Total Eradication Research Articles

Bendamustine Followed By Obinutuzumab and Idelalisib in Patients with Chronic Lymphocytic Leukemia (CLL): CLL2-BCG Trial of the German CLL Study Group (GCLLSG)

Bendamustine Followed By Obinutuzumab and Idelalisib in Patients with Chronic Lymphocytic Leukemia (CLL): CLL2-BCG Trial of the German CLL Study Group (GCLLSG)

Systematic Comparative Study of Selected Antibiotics and Sulphur/ Medicinal Plant Mediated Nano-particles against Non-Leguminous Endophytic Bacteria and Clinical Isolates

The rapid emergence of resistant bacteria is occurring worldwide, endangering the efficacy of antibiotics, therefore, there is a need for a systematic approach to the menace of resistant bacteria. Green synthesized nanoparticle (NPs) of medicinal plant based as become an alternative way out to total eradication of resistant microorganisms, Therefore, the search for new, effective bactericidal agents is imminent significantly, for combating drug resistance microorganism. This research work aims to isolate, identify and characterize endophytic bacteria from five non-leguminous plants, namely Carica papaya, Helianthus annuus, Talinum fruticosum, Phoenix dactylifera, and Solanum lycopersicum. The surface of the plants were sterilized, Isolation, characterization and identification using biochemical characterization of the endophytic bacteria were examined according to Bergey’s manual of Systemic Bacteriology. The sulfur/medicinal plant mediated Nanoparticle with and without Ocimum gratissimum were tested against the endophytic bacteria and selected clinical isolates, for their antimicrobial susceptibility test as described Kirby-Bauer Disc diffusion method. SNP1 was prepared from sodium thiosulfate penthahydrate, citric acid, with fresh leaves of O. gratissimum and characterized by using Shimadzu UV-VIS-NIR Spectrophotometer UV-3100 with a MPCF-3100 sample compartment while SNP2 was prepared using the same method but without O. gratissimum. The endophyte showed resistant to cephalosporin antibiotics family and SNP2, while all the endophytic bacteria were susceptible to ciprofloxacin (100%), pefloxacin (100%). Streptococcus infectinalis and Cellumonas flavigena showed high susceptibility to sulfur/ plant nanoparticle mediated with Ocimum gratissimum extract (SNP1). The study showed that sulfur/medicinal plant mediated nanoparticle can be a promising antimicrobial agent against a wide range of pathogenic and multiple drug resistance bacteria including both clinical isolates, its uses and practice should be encouraged especially against multiple drug resistance bacteria.

Pterygodermatites nycticebi infections in golden lion tamarins (Leontopithecus rosalia rosalia) and aye-ayes (Daubentonia madagascariensis) from a German zoo.

In a golden lion tamarin (Leontopithecus rosalia rosalia) colony kept indoors in a German zoo, two animals presented a sudden onset of reduced general condition, lethargy, and diarrhea. At animal capture for clinical examination, adult nematode stages were observed after stress-induced defecation. Despite treatment, two golden lion tamarins died in the following 2 days. At necropsy, spirurid stages were found in the lungs and intestine. Additionally, adult Pterygodermatites spp. were identified in histopathological samples of intestine and pancreas, confirming the previous diagnosis. Upon diagnosis, all animals were treated with ivermectin (0.2 mg/kg; SC). Thereafter, the general condition of the golden lion tamarins improved, whereby some of them excreted spirurid nematodes over 3 days. Four weeks after treatment, 20 fecal samples from the colony were examined and proved negative for parasitic stages. Given that common German cockroaches (Blattella germanica) are suitable intermediate hosts of Pterygodermatites nycticebi, 30 specimens were collected from seven different locations around the golden lion tamarins housing. Third-stage larvae of Pterygodermatites spp. were recovered from those cockroaches. Regular anthelmintic treatments, coprological screenings, and controls for intermediate hosts were recommended. More than 2 years later, P. nycticebi infection was diagnosed again histopathologically in an aye-aye (Daubentonia madagascariensis) which suddenly died. Coprological analysis confirmed the presence of spirurid eggs. Due to prosimian primates' cockroach-eating habits and given that total cockroach eradication proved impossible, continuous cockroach control strategies and regular treatments of primates are currently performed to prevent further P. nycticebi infections.

Prevalence of Urinary Schistosomiasis among Clients Attending Private Medical Laboratory Diagnostic Center in Karshi, Abuja, Nigeria

Urinary Schistomiasis is one of the global public health problems. A study on the prevalence of urinary Schistosomiasis was carried out among clients attending private medical laboratory center in Karshi, Abuja, Nigeria. The study was carried out among 210 clients comprised 50 males and 70 females aged 11-50years between August 2019 to February, 2020.Single urine samples were collected from the clients between 10.00hours and 14.00hours were examined for the presence of S. haematobium in eggs using centrifuged techniques. Morbidity indicators of haematuria and proteinuria was determined using reagents strips. Out of 210 subjects examined 16(7.6%) had the eggs of S. haematobium in their urine. The results show that males were more infected than the females with 4.8% and 2.8% respectively. The infection rate varied according to age group where 21-30 years age group had highest infection rate 3.3% and age 41-50years had the least prevalence rate 1.0%.The chemical analysis carried out shows that proteinuria had highest prevalence 20.5% and haematuria had 16.7%.Distribution according to marital status show that single had higher prevalence of 5.7% and married had the least 1.9%.There was no statistically significance relationship between all the variables and prevalence of urinary schistosomiasis. From the results of this study, it was concluded that schistosoma haematobium was less prevalent in this study area. Studies strongly suggest that health education on the modes of transmission be promoted and strengthened to achieved total eradication of the disease in the area. Authors recommended the inclusion of private medical laboratory into the government health policies on urinary schistosomiasis.

Factors affecting the recovery of hepatic reserve after sustained virologic response by direct-acting antiviral agents in chronic hepatitis C virus-infected patients.

Since the advent of direct-acting antiviral (DAA) therapy, the total eradication of hepatitis C virus has been achievable with the recovery of hepatic reserve after achievement of sustained virologic response (SVR). Hence, here, we examined the factors affecting the recovery of hepatic reserve. We followed up 403 patients (male: 164, female: 239; genotype 1: 299, genotype 2: 104; median age: 69years) for at least 3years after they achieved SVR to DAA therapy. Of these patients, 75 (18.6%) had a history of hepatocellular carcinoma (HCC). Biochemical tests were periodically performed, and the hepatic reserve was evaluated based on the albumin-bilirubin grade. We examined background factors such as age, biochemical test results, HCC occurrence and portosystemic shunt by computed tomography. At the start of treatment, the albumin-bilirubin grades were grades 1, 2, and 3 in 241, 157, and 5 patients, respectively, and 3years later, 117 of 162 (72%) patients with grade 2 or 3 improved to grade 1. Multivariate analysis identified the HCC occurrence after achievement of SVR (hazard ratio [HR]: 3.08, P<0.0138), male sex (HR: 3.45, P=0.0143), hemoglobin level of <11.5g/dL (HR: 4.19, P=0.0157), the presence of a portosystemic shunt (HR: 3.07, P=0.0349), and alanine aminotransferase levels <45U/L (HR: 2.67, P=0.0425) as factors inhibiting improvement to grade 1. However, old age was not an inhibitory factor. Our results demonstrate that hepatic reserve could be improved even in elderly patients over a long course of time.

Multiplex Recombinase Polymerase Amplification Assay for Simultaneous Detection of Treponema pallidum and Haemophilus ducreyi in Yaws-Like Lesions.

Yaws is a skin debilitating disease caused by Treponema pallidum subspecies pertenue with most cases reported in children. World Health Organization (WHO) aims at total eradication of this disease through mass treatment of suspected cases followed by an intensive follow-up program. However, effective diagnosis is pivotal in the successful implementation of this control program. Recombinase polymerase amplification (RPA), an isothermal nucleic acid amplification technique offers a wider range of differentiation of pathogens including those isolated from chronic skin ulcers with similar characteristics such as Haemophilus ducreyi (H. ducreyi). We have developed a RPA assay for the simultaneous detection of Treponema pallidum (T. pallidum) and H. ducreyi (TPHD-RPA). The assay demonstrated no cross-reaction with other pathogens and enable detection of T. pallidum and H. ducreyi within 15 min at 42 °C. The RPA assay was validated with 49 clinical samples from individuals confirmed to have yaws by serological tests. Comparing the developed assay with commercial multiplex real-time PCR, the assay demonstrated 94% and 95% sensitivity for T. pallidum and H. ducreyi, respectively and 100% specificity. This simple novel TPHD-RPA assay enables the rapid detection of both T. pallidum and H. ducreyi in yaws-like lesions. This test could support the yaws eradication efforts by ensuring reliable diagnosis, to enable monitoring of program success and planning of follow-up interventions at the community level.

Levofloxacin-Based Regimen Versus Bismuth Quadruple Regimen for Helicobacter pylori Eradication in Kurdistan Region, Iraq

Background: Helicobacter pylori infection is associated with peptic ulcer diseases and gastric adenocarcinoma. Accordingly, the aim of this study was to assess the efficiency of tetracycline quadruple therapy versus levofloxacin-based regimen (LBR) for the eradication of H. pylori. Methods: To this end, 197 subjects with H. pylori infection were recruited in this randomized clinical study in Kurdistan region, Iraq between October 2018 and May 2019 and randomly divided into 2 groups. The LBR group received levofloxacin 500 mg one time per day, amoxicillin 1000 mg two times per day, and omeprazole 20 mg two times per day for two weeks. In addition, the tetracycline-metronidazole-bismuth (TMB) group received bismuth subcitrate 140 mg, metronidazole 125 mg, and tetracycline 125 mg plus omeprazole 20 mg twice per day for 10 days. Finally, 28 days after the completion of the treatment course, the eradication of H. pylori was evaluated by the 14C urease breath test. Results: The total eradication rate of H. pylori infection was 149/197 (75.6%). Although the success eradication rate in the LBR regimen was 70/112 (62.5%), the eradication success rate was 79/85 (92.9%) in the TMB regimen (P = 0.001, odds ratio = 7.9, confidence interval = 3.17-19.7). Finally, gender and age represented on the effect of the eradication rate. Conclusions: In general, the bismuth-based regimen could eradicate a high rate of H. pylori infection. Therefore, this regimen can be used to overcome treatment failure in areas with a high prevalence of antibiotics resistance.

Simultaneous nitrification-denitrification by phosphate accumulating microorganisms.

Nitrogen and phosphorous are important inorganic water pollutants that pose a major threat to the environment and health of both humans and animals. The physical and chemical ways to remove these pollutants from water and soil are expensive and harsh, so biological removal becomes the method of choice to alleviate the problem without any side effects. The identification of microorganisms capable of simultaneous heterotrophic nitrification and aerobic denitrification has greatly simplified the sequestration of nitrogen from ammonium (NH4+) into dinitrogen (N2). Further, the discovery of phosphorous accumulating organisms offers greater economic benefits because these organisms can favourably and simultaneously remove both nitrogen and phosphorous from wastewaters hence reducing the nutrient burden. The stability of the system and removal efficiency of inorganic pollutants can be enhanced by the use of immobilized organisms. However, limited work has been done so far in this direction and there is a need to further the efforts towards refining process efficiency by testing low-cost substrates and diverse microbial populations for the total eradication of these contaminants from wastewaters.

HIV-1 Sanctuary Sites-the Role of Membrane-Associated Drug Transporters and Drug Metabolic Enzymes.

Despite significant advances in the treatment of human immunodeficiency virus-1 (HIV) infection with highly active antiretroviral drug therapy, the persistence of the virus in cellular and anatomic reservoirs is a major obstacle preventing total HIV eradication. Viral persistence could result from a variety of contributing factors including, but not limited to, non-adherence to treatment and adverse drug reactions, latently infected cells carrying replication-competent virus, drug-drug interactions, and inadequate antiretroviral drug (ARV) concentrations reached in several anatomic sites such as the brain, testis, and gut-associated lymphoid tissues. The distribution of ARVs at specific sites of infection is primarily dependent on drug physicochemical properties and drug plasma protein binding, as well as drug efflux, influx, and metabolic processes. A thorough understanding of the functional roles of drug transporters and metabolic enzymes in the disposition of ARVs in immune cell types and tissues that are characterized as HIV reservoirs and sanctuaries is critical to overcome the challenge of suboptimal drug distribution at sites of persistent HIV infection. This review summarizes the current knowledge related to the expression and function of drug transporters and metabolic enzymes in HIV cellular and anatomic reservoirs, and their potential contribution to drug-drug interactions and insufficient drug concentration at these sites.

Current status of Helicobacter pylori eradication and risk factors for eradication failure.

BACKGROUNDThe Helicobacter pylori (H. pylori) eradication rate is decreasing in the general population of China.AIMTo evaluate the H. pylori eradication status in real-world clinical practice and to explore factors related to eradication failure.METHODSPatients with H. pylori infection who were treated with standard 14-d quadruple therapy and received a test of cure at a provincial medical institution between June 2018 and May 2019 were enrolled. Demographic and clinical data were recorded. Eradication rates were calculated and compared between regimens and subgroups. Multivariate analysis was performed to identify predictors of eradication failure.RESULTSOf 2610 patients enrolled, eradication was successful in 1999 (76.6%) patients. Amoxicillin-containing quadruple regimens showed a higher eradication rate than other quadruple therapy regimens (83.0% vs 69.0%, P < 0.001). The quadruple therapy containing amoxicillin plus clarithromycin achieved the highest eradication rate (83.5%). Primary therapy had a higher eradication rate than rescue therapy (78.3% vs 66.5%, P < 0.001). In rescue therapy, the amoxicillin- and furazolidone-containing regimens achieved the highest eradication rate (80.8%). Esomeprazole-containing regimens showed a higher eradication rate than those containing other proton pump inhibitors (81.8% vs 74.9%, P = 0.001). Multivariate regression analysis found that older age, prior therapy, and use of omeprazole or pantoprazole were associated with an increased risk of eradication failure.CONCLUSIONThe total eradication rate is 76.6%. Amoxicillin-containing regimens are superior to other regimens. Age, prior therapy, and use of omeprazole or pantoprazole are independent risk factors for eradication failure.

Awareness on the Prevention and Treatment of Malaria among Residents in Abraka, Delta State, Nigeria

Nigeria, the most populous nation in the Sub-Saharan African region, remains ravaged with a high occurrence of malaria infections which accounts for one-fourth of malaria cases globally. Communal awareness is important in the total eradication of malaria in Africa and the world at large. This study is to ascertain the awareness of individuals in Abraka communities on the transmission, prevention and treatment of malaria. A cross- sectional survey was carried out among people of Abraka, Delta State, Nigeria, using 200 structured questionnaires. Data was presented as percentage (%) using descriptive statistics. Majority of the respondents were females (51%), 83.5% practiced Christianity, 63% of the subjects are single, and a total of 60.4% either into business, employed or selfemployed with 38% being students. Eighty-nine percent (89%) of the respondents indicated that mosquito bite is the mode of transmission of malaria and 82.5% of the respondents stated that refuse dump is the major factor that breed mosquito. A large number of the respondents (95%) have been engaged in one or more malaria preventive (control) methods. A greater percent (30%) commonly used artesunate in treating malaria, while 25% took Coartem® (artemether/lumefantrine), 23% took Lonart® (artemether/lumefantrine), 10% took quinine and 12% had other drugs they took for the treatment of malaria. There was much awareness on the spread, prevention and treatment of malaria in Abraka, Delta State.&#x0D; Keywords: Antimalarial, communal awareness, artemisinin-based combination therapy (ACT), Abraka.

2-(Aryl Oxy Methyl)-1H- Benzimidazoles: Synthesis, Characterization and Biological Evaluation

Helminthiasis is a macro, parasitic disease of humans and animals in which a part of the body is infected with Helminth parasites. It is one of the most deadly, neglected, tropical diseases and many die annually from this disease. The total eradication from this problem is very difficult. The drugs which expel Helminth parasites from the body either by stunning or killing them without causing significant damage to the host are called Anthelmintics. The most commonly used class of Anthelmintics are Benzimidazoles, whose mode of action is by blocking transportation of secretory granules and movement of other cell organelles by binding to beta-tubulin and inhibit polymerization of microtubules in the cytoskeleton of the Helminthic parasite. Most of the Anthelmintics are non-selective, with a narrow spectrum of activity, high toxicity, unsafe for undernourished children and pregnant women, requires follow up purgation and development of resistance by the parasite. So there is a need for search and development of new Anthelmintics preferably with a novel mode of action and minimum side effects. Because of this, a scheme was designed which involved synthesis, characterization and Anthelmintic evaluation of some 2-(Aryl Oxy Methyl)-1H-Benzimidazoles. The identification and characterization of the synthesized compounds were carried out by a melting point, thin layer chromatography, FT-IR, 1H-NMR, to ascertain that the synthesized compounds are of different chemical nature than the respective parent compound. The synthesized compounds were preliminarily screened for the in vitro anthelmintic activity using Piperazine Citrate as standard.

Effect of actively targeted copolymer coating on solid tumors eradication by gold nanorods-induced hyperthermia.

Efforts in the field of anticancer therapy are increasingly focusing on the development of localized and selective treatments. Photothermal therapy (PTT) can lead to a spatially confined death of cancer cells, exploiting an increasing in temperature generated after UV-NIR irradiation of peculiar materials. Herein, a new actively targeted gold-based drug delivery system, named PHEA-LA-Fol-AuNRs/Iri, was explored for hyperthermia and chemotherapy colon cancer treatment. Gold nanorods were stabilized using a folate-derivative of α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA-LA-PEG-FA) as coating agent and then loaded with the antineoplastic drug irinotecan (Iri). The efficacy of empty and irinotecan-bearing systems was investigated in vitro on human colon cancer (HCT116) cell line, as well as in vivo, employing a xenograft mouse model of colon cancer. After laser treatment, both nanostructures tested induced a considerable deceleration in tumor growth overtime, achieving the total eradication of the cancer when the nanosystems produced were intratumorally administered. Biodistribution data showed that the polymer coated nanorods were able to preferentially accumulate in the tumor site. Considering the excellent stability in aqueous media, the capacity to reach the tumor site and, finally, the in vivo efficacy, PHEA-LA-Fol-AuNRs/Iri might be recommended as an effective tool in the chemotherapy and PTT of colon cancer.

Israeli strategic deterrence doctrine and practice

Israel is the only country whose neighbors have threatened it for most of its existence with total eradication. Despite Israel’s military advantages, Israel’s defense doctrine views war as the “no choice option” which carries a heavy social and economic price tag. Therefore, Israeli doctrine relies heavily on the projection of deterrence. Events over the years have given rise to debates in the Israeli public regarding the “erosion” of Israeli deterrence. However, these debates are replete with fallacies. An understanding of Israeli deterrence doctrine must be based on the distinction between three national situation levels in the context of which deterrence must be achieved: “Routine”, “Emergency” and “War” and the role of “compellence” and pre-emption of offensive capabilities of the enemy as an instrument for inducing deterrence (“pre-terrence”). Ultimately, Israel has succeeded in maintaining strategic deterrence vis-à-vis neighboring states. This article provides an understanding of the evolution of Israel’s deterrence doctrine, its successes and its failures, and, mutatis mutandis, lessons that it can offer to deterrence doctrine in general and to that of the United States in particular.

Multidisciplinary total eradication therapy (TET) in men with newly diagnosed oligometastatic prostate cancer

To evaluate the outcomes of total eradication therapy (TET), designed to eradicate all sites of visible cancer and micrometastases, in men with newly diagnosed oligometastatic prostate cancer (OMPCa). Men with ≤ 5 sites of metastases were enrolled in a prospective registry study, underwent neoadjuvant chemohormonal therapy, followed by radical prostatectomy, adjuvant radiation (RT) to prostate bed/pelvis, stereotactic body radiation therapy (SBRT) to oligometastases, and adjuvant hormonal therapy (HT). When possible, the prostate-specific membrane antigen targeted 18F-DCFPyL PET/CT (18F-DCFPyL) scan was obtained, and abiraterone was added to neoadjuvant HT. Twelve men, median 55 years, ECOG 0, median PSA 14.7 ng/dL, clinical stages M0—1/12 (8%), M1a—3/12 (25%) and M1b—8/12 (67%), were treated. 18F-DCFPyL scan was utilized in 58% of cases. Therapies included prostatectomy 12/12 (100%), neoadjuvant [docetaxel 11/12 (92%), LHRH agonist 12/12 (100%), abiraterone + prednisone 6/12 (50%)], adjuvant radiation [RT 2/12 (17%), RT + SBRT 4/12 (33%), SBRT 6/12 (50%)], and LHRH agonist 12/12 (100%)]. 2/5 (40%) initial patients developed neutropenic fever (NF), while 0/6 (0%) subsequent patients given modified docetaxel dosing developed NF. Otherwise, TET resulted in no additive toxicities. Median follow-up was 48.8 months. Overall survival was 12/12 (100%). 1-, 2-, and 3-year undetectable PSA’s were 12/12 (100%), 10/12 (83%) and 8/12 (67%), respectively. Median time to biochemical recurrence was not reached. The outcomes suggest TET in men with newly diagnosed OMPCa is safe, does not appear to cause additive toxicities, and may result in an extended interval of undetectable PSA.

A review of the use of physical barriers to stop the spread of non-indigenous crayfish species

Invasive non-indigenous crayfish species (NICS) are a global threat to local flora and fauna. Total eradication of an entire population of invasive NICS is a difficult task; several methods have been tested and are still being used, with varying success. Most methods reduce population size and control the species within the targeted area but do not majorly prevent further spread of NICS. However, construction of crayfish barriers can stop the spread of NICS and can therefore, be used to protect indigenous crayfish species (ICS). There are currently very few published scientific papers about this topic. This review reflects current knowledge on how to stop migration when NICS are established and provides useful information for the construction of barriers. The most important findings related to building a crayfish barrier are: the need for a vertical wall with an overhanging lip above the water surface; smooth sections to prevent crayfish from walking or climbing over the obstacle, combined with flow velocities of 0.65 m/s act as a barrier within the waterbody. Additionally, modifications to existing structures, bridges, culverts and dams reduce costs and increase effectiveness in stopping upstream migration of NICS. Barriers can negatively impact certain aquatic species, mainly benthic and slow swimming fish by preventing their migration and genetic exchange. However, they can have positive impacts for ICS and other indigenous organisms against the negative effects of NICS. Local legislation should support barrier construction to prevent the spread of invasive crayfish and other aquatic invaders to protect ark sites for ICS.

The Assessment of clinical efficacy of Vaman Karma followed by Virechan and Basti Karma in the management of Dadru with special reference to Dermatophytosis.

Dadru is described in Kshudra kushtha by acharya Charak. The symptoms like Kandu (Itching), Raga (Erythema), Pidaka (Exanthemas) and Mandala (Discoid lesions with elevated borders) seen in Dadru is analogous to the symptoms of Dermatophytosis. Most of skin infections caused by dermatophytes are referred as tinea and often severe as well as recurrent. Ringworm infections are also called as dermatophytosis which is characterized by the infection of keratinized tissues like epidermis, hair and nails. In modern science, tropical anti-fungal drugs, oral anti-fungal drugs are used to treat ring worms at various stages. Nowadays resistance is increasing to anti-fungal allopathic drugs. So, there is a need to study and research the effective, safe and affordable Ayurverdic treatment for the management of Dadru So, I decided to work on this topic.&#x0D; Kapha and pitta doshas are predominant in Dadru. As Dadru is type of kshudra kushta, shodhan therapy must be primary treatment for elimination of vitiated doshas. So panchakarma therapies like Vaman, Virechana and Basti given to the patient as stated in ayurvedic classics. Total effect of Vaman therapy was 29.19 %, Total effect of Vaman followed by Virechana therapy was 58.66 %, Total effect of Vaman followed by Virechana and Basti therapy was 77.58 %. Hence, we can conclude that shodhan therapy effective in management of Dadru but it needs frequent shodhana for total eradication of disease according to bala of patient.&#x0D; &#x0D; Dadru, Dermatophytosis, Shodhana therapy, Vaman, Virechan, Basti

A case study on mortality of neon tetra (Paracheirodon innesi) associated with the seasonal climate transitions in West Java – Indonesia

This study aimed to identify pathological agent and determine the impact of water quality during climate transitions on mass mortalities of neon tetra (Paracheirodon innesi) in the West Java region of Indonesia. Ten thousand fishes reported died each day during the seasonal. Samples of 10 fish/tank were taken and tested for parasites, fungal, and bacteria. The investigations tests showed that the primary disease was caused by parasite from protozoa Pleistophora spp. (Microsporidia). It was confirmed by taxonomic descriptions and histopathological diagnosis. This parasite causes histozoic infection. Fungus was not detected, and bacteria were identified as Aeromonas sp. and Pseudomonas sp.. The water temperature fluctuation was recorded higher than 7°C between daylight and night. Mortality was recorded in every size of fish. The clinical signs of fish on the outbreak were pale body, discoloration of the lateral line, the appearance of white patches under the skin, lethargy, swimming disorder, and losing weight. The recommendations due to the outbreaks were total eradication for infected fish populations, separating newly arrived fish (quarantine) at least 2 weeks, maintaining water quality in the optimal range, and proper cleaning (sanitizing) must be performed.

Functionality-packed additively manufactured porous titanium implants.

The holy grail of orthopedic implant design is to ward off both aseptic and septic loosening for long enough that the implant outlives the patient. Questing this holy grail is feasible only if orthopedic biomaterials possess a long list of functionalities that enable them to discharge the onerous task of permanently replacing the native bone tissue. Here, we present a rationally designed and additive manufacturing (AM) topologically ordered porous metallic biomaterial that is made from Ti-6Al-4V using selective laser melting and packs most (if not all) of the required functionalities into a single implant. In addition to presenting a fully interconnected porous structure and form-freedom that enables realization of patient-specific implants, the biomaterials developed here were biofunctionalized using plasma electrolytic oxidation to locally release both osteogenic (i.e. strontium) and antibacterial (i.e. silver ions) agents. The same single-step biofunctionalization process also incorporated hydroxyapatite into the surface of the implants. Our measurements verified the continued release of both types of active agents up to 28 days. Assessment of the antibacterial activity in vitro and in an ex vivo murine model demonstrated extraordinarily high levels of bactericidal effects against a highly virulent and multidrug-resistant Staphylococcus aureus strain (i.e. USA300) with total eradication of both planktonic and adherent bacteria. This strong antibacterial behavior was combined with a significantly enhanced osteogenic behavior, as evidenced by significantly higher levels of alkaline phosphatase (ALP) activity compared with non-biofunctionalized implants. Finally, we discovered synergistic antibacterial behavior between strontium and silver ions, meaning that 4–32 folds lower concentrations of silver ions were required to achieve growth inhibition and total killing of bacteria. The functionality-packed biomaterial presented here demonstrates a unique combination of functionalities that make it an advanced prototype of future orthopedic biomaterials where implants will outlive patients.

Key Players in HIV-1 Transcriptional Regulation: Targets for a Functional Cure.

HIV-1 establishes a life-long infection when proviral DNA integrates into the host genome. The provirus can then either actively transcribe RNA or enter a latent state, without viral production. The switch between these two states is governed in great part by the viral protein, Tat, which promotes RNA transcript elongation. Latency is also influenced by the availability of host transcription factors, integration site, and the surrounding chromatin environment. The latent reservoir is established in the first few days of infection and serves as the source of viral rebound upon treatment interruption. Despite effective suppression of HIV-1 replication by antiretroviral therapy (ART), to below the detection limit, ART is ineffective at reducing the latent reservoir size. Elimination of this reservoir has become a major goal of the HIV-1 cure field. However, aside from the ideal total HIV-1 eradication from the host genome, an HIV-1 remission or functional cure is probably more realistic. The “block-and-lock” approach aims at the transcriptional silencing of the viral reservoir, to render suppressed HIV-1 promoters extremely difficult to reactivate from latency. There are unfortunately no clinically available HIV-1 specific transcriptional inhibitors. Understanding the mechanisms that regulate latency is expected to provide novel targets to be explored in cure approaches.