Using timeliness metrics for household contact tracing and TB preventive therapy in the private sector, India.

Although screening of household contacts (HHCs) of TB patients and provision of TB preventive therapy (TPT) is a key intervention to end the TB epidemic, their implementation globally is dismal. We assessed whether introducing a '7-1-7' timeliness metric was workable for implementing HHC screening among index patients with pulmonary TB diagnosed by private providers in Chennai, India, between November 2022 and March 2023.This was an explanatory mixed-methods study (quantitative-cohort and qualitative-descriptive).There were 263 index patients with 556 HHCs. In 90% of index patients, HHCs were line-listed within 7 days of anti-TB treatment initiation. Screening outcomes were ascertained in 48% of HHCs within 1 day of line-listing. Start of anti-TB treatment, TPT or a decision to receive neither was achieved in 57% of HHC within 7 days of screening. Overall, 24% of screened HHCs in the '7-1-7' period started TPT compared with 16% in a historical control (P < 0.01). Barriers to achieving '7-1-7' included HHC reluctance for evaluation or TPT, refusal of private providers to prescribe TPT and reliance on facility-based screening of HHCs instead of home visits by health workers for screening.Introduction of a timeliness metric is a workable intervention that adds structure to HHC screening and timely management..

Does Pectoralis Major Myocutaneous Flap Cause the Shoulder Morbidity: A Clinical Comparative Study.

The aim was to compare the morbidity of shoulder function following modified radical neck dissection with and without Pectoralis Major Myocutaneous muscle flap (PMMC) harvest in head and neck cancer patient to determine the effect of PMMC flap harvest on shoulder function and also to determine the effect of physiotherapy. Materials and methods: Prospective study involving two groups study group of 20 patients with MRND, with PMMC flap reconstruction as part of head and neck cancer surgery and control group of 20 patients who had undergone MRND(IJV & SAN sparing) without PMMC flap in same period were included. All patients were assessed at 3rd and 6th month following completion of surgery using subjective (Shoulder Disability Questionnaire) and objective (goniometer and manual muscle testing) parameters. 40 patients were included in the study, 33 (82.5%) male and 7 (17.5%) female with a mean age of 49 years with stage III/IV carcinoma In Group-1 and Group-2 the shoulder disability decreased significantly after physiotherapy intervention and also at 6thmonth postoperatively both groups showed improvements in shoulder range of motion and muscle strength. Harvesting of PMMC flap does not intensify the morbidity of shoulder which is common in RND and during MRND. A regimen of home-based exercises and patient education are effective tools to reduce shoulder disability and improving shoulder function.

Rehabilitation of a Midfacial Defect Using a Two-Piece Maxillofacial Prosthesis: A Case Report.

Maxillofacial defects and their rehabilitation are a major concern in this socially productive era. The rehabilitation of these massive defects in the oral and maxillofacial region poses a challenge to the prosthodontist in terms of selection of material, retentive aids, the adaptive capability of the patient, and cost. This case report describes the management of the midfacial defect involving the orbit, zygoma, maxilla, and their soft tissue counterparts with a removable silicone extraoral compartment and an acrylic intraoral compartment, which are retained with strong cobalt samarium magnets, an elastic loop around the occiput, and spectacles. The maxillofacial prosthesis fabricated for this patient restored the patient's facial esthetics, speech, dental articulation, lip support, mastication, and anterior maxillary seal.

Synthesis, spectral studies, DNA binding, photocleavage, antimicrobial and anticancer activities of isoindol Ru(II) polypyridyl complexes.

Three new Ru(II) polypyridyl complexes [Ru(phen)2CIIP]2+ (1) {CIIP = 2-(5-Chloro-3a H-Isoindol-3-yl)-1H-Imidazo[4,5-f][1, 10]phenantholine} (phen = 1, 10 phenanthroline), [Ru(bpy)2CIIP]2+ (2) (bpy = 2, 2' bipyridine) and [Ru(dmb)2CIIP]2+ (3) (dmb = 4, 4'-dimethyl 2, 2' bipyridine) were synthesized and characterized by different spectral methods. The DNA-binding behavior of these complexes was investigated by absorption, emission spectroscopic titration and viscosity measurements, indicating that these three complexes bind to CT-DNA in an intercalative mode, but binding affinities of these complexes were different. The DNA-binding constants Kb of complexes 1, 2 and 3 were calculated in the order of 106. All three complexes cleave pBR322 DNA in photoactivated cleavage studies and exhibit good antimicrobial activity. Anticancer activity of these Ru(II) complexes was evaluated in MCF7 cells. Cytotoxicity by MTT assay showed growth inhibition in a dose dependent manner. Cell cycle analysis by flow cytometry data showed an increase in Sub G1 population. Annexin V FITC/PI staining confirms that these complexes cause cell death by the induction of apoptosis.

Anti-vascular endothelial growth factor for neovascular age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is the most common cause of uncorrectable severe vision loss in people aged 55 years and older in the developed world. Choroidal neovascularization (CNV) secondary to AMD accounts for most cases of AMD-related severe vision loss. Intravitreous injection of anti-vascular endothelial growth factor (anti-VEGF) agents aims to block the growth of abnormal blood vessels in the eye to prevent vision loss and, in some instances, to improve vision. OBJECTIVES: • To investigate ocular and systemic effects of, and quality of life associated with, intravitreous injection of three anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) versus no anti-VEGF treatment for patients with neovascular AMD• To compare the relative effects of one of these anti-VEGF agents versus another when administered in comparable dosages and regimens SEARCH METHODS: To identify eligible studies for this review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Eyes and Vision Trials Register (searched January 31, 2018); MEDLINE Ovid (1946 to January 31, 2018); Embase Ovid (1947 to January 31, 2018); the Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to January 31, 2018); the International Standard Randomized Controlled Trials Number (ISRCTN) Registry (www.isrctn.com/editAdvancedSearch - searched January 31, 2018); ClinicalTrials.gov (www.clinicaltrials.gov - searched November 28, 2018); and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en - searched January 31, 2018). We did not impose any date or language restrictions in electronic searches for trials. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that evaluated pegaptanib, ranibizumab, or bevacizumab versus each other or versus a control treatment (e.g. sham treatment, photodynamic therapy), in which participants were followed for at least one year. DATA COLLECTION AND ANALYSIS: Two review authors independently screened records, extracted data, and assessed risks of bias. We contacted trial authors for additional data. We compared outcomes using risk ratios (RRs) or mean differences (MDs). We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 16 RCTs that had enrolled a total of 6347 participants with neovascular AMD (the number of participants per trial ranged from 23 to 1208) and identified one potentially relevant ongoing trial. Six trials compared anti-VEGF treatment (pegaptanib, ranibizumab, or bevacizumab) versus control, and 10 trials compared bevacizumab versus ranibizumab. Pharmaceutical companies conducted or sponsored four trials but funded none of the studies that evaluated bevacizumab. Researchers conducted these trials at various centers across five continents (North and South America, Europe, Asia, and Australia). The overall certainty of the evidence was moderate to high, and most trials had an overall low risk of bias. All but one trial had been registered prospectively.When compared with those who received control treatment, more participants who received intravitreous injection of any of the three anti-VEGF agents had gained 15 letters or more of visual acuity (risk ratio [RR] 4.19, 95% confidence interval [CI] 2.32 to 7.55; moderate-certainty evidence), had lost fewer than 15 letters of visual acuity (RR 1.40, 95% CI 1.27 to 1.55; high-certainty evidence), and showed mean improvement in visual acuity (mean difference 6.7 letters, 95% CI 4.4 to 9.0 in one pegaptanib trial; mean difference 17.8 letters, 95% CI 16.0 to 19.7 in three ranibizumab trials; moderate-certainty evidence) after one year of follow-up. Participants treated with anti-VEGF agents showed improvement in morphologic outcomes (e.g. size of CNV, central retinal thickness) compared with participants not treated with anti-VEGF agents (moderate-certainty evidence). No trial directly compared pegaptanib versus another anti-VEGF agent and followed participants for one year; however, when compared with control treatments, ranibizumab and bevacizumab each yielded larger improvements in visual acuity outcomes than pegaptanib.Visual acuity outcomes after bevacizumab and ranibizumab were similar when the same RCTs compared the same regimens with respect to gain of 15 or more letters of visual acuity (RR 0.95, 95% CI 0.81 to 1.12; high-certainty evidence) and loss of fewer than 15 letters of visual acuity (RR 1.00, 95% CI 0.98 to 1.02; high-certainty evidence); results showed similar mean improvement in visual acuity (mean difference [MD] -0.5 letters, 95% CI -1.5 to 0.5; high-certainty evidence) after one year of follow-up, despite the substantially lower cost of bevacizumab compared with ranibizumab. Reduction in central retinal thickness was less among bevacizumab-treated participants than among ranibizumab-treated participants after one year (MD -11.6 µm, 95% CI -21.6 to -1.7; high-certainty evidence); however, this difference is within the range of measurement error, and we did not interpret it to be clinically meaningful.Ocular inflammation and increased intraocular pressure (IOP) after intravitreal injection were the most frequently reported serious ocular adverse events. Researchers reported endophthalmitis in less than 1% of anti-VEGF-treated participants and in no cases among control groups. The occurrence of serious systemic adverse events was comparable across anti-VEGF-treated groups and control groups; however, the numbers of events and trial participants may have been insufficient to show a meaningful difference between groups (evidence of low- to moderate-certainty). Investigators rarely measured and reported data on visual function, quality of life, or economic outcomes. AUTHORS' CONCLUSIONS: Results of this review show the effectiveness of anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) in terms of maintaining visual acuity; studies show that ranibizumab and bevacizumab improved visual acuity in some eyes that received these agents and were equally effective. Available information on the adverse effects of each medication does not suggest a higher incidence of potentially vision-threatening complications with intravitreous injection of anti-VEGF agents compared with control interventions; however, clinical trial sample sizes were not sufficient to estimate differences in rare safety outcomes. Future Cochrane Reviews should incorporate research evaluating variable dosing regimens of anti-VEGF agents, effects of long-term use, use of combination therapies (e.g. anti-VEGF treatment plus photodynamic therapy), and other methods of delivering these agents.

Study of the interaction of Co(III) polypyridyl complexes with DNA: an experimental and computational approach.

Three new cobalt(III) polypyridyl complexes, [Co(L - L)2IIP]3+ where IIP = 2-(2H-isoindol-1-yl)-2H-imidazo[4,5-f][1, 10]phenanthroline, L = 1) phen (1,10-phenanthroline), 2) bpy (2,2'bipyridyl), 3) dmb (4, 4-dimethyl 2, 2'-bipyridine) have been synthesized, characterized (UV -VIS, IR, 1HNMR and 13C NMR spectroscopy) and screened for their in vitro antibacterial activity against E.coli, Staphylococcus aureus and Bacillus subtilis. The binding of these complexes with calf-thymus DNA (CT-DNA) has been investigated by absorption and fluorescence spectroscopy, viscosity measurements. The experimental studies indicate that complexes bind to CT-DNA by means of intercalation, but with different binding affinities due to differences in the planarity of the ancillary ligand. The complexes promote photocleavage of plasmid DNA from super coiled form I to the open circular form II. The antibacterial activities suggest that the metal complexes are more active as compared to the prepared un-complexed IIP ligand. In addition, a conformational search was carried out by Molecular Dynamics Simulations, and docking revealed that complexes intercalate between base pairs of DNA. The experimental and computational approaches reveal that the length of the intercalator and the nature of ancillary ligand are highly important factors for DNA binding.

How can integrated care and research assist in achieving the SDG targets for diabetes, tuberculosis and HIV/AIDS?

Integrating the management and care of communicable diseases, such as tuberculosis (TB) and human immunodeficiency virus/acquired immune-deficiency syndrome (HIV/AIDS), and non-communicable diseases, particularly diabetes mellitus (DM), may help to achieve the ambitious health-related targets of the Sustainable Development Goals (SDG 3.3 and 3.4) by 2030. There are five important reasons to integrate. First, we need to integrate to prevent disease. In sub-Saharan Africa, in particular, HIV infection is the main driver of the TB epidemic, and antiretroviral therapy combined with isoniazid preventive therapy (IPT) can reduce TB case notification rates. In Asia, DM is another important driver of the TB epidemic, and preventing or controlling DM can reduce the risk of TB. Second, we need to integrate to diagnose cases. Between a third to a half of those living with HIV, TB or DM do not know they have the disease, and bi-directional screening, whereby TB patients are screened for HIV and DM or people living with HIV and DM are screened for TB, can help to identify these 'missing cases'. Third, we need to integrate to better treat and manage patients who have a combination of two or more of these diseases, so that treatment success and retention on treatment can be optimised. Fourth, we should integrate to ensure better infection control practices for both TB and HIV infection in health facilities and congregate settings, such as prisons. Finally, we should integrate and learn how to monitor, record and report, particularly in relation to the cascade of events implicit in the HIV/AIDS and TB 90-90-90 targets.

Treatment outcome of tuberculosis patients detected using accelerated vs. passive case finding in Myanmar.

SETTING: Several projects involving accelerated or active case finding (ACF) of tuberculosis (TB) cases are being implemented in Myanmar. However, there is a concern that patients detected using ACF have poorer TB treatment outcomes than those detected using passive case finding (PCF). OBJECTIVE: To assess differences in the demographics, clinical profile and treatment outcomes of patients detected using ACF and PCF. DESIGN: Retrospective cohort study of TB patients diagnosed and enrolled for treatment during 2014-2016. RESULTS: Of 16 048 patients enrolled, 2226 (16%) were detected using ACF; the treatment success rate (cured and completed) was 88%. A higher proportion of cases detected using ACF were aged 55 years, human immunodeficiency virus (HIV) negative and sputum smear-positive pulmonary TB. After adjusting for differences in demographic and clinical characteristics, we found that treatment outcomes in patients detected using ACF and PCF were not significantly different (adjusted relative risk [aRR] 0.89, 95%CI 0.78-1.00). Male sex, age  55 years, patients with a previous history of TB and HIV positivity were independently associated with unsuccessful outcomes. CONCLUSION: ACF detected a significant proportion of TB cases in study townships; treatment outcomes in cases detected using ACF and those detected using PCF were similar. More tailored interventions are needed to improve treatment outcomes in patients at a higher risk of unsuccessful treatment outcomes.

Evaluation of a tuberculosis active case finding project in peri-urban areas, Myanmar: 2014-2016.

OBJECTIVES: We assessed the effect of an active case finding (ACF) project on tuberculosis (TB) case notification and the yields from a household and neigbourhood intervention (screening contacts of historical index TB patients diagnosed >24months ago) and a community intervention (screening attendants of health education sessions/mobile clinics). DESIGN: Cross-sectional analysis of project records, township TB registers and annual TB reports. RESULTS: In the household and neigbourhood intervention, of 56,709 people screened, 1,076 were presumptive TB and 74 patients were treated for active TB with a screening yield of 0.1% and a yield from presumptive cases of 6.9%. In the community intervention, of 162,881 people screened, 4,497 were presumptive TB and 984 were treated for active TB with a screening yield of 0.6% and yield from presumptive cases of 21.9%. Of active TB cases, 94% were new, 89% were pulmonary, 44% were bacteriologically-confirmed and 5% had HIV. Case notification rates per 100,000 in project townships increased from 142 during baseline (2011-2013) to 148 during intervention (2014-2016) periods. CONCLUSIONS: The yield from household and neigbourhood intervention was lower than community intervention. This finding highlights reconsidering the strategy of screening of contacts from historical index cases. Strategies to reach high-risk groups should be explored for future ACF interventions to increase yield of TB.

Surgery for postvitrectomy cataract.

BACKGROUND: Cataract formation or acceleration can occur after intraocular surgery, especially following vitrectomy, a surgical technique for removing the vitreous that is used in the treatment of many disorders that affect the posterior segment of the eye. The underlying problem that led to vitrectomy may limit the benefit from removal of the cataractous lens. OBJECTIVES: To evaluate the effectiveness and safety of surgery versus no surgery for postvitrectomy cataract with respect to visual acuity, quality of life, and other outcomes. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 5), MEDLINE Ovid (1946 to 17 May 2017), Embase.com (1947 to 17 May 2017), PubMed (1946 to 17 May 2017), Latin American and Caribbean Health Sciences Literature database (LILACS) (January 1982 to 17 May 2017), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com); last searched May 2013, ClinicalTrials.gov (www.clinicaltrials.gov); searched 17 May 2017, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 17 May 2017. We did not use any date or language restrictions in the electronic searches for trials. SELECTION CRITERIA: We planned to include randomized controlled trials (RCTs) and quasi-RCTs that had compared surgery versus no surgery to remove the lens from eyes of adults in which cataracts had developed following vitrectomy. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results according to the standard methodological procedures expected by Cochrane. MAIN RESULTS: We found no RCTs or quasi-RCTs that had compared surgery versus no surgery to remove the lens from eyes of adults in which cataracts had developed following vitrectomy. AUTHORS' CONCLUSIONS: There is no evidence from RCTs or quasi-RCTs on which to base clinical recommendations for surgery for postvitrectomy cataract. There is a clear need for RCTs to address this evidence gap. Such trials should stratify participants by their age, the retinal disorder leading to vitrectomy, and the status of the underlying disease process in the contralateral eye. Outcomes assessed in such trials may include changes (both gains and losses) of visual acuity, quality of life, and adverse events such as posterior capsular rupture and retinal detachment. Both short-term (six-month) and long-term (one- or two-year) outcomes should be examined.

Closure methods for laparotomy incisions for preventing incisional hernias and other wound complications.

BACKGROUND: Surgeons who perform laparotomy have a number of decisions to make regarding abdominal closure. Material and size of potential suture types varies widely. In addition, surgeons can choose to close the incision in anatomic layers or mass ('en masse'), as well as using either a continuous or interrupted suturing technique, of which there are different styles of each. There is ongoing debate as to which suturing techniques and suture materials are best for achieving definitive wound closure while minimising the risk of short- and long-term complications. OBJECTIVES: The objectives of this review were to identify the best available suture techniques and suture materials for closure of the fascia following laparotomy incisions, by assessing the following comparisons: absorbable versus non-absorbable sutures; mass versus layered closure; continuous versus interrupted closure techniques; monofilament versus multifilament sutures; and slow absorbable versus fast absorbable sutures. Our objective was not to determine the single best combination of suture material and techniques, but to compare the individual components of abdominal closure. SEARCH METHODS: On 8 February 2017 we searched CENTRAL, MEDLINE, Embase, two trials registries, and Science Citation Index. There were no limitations based on language or date of publication. We searched the reference lists of all included studies to identify trials that our searches may have missed. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared suture materials or closure techniques, or both, for fascial closure of laparotomy incisions. We excluded trials that compared only types of skin closures, peritoneal closures or use of retention sutures. DATA COLLECTION AND ANALYSIS: We abstracted data and assessed the risk of bias for each trial. We calculated a summary risk ratio (RR) for the outcomes assessed in the review, all of which were dichotomous. We used random-effects modelling, based on the heterogeneity seen throughout the studies and analyses. We completed subgroup analysis planned a priori for each outcome, excluding studies where interventions being compared differed by more than one component, making it impossible to determine which variable impacted on the outcome, or the possibility of a synergistic effect. We completed sensitivity analysis, excluding trials with at least one trait with high risk of bias. We assessed the quality of evidence using the GRADEpro guidelines. MAIN RESULTS: Fifty-five RCTs with a total of 19,174 participants met the inclusion criteria and were included in the meta-analysis. Included studies were heterogeneous in the type of sutures used, methods of closure and patient population. Many of the included studies reported multiple comparisons.For our primary outcome, the proportion of participants who developed incisional hernia at one year or more of follow-up, we did not find evidence that suture absorption (absorbable versus non-absorbable sutures, RR 1.07, 95% CI 0.86 to 1.32, moderate-quality evidence; or slow versus fast absorbable sutures, RR 0.81, 95% CI 0.63 to 1.06, moderate-quality evidence), closure method (mass versus layered, RR 1.92, 95% CI 0.58 to 6.35, very low-quality evidence) or closure technique (continuous versus interrupted, RR 1.01, 95% CI 0.76 to 1.35, moderate-quality evidence) resulted in a difference in the risk of incisional hernia. We did, however, find evidence to suggest that monofilament sutures reduced the risk of incisional hernia when compared with multifilament sutures (RR 0.76, 95% CI 0.59 to 0.98, I2 = 30%, moderate-quality evidence).For our secondary outcomes, we found that none of the interventions reduced the risk of wound infection, whether based on suture absorption (absorbable versus non-absorbable sutures, RR 0.99, 95% CI 0.84 to 1.17, moderate-quality evidence; or slow versus fast absorbable sutures, RR 1.16, 95% CI 0.85 to 1.57, moderate-quality evidence), closure method (mass versus layered, RR 0.93, 95% CI 0.67 to 1.30, low-quality evidence) or closure technique (continuous versus interrupted, RR 1.13, 95% CI 0.96 to 1.34, moderate-quality evidence).Similarily, none of the interventions reduced the risk of wound dehiscence whether based on suture absorption (absorbable versus non-absorbable sutures, RR 0.78, 95% CI 0.55 to 1.10, moderate-quality evidence; or slow versus fast absorbable sutures, RR 1.55, 95% CI 0.92 to 2.61, moderate-quality evidence), closure method (mass versus layered, RR 0.69, 95% CI 0.31 to 1.52, moderate-quality evidence) or closure technique (continuous versus interrupted, RR 1.21, 95% CI 0.90 to 1.64, moderate-quality evidence).Absorbable sutures, compared with non-absorbable sutures (RR 0.49, 95% CI 0.26 to 0.94, low-quality evidence) reduced the risk of sinus or fistula tract formation. None of the other comparisons showed a difference (slow versus fast absorbable sutures, RR 0.88, 95% CI 0.05 to 16.05, very low-quality evidence; mass versus layered, RR 0.49, 95% CI 0.15 to 1.62, low-quality evidence; continuous versus interrupted, RR 1.51, 95% CI 0.64 to 3.61, very low-quality evidence). AUTHORS' CONCLUSIONS: Based on this moderate-quality body of evidence, monofilament sutures may reduce the risk of incisional hernia. Absorbable sutures may also reduce the risk of sinus or fistula tract formation, but this finding is based on low-quality evidence.We had serious concerns about the design or reporting of several of the 55 included trials. The comparator arms in many trials differed by more than one component, making it impossible to attribute differences between groups to any one component. In addition, the patient population included in many of the studies was very heterogeneous. Trials included both emergency and elective cases, different types of disease pathology (e.g. colon surgery, hepatobiliary surgery, etc.) or different types of incisions (e.g. midline, paramedian, subcostal).Consequently, larger, high-quality trials to further address this clinical challenge are warranted. Future studies should ensure that proper randomisation and allocation techniques are performed, wound assessors are blinded, and that the duration of follow-up is adequate. It is important that only one type of intervention is compared between groups. In addition, a homogeneous patient population would allow for a more accurate assessment of the interventions.

Correlation Between Molecular Modelling and Spectroscopic Techniques in Investigation With DNA Binding Interaction of Ruthenium(II) Complexes.

The DNA binding studies of rutheniumu(II) polypyridyl complexes {[Ru(phen)2Mipc]2+, [Ru(bpy)2Mipc]2+, [Ru(dmb)2Mipc]2+, [Ru(phen)2BrIPC]2+, [Ru(bpy)2BrIPC]2+, [Ru(dmb)2BrIPC]2+, [Ru(phen)2PIP-Cl]2+, [Ru(bpy)2PIP-Cl]2+, [Ru(dmb)2PIP-Cl]2+, [Ru(phen)2IPPBA]2+, [Ru(bpy)2IPPBA]2+, [Ru(dmb)2IPPBA]2+} with DNA investigated by electronic absorption titration, emission and molecular modelling studies to identify the binding interactions. All these complexes are showing good binding constant values ~104 to 105. The intercalative ligands makes the binding of the ruthenium(II) complex with DNA as intercalation mode. The ancillary ligands 1,10-phenanthroline (phen), 4,4'-Dimethyl-2,2'-dipyridyl (dmb) and 2,2'-dipyridine (bpy) having been discovered found to be involved in bond formation with the phosphate backbone of nucleotide base pairs in ruthenium(II) complex-DNA docked complex. The molecular docking results are good agreement with experimental results. The molecular modelling technic should help to extend knowledge about the nature (or) mode of binding of these ruthenium(II) complexes with (calf thymus) CT-DNA.

Studies on Photocleavage, DNA Binding, Cytotoxicity, and Docking Studies of Ruthenium(II) Mixed Ligand Complexes.

This article describes the synthesis and characterization of three new Ru(II) polypyridyl complexes including [Ru(phen)2(dpphz)]2+ (1), [Ru(bpy)2(dpphz)]2+ (2) and [Ru(dmb)2(dpphz)]2+ (3) where dpphz = dipyrido[3,2-a:2',3'-c] phenazine-11-hydrazide, phen =1,10-phenanthroline, bpy = 2,2'-bipyridine and dmb = 4,4'-dimethyl2,2'-bipyridine. The binding behaviors of these complexes to calf thymus DNA (CT-DNA) were explored by spectroscopic titrations, viscosity measurements. Results suggest that these complexes can bind to CT-DNA through intercalation. However, their binding strength differs from each other; this may be attributed to difference in the ancillary ligand. The cytotoxicity of 1-3 was evaluated by MTT assay; results indicated that all complexes have significant dose dependent cytotoxicity with HeLa tumor cell line. All complexes exhibited efficient photocleavage of pBR322 DNA upon irradiation. The DNA binding ability of 1-3 was also studied by docking the complexes into B-DNA using docking program.

Intravitreal Bevacizumab Versus Ranibizumab for Treatment of Neovascular Age-Related Macular Degeneration: Findings from a Cochrane Systematic Review.

TOPIC: To summarize the relative effects of bevacizumab (Avastin; Genentech, Inc, South San Francisco, CA) and ranibizumab (Lucentis; Genentech, Inc.), using findings from a Cochrane Eyes and Vision Group systematic review. CLINICAL RELEVANCE: Neovascular age-related macular degeneration (NVAMD) is the most common cause of uncorrectable vision loss among the elderly in developed countries. Bevacizumab and ranibizumab are the most frequently used anti-vascular endothelial growth factor (VEGF) agents injected intravitreally to treat NVAMD. METHODS: For this systematic review, we included only randomized controlled trials in which the 2 anti-VEGF agents had been compared directly. The primary outcome was 1-year gain in best-corrected visual acuity (BCVA) of ≥15 letters. We followed Cochrane methods for trial selection, data extraction, and data analyses. Relative effects of bevacizumab versus ranibizumab are presented as estimated risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). RESULTS: We identified 6 eligible randomized controlled trials with 2809 participants. The proportion of eyes that gained ≥15 letters of BCVA by 1 year was similar for the 2 agents when the same regimens were compared (RR, 0.90; 95% CI, 0.73-1.11). The mean change in BCVA from baseline also was similar (MD, -0.5 letter; 95% CI, -1.6 to +0.6). Other BCVA and quality of life outcomes were similar for the 2 agents. One-year treatment cost with ranibizumab was 5.1 and 25.5 times the cost for bevacizumab in the 2 largest trials. Ocular adverse events were uncommon (<1%), and rates were similar for the 2 agents. CONCLUSIONS: We found no important difference in effectiveness or safety between bevacizumab and ranibizumab for NVAMD treatment, but there was a large cost difference.

Diabetes mellitus and tuberculosis: programmatic management issues.

In August 2011, the World Health Organization and the International Union Against Tuberculosis and Lung Disease launched the Collaborative Framework for Care and Control of Tuberculosis (TB) and diabetes mellitus (DM) to guide policy makers and implementers in combatting the epidemics of both diseases. Progress has been made, and includes identifying how best to undertake bidirectional screening for both diseases, how to provide optimal treatment and care for patients with dual disease and the most suitable framework for monitoring and evaluation. Key programmatic challenges include the following: whether screening should be directed at all patients or targeted at those with high-risk characteristics; the most suitable technologies for diagnosing TB and diabetes in routine settings; the best time to screen TB patients for DM; how to provide an integrated, coordinated approach to case management; and finally, how to persuade non-communicable disease programmes to adopt a cohort analysis approach, preferably using electronic medical records, for monitoring and evaluation. The link between DM and TB and the implementation of the collaborative framework for care and control have the potential to stimulate and strengthen the scale-up of non-communicable disease care and prevention programmes, which may help in reducing not only the global burden of DM but also the global burden of TB.

Antiangiogenic activity of mononuclear copper(II) polypyridyl complexes for the treatment of cancers.

A series of four new mononuclear copper(II) polypyridyl complexes (1-4) have been designed, developed, and thoroughly characterized by several physicochemical techniques. The CT-DNA binding properties of 1-4 have been investigated by absorption, emission spectroscopy, and viscosity measurements. All the complexes especially 1 and 4 exhibit cytotoxicity toward several cancer cell lines, suggesting their anticancer properties as observed by several in vitro assays. Additionally, the complexes show inhibition of endothelial cell (HUVECs) proliferation, indicating their antiangiogenic nature. In vivo chick embryo angiogenesis assay again confirms the antiangiogenic properties of 1 and 4. The formation of excessive intracellular ROS (H2O2 and O2(•-)) and upregulation of BAX induced by copper(II) complexes may be the plausible mechanisms behind their anticancer activities. The present study may offer a basis for the development of new transition metal complexes through suitable choice of ligands for cancer therapeutics by controlling tumor angiogenesis.

Model for bidirectional movement of cytoplasmic dynein.

Cytoplasmic dynein exhibits a directional processive movement on microtubule filaments and is known to move in steps of varying length based on the number of ATP molecules bound to it and the load that it carries. It is experimentally observed that dynein takes occasional backward steps and the frequency of such backward steps increases as the load approaches the stall force. Using a stochastic process model, we investigate the bidirectional movement of single head of a dynein motor. The probability for backward step is implemented based on fluctuation theorem of non-equilibrium statistical mechanics. We find that the movement of dynein motor is characterized with negative velocity implying backward motion beyond stall force. We observe that the motor moves backward for super stall forces by hydrolyzing the ATP exactly the same way as it does while moving forward for sub-stall forces. Movement of dynein is also simulated using a kinetic Monte Carlo method and the simulated velocities are in good agreement with velocities obtained using a stochastic rate equation model.

A rho GDP dissociation inhibitor produced by apoptotic T-cells inhibits growth of Mycobacterium tuberculosis.

In this study, we found that a subpopulation of CD4(+)CD25(+) (85% Foxp3(+)) cells from persons with latent tuberculosis infection (LTBI) inhibits growth of M. tuberculosis (M. tb) in human monocyte-derived macrophages (MDMs). A soluble factor, Rho GDP dissociation inhibitor (D4GDI), produced by apoptotic CD4(+)CD25(+) (85% Foxp3(+)) cells is responsible for this inhibition of M. tb growth in human macrophages and in mice. M. tb-expanded CD4(+C)D25(+)Foxp3(+)D4GDI(+) cells do not produce IL-10, TGF-ß and IFN-γ. D4GDI inhibited growth of M. tb in MDMs by enhancing production of IL-1ß, TNF-α and ROS, and by increasing apoptosis of M. tb-infected MDMs. D4GDI was concentrated at the site of disease in tuberculosis patients, with higher levels detected in pleural fluid than in serum. However, in response to M. tb, PBMC from tuberculosis patients produced less D4GDI than PBMC from persons with LTBI. M. tb-expanded CD4+CD25+ (85% Foxp3(+)) cells and D4GDI induced intracellular M. tb to express the dormancy survival regulator DosR and DosR-dependent genes, suggesting that D4GDI induces a non-replicating state in the pathogen. Our study provides the first evidence that a subpopulation of CD4(+)CD25(+) (85% Foxp3+) cells enhances immunity to M. tb, and that production of D4GDI by this subpopulation inhibits M. tb growth.

Synthesis, characterization; DNA binding and antitumor activity of ruthenium(II) polypyridyl complexes.

Three new ruthenium(II) polypyridyl complexes [Ru(phen)2BrIPC](2+) (1), [Ru(bpy)2 BrIPC](2+) (2) and [Ru(dmb)2BrIPC](2+) (3) where, BrIPC = (6-bromo-3-(1H-imidazo[4,5-f] [1,10]-phenanthroline, phen = 1,10-phenanthroline, bpy = 2,2' bipyridine, dmb = 4,4'-dimethyl 2,2' bipyridine, were synthesised and characterised. DNA-binding nature was investigated by spectroscopic titrations and mode of binding was assessed by viscosity measurements. The DNA-binding constants Kb of complexes 1, 2 and 3 were determined to be in the order of 10(5). Experimental results showed that these complexes interact with CT-DNA by intercalative mode. Photocleavage and antimicrobial activities were complex concentration dependent, at high concentration, high activity and vice versa. MTT assay was performed on HeLa cell lines, IC50 values of complexes in the order of 3 > 2 > 1 > cisplatin. From comet assay, cellular uptake studies, we observed that complexes could enter into the cell membrane and accumulate inside the nucleus. Molecular docking studies support the DNA binding affinity with hydrogen bonding and van der Waals attractions between base pairs and phosphate backbone of DNA with metal complexes.