed that forest area, vegetation, and wetland percentages were positively associated with DVC frequency, whereas the percentage of developed land use was negatively associated with DVC frequency. The findings of this study suggest that the deer population plays an important role in DVCs, which indicates that deer population management is necessary to minimize the DVC risks. Using the final Type-I spatiotemporal interaction model, 65 "High-High" CTs were identified, where both the posterior mean of the decision parameter (potential for safety improvement) and the area-specific trend were higher. The distribution of the identified hotspots showed that the risk of DVCs was more in suburban areas with mixed land use conditions. These CTs represent high-risk zones, which need immediate safety improvement measures to reduce the DVC risks. As DVC can occur at any roadway segment location, DVC hotspots information is important for safety engineers and policymakers to implement area specific countermeasures.

2-Anilinonicotinyl linked 2-aminobenzothiazoles and [1,2,4]triazolo[1,5-b] [1,2,4]benzothiadiazine conjugates as potential mitochondrial apoptotic inducers.

A series of N-(2-anilino-pyridyl) linked 2-amino benzothiazoles (4a-n) and [1,2,4]triazolo [1,5-b]benzothiadiazine conjugates (5a-j) have been designed, synthesized and evaluated for their antiproliferative activity. Some of these compounds (4h-k, 4n, and 5e) have exhibited potent cytotoxicity specifically against human leukemia HL-60 cell lines with IC(50) values in the range of 0.08-0.70 µM. All these compounds were tested for their effects on the cell cycle perturbations and induction of apoptosis. Morphological evidences of apoptosis, including fragmentation of nuclei and inter nucleosomal DNA laddering formation were clearly observed after 24h exposure to compound 4i. Flow cytometry analysis revealed that compound 4i showed drastic cell cycle perturbations due to concentration dependant increase in the sub-G0 region which comprises of both the apoptotic and debris fraction, thus implying the extent of cell death. These compounds trigger the mitochondrial apoptotic pathway that results in the loss of mitochondrial membrane potential through activation of multiple caspases followed by activation of caspase-3, and finally cleavage of PARP. Further the mechanism of cell death was analysed by fluorescent microscopic analysis and also by scanning electron microscopy. The cytotoxicity of 4i correlated with induction of apoptosis, caspases activation and DNA damage and thus indicating the apoptotic pathway of anticancer effect of these compounds.