Lessons and implications from a mass immunization campaign in squatter settlements of Karachi, Pakistan: an experience from a cluster-randomized double-blinded vaccine trial [NCT00125047]

OBJECTIVE: To determine the safety and logistic feasibility of a mass immunization strategy outside the local immunization program in the pediatric population of urban squatter settlements in Karachi, Pakistan. METHODS: A cluster-randomized double blind preventive trial was launched in August 2003 in 60 geographic clusters covering 21,059 children ages 2 to 16 years. After consent was obtained from parents or guardians, eligible children were immunized parenterally at vaccination posts in each cluster with Vi polysaccharide or hepatitis A vaccine. Safety, logistics, and standards were monitored and documented. RESULTS: The vaccine coverage of the population was 74% and was higher in those under age 10 years. No life-threatening serious adverse events were reported. Adverse events occurred in less than 1% of all vaccine recipients and the main reactions reported were fever and local pain. The proportion of adverse events in Vi polysaccharide and hepatitis A recipients will not be known until the end of the trial when the code is broken. Throughout the vaccination campaign safe injection practices were maintained and the cold chain was not interrupted. Mass vaccination in slums had good acceptance. Because populations in such areas are highly mobile, settlement conditions could affect coverage. Systemic reactions were uncommon and local reactions were mild and transient. Close community involvement was pivotal for information dissemination and immunization coverage. CONCLUSION: This vaccine strategy described together with other information that will soon be available in the area (cost/effectiveness, vaccine delivery costs, etc) will make typhoid fever control become a reality in the near future

Safeguarding human–wildlife cooperation

Human–wildlife cooperation occurs when humans and free-living wild animals actively coordinate their behavior to achieve a mutually beneficial outcome. These interactions provide important benefits to both the human and wildlife communities involved, have wider impacts on the local ecosystem, and represent a unique intersection of human and animal cultures. The remaining active forms are human–honeyguide and human–dolphin cooperation, but these are at risk of joining several inactive forms (including human–wolf and human–orca cooperation). Human–wildlife cooperation faces a unique set of conservation challenges, as it requires multiple components—a motivated human and wildlife partner, a suitable environment, and compatible interspecies knowledge—which face threats from ecological and cultural changes. To safeguard human–wildlife cooperation, we recommend: (i) establishing ethically sound conservation strategies together with the participating human communities; (ii) conserving opportunities for human and wildlife participation; (iii) protecting suitable environments; (iv) facilitating cultural transmission of traditional knowledge; (v) accessibly archiving Indigenous and scientific knowledge; and (vi) conducting long-term empirical studies to better understand these interactions and identify threats. Tailored safeguarding plans are therefore necessary to protect these diverse and irreplaceable interactions. Broadly, our review highlights that efforts to conserve biological and cultural diversity should carefully consider interactions between human and animal cultures. Please see AfricanHoneyguides.com/abstract-translations for Kiswahili and Portuguese translations of the abstract

Safeguarding human–wildlife cooperation

Human–wildlife cooperation occurs when humans and free-living wild animals actively coordinate their behavior to achieve a mutually beneficial outcome. These interactions provide important benefits to both the human and wildlife communities involved, have wider impacts on the local ecosystem, and represent a unique intersection of human and animal cultures. The remaining active forms are human–honeyguide and human–dolphin cooperation, but these are at risk of joining several inactive forms (including human–wolf and human–orca cooperation). Human–wildlife cooperation faces a unique set of conservation challenges, as it requires multiple components—a motivated human and wildlife partner, a suitable environment, and compatible interspecies knowledge—which face threats from ecological and cultural changes. To safeguard human–wildlife cooperation, we recommend: (i) establishing ethically sound conservation strategies together with the participating human communities; (ii) conserving opportunities for human and wildlife participation; (iii) protecting suitable environments; (iv) facilitating cultural transmission of traditional knowledge; (v) accessibly archiving Indigenous and scientific knowledge; and (vi) conducting long-term empirical studies to better understand these interactions and identify threats. Tailored safeguarding plans are therefore necessary to protect these diverse and irreplaceable interactions. Broadly, our review highlights that efforts to conserve biological and cultural diversity should carefully consider interactions between human and animal cultures

A Model of Oxidative Stress Management: Moderation of Carbohydrate Metabolizing Enzymes in SOD1-Null Drosophila melanogaster

The response to oxidative stress involves numerous genes and mutations in these genes often manifest in pleiotropic ways that presumably reflect perturbations in ROS-mediated physiology. The Drosophila melanogaster SOD1-null allele (cSODn108) is proposed to result in oxidative stress by preventing superoxide breakdown. In SOD1-null flies, oxidative stress management is thought to be reliant on the glutathione-dependent antioxidants that utilize NADPH to cycle between reduced and oxidized form. Previous studies suggest that SOD1-null Drosophila rely on lipid catabolism for energy rather than carbohydrate metabolism. We tested these connections by comparing the activity of carbohydrate metabolizing enzymes, lipid and triglyceride concentration, and steady state NADPH:NADP+ in SOD1-null and control transgenic rescue flies. We find a negative shift in the activity of carbohydrate metabolizing enzymes in SOD1-nulls and the NADP+-reducing enzymes were found to have significantly lower activity than the other enzymes assayed. Little evidence for the catabolism of lipids as preferential energy source was found, as the concentration of lipids and triglycerides were not significantly lower in SOD1-nulls compared with controls. Using a starvation assay to impact lipids and triglycerides, we found that lipids were indeed depleted in both genotypes when under starvation stress, suggesting that oxidative damage was not preventing the catabolism of lipids in SOD1-null flies. Remarkably, SOD1-nulls were also found to be relatively resistant to starvation. Age profiles of enzyme activity, triglyceride and lipid concentration indicates that the trends observed are consistent over the average lifespan of the SOD1-nulls. Based on our results, we propose a model of physiological response in which organisms under oxidative stress limit the production of ROS through the down-regulation of carbohydrate metabolism in order to moderate the products exiting the electron transport chain

Transformations and Cracks in Zirconia Films Leading to Breakaway Oxidation of Zircaloy

Using combined Raman spectroscopy, atomic force microscopy and optical microscopy, this paper suggests that breakaway oxidation of Zircaloy is caused by the change of circumferential stress sign from compressive to tensile, which triggers catastrophic cracks to propagate from the oxide free surface toward the oxide-metal interface. The stress sign changes at a critical oxide thickness, which depends on the circumferential stress at the interface. This biaxial interfacial stress is promoted by a lattice expansion stress that accompanies the tetragonal to monoclinic crystal phase transition. In contrast with current research in the literature, this allotropic transformation is suggested to be beneficial, not detrimental, because it contributes to retard the thresholds for the change of circumferential stress sign, and thus breakaway oxidation. The tetragonal phase was revealed to localize at the interface and adopt the shape of prismatic isosceles triangles detected at early stages of oxidation. These growth morphologies are consistent with a cationic oxidation mechanism. Upon phase transition, the monoclinic variant quickly dominates the oxide scale above the interfacial regions and forces the overall oxidation to proceed by an anionic diffusion mechanism. The results of Raman spectroscopy compared well with those of atomic force microscopy

Sexual-Sparing Robot Assisted Radical Cystectomy in Female: A Step-By-Step Guide

Objective: To show different approaches for sexual-sparing robot assisted radical cystectomy in women. Materials And Methods: Radical cystectomy (RC) is a mainstay treatment for localized muscle invasive bladder cancer and high-risk non muscle invasive bladder cancer not responding to adequate endovesical therapy.1 In women traditionally RC is performed with hystero-adnexectomy and resection of the anterior vaginal wall, but this technique often brings sexual disorders. With time, vaginal sparing techniques have been developed to improve functional outcomes in women motivated to preserve their sexual function.2-4 The indications for vaginal-sparing RC are absence of tumor in bladder neck or urethra and no sign of infiltration of anterior vaginal wall and parametria at preoperative staging. Results: Procedure steps as follows. Step 1: Bilateral adnexectomy and ureteral isolation until their distal portion. Step 2: Vesico-vaginal dissection. Step 3: Bilateral pelvic and common iliac node dissection. Step 4: Ureteral clamping and section. Step5: Posterolateral bladder pedicle dissection. Step 6: Anterior dissection of the bladder towards the urethra. In women, this should be achieved without injuring the Santorini plexus and innervation of the clitoris. Step 7: Bladder neck identification and urethral dissection. Cystectomy is completed. Step 8: En bloc hystero-adnexectomy with anterior vaginal wall preservation; the vaginal pedicles are spared too. Step 9: Specimen extraction from the vagina and vaginal suture.It is also possible to perform a fully sexual-sparing robotic RC by following the vesico-vaginal plan without dissecting the vaginal dome and leaving internal genitalia intact. This technique is typically carried out in case of young women with no pathological uterine and ovarian findings.Vesico-vaginal plan can also be developed after opening the vaginal dome. This approach gives the possibility to subsequently dissect the cervix, to identify and spare the vaginal pedicles and to perform an \u201cen bloc\u201d radical cystectomy, with preservation of the anterior vaginal wall.In case of neobladder, diversion is carried out intracorporeally following the principles of the Saint Augustin neobladder.5 Conclusions: Robot assisted anterior pelvectomy with anterior vaginal wall preservation is a feasible and mini-invasive technique. For a satisfying functional result, it is crucial to preserve the vaginal neurovascular pedicles. This sexual-sparing approach must be carried out after a correct patient selection: women motivated to preserve their sexual function and ideally in the neobladder setting, when a posterior support for the urinary diversion is needed. Absence of tumor in bladder neck and urethra at magnetic resonance imaging could help patient selection

Multi-ancestry GWAS analysis identifies two novel loci associated with diabetic eye disease and highlights APOL1 as a high risk locus in patients with diabetic macular edema.

Diabetic retinopathy (DR) is a common complication of diabetes. Approximately 20% of DR patients have diabetic macular edema (DME) characterized by fluid leakage into the retina. There is a genetic component to DR and DME risk, but few replicable loci. Because not all DR cases have DME, we focused on DME to increase power, and conducted a multi-ancestry GWAS to assess DME risk in a total of 1,502 DME patients and 5,603 non-DME controls in discovery and replication datasets. Two loci reached GWAS significance (p<5x10-8). The strongest association was rs2239785, (K150E) in APOL1. The second finding was rs10402468, which co-localized to PLVAP and ANKLE1 in vascular / endothelium tissues. We conducted multiple sensitivity analyses to establish that the associations were specific to DME status and did not reflect diabetes status or other diabetic complications. Here we report two novel loci for risk of DME which replicated in multiple clinical trial and biobank derived datasets. One of these loci, containing the gene APOL1, is a risk factor in African American DME and DKD patients, indicating that this locus plays a broader role in diabetic complications for multiple ancestries. Trial Registration: NCT00473330, NCT00473382, NCT03622580, NCT03622593, NCT04108156