Anti-Inflammatory, Wound Healing, and Anti-Diabetic Effects of Pure Active Compounds Present in the Ryudai Gold Variety of Curcuma longa.

Turmeric (Curcuma longa) contains curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC). Nevertheless, curcumin is the most researched active ingredient for its numerous pharmacological effects. We investigated the impact of these curcuminoids found in Ryudai gold, an approved cultivar of Curcuma longa, on wound healing, inflammation, and diabetes. Sub-planter injections of carrageenan induced acute paw inflammation in rats. The wound-healing ability of 1% curcuminoids was examined by making a 6 mm round wound on the shaved dorsum of the mice with a biopsy punch. A single intraperitoneal injection of streptozotocin (50 mg/kg) was used to induce diabetes in mice. Curcuminoids at a dose rate of 100 mg/kg body weight were used with feed and as a gastric gavage to treat diabetes and inflammation in experimental animals. Paw thickness was measured at 1, 3, and 6 h following carrageenan injection. After three hours, mean paw volume was 58% in carrageenan-injected mice, which was 35%, 37%, and 31% in the curcumin, DMC, and BDMC groups, respectively. Histopathology of the paw tissue demonstrated severe infiltration of inflammatory cells and thickening of the dermis, which were remarkably improved by the curcuminoids. The wound-healing abilities were significantly higher in the curcumin- (95.0%), DMC- (93.17%), and BDMC-treated (89.0%) groups, in comparison to that of the control (65.09%) group at day nine. There were no significant differences in wound-healing activity among the groups treated with 1% curcuminoids throughout the study. Streptozotocin-induced diabetes was characterized by an increased blood glucose (552.2 mg/dL) and decreased body weight (31.2 g), compared to that of the control rats (145.6 mg/dL and 46.8 g blood glucose and body weight, respectively). It also caused an increase in serum alanine aminotransferase (ALT; 44.2 U/L) and aspartate aminotransferase (AST; 55.8 U/L) compared to that of the control group (18.6 U/L and 20.1 U/L, respectively). Histopathological examination of the liver showed that diabetes caused hepatic cellular necrosis, congestion of the central vein, and parenchymatous degeneration. However, all three curcuminoids significantly decreased blood glucose levels, ALT, and AST and improved the histopathological score of the liver. These results evidenced that not only curcumin but also DMC and BDMC have potent anti-inflammatory, wound healing, and anti-diabetic efficacy, and the Ryudai gold variety of turmeric could be used as a functional food supplement.

ATM depletion induces proteasomal degradation of FANCD2 and sensitizes neuroblastoma cells to PARP inhibitors.

BACKGROUND: Genomic alterations, including loss of function in chromosome band 11q22-23, are frequently observed in neuroblastoma, which is the most common extracranial childhood tumour. In neuroblastoma, ATM, a DNA damage response-associated gene located on 11q22-23, has been linked to tumorigenicity. Genetic changes in ATM are heterozygous in most tumours. However, it is unclear how ATM is associated with tumorigenesis and cancer aggressiveness. METHODS: To elucidate its molecular mechanism of action, we established ATM-inactivated NGP and CHP-134 neuroblastoma cell lines using CRISPR/Cas9 genome editing. The knock out cells were rigorously characterized by analyzing proliferation, colony forming abilities and responses to PARP inhibitor (Olaparib). Western blot analyses were performed to detect different protein expression related to DNA repair pathway. ShRNA lentiviral vectors were used to knockdown ATM expression in SK-N-AS and SK-N-SH neuroblastoma cell lines. ATM knock out cells were stably transfected with FANCD2 expression plasmid to over-expressed the FANCD2. Moreover, knock out cells were treated with proteasome inhibitor MG132 to determine the protein stability of FANCD2. FANCD2, RAD51 and γH2AX protein expressions were determined by Immunofluorescence microscopy. RESULTS: Haploinsufficient ATM resulted in increased proliferation (p < 0.01) and cell survival following PARP inhibitor (olaparib) treatment. However, complete ATM knockout decreased proliferation (p < 0.01) and promoted cell susceptibility to olaparib (p < 0.01). Complete loss of ATM suppressed the expression of DNA repair-associated molecules FANCD2 and RAD51 and induced DNA damage in neuroblastoma cells. A marked downregulation of FANCD2 expression was also observed in shRNA-mediated ATM-knockdown neuroblastoma cells. Inhibitor experiments demonstrated that the degradation of FANCD2 was regulated at the protein level through the ubiquitin-proteasome pathway. Reintroduction of FANCD2 expression is sufficient to reverse decreased proliferation mediated by ATM depletion. CONCLUSIONS: Our study revealed the molecular mechanism underlying ATM heterozygosity in neuroblastomas and elucidated that ATM inactivation enhances the susceptibility of neuroblastoma cells to olaparib treatment. These findings might be useful in the treatment of high-risk NB patients showing ATM zygosity and aggressive cancer progression in future.

Real-time organic compound monitoring in advanced oxidation process (AOP) of anaerobic digestion effluent: introduction of UV-VIS spectrum representative index by discrete Fourier transform.

Anaerobic digestion effluent from sewage treatment plants (STP) poses a challenge to the operator because of its high organic matter and inorganic nitrogen concentrations, which require an effective process for biological treatment. This study aimed to introduce a UV-VIS spectrum representative index by discrete Fourier transform (DFT) and apply UV-Vis spectrophotometric techniques for real-time organic compound monitoring in the AOP process using anaerobic digestion tank effluent wastewater. The effect of advanced oxidation on the organic compounds of effluent using ozonation was examined. In this research, after treating secondary treated water with the UV-AOP process and anaerobic digestion effluent with ozone microbubble systems, changes in organic substances were expressed by the UV-Vis spectrum and compared with conventional water quality parameters. The anaerobic digestion process effluent was treated through ozone oxidation, had a high curve, and fell gently from 230 to 667 nm. Discrete Fourier transform (DFT) was applied to obtain representative values from the obtained spectrum. From among the coefficients obtained by analyzing the UV-Vis spectrum through DFT, an expected value was selected, and the correlation between CODMn and a3 was the highest (correlation function = 0.694, RSQ = 0.482). Therefore, a linear regression analysis was performed to determine which water quality factor it was related to.

Polycomb EZH1 regulates cell cycle/5-fluorouracil sensitivity of neuroblastoma cells in concert with MYCN.

In the present study, we found that EZH1 depletion in MYCN-amplified neuroblastoma cells resulted in significant cell death as well as xenograft inhibition. EZH1 depletion decreased the level of H3K27me1; the interaction and protein stabilization of MYCN and EZH1 appear to play roles in epigenetic transcriptional regulation. Transcriptome analysis of EZH1-depleted cells resulted in downregulation of the cell cycle progression-related pathway. In particular, Gene Set Enrichment Analysis revealed downregulation of reactome E2F-mediated regulation of DNA replication along with key genes of this process, TYMS, POLA2, and CCNA1. TYMS and POLA2 were transcriptionally activated by MYCN and EZH1-related epigenetic modification. Treatment with the EZH1/2 inhibitor UNC1999 also induced cell death, decreased H3K27 methylation, and reduced the levels of TYMS in neuroblastoma cells. Previous reports indicated neuroblastoma cells are resistant to 5-fluorouracil (5-FU) and TYMS (encoding thymidylate synthetase) has been considered the primary site of action for folate analogues. Intriguingly, UNC1999 treatment significantly sensitized MYCN-amplified neuroblastoma cells to 5-FU treatment, suggesting that EZH inhibition could be an effective strategy for development of a new epigenetic treatment for neuroblastoma.

How do they grow out of their cancer experience? Korean adolescent and young adult cancer survivors' stories.

Objectives: Cancer experiences can bring positive as well as negative impacts. The current literature, however, focuses mainly on the negative impacts. This qualitative study examines Korean childhood cancer survivors' post-traumatic growth, which concerns how they respond positively to the cancer experience and how they change as a result of their experience.Design: In-person or telephone interviews were conducted with 31 adolescent and young adult survivors of childhood cancer post-treatment who were living in Korea.Results: Thematic analysis found that childhood cancer survivors experienced growth by feeling gratitude (being content with the present, making comparisons with worse situations), engaging in self-affirmation ('I am strong'; 'My example can help others'; 'I am ready for new challenges'), deepening faith (communicating with God, trusting God's direction), and finding the social meaning of cancer (becoming a self-advocate, mapping out a career path).Conclusions: The study findings can be used by psychosocial care professionals to support Korean cancer survivors to recognize post-traumatic growth and, thus, achieve improved well-being.

Programmed expression of pro-apoptotic BMCC1 during apoptosis, triggered by DNA damage in neuroblastoma cells.

BACKGROUND: The multi-functional BMCC1 (BCH motif-containing molecule at the carboxyl terminal region 1)/PRUNE2 plays a clear role in suppression of tumor activity. In the patients with neuroblastoma (NB), reduced expression of BMCC1 in primary tumor tissues was associated with poor prognosis. By contrast, enforced expression of BMCC1 as well as elevated expression of BMCC1 in response to DNA-damage promotes apoptosis by abrogating Akt-mediated survival pathways. METHODS: We addressed molecular mechanisms underlying changes in regulation of BMCC1 expression during the process of apoptosis, which was promoted by a DNA-damaging drug Cisplatin (CDDP), in NB-derived cells. RESULTS: Elevated expression of BMCC1 was identified as an early response to DNA damage, which is accompanied by phosphorylation of ataxia telangiectasia mutated kinase (ATM) and accumulation of E2F1. Indeed, inhibition of ATM using an ATM inhibitor resulted in a decrease in expression of BMCC1 at mRNA levels. In addition, an E2F-binding sight was required for activation of BMCC1 promoter in response to DNA damage. On the other hand, knockdown of E2F1 yielded abrogated induction of BMCC1 in the cells after treatment with CDDP, suggesting that BMCC1 accumulation was caused by ATM-E2F1-dependent transcription. Finally, we demonstrated that full-length BMCC1 was proteolytically cleaved by apoptosis-activated caspase-9 during advanced stages of apoptosis in SK-N-AS cells. CONCLUSIONS: In this study, we demonstrated the programmed expression of full-length BMCC1 in human NB cells undergoing DNA damage-induced apoptosis. The elucidation of the molecular mechanisms controlling the regulation of BMCC1 during apoptosis initiated by DNA damage provides useful information for understanding drug resistance of tumor cells and spontaneous regression of NB.

Polymyxin B in Combination with Enrofloxacin Exerts Synergistic Killing against Extensively Drug-Resistant Pseudomonas aeruginosa.

Polymyxins are increasingly used as a last-resort class of antibiotics against extensively drug-resistant (XDR) Gram-negative bacteria. However, resistance to polymyxins can emerge with monotherapy. As nephrotoxicity is the major dose-limiting factor for polymyxin monotherapy, dose escalation to suppress the emergence of polymyxin resistance is not a viable option. Therefore, novel approaches are needed to preserve this last-line class of antibiotics. This study aimed to investigate the antimicrobial synergy of polymyxin B combined with enrofloxacin against Pseudomonas aeruginosa Static time-kill studies were conducted over 24 h with polymyxin B (1 to 4 mg/liter) and enrofloxacin (1 to 4 mg/liter) alone or in combination. Additionally, in vitro one-compartment model (IVM) and hollow-fiber infection model (HFIM) experiments were performed against P. aeruginosa 12196. Polymyxin B and enrofloxacin in monotherapy were ineffective against all of the P. aeruginosa isolates examined, whereas polymyxin B-enrofloxacin in combination was synergistic against P. aeruginosa, with ≥2 to 4 log10 kill at 24 h in the static time-kill studies. In both IVM and HFIM, the combination was synergistic, and the bacterial counting values were below the limit of quantification on day 5 in the HFIM. A population analysis profile indicated that the combination inhibited the emergence of polymyxin resistance in P. aeruginosa 12196. The mechanism-based modeling suggests that the synergistic killing is a result of the combination of mechanistic and subpopulation synergy. Overall, this is the first preclinical study to demonstrate that the polymyxin-enrofloxacin combination is of considerable utility for the treatment of XDR P. aeruginosa infections and warrants future clinical evaluations.

Pediatric oncology social workers' experience of compassion fatigue.

Pediatric oncology social workers play an important role in supporting cancer patients and their families as they learn to talk about and cope with the physical and psychological impacts of cancer. As a result, social workers are particularly vulnerable to compassion fatigue and the associated psychological and physical impacts. The purpose of this qualitative study was to understand the experience of compassion fatigue among 27 pediatric oncology social workers. Four main themes emerged throughout the five focus groups: Conditions that contribute to compassion fatigue; the influence of compassion fatigue; coping strategies to alleviate compassion fatigue; and desire for systematic support to prevent compassion fatigue. Our study findings emphasize the importance of developing programs, policies and research geared toward the prevention of compassion fatigue, in addition to coping with symptoms. Further, this study brings attention to the importance of including pediatric oncology social workers in efforts to develop and implement systemic supports.

Knowledge attitude and practice regarding diabetes mellitus among Nondiabetic and diabetic study participants in Bangladesh.

BACKGROUND: Increased awareness amongst large population groups is a major determinant for the prevention of diabetes and its complications as well as related metabolic disorders. Knowledge and attitude are the principal markers of awareness that need to be studied in various population groups in specific racial and cultural contexts. The present study was undertaken to explore knowledge, attitude and practice (KAP) regarding -diabetes mellitus (DM) among nondiabetic (nonDM) and type 2 diabetes mellitus (T2DM) patients in Bangladesh. METHODS: A cross-sectional study was conducted among 18,697 adults (aged 18 years and above; 7796 male and 10,901 female; 6780 nonDM and 11,917 T2DM) selected purposively from the OPD of 19 healthcare centres in and around Dhaka and in northern parts of Bangladesh. KAP were assessed by a pre-structured, interviewer-administered questionnaire and categorised using predefined scores of poor (mean + 1 SD). Univariate and bivariate statistical analysis were done as appropriate. Multivariate linear regression was done to examine the association between diabetes related KAP and other covariates. RESULTS: The mean (±SD) age (years) of all the study participants was 46 ± 14, mean BMI 24.4 ± 4.1 and mean waist-hip ratio (WHR) was 0.93 ± 0.07. The proportion of poor, average and good knowledge scores among T2DM subjects were 17%, 68% and 15% respectively. The corresponding values for attitude score were 23%, 67% and 10% respectively. The KAP regarding diabetes was found to be better among people who were living with diabetes compared to their counterparts. DM males showed better knowledge and practice regarding diabetes, compared to nonDM counterparts (M ± SD; 44.18 ± 16.13 vs 40.88 ± 15.62, p = <0.001; 66.00 ± 29.68 vs 64.21 ± 31.79, p < 0.001, respectively). Females showed better attitude score compared to males. Overall KAP were found to be significantly higher (p < 0.001) in middle aged (31-50 years) participants in each group. Participants from urban residents, higher educational background and upper socio-economic class demonstrated significantly greater score in terms of KAP in both nonDM and T2DM groups (p < 0.001). On linear regression analysis, knowledge scores correlated strongly with education, income, residence, diabetic state, BMI and attitude. CONCLUSIONS: The overall level of knowledge and practice concerning diabetes among Bangladeshi population is average, but the overall level of attitude is good both in nonDM and T2DM subjects. To prevent diabetes and its complications there is an urgent need for coordinated educational campaigns with a prioritized focus on poorer, rural and less educated groups.

Transcriptional regulation of BMCC1 mediated by E2F1 in neuroblastoma cells.

BCH motif-containing molecule at the carboxyl terminal region 1 (BMCC1)/PRUNE2 is highly expressed in patients with favorable neuroblastoma (NB), encoding a multifunctional scaffold protein that modulates several signaling networks including RhoA and AKT pathways. Accumulating evidence suggests that BMCC1 acts as a tumor-suppressor. In this study, we addressed molecular mechanism underlying transcriptional regulation of BMCC1 in NBs. We found that transcription factor E2F1 was recruited to E2F-binding site in the promoter region of BMCC1 gene. Indeed, overexpression of E2F1 resulted in an increase in the expression level of BMCC1 in NB cell lines. On the other hand, knockdown of E2F1 in NB cells yielded down-regulation of BMCC1. Also, we showed that BMCC1 and E2F1 were simultaneously induced at G1 to S phase transition. Therefore, we conclude that E2F1 directly facilitated BMCC1 transcription. Taking together, these results suggest that BMCC1 induced by E2F1 acts as a tumor suppressor through its pro-apoptotic function, resulted in favorable prognosis of NB.

Major pathways of polymyxin-induced apoptosis in rat kidney proximal tubular cells.

Identifying the pathways involved in the apoptotic cell death that is associated with polymyxin-induced nephrotoxicity is crucial for the development of strategies to ameliorate this dose-limiting side effect and for the development of novel safer polymyxins. The primary aim of this study was to identify the major pathways which lead to polymyxin-induced apoptosis in cultured rat kidney proximal tubular cells (NRK-52E). Caspase-3, -8, and -9 were activated by polymyxin B treatment in a concentration-dependent manner. Concentration- and time-dependent expression of FasL and deformation of mitochondrial morphology were revealed following polymyxin B treatment. The proportion of cells with filamentous mitochondria (regular morphology) following an 8-h treatment with 1.0 mM polymyxin B was 56.2% ± 9.7% (n = 3). This was decreased to 30.7% ± 7.5% when the polymyxin B concentration was increased to 2.0 mM. The mitochondrial membrane potential (Δψm) decreased to 14.1% ± 2.9% in the cells treated with 1.0 mM polymyxin B for 24 h (n = 3) compared to that in the untreated control group. Concomitantly, concentration- and time-dependent production of mitochondrial superoxide was also observed. This study is the first to have demonstrated that polymyxin-induced apoptosis is mediated through both the death receptor and mitochondrial pathways in cultured renal tubular cells. It provides key information not only for the amelioration of polymyxin-induced nephrotoxicity but also for the discovery of novel safer polymyxin-like antibiotics against Gram-negative "superbugs."

Factors associated with maternal anaemia among pregnant women in Dhaka city.

BACKGROUND: Maternal anaemia is a common problem in pregnancy, particularly in developing countries. The study was aimed at determining the factors associated with anaemia among a group of pregnant mothers who attended an antenatal clinic in Dhaka city. METHODS: This cross-sectional study included 224 pregnant women, who visited the antenatal clinic of the Marie Stops, Dhaka. Demographic data and information on maternal age, gestational age, educational and income level, and socioeconomic status were collected from all the subjects. Haemoglobin status was measured to assess their anaemia. A qualified technician drew venous blood samples from them. The reference values of haemoglobin were categorized according to the World Health Organization (WHO) criteria as follows: normal (11 g/dL or higher), mild (10-10.9 g/dL), and moderate (7-9.9 g/dL). Mild and moderate levels of haemoglobin were defined as anaemic (haemoglobin levels of <11 g/dL). The SPSS software (Windows version 16.0. SPSS Inc, Chicago, USA) was used for analyzing data. RESULTS: The mean (±SD) age of the subjects was 26.4 ± 2.81 years. Sixty-three percent of the subjects had normal level of haemoglobin, and 37% were anaemic 26% mild and 11% moderate. Maternal anaemia was significantly associated with age (p = 0.036), education (p = 0.002), income (p = 0.001), living area (p = 0.031). Results of binary logistic regression analysis showed that maternal anaemia was also significantly associated with age (p = 0.006), educational status (primary to 8th grade, p = 0.004; secondary and above, p = 0.002), living area (0.022), and income (0.021). DISCUSSION: A significant proportion of pregnant women were found anaemic. Most data showed education has animpact on awareness to use of health services and iron supplementation should be encouraged to improve the haemoglobin levels in pregnancy. CONCLUSIONS: The results indicate that anaemia is alarmingly high among pregnant women in Dhaka city. Maternal anaemia is associated with age, education level, income level, and living area. The results suggest that pregnant women and members of their families should be urgently educated to understand the importance of antenatal care.

Intracellular fragment of NLRR3 (NLRR3-ICD) stimulates ATRA-dependent neuroblastoma differentiation.

We have previously identified neuronal leucine-rich repeat protein-3 (NLRR3) gene which is preferentially expressed in favorable human neuroblastomas as compared with unfavorable ones. In this study, we have found for the first time that NLRR3 is proteolytically processed by secretases and its intracellular domain (NLRR3-ICD) is then released to translocate into cell nucleus during ATRA-mediated neuroblastoma differentiation. According to our present observations, NLRR3-ICD was induced to accumulate in cell nucleus of neuroblastoma SH-SY5Y cells following ATRA treatment. Since the proteolytic cleavage of NLRR3 was blocked by α- or γ-secretase inhibitor, it is likely that NLRR3-ICD is produced through the secretase-mediated processing of NLRR3. Intriguingly, forced expression of NLRR3-ICD in neuroblastoma SK-N-BE cells significantly suppressed their proliferation as examined by a live-cell imaging system and colony formation assay. Similar results were also obtained in neuroblastoma TGW cells. Furthermore, overexpression of NLRR3-ICD stimulated ATRA-dependent neurite elongation in SK-N-BE cells. Together, our present results strongly suggest that NLRR3-ICD produced by the secretase-mediated proteolytic processing of NLRR3 plays a crucial role in ATRA-mediated neuronal differentiation, and provide a clue to develop a novel therapeutic strategy against aggressive neuroblastomas.

Probing the penetration of antimicrobial polymyxin lipopeptides into gram-negative bacteria.

The dry antibiotic development pipeline coupled with the emergence of multidrug resistant Gram-negative 'superbugs' has driven the revival of the polymyxin lipopeptide antibiotics. Polymyxin resistance implies a total lack of antibiotics for the treatment of life-threatening infections. The lack of molecular imaging probes that possess native polymyxin-like antibacterial activity is a barrier to understanding the resistance mechanisms and the development of a new generation of polymyxin lipopeptides. Here we report the regioselective modification of the polymyxin B core scaffold at the N-terminus with the dansyl fluorophore to generate an active probe that mimics polymyxin B pharmacologically. Time-lapse laser scanning confocal microscopy imaging of the penetration of probe (1) into Gram-negative bacterial cells revealed that the probe initially accumulates in the outer membrane and subsequently penetrates into the inner membrane and finally the cytoplasm. The implementation of this polymyxin-mimetic probe will advance the development of platforms for the discovery of novel polymyxin lipopeptides with efficacy against polymyxin-resistant strains.

Osteopenia and osteoporosis among 16-65 year old women attending outpatient clinics.

Women living in developing countries are more prone to osteoporotic fractures than women in developed countries. The objectives of this study were to estimate the burden of osteopenia and osteoporosis and examine their correlates among Bangladeshi women. This cross-sectional study consisted of 500 women aged 16-65 years attending gynecology and family planning clinics of a tertiary hospital which cares urban/suburban low income population in Dhaka, Bangladesh. Bone mineral density (BMD) was measured at the lumbar spine and femoral neck using dual X-ray absorptiometry. We calculated T scores based on sex-matched reference data from Caucasian women provided by the manufacturer. Osteoporosis was defined as a BMD at either site more than 2.5 standard deviations (SD) below the young healthy adult woman mean while the osteopenia was defined as a BMD between 1 and 2.5 SD below the mean as suggested by the World Health Organization. Separate multivariable logistic regression analysis was used to examine the correlates of osteopenia/osteoporosis among 16-45 and 46-65 year old women. Overall, 43.6 and 5.5 % of 16-45 year old women, and 40.7 and 41.8 % of 46-65 year old women had osteopenia and osteoporosis based on T scores either of the two sites (lumbar spine or femoral neck), respectively. Body mass index was negatively associated with osteopenia/osteoporosis at both lumbar spine and femoral neck, while age was positively associated. The burden of osteopenia/osteoporosis is very high in Bangladeshi women which warrants appropriate interventional strategies to minimize future fractures and reduce related social and economic burden of the society.

The coding complete genomic sequence of a feline panleukopenia virus detected from a domestic cat (Felis catus) in Chattogram, Bangladesh.

The coding complete genome sequence of the feline panleukopenia virus (FPLV), detected from an indigenous cat in Bangladesh, has been determined. The genome spans 4,842 bp and contains four protein-coding genes. The genome will contribute to a comprehensive understanding of the genetic traits and evolutionary trends of FPLV.

Comparison of adsorption-extraction (AE) workflows for improved measurements of viral and bacterial nucleic acid in untreated wastewater.

The lack of standardized methods and large differences in virus concentration and extraction workflows have hampered Severe Acute Respiratory Syndrome (SARS-CoV-2) wastewater surveillance and data reporting practices. Numerous studies have shown that adsorption-extraction (AE) method holds promise, yet several uncertainties remain regarding the optimal AE workflow. Several procedural components may influence the recovered concentrations of target nucleic acid, including membrane types, homogenization instruments, speed and duration, and lysis buffer. In this study, 42 different AE workflows that varied these components were compared to determine the optimal workflow by quantifying endogenous SARS-CoV-2, human adenovirus 40/41 (HAdV 40/41), and a bacterial marker gene of fecal contamination (Bacteroides HF183). Our findings suggest that the workflow chosen had a significant impact on SARS-CoV-2 concentrations, whereas it had minimal impact on HF183 and no effect on HAdV 40/41 concentrations. When comparing individual components in a workflow, such as membrane type (MF-Millipore™ 0.45 µm MCE vs. Isopore™ 0.40 µm), we found that they had no impact on SARS-CoV-2, HAdV 40/41, and HF183 concentrations. This suggests that at least some consumables and equipment are interchangeable. Buffer PM1 + TRIzol-based workflows yielded higher concentrations of SARS-CoV-2 than other workflows. HF183 concentrations were higher in workflows without chloroform. Similarly, higher homogenization speeds (5000-10,000 rpm) led to increased concentrations of SARS-CoV-2 and HF183 but had no effect on HAdV 40/41. Our findings indicate that minor enhancements to the AE workflow can improve the recovery of viruses and bacteria from the wastewater, leading to improved outcomes from wastewater surveillance efforts.

Psychometric validation of diabetes distress scale in Bangladeshi population.

Diabetes Distress (DD)-an emotional or affective state arise from challenge of living with diabetes and the burden of self-care-negatively impact diabetes management and quality of life of T2DM patients. Early detection and management of DD is key to efficient T2DM management. The study aimed at developing a valid and reliable instrument for Bangladeshi patients as unavailability such a tool posing challenge in diabetes care. Linguistically adapted, widely used, 17-item Diabetes Distress Scale (DDS), developed through forward-backward translation from English to Bengali, was administered on 1184 T2DM patients, from four diabetes hospitals in Bangladesh. Psychometric assessment of the instrument included, construct validity using principal component factor analysis, internal consistency using Cronbach's α and discriminative validity through independent t-test and test-retest reliability using intraclass-correlation coefficient (ICC) and Kappa statistics. Factor analysis extracted 4 components similar to original DDS domains, confirms the construct validity. The scale demonstrated satisfactory internal consistency (α = 0.838), stability (test-retest ICC = 0.941) and good agreement across repeated measurements (Kappa = 0.584). Discriminative validity revealed that patients with complication (p < 0.001) and those are on insulin (p < 0.001) had significantly higher distress scores in all domains. Bengali version of DDS is a valid and reliable tool for assessing distress among Bangladeshi T2DM patients.

How Do Telomere Abnormalities Regulate the Biology of Neuroblastoma?

Telomere maintenance plays important roles in genome stability and cell proliferation. Tumor cells acquire replicative immortality by activating a telomere-maintenance mechanism (TMM), either telomerase, a reverse transcriptase, or the alternative lengthening of telomeres (ALT) mechanism. Recent advances in the genetic and molecular characterization of TMM revealed that telomerase activation and ALT define distinct neuroblastoma (NB) subgroups with adverse outcomes, and represent promising therapeutic targets in high-risk neuroblastoma (HRNB), an aggressive childhood solid tumor that accounts for 15% of all pediatric-cancer deaths. Patients with HRNB frequently present with widely metastatic disease, with tumors harboring recurrent genetic aberrations (MYCN amplification, TERT rearrangements, and ATRX mutations), which are mutually exclusive and capable of promoting TMM. This review provides recent insights into our understanding of TMM in NB tumors, and highlights emerging therapeutic strategies as potential treatments for telomerase- and ALT-positive tumors.

NLRR1 Is a Potential Therapeutic Target in Neuroblastoma and MYCN-Driven Malignant Cancers.

Receptor tyrosine kinases (RTKs) receive different modulation before transmitting proliferative signals. We previously identified neuronal leucine-rich repeat 1 (NLRR1) as a positive regulator of EGF and IGF-1 signals in high-risk neuroblastoma cells. Here, we show that NLRR1 is up-regulated in various adult cancers and acts as a key regulator of tumor cell proliferation. In the extracellular domains of NLRR1, fibronectin type III (FNIII) domain is responsible for its function to promote cell proliferation. We generated monoclonal antibodies against the extracellular domains of NLRR1 (N1mAb) and screened the positive N1mAbs for growth inhibitory effect. The treatment of N1mAbs reduces tumor cell proliferation in vitro and in vivo, and sensitizes the cells to EGFR inhibitor, suggesting that NLRR1 is a novel regulatory molecule of RTK function. Importantly, epitope mapping analysis has revealed that N1mAbs with growth inhibitory effect recognize immunoglobulin-like and FNIII domains of NLRR1, which also indicates the importance of FNIII domain in the function of NLRR1. Thus, the present study provides a new insight into the development of a cancer therapy by targeting NLRR1 as a modulator of proliferative signals on cellular membrane of tumor cells.