The use of morphological and cell wall chemical markers in the identification of Streptomyces species associated with Actinomycetoma

Most aerobic, filamentous, spore-forming actinomycetes are saprophytes but some are considered pathogens of humans and animals, notable examples are the causal agents of mycetoma. The present study aimed to identify Streptomyces spp. isolated from actinomycetoma cases in Sudan by examining some morphological traits and analyzing the cell wall composition. Nineteen Streptomyces strains isolated from purulent materials of patients with mycetoma (human) or fistulous withers (donkeys) were included in the study. Isolates were tentatively identified as Streptomyces species based on morphological and cultural characteristics. Cell wall analysis of isolates yielded LLdiaminopimelicacid (LL-DAP) which authenticates that the isolates are members of genus Streptomyces. The isolates, though they are Streptomyces, but are variable phenotypes. The study concluded that using few selected criteria, as above, would allow identification of unknown actinomycetoma agent to the genus level. The study also assumes that apparently limitless, numbers of saprophytic Streptomyces enter human or animal skin tissue causing actinomycetoma and perhaps other complications in man and animals.KEYWORDS: Actinomycetoma, Streptomyces species, Madura foot, Suda

Comparison of Egyptian and Saudi Mesembryanthemum forskalii Hochst. ex Boiss. as an unconventional alternative protein of wheat and barley

Mesembryanthemum forskalii, commonly called Forskal Fig-marigold, is a wild plant, grown naturally in Saudi and Egyptian deserts and in many countries around the world. However, nutrition value, especially its protein content, has not been studied until now. Here, we explored this plant as a new source of protein, particularly in drought or salted lands that can't be cultivated with grains and to meet the increasing of human requirements for protein. Analysis of amino acids contents showed seven essential amino acids in Egyptian and Saudi M. forskalii. Moreover, both M. forskalii have some amino acids their concentrations higher than that of wheat and barley. In addition, SDS-PAGE protein results revealed the appearance of 7 monomorphic bands in all samples; two bands appeared only in M. forskalii and not found in wheat or barley. HDN protein profile exhibited Rubisco band in all samples. The CDDP analysis indicated that M. forskalii has significant similarity with wheat or barley and share some genes with them. The observations suggest M. forskalii to be a potential new source of protein. It has many important amino acids and a valuable content of protein and can be combined or substituted with flour from cereals to enrich the diets of Saharan communities

Comparison of Egyptian and Saudi Mesembryanthemum forskalii Hochst. ex Boiss. as an unconventional alternative protein of wheat and barley

194-201Mesembryanthemum forskalii, commonly called Forskal Fig-marigold and locally, Samh, is a wild plant, grown naturally in Saudi and Egyptian deserts and in many countries around the world. However, nutrition value, especially its protein content, has not been studied until now. Here, we explored this plant as a new source of protein, particularly in drought or salted lands that can't be cultivated with grains and to meet the increasing of human requirements for protein. Analysis of amino acids contents showed seven essential amino acids in Egyptian and Saudi M. forskalii. Moreover, both M. forskalii have some amino acids their concentrations higher than that of wheat and barley. In addition, SDS-PAGE protein results revealed the appearance of 7 monomorphic bands in all samples; two bands appeared only in M. forskalii and not found in wheat or barley. HDN protein profile exhibited Rubisco band in all samples. The CDDP analysis indicated that M. forskalii has significant similarity with wheat or barley and share some genes with them. The observations suggest M. forskalii to be a potential new source of protein. It has many important amino acids and a valuable content of protein and can be combined or substituted with flour from cereals to enrich the diets of Saharan communities

Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior

Midbrain dopamine neurons are crucial for many behavioral and cognitive functions. As the major excitatory input, glutamatergic afferents are important for control of the activity and plasticity of dopamine neurons. However, the role of glutamatergic input as a whole onto dopamine neurons remains unclear. Here we developed a mouse line in which glutamatergic inputs onto dopamine neurons are specifically impaired, and utilized this genetic model to directly test the role of glutamatergic inputs in dopamine-related functions. We found that while motor coordination and reward learning were largely unchanged, these animals showed prominent deficits in effort-related behavioral tasks. These results provide genetic evidence that glutamatergic transmission onto dopaminergic neurons underlies incentive motivation, a willingness to exert high levels of effort to obtain reinforcers, and have important implications for understanding the normal function of the midbrain dopamine system.Fil: Hutchison, M. A.. National Institutes of Health; Estados UnidosFil: Gu, X.. National Institutes of Health; Estados UnidosFil: Adrover, Martín Federico. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Lee, M. R.. National Institutes of Health; Estados UnidosFil: Hnasko, T. S.. University of California at San Diego; Estados UnidosFil: Alvarez, V. A.. National Institutes of Health; Estados UnidosFil: Lu, W.. National Institutes of Health; Estados Unido

The Prevalence of Renal Scar in Urinary Tract Infection Using Dimercaptosuccinic Acid (DMSA) Scan, and Related Factors in Children under 16 Years Old during the Years 2012-2016 in Sari City, Iran

Background: Urinary tract infection is one of the main causes of renal scar that can lead to serious complications such as hypertension or chronic renal failure. Therefore, accurate and timely diagnosis of urinary tract infection and other risk factors related to scar is very important. This study aimed to determine the prevalence of renal scar using dimercaptosuccinic acid (DMSA) scan after urinary tract infection in children under 16 years old in Bu Ali Sina hospital located in Sari City, Iran, during the years 2012 to 2016. Methods: In this cross-sectional study, the data were extracted from files related to those patients suffering UTI referred to Bu Ali Sina hospital, for whom DMSA scan was performed. Results: Of 208 enrolled children, 83.2% were girls and 16.8% were boy with mean age of 32.80 ± 32.57 months. Based on the first DMSA scan, the prevalence of scars was about 40%; and based on second DMSA scan (delayed), the prevalence was about 34%. In people who had scar, the frequency of UTI was more. In these patients, the most common organisms were Escherichia coli (71.4%), Proteus (14.3%), and Klebsiella (10.7%). Proteus significantly led to scar formation more than the others. Vesicoureteral reflux (VUR) with prevalence of 67.9% was the most common observed disease; and all patients with severe scars suffered from VUR. Scar in DSMA scan had no significant relationship with age and gender. Conclusion: Scar is a relatively common complication of UTI in children and VUR is an important risk factor for permanent damage. It is mandatory to think to this critical complications in children with UTI. Keywords Urinary tract infection; Scar; DMS

Recruitment of heterosexual couples in public health research: a study protocol

BACKGROUND: Public health research involving social or kin groups (such as sexual partners or family members), rather than samples of unrelated individuals, has become more widespread in response to social ecological approaches to disease treatment and prevention. This approach requires the development of innovative sampling, recruitment and screening methodologies tailored to the study of related individuals. METHODS: In this paper, we describe a set of sampling, recruitment and screening protocols developed to enlist urban, drug-using, heterosexual couples into a public health research study. This population is especially hard to reach because they are engaged in illegal and/or stigmatized behaviors. The protocols were designed to integrate adaptive sampling, street- and referral-based recruitment, and screening procedures to verify study eligibility and relationship status. DISCUSSION: Recruitment of heterosexual couples through one partner, preferably the female, can be an effective enlistment technique. Verification of relationship status is an important component of dyadic research. Comparison of parallel questionnaires administered to each member of a dyad can aid in the assessment of relationship status. However, multiple independent sources of information should be used to verify relationship status when available. Adaptive sampling techniques were effective in reaching drug-using heterosexual couples in an urban setting, and the application of these methods to other groups of related individuals in clinical and public health research may prove to be useful. However, care must be taken to consider potential sources of sampling bias when interpreting and generalizing study results

Midgut microbiota of the malaria mosquito vector Anopheles gambiae and Interactions with plasmodium falciparum Infection

The susceptibility of Anopheles mosquitoes to Plasmodium infections relies on complex interactions between the insect vector and the malaria parasite. A number of studies have shown that the mosquito innate immune responses play an important role in controlling the malaria infection and that the strength of parasite clearance is under genetic control, but little is known about the influence of environmental factors on the transmission success. We present here evidence that the composition of the vector gut microbiota is one of the major components that determine the outcome of mosquito infections. A. gambiae mosquitoes collected in natural breeding sites from Cameroon were experimentally challenged with a wild P. falciparum isolate, and their gut bacterial content was submitted for pyrosequencing analysis. The meta-taxogenomic approach revealed a broader richness of the midgut bacterial flora than previously described. Unexpectedly, the majority of bacterial species were found in only a small proportion of mosquitoes, and only 20 genera were shared by 80% of individuals. We show that observed differences in gut bacterial flora of adult mosquitoes is a result of breeding in distinct sites, suggesting that the native aquatic source where larvae were grown determines the composition of the midgut microbiota. Importantly, the abundance of Enterobacteriaceae in the mosquito midgut correlates significantly with the Plasmodium infection status. This striking relationship highlights the role of natural gut environment in parasite transmission. Deciphering microbe-pathogen interactions offers new perspectives to control disease transmission.Institut de Recherche pour le Developpement (IRD); French Agence Nationale pour la Recherche [ANR-11-BSV7-009-01]; European Community [242095, 223601]info:eu-repo/semantics/publishedVersio

Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study.

BACKGROUND: Patients with advanced melanoma have limited treatment options after progression on immune checkpoint inhibitors (ICI). Lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, demonstrated an investigator-assessed objective response rate (ORR) of 36% in 66 patients who progressed after ICI and targeted therapy. Herein, we report independent review committee (IRC)-assessed outcomes of 153 patients treated with lifileucel in a large multicenter Phase 2 cell therapy trial in melanoma. METHODS: Eligible patients had advanced melanoma that progressed after ICI and targeted therapy, where appropriate. Melanoma lesions were resected (resected tumor diameter ≥1.5 cm) and shipped to a central good manufacturing practice facility for 22-day lifileucel manufacturing. Patients received a non-myeloablative lymphodepletion regimen, a single lifileucel infusion, and up to six doses of high-dose interleukin-2. The primary endpoint was IRC-assessed ORR (Response Evaluation Criteria in Solid Tumors V.1.1). RESULTS: The Full Analysis Set consisted of 153 patients treated with lifileucel, including longer-term follow-up on the 66 patients previously reported. Patients had received a median of 3.0 lines of prior therapy (81.7% received both anti-programmed cell death protein 1 and anti-cytotoxic lymphocyte-associated protein 4) and had high disease burden at baseline (median target lesion sum of diameters (SOD): 97.8 mm; lactate dehydrogenase (LDH) >upper limit of normal: 54.2%). ORR was 31.4% (95% CI: 24.1% to 39.4%), with 8 complete responses and 40 partial responses. Median duration of response was not reached at a median study follow-up of 27.6 months, with 41.7% of the responses maintained for ≥18 months. Median overall survival and progression-free survival were 13.9 and 4.1 months, respectively. Multivariable analyses adjusted for Eastern Cooperative Oncology Group performance status demonstrated that elevated LDH and target lesion SOD >median were independently correlated with ORR (p=0.008); patients with normal LDH and SOD <median had greater likelihood of response than those with either (OR=2.08) or both (OR=4.42) risk factors. The most common grade 3/4 treatment-emergent adverse events (≥30%) were thrombocytopenia (76.9%), anemia (50.0%), and febrile neutropenia (41.7%). CONCLUSIONS: Investigational lifileucel demonstrated clinically meaningful activity in heavily pretreated patients with advanced melanoma and high tumor burden. Durable responses and a favorable safety profile support the potential benefit of one-time lifileucel TIL cell therapy in patients with limited treatment options in ICI-refractory disease

What have transgenic and knockout animals taught us about respiratory disease?

Over the past decade there has been a significant shift to the use of murine models for investigations into the molecular basis of respiratory diseases, including asthma and chronic obstructive pulmonary disease. These models offer the exciting prospect of dissecting the complex interaction between cytokines, chemokines and growth related peptides in disease pathogenesis. Furthermore, the receptors and the intracellular signalling pathways that are subsequently activated are amenable for study because of the availability of monoclonal antibodies and techniques for targeted gene disruption and gene incorporation for individual mediators, receptors and proteins. However, it is clear that extrapolation from these models to the human condition is not straightforward, as reflected by some recent clinical disappointments. This is not necessarily a problem with the use of mice itself, but results from our continued ignorance of the disease process and how to improve the modelling of complex interactions between different inflammatory mediators that underlie clinical pathology. This review highlights some of the strengths and weaknesses of murine models of respiratory disease

Remote Ischaemic Conditioning in STEMI Patients in Sub-Saharan AFRICA: Rationale and Study Design for the RIC-AFRICA Trial

Purpose: Despite evidence of myocardial infarct size reduction in animal studies, remote ischaemic conditioning (RIC) failed to improve clinical outcomes in the large CONDI-2/ERIC-PPCI trial. Potential reasons include that the predominantly low-risk study participants all received timely optimal reperfusion therapy by primary percutaneous coronary intervention (PPCI). Whether RIC can improve clinical outcomes in higher-risk STEMI patients in environments with poor access to early reperfusion or PPCI will be investigated in the RIC-AFRICA trial. // Methods: The RIC-AFRICA study is a sub-Saharan African multi-centre, randomized, double-blind, sham-controlled clinical trial designed to test the impact of RIC on the composite endpoint of 30-day mortality and heart failure in 1200 adult STEMI patients without access to PPCI. Randomized participants will be stratified by whether or not they receive thrombolytic therapy within 12 h or arrive outside the thrombolytic window (12–24 h). Participants will receive either RIC (four 5-min cycles of inflation [20 mmHg above systolic blood pressure] and deflation of an automated blood pressure cuff placed on the upper arm) or sham control (similar protocol but with low-pressure inflation of 20 mmHg and deflation) within 1 h of thrombolysis and applied daily for the next 2 days. STEMI patients arriving greater than 24 h after chest pain but within 72 h will be recruited to participate in a concurrently running independent observational arm. // Conclusion: The RIC-AFRICA trial will determine whether RIC can reduce rates of death and heart failure in higher-risk sub-optimally reperfused STEMI patients, thereby providing a low-cost, non-invasive therapy for improving health outcomes