Enhancing Reniform Nematode Management in Sweetpotato by Complementing Host-Plant Resistance with Nonfumigant Nematicides.

The reniform nematode (Rotylenchulus reniformis Linford and Oliveira) adversely impacts the quality and quantity of sweetpotato storage roots. Management of R. reniformis in sweetpotato remains a challenge because host plant resistance is not available, fumigants are detrimental to the environment and health, and crop rotation is not effective. We screened a core set of 24 sweetpotato plant introductions (PIs) against R. reniformis. Four PIs were resistant, and 10 were moderately resistant to R. reniformis, suggesting these PIs can serve as sources of resistance for sweetpotato resistance breeding programs. PI 595869, PI 153907, and PI 599386 suppressed 83 to 89% egg production relative to the susceptible control 'Beauregard', and these PIs were employed in subsequent experiments to determine if their efficacy against R. reniformis can be further increased by applying nonfumigant nematicides oxamyl, fluopyram, and fluensulfone. A 34 to 93% suppression of nematode reproduction was achieved by the application of nonfumigant nematicides, with oxamyl providing the best suppression followed by fluopyram and fluensulfone. Although sweetpotato cultivars resistant to R. reniformis are currently not available and there is a need for the development of safer yet highly effective nonfumigant nematicides, results from the current study suggest that complementing host plant resistance with nonfumigant nematicides can serve as an important tool for effective and sustainable nematode management.

Impact of non-fumigant nematicides on reproduction and pathogenicity of Meloidogyne enterolobii and disease severity in tobacco.

Meloidogyne enterolobii is a highly aggressive quarantine pathogen which threatens the multibillion-dollar tobacco industry and is not manageable with the currently available management methods in tobacco. There is currently no known host plant resistance in tobacco and previous studies have shown that the lower level of the currently recommended rate of non-fumigant nematicides does not provide satisfactory management of M. enterolobii. The current study was conducted with the hypothesis that M. enterolobii can be better managed using a single soil application of the maximum allowed rate of non-fumigant nematicides. Treatments involved three non-fumigant chemical nematicides (oxamyl, fluopyram, and fluensulfone), a biological nematicide derived from Burkholderia, and a non-treated control. Fluensulfone significantly suppressed the nematode reproduction relative to the control, the suppression being 71% for eggs and 86% for the second stage juveniles (J2). Fluopyram also suppressed nematode reproduction, although this was statistically insignificant, with the suppression being 26% and 37% for eggs and J2, respectively. Oxamyl significantly suppressed J2 (80%), but not eggs (50%) in relation to the control. The most significant reduction of disease severity was achieved by the application of fluensulfone (64%), followed by oxamyl (54%) and fluopyram (48%). Except for fluensulfone, which significantly reduced the root biomass, none of the nematicides significantly impacted root and shoot biomass. The biological nematicide did not significantly affect nematode reproduction, pathogenicity, or disease severity. The results from the current study suggest that while the non-fumigant nematicides provided a good level of the nematode suppression, more research is needed to improve the efficacy of non-fumigant nematicides through employing better application methods or finding better chemistries.

Discovery of novel DprE1 inhibitors via computational bioactivity fingerprints and structure-based virtual screening.

Decaprenylphosphoryl-ß-D-ribose oxidase (DprE1) plays important roles in the biosynthesis of mycobacterium cell wall. DprE1 inhibitors have shown great potentials in the development of new regimens for tuberculosis (TB) treatment. In this study, an integrated molecular modeling strategy, which combined computational bioactivity fingerprints and structure-based virtual screening, was employed to identify potential DprE1 inhibitors. Two lead compounds (B2 and H3) that could inhibit DprE1 and thus kill Mycobacterium smegmatis in vitro were identified. Moreover, compound H3 showed potent inhibitory activity against Mycobacterium tuberculosis in vitro (MICMtb = 1.25 µM) and low cytotoxicity against mouse embryo fibroblast NIH-3T3 cells. Our research provided an effective strategy to discover novel anti-TB lead compounds.

Sterilizing Effects of Novel Regimens Containing TB47, Clofazimine, and Linezolid in a Murine Model of Tuberculosis.

TB47, a new drug candidate targeting QcrB in the electron transport chain, has shown a unique synergistic activity with clofazimine and forms a highly sterilizing combination. Here, we investigated the sterilizing effects of several all-oral regimens containing TB47 plus clofazimine and linezolid as a block and the roles of fluoroquinolones and pyrazinamide in them. All these regimens cured tuberculosis within 4 to 6 months in a well-established mouse model, and adding pyrazinamide showed a significant difference in bactericidal effects.

Additive Opto-Thermomechanical Nanoprinting and Nanorepairing under Ambient Conditions.

We demonstrate an opto-thermomechanical (OTM) nanoprinting method that allows us not only to additively print nanostructures with sub-100 nm accuracy but also to correct printing errors for nanorepairing under ambient conditions. Different from other existing nanoprinting methods, this method works when a nanoparticle on the surface of a soft substrate is illuminated by a continuous-wave (cw) laser beam in a gaseous environment. The laser heats the nanoparticle and induces a rapid thermal expansion of the soft substrate. This thermal expansion can either release a nanoparticle from the soft surface for nanorepairing or transfer it additively to another surface in the presence of optical forces for nanoprinting with sub-100 nm accuracy. Details of the printing mechanism and parameters that affect the printing accuracy are investigated. This additive OTM nanoprinting technique paves the way for rapid and affordable additive manufacturing or 3D printing at the nanoscale under ambient conditions.

Print metallic nanoparticles on a fiber probe for 1064-nm surface-enhanced Raman scattering.

This Letter presents 1064-nm surface-enhanced Raman scattering (SERS) on an optical fiber probe, or 1064-nm-SERS-on-fiber. Metallic nanoparticles are printed on an optical fiber probe by using optothermal surface bubbles under ambient conditions. An optothermal surface bubble is a laser-induced micro-sized bubble that is formed on a solid-liquid interface. The SERS activity of the optical fiber probe for 1064-nm Raman microscopy is tested with rhodamine 6G in aqueous solution. The 1064-nm-SERS-on-fiber can reduce the fluorescent background noise that commonly exists in other Raman systems. It can also compensate for the decreased Raman signal due to the use of an infrared Raman laser. The 1064-nm-SERS-on-fiber will find potential applications in low-background-noise biosensing and endoscopy.

Current status of gonococcal antimicrobial susceptibility with special reference to Azithromycin and Ceftriaxone: Report from a tertiary care hospital in Bangladesh.

OBJECTIVES: Successful treatment of gonorrhea has always been jeopardized by the emergence of resistance to antibiotics recommended as first-line therapies. The present investigation was carried out to demonstrate the current status of antimicrobial susceptibility of N. gonorrhoeae with a special reference to azithromycin and ceftriaxone. METHODS: Microscopical detection in Gram-stained smear and isolation by culture in Thayer-Martin medium were done for 60 clinically suspected gonorrhea patients using urethral discharge or prostatic secretion for male and endocervical secretion for female. Isolates of N. gonorrhoeae were subjected to antimicrobial susceptibility testing by modified Kirby Bauer disk diffusion method against eight antimicrobial drugs including azithromycin and ceftriaxone. RESULTS: Culture yielded a total of 25(42%) isolates of N. gonorrhoeae from 60 clinically suspected patients of both sexes; 21 from male (17 from urethral discharge and 04 from prostatic secretion) and 04 from female (endocervical secretion). Isolates of N. gonorrhoeae showed moderate to high resistance (60 to 88%) to penicillin, tetracycline, cotrimoxazole, erythromycin, ciprofloxacin and cefixime. While resistance to azithromycin and ceftriaxone was 60% and 48% respectively, which was also moderate. CONCLUSION: Our findings indicate moderate to the high resistance of N. gonorrhoeae to conventional antibiotics. It also showed moderate resistance to azithromycin and ceftriaxone, current dual therapy recommended by the WHO for the treatment of genital gonorrhea, which is alarming.

Effects of In-country and Cross-Border Mobility on Condom Use Among Transgender Women (hijras) in Bangladesh: A Cross-Sectional Study.

In Bangladesh transgender women (hijras) are thought to be highly mobile that may be an impediment to condom use. This cross-sectional study was conducted to determine the extent of mobility of hijras, in-country and cross-border, and whether mobility affects condom use in anal intercourse. Hijras ≥15 years of age, receiving services from the Global Fund supported HIV prevention program were enrolled. A behavioral questionnaire was administered and blood was tested for antibodies to HIV and syphilis. Of 889 hijras sampled, 41.3 % never traveled, 26.4 % traveled in-country and 32.3 % crossed the border in the last year. HIV and active syphilis was at 0.8 and 1.8 % respectively. Among hijras who crossed the border condom use was less likely in last anal intercourse (AOR 0.68; 95 % CI 0.48-0.96), and consistently with new (AOR 0.59; 95 % CI 0.34-1.01) and regular clients (AOR 0.45; 95 % CI 0.27-0.76) in the last week. This study concludes that in Bangladesh hijras are highly mobile and cross-border mobility negatively affects condom use.

Effects of resveratrol on growth and skeletal muscle physiology of juvenile southern flounder.

Resveratrol is a naturally occurring antioxidant that has been widely studied in mammals due to its potential to extend lifespan. However, antioxidants may also limit protein damage and therefore reduce rates of protein degradation, providing a potential avenue for enhancing growth in an aquaculture setting. The present study tested the hypotheses that in Southern flounder, Paralichthys lethostigma, resveratrol would decrease protein carbonylation and 4-HNE (indicators of protein and lipid oxidative damage, respectively), levels of ubiquitinylation and LC3 (indicators of non-lysosomal and lysosomal protein degradation, respectively), while having no effect on S6K activation (indicator of protein synthesis). These effects were predicted to increase growth rate. Mitochondrial volume density was also examined since resveratrol may lead to the proliferation of mitochondria, which are the principal source of reactive oxygen species (ROS) that cause oxidative damage. Juvenile fish (n=142) were fed a control diet or a diet supplemented with 600 µg resveratrol per g of food for 16 weeks. Fish treated with resveratrol had a 9% greater length and 33% greater body mass than control fish after 16 weeks. Additionally, there was lower protein carbonylation and lipid 4-HNE within the muscle tissues of treated fish, indicating decreased oxidative damage, and reduced protein ubiquitinylation in the resveratrol fed flounder, indicating less protein degradation. However, there was not a significant difference in LC3, S6K activation, or mitochondrial volume density. These results suggest that resveratrol has positive effects on growth due to its antioxidant properties that reduce non-lysosomal protein degradation.

Performance Impact of Lead-Free CsSn0.5Ge0.5I3 Based Perovskite Solar Cells with HTL-Free Incorporation.

Lead-containing halide perovskites show promise for solar energy but pose ecological and health risks. To address these, researchers are exploring inorganic binary metal perovskites. This study proposes an eco-friendly, durable hole transport layer (HTL)-free design of CsSn0.5Ge0.5I3 with high power conversion efficiency (PCE). Using the SCAPS-1D simulator, we assessed the efficiency of an HTL-free planar heterojunction, while the Density Functional Theory (DFT)-based CASTEP simulator evaluated the optical properties of CsSn0.5Ge0.5I3 in an orthorhombic structure. Key findings highlight enhanced performance under 100 Wm-2 AM 1.5G illumination by optimizing absorber layer thickness to 800 nm and reducing defect densities in both the perovskite absorber layer and interfaces to 1 × 1014 cm-3.Additonally, the effects of different electron transport materials (ETMs), optimization of electron transport layer (ETL) thickness (30-50 nm), and back contact design improvements were examined. The simulation's results included an increase over the highest values reported in the literature: an open circuit voltage (Voc) of 1.06 V, a short circuit current density (Jsc) of 28.52 mA/cm2, a fill factor (FF) of 86.57%, and a PCE of 26.18% for the FTO/Zn0.875Mg0.125O/CsSn0.5Ge0.5I3/Se perovskite solar cell (PSC). This research provides theoretical insights for developing high-efficiency power modules without HTLs with significant industrial and research potential.

Vertebral Artery Injury in Cervical Spine Fracture Dislocation: An Observational Study in a Tertiary Care Center.

BACKGROUND: The incidence of traumatic vertebral artery injury (VAI) associated with cervical spine trauma varies widely in published trauma series. The primary aim of this study was to determine the incidence of traumatic VAI in patients who suffered cervical spine injuries by means of routine magnetic resonance imaging, and the secondary objective was to identify any associations with injury mechanism, level of injury, and neurologic injury severity.  Materials and methods: A retrospective review was conducted on 96 patients who suffered cervical spine fracture dislocation with or without an associated spinal cord injury (SCI) in Indian Spinal Injuries Center (ISIC), New Delhi, India from January 2013 to April 2023. Cervical magnetic resonance imaging (MRI) was used to diagnose VAI. Patient's age, sex, cervical injury level, mechanism of injury, neurologic level of injury, association with foraminal fracture, facet dislocation, and clinical sequelae of vertebral artery injury were analyzed. RESULTS: In this study, of 96 patients who met the inclusion criteria, 18 patients (18.75%) had VAI on the MRI study. Thirteen (72.22%) of the eighteen patients had right-sided injuries, four (22.22%) had left-sided injuries, and one (5.55%) had bilateral injuries. There was an associated SCI in every VAI patient. VAI was significantly more common in patients who had ASIA A (61%, n = 11) and ASIA B (22%, n = 4) injuries, and no VAI was noted in neurologically intact patients (p<0.001). The incidence of VAI was higher in the flexion distraction type of injury (n = 12, 66%). The most commonly involved cervical spine injury level was C5-C6 (27%, n = 5), followed by 22% (n = 4) at C4-C5 and C6-C7 levels. About 27.8% (n = 5) of VAI was associated with foraminal fractures, and 72% (n = 13) of VAI was associated with facet dislocations, of which 44% (n = 8) were bifacetal and 28% (n = 5) were unifacetal dislocations. On clinical symptoms, only one (5.56%) patient had a headache, and 17 (94.4%) had no clinical features due to VAI. CONCLUSION: The incidence of traumatic vertebral artery disease is not very uncommon and requires careful and meticulous screening and management. Otherwise, complications like pseudoaneurysm, neurologic deficit, late-onset hemorrhage, infarction, and death can happen. Mostly, it is associated with high-velocity injuries and neurological injuries. MRI can be used as a good screening tool, which can be aided by a CT angiogram or digital subtraction angiography for confirmation. Proper pre-operative evaluation of vascular injury in cervical spine fracture dislocation is very important for patient counseling, patient management, and surgical planning.

Exploring phosphate impact on arsenate uptake and distribution in freshwater phytoplankton: Insights from single-cell ICP-MS.

In this study, we investigated the interaction between arsenate (AsV) and phosphate (PO43-) in freshwater phytoplankton using single-cell inductively coupled plasma mass spectrometry (SC-ICP-MS). This study aimed to elucidate the influence of varying PO43- concentrations on arsenic (As) uptake and distribution at the single-cell level, providing insights into intraspecies diversity. Two species of freshwater phytoplanktons, Scenedesmus acutus and Pediastrum duplex, were cultured under different concentrations of PO43- and AsV in a controlled laboratory environment. Scenedesmus acutus, a species with strong salt tolerance, and Pediastrum duplex, known for its weak salt tolerance, were selected based on their contrasting behaviors in previous studies. SC-ICP-MS revealed non-uniform uptake of As by individual phytoplankton cells, with distinct variations in response to PO43- availability. Arsenic uptake by both species declined with a high PO43- level after 7 days of exposure. However, after 14 days, As uptake increased in S. acutus with higher PO43- concentrations, but decreased in P. duplex. Moreover, our findings revealed differences in cell morphology and membrane integrity between the two species in response to AsV and various PO43- concentrations. S. acutus maintained cell integrity under all experimental culture conditions, whereas P. duplex experienced cell lysis at elevated AsV and PO43- concentrations. This study highlights the varying responses of freshwater phytoplankton to changes in AsV and PO43- levels and underscores the advantages of SC-ICP-MS over conventional ICP-MS in providing detailed, cellular level insights. These findings are crucial for understanding and managing As pollution in aquatic ecosystems.

Discovery of N-(1-(6-Oxo-1,6-dihydropyrimidine)-pyrazole) Acetamide Derivatives as Novel Noncovalent DprE1 Inhibitors against Mycobacterium tuberculosis.

Decaprenylphosphoryl-ß-d-ribose oxidase (DprE1) is a promising target for treating tuberculosis (TB). Currently, most novel DprE1 inhibitors are discovered through high-throughput screening, while computer-aided drug design (CADD) strategies are expected to promote the discovery process. In this study, with the aid of structure-based virtual screening and computationally guided design, a series of novel scaffold N-(1-(6-oxo-1,6-dihydropyrimidine)-pyrazole) acetamide derivatives with significant antimycobacterial activities were identified. Among them, compounds LK-60 and LK-75 are capable of effectively suppressing the proliferation of Mtb with MICMtb values of 0.78-1.56 µM, comparable with isoniazid and much superior to the phase II candidate TBA-7371 (MICMtb = 12.5 µM). LK-60 is also the most active DprE1 inhibitor derived from CADD so far. Further studies confirmed their high affinity to DprE1, good safety profiles to gut microbiota and human cells, and synergy effects with either rifampicin or ethambutol, indicating their broad potential for clinical applications.

Investigating the role of MAB_1915 in intrinsic resistance to multiple drugs in Mycobacterium abscessus.

The increasing clinical significance of Mycobacterium abscessus is owed to its innate high-level, broad-spectrum resistance to antibiotics and therefore rapidly evolves as an important human pathogen. This warrants the identification of novel targets for aiding the discovery of new drugs or drug combinations to treat M. abscessus infections. This study is inspired by the drug-hypersensitive profile of a mutant M. abscessus (U14) with transposon insertion in MAB_1915. We validated the role of MAB_1915 in intrinsic drug resistance in M. abscessus by constructing a selectable marker-free in-frame deletion in MAB_1915 and complementing the mutant with the same or extended version of the gene and then followed by drug susceptibility testing. Judging by the putative function of MAB_1915, cell envelope permeability was studied by ethidium bromide accumulation assay and susceptibility testing against dyes and detergents. In this study, we established genetic evidence of the role of MAB_1915 in intrinsic resistance to rifampicin, rifabutin, linezolid, clarithromycin, vancomycin, and bedaquiline. Disruption of MAB_1915 has also been observed to cause a significant increase in cell envelope permeability in M. abscessus. Restoration of resistance is observed to depend on at least 27 base pairs upstream of the coding DNA sequence of MAB_1915. MAB_1915 could therefore be associated with cell envelope permeability, and hence its role in intrinsic resistance to multiple drugs in M. abscessus, which presents it as a novel target for future development of effective antimicrobials to overcome intrinsic drug resistance in M. abscessus. IMPORTANCE: This study reports the role of a putative fadD (MAB_1915) in innate resistance to multiple drugs by M. abscessus, hence identifying MAB_1915 as a valuable target and providing a baseline for further mechanistic studies and development of effective antimicrobials to check the high level of intrinsic resistance in this pathogen.

Efficacy, Safety, and Reliability of the Single Anterior Approach for Subaxial Cervical Spine Dislocation.

Background Though there is ongoing controversy regarding the best treatment option for cervical spine dislocation (CSD), anterior cervical surgery with direct decompression is becoming widely accepted. However, managing all cases of subaxial CSD entirely by a single anterior approach is rarely seen in the published literature. Methods The study comprised patients with subaxial CSD who underwent surgical stabilization utilizing a single anterior approach. Most of the CSD was reduced and anterior cervical discectomy and fusion (ACDF) were performed. Anterior cervical corpectomy and fusion (ACCF) were done in unreduced dislocations. The patient's neurological condition, radiological findings, and functional outcomes were assessed. SPSS version 25.0 (IBM Corp., Armonk, NY) was used for statistical analysis. Results The total number of operated cases was 64, with an average of 42 months of follow-up. The mean age was 34.50±11.92 years. The most prevalent level of injury was C5/C6 (57.7%). Reduction was achieved in 92.2% of cases; only 7.8% of patients needed corpectomy. The typical operative time was 84.25±9.55 minutes, with an average blood loss of 112.12±25.27 ml. All cases except complete spinal cord injury (CSI) were improved neurologically (87.63%). The mean Neck Disability Index (NDI) was 11.14±11.43, and the pre-operative mean visual analog score (VAS) was finally improved to 2.05±0.98 (P<0.05). In all cases, fusion was achieved. The most common complication was transient dysphagia (23.4%). After surgery, no patient developed or aggravated a neurological impairment. Implant failure was not observed at the final follow-up except for two cases where screws were pulled out partially. Conclusion Based on the results of this study, a single anterior approach is a safe and effective procedure for subaxial CSD treatment with favorable radiological, neurological, and functional outcomes.

Long-Segment Versus Short-Segment Pedicle Screw Fixation Including Fractured Vertebrae for the Management of Unstable Thoracolumbar Burst Fractures.

Background For the treatment of unstable thoracolumbar fractures, this study compared the results of short-segment fixation with fracture level inclusion (SSFIFL) with long-segment pedicle fixation (LSPF). Methodology In this prospective case series study conducted from January 2015 to January 2019, 80 patients with partial spinal cord lesions were investigated. For the comparison, two groups of 40 patients each were chosen and treated with SSFIFL and LSPF. The outcomes were measured using pre and postoperative radiological parameters and clinical parameters. The radiographic variables included the kyphotic angle with loss of correction, kyphotic deformation, and the Beck index. Mean blood loss, operative time, and cost-effectiveness were also examined for clinical indicators such as the American Spinal Injury Association Impairment Scale, Visual Analog Scale (VAS), and Oswestry Disability Index (ODI). Results There were no substantial variations between the groups regarding age or gender, trauma etiology, fracture level, or fracture pattern. Between the two categories, there appeared to be no notable change in radiological indicators such as kyphotic angle, kyphotic deformation, and Beck index at the end of follow-up (p = 0.120, 0.360, and 0.776, respectively). Both groups had similar neurological outcomes (p = 0.781). In terms of ODI and VAS, statistically, there was no discernible difference (p = 0.567 and 0.161, respectively). In this study, however, there was less surgical time, blood loss, and implant cost (p = 0.05). Conclusions When fracture level is included in a short-segment fixation, the radiological and clinical results are comparable to long-segment posterior fixation. Ultimately, this treatment has proven to be not only a motion segment-saving procedure but also cost-effective.

Trends and inequity in improved sanitation facility utilisation in Bangladesh: Evidence from Bangladesh Demographic and Health Surveys.

Improved sanitation is indispensable to human health. However, lack of access to improved sanitation remains one of the most daunting public health challenges of the twenty-first century in Bangladesh. The aim of the study was to describe the trends in access to improved sanitation facilities following the inequity gap among households in different socioeconomic groups in Bangladesh. Data from the Bangladesh Demographic and Health Survey (BDHS) 2007, 2011, 2014, and 2017-18 were extracted for this study. Inequity in access to improved sanitation was calculated using rich-poor ratio and concentration index to determine the changes in inequity across the time period. In Bangladesh, the proportion of households with access to improved sanitation increased steadily from 25.4% to 45.4% between 2007 and 2014, but slightly decreased to 44.0% in 2017-18. Age, educational status, marital status of household head, household wealth index, household size, place of residence, division, and survey year were significantly associated with the utilisation of improved sanitation. There is a pro-rich situation, which means that utilisation of improved sanitation was more concentrated among the rich across all survey years (Concentration Index ranges: 0.40 to 0.27). The government and other relevant stakeholders should take initiatives considering inequity among different socioeconomic groups to ensure the use of improved sanitation facilities for all, hence achieving universal health coverage.

Novel Derivatives of Quinoxaline-2-carboxylic Acid 1,4-Dioxides as Antimycobacterial Agents: Mechanistic Studies and Therapeutic Potential.

The World Health Organization (WHO) reports that tuberculosis (TB) is one of the top 10 leading causes of global mortality. The increasing incidence of multidrug-resistant TB highlights the urgent need for an intensified quest to discover innovative anti-TB medications In this study, we investigated four new derivatives from the quinoxaline-2-carboxylic acid 1,4-dioxide class. New 3-methylquinoxaline 1,4-dioxides with a variation in substituents at positions 2 and 6(7) were synthesized via nucleophilic aromatic substitution with amines and assessed against a Mycobacteria spp. Compound 4 showed high antimycobacterial activity (1.25 µg/mL against M. tuberculosis) and low toxicity in vivo in mice. Selection and whole-genomic sequencing of spontaneous drug-resistant M. smegmatis mutants revealed a high number of single-nucleotide polymorphisms, confirming the predicted mode of action of the quinoxaline-2-carboxylic acid 1,4-dioxide 4 as a DNA-damaging agent. Subsequent reverse genetics methods confirmed that mutations in the genes MSMEG_4646, MSMEG_5122, and MSMEG_1380 mediate resistance to these compounds. Overall, the derivatives of quinoxaline-2-carboxylic acid 1,4-dioxide present a promising scaffold for the development of innovative antimycobacterial drugs.

Molecular mechanisms of resistance and treatment efficacy of clofazimine and bedaquiline against Mycobacterium tuberculosis.

Clofazimine (CFZ) and bedaquiline (BDQ) are currently used for the treatment of multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) strains. In recent years, adding CFZ and BDQ to tuberculosis (TB) drug regimens against MDR Mtb strains has significantly improved treatment results, but these improvements are threatened by the emergence of MDR and extensively drug-resistant (XDR) Mtb strains. Recently, CFZ and BDQ have attracted much attention for their strong clinical efficacy, although very little is known about the mechanisms of action, drug susceptibility test (DST), resistance mechanisms, cross-resistance, and pharmacokinetics of these two drugs. In this current review, we provide recent updates on the mechanisms of action, DST, associated mutations with individual resistance and cross-resistance, clinical efficacy, and pharmacokinetics of CFZ and BDQ against Mtb strains. Presently, known mechanisms of resistance for CFZ and/or BDQ include mutations within the Rv0678, pepQ, Rv1979c, and atpE genes. The cross-resistance between CFZ and BDQ may reduce available MDR-/XDR-TB treatment options. The use of CFZ and BDQ for treatment in the setting of limited DST could allow further spread of drug resistance. The DST and resistance knowledge are urgently needed where CFZ and BDQ resistance do emerge. Therefore, an in-depth understanding of clinical efficacy, DST, cross-resistance, and pharmacokinetics for CFZ and BDQ against Mtb can provide new ideas for improving treatment outcomes, reducing mortality, preventing drug resistance, and TB transmission. Along with this, it will also help to develop rapid molecular diagnostic tools as well as novel therapeutic drugs for TB.

Climatic factors influencing dengue cases in Dhaka city: a model for dengue prediction.

BACKGROUND & OBJECTIVES: Transmission of dengue virus depends on the presence of Aedes mosquito. Mosquito generation and development is known to be influenced by the climate. This study was carried out to examine whether the climatic factors data can be used to predict yearly dengue cases of Dhaka city, Bangladesh. METHODS: Monthly reported dengue cases and climate data for the years 2000-2008 were obtained from the Directorate General of Health Services (DGHS) and Meteorological Department of Dhaka, Bangladesh, respectively. Data for the period 2000 to 2007 were used for development of a model through multiple linear regressions. Retrospective validation of the model was done with 2001, 2003, 2005 and 2008 data. Log transformation of the dependent variable was done to normalize data for linear regression. Average monthly humidity, rainfall, minimum and maximum temperature were used as independent variables and number of dengue cases reported monthly was used as dependent variable. Accuracy of the model for predicting outbreak was assessed through receiver operative characteristics (ROC) curve. RESULTS: Climatic factors, i.e. rainfall, maximum temperature and relative humidity were significantly correlated with monthly reported dengue cases. The model incorporating climatic data of two-lag month explained 61 per cent of variation in number of reported dengue cases and this model was found to predict dengue outbreak (≥ 200 cases) with considerable accuracy [area under ROC curve = 0.89, 95%CI = (0.89-0.98)]. INTERPRETATION & CONCLUSIONS: Our results showed that the climate had a major effect on the occurrence of dengue infection in Dhaka city. Though the prediction model had some limitations in predicting the monthly number of dengue cases, it could forecast possible outbreak two months in advance with considerable accuracy.