bluuebunny/crossref_metadata_2025 huggingface dataset:
Valorisation touristique de la mer Égée comme espace transfrontalier entre la Turquie et la Grèce
Authors: Oter Zafer , Ozdogan Osman Nuri , Vo Thanh Tan
Published: January 2021

La Mer Egée avec ses nombreuses îles partagées par la Turquie et la Grèce est un espace peu valorisé au sens touristique. Les deux pays ambitieux dans le marché global du tourisme ont plutôt focalisé sur les aspects compétitifs historiquement au lieu de se serrer la main pour un intérêt réciproque. Les potentiels de l’espace transfrontalier peuvent résulter aux bénéfices bilatéraux dans le cas de la Mer Egée.Dans cette étude, on essaiera d’analyser les conditions de la valorisation touristique de cet espace transfrontalier gréco turc. La globalisation et la construction d’un espace européen visant l’établissement d’une identité collective nécessitent la valorisation des espaces transfrontaliers qui sont souvent les territoires de débats politiques, mêmes militaires. La Turquie et la Grèce partagent une histoire longue qui provoque parfois des tensions. Il s’agit par exemple de la crise de l’île d’Imia (Kardak) et de la crise au Chypre en 1974. Cependant, une approche plus tranquille peut dévoiler plusieurs opportunités de collaboration dans les zones transfrontalières. Visites quotidiennes, exonération de visa ou facilitation des procédures de visa, shopping touristique, création des itinéraires touristiques bilatérales et d’autres solutions peuvent renforcer le développement de ces zones transfrontalières.Dans cette étude, la problématique sera analysée avec la méthode d’analyse des documents et des interviews avec les experts du domaine conformément à l’approche qualitative. On essaiera de recueillir des données à partir de diverses ressources secondaires (livres, journaux, sites Internet, ...) et primaires (interview avec une responsable grecque du tourisme) pour les interprétations. Finalement, on essaiera de fournir les recommandations pour la valorisation touristique de la Mer Egée comme espace transfrontalier.
L’activité d’une enseignante de 6e SEGPA lors des trajets reliant le collège et l’installation sportive : analyse d’une spécificité de l’EPS oubliée des chercheurs
Authors: Petiot Oriane
Published: January 2021

L’objet de cette recherche exploratoire était d’analyser l’activité d’une enseignante experte en EPS, exerçant en 6e SEPGA, lors des trajets entre le collège et l’installation sportive. Menée à partir d’une approche située incluant l’enregistrement audio-vidéo des quatorze premières leçons de l’année scolaire et la réalisation d’entretiens d’autoconfrontation avec l’enseignante après chaque leçon, cette étude lève le voile sur une spécificité de l’EPS jusqu’ici oubliée des chercheurs. Pour l’enseignante, les trajets permettent de se montrer disponible et à l’écoute des élèves, d’exercer une autorité pour limiter les comportements inappropriés, de se projeter dans les leçons à venir, et de construire un groupe classe. Contribuant à préparer, prolonger et même dépasser la leçon proprement dite, ils devraient faire l’objet d’une attention particulière dans le cadre de la formation des enseignants.
Débat d’idées et secondarisation en EPS en contexte difficile : entre émancipation et double empêchement
Authors: Poggi Marie-Paule , Bonbonne Cathy
Published: January 2021

Dans le cadre d’une approche socio-didactique, cette recherche vise à comprendre de quelle façon l’intervention enseignante contribue à l’accroissement ou à la réduction des inégalités sociales d’accès aux savoirs. Nous ciblons un dispositif particulier, le « débat d’idées », qui organise l’entrée des élèves dans un processus de secondarisation les invitant à passer d’une maîtrise pratique des savoirs scolaires en EPS à une construction réflexive, décontextualisée puis recontextualisée. Sept moments de secondarisation d’un cycle de basket de 6 leçons, auprès d’une classe de seconde CAP en contexte difficile ont été recensés, retranscrits puis traités en lien avec l’analyse des entretiens de l’enseignant. Les résultats montrent que les élèves s’approprient le dispositif de « débat d’idées » de façon inattendue. Par ailleurs, la prise de parole des élèves est à la fois favorisée par le dispositif mis en place et doublement empêchée. En effet, elle est limitée par un temps de parole largement saturé par les interventions de l’enseignant, et par les élèves eux-mêmes qui ne s’autorisent pas cette disposition à la distanciation.
Emergent First-Time Leadership in Patient Advocacy Organizations
Authors: Muller Nancy J.
Published: January 2021

Leadership in effecting change and transformation of the healthcare landscape on behalf of patients resides chiefly in patient advocacy organizations. The purpose of this chapter is to focus on leadership among not-for-profit patient advocacy organizations both in the U.S. and Europe by examining case studies of first-time leaders emerging in recent decades. Characteristics of these selected individuals are analyzed in the context of established leadership theories. Because of the necessity of securing funds to fulfill an organization's mission, transparency is of growing importance as an on-going and future challenge. Social entrepreneurism is introduced at the chapter's conclusion for its possible relevance to tomorrow's leaders emerging in patient advocacy organizations. Such thinking opens the door to future research to identify essential elements of success in the examination of first-time leadership in patient advocacy and to determine how it is best nurtured, mentored, and applauded.
System Identification Guidance for Multirotor Aircraft: Dynamic Scaling and Test Techniques
Authors: Ivler Christina  M. , Rowe Elizabeth  S. , Martin James , Lopez Mark  J.S. , Tischler Mark  B.
Published: January 2021

State-space system identification was performed to extract flight dynamic models for hovering flight of a 55 cm, 1.56 kg hexacopter unmanned aerial vehicle. Different input excitation techniques were tested to determine which maneuvers provided high-quality system identification results for small-scale multirotor vehicles. These input excitation techniques included automated frequency sweeps, varying in amplitude, and multisine sweeps. Coherence, Cramer–Rao bounds, and insensitivities were used as metrics for comparing the system identification results. A parametric variation of frequency sweep amplitudes were performed in all axes (roll, yaw, pitch, and heave) to provide guidance on frequency sweep amplitude for small-scale multirotor unmanned aerial systems. The dynamics of the 55 cm hexacopter were used to estimate the dynamics of a larger 127-cm hexacopter via Froude scaling based on hub-to-hub distance as the characteristic length. The scaled results were compared to an actual system identification model of a 127-cm hexacopter.
A qualitative study exploring the experience of psychotherapists working with birth trauma
Authors: Gough Elizabeth , Giannouli Vaitsa
Published: January 2021

As many as 45% of women experience birth trauma. Psychotherapists’ knowledgeable insights are largely absent in literature, and therefore the objective of this research is to gain a comprehensive understanding of how psychotherapists in the UK experience the therapeutic process when working with women who have experienced a traumatic birth. Interpretive Phenomenological Analysis (IPA) was employed to examine the data coming from psychotherapists working with birth trauma. Three ostensible areas of focus were revealed: i) Hearing the story: discovering the altered-self, ii) Working with the story: enabling redemption of the altered-self, and iii) Professional challenges and the wider story: advocating for the altered-self. Birth trauma commonly leads to an altered sense of self, intertwined with a perception of loss regarding the birth experience and autonomy. Working with the client’s birth story, to enable redemption and restore reasoning, is integral to the therapeutic process. Stabilisation and consideration of the presence of the baby are also significant. Integrating approaches produces positive outcomes. There is a purported gap in NHS services, professionals either lacking knowledge and misdiagnosing, or being limited by the emphasis placed on Cognitive Behavioural Therapy. For the therapeutic process consider: the sense of loss associated with the birth; working with the client’s birth story to enable redemption and restore reasoning; the impact of the presence of the baby and the need for stabilisation; birth trauma as unique. For frontline health professionals: implementing existing screening protocols and undergoing training to recognise birth trauma may reduce misdiagnosis.
In-depth analysis of multi- and extensively drug-resistant mycobacterium tuberculosis isolates in the capital of iran
Authors: Vaziri Farzam
Published: January 2021

Aims and objectives:

The emergence and spread of multidrug resistant (MDR) Mycobacterium tuberculosis (M. tuberculosis) strains is a critical global health problem. In order to shorten the course of treatment and its effectiveness, it is essential to gain an in-depth insight into the genetic diversity, drug resistance mechanisms and host-pathogen interactions of drug resistant M. tuberculosis.

Methods:

Between 2014 and 2018, 606 MTBC strains were isolated from 13,892 suspected pulmonary tuberculosis (TB) patients in Tehran, Iran, including 16 MDR-TB cases. A combination of phenotypic (conventional drug susceptibility testing, MIC, Verapamil effectiveness) and genotypic methods (whole-genome sequencing and qPCR) was employed for the identification of additional drug resistances, the role of efflux pumps and strain-to-strain genetic distances as a marker for recent transmission events. Finally, the consequences of mutations in genes encoding the beta subunit of RNA polymerase (rpoB) for host-pathogen interactions was investigated by means of THP-1-derived macrophages infection and Cytokines and Chemokines Real-Time RT2 Profiler PCR Array.

Results:

MDR and extensively drug-resistant (XDR) TB cases were almost exclusively infected by lineage 2/Beijing strains (14/16, P < 0.001). Out of the 16 MDR/pre-XDR/XDR isolates, 6 (37.5%) and 3 (18.8%) isolates demonstrated a significant decrease in rifampicin (RIF) MIC and isoniazid (INH) MIC due to the Verapamil exposure (64 μg/mL), respectively. More importantly, it was found that the administration of Verapamil profoundly decreased the MIC of Bedaquiline (BDQ) among most of the studied clinical isolates. Moreover, the efflux pump genes of Rv2938, Rv2936, Rv1145, Rv1146, Rv933, Rv1250, Rv876, Rv2333, Rv2459, Rv849, and Rv1819 were overexpressed in the presence of anti-TB drugs, showing the contribution of these efflux pumps to the overall resistance phenotype. Finally, the macrophages immune responses induced in response to infection with drug-resistant M. tuberculosis (RMR strain) may not be substantially different from drug susceptible M. tuberculosis (H37Rv strain), but the severity of the responses was different in some cases specially IL-6, IL-8, CNTF, IL-13, TNFSF10 and CD40LG in response to RMR and H37Rv strains. In addition, RMR strain showing significantly higher intracellular bacillary growth compared to H37Rv strain.

Conclusions:

The crucial finding is that almost all of our MDR/pre-XDR/XDR strains are of the Beijing lineage (14/16) and more than half of them are probably from recent transmission (8/14). Our results clearly showed that efflux systems, besides spontaneous mutations, play a role in the development of INH/RIF resistance. In addition, Verapamil was very successful at the phenotypic level specially in response to BDQ. Finally, the results initially demonstrate that the M. tuberculosis carrying the rpoB-S450L can modulate macrophage responses to mediate bacterial survival.
Description of a novel selective medium (abscessus selective agar; asa) for the isolation of mycobacterium abscessus complex
Authors: Moore John E , Millar Beverley C
Published: January 2021

Aims and objectives:

Mycobacterium abscessus complex consisting of M. abscessus subsp. massiliense, M. abscessus subsp. bolletii and M. abscessus subsp. abscessus, have now emerged as clinically important NTM pathogens in patients with cystic fibrosis (CF). Culturally, these organisms are difficult to isolate from sputum amongst mixed populations of extremely rapidly growing Gram-negatives, particularly Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Achromobacter spp. Our objective was to develop a highly selective medium, not requiring decontamination of CF sputum but which exploited M. abscessus complex's resistance to several antibiotics.

Methods:

ASA medium was formulated employing Glucose, 16g/l; Agar, 20g/l; Yeast extract, 30g/l; Peptone, 6.8g/l; Chloramphenicol, 50mg/l; Ceftazidime, 32mg/l; Colistin, 24mg/l; Trimethoprim, 21.33mg/l; Sulfamethoxazole, 106.67mg/l and Novobiocin, 50mg/l. Mycobacterium abscessus complex organisms consisting of M. abscessus subsp. massiliense (n=2), M. abscessus subsp. bolletii (n=2) and M. abscessus subsp. abscessus (n=2) [circa 106 colony forming units (CFU)] were plated onto ASA medium and cultured aerobically for 2 weeks at 30o C. In addition, the following non-NTM organisms were also plated onto ASA medium, as above, Gram-positive: Enterococcus faecalis, Staphylococcus aureus (n=6), Staphylococcus aureus (mucoid), MRSA (Hospital-associated), MRSA (Livestock-associated cc398); Gram-negative: Achromobacter sp. (n=4), Burkholderia gladioli, Burkholderia multivorans, Escherichia coli (n=2), Pseudomonas aeruginosa (n=7), Salmonella enterica subsp. enterica serotype Nottingham, Salmonella enterica subsp. enterica serotype Typhimurium & Stenotrophomonas maltophilia. Following incubation, growth was assessed semiquantitatively, as +++, ++, +, few or no growth.

Results:

ASA medium supported the prolific growth (+++) of all M. abscessus complex organisms, but inhibited all non NTM organisms from growing (no growth).

Conclusions:

ASA medium is highly selective, which allowed for the proliferation of all members of the Mycobacterium abscessus complex, but successfully inhibited all other bacterial flora in CF sputum. This medium shows potential in isolating M. abscessus complex organisms from polymicrobial specimens/environments.
Tuberculosis and COVID-19 Co-Infection
Authors: Rezaei Mitra , Babamahmoodi Abdolreza , Marjani Majid
Published: January 2021

Aims and objectives:

Because the world is mobilized with all its might to fight the COVID-19 epidemic, control of common but deadly diseases such as tuberculosis may be neglected. With a conservative estimate and modeling working, we can show that if too much attention to the COVID-19 continuing it can leads to a 25% reduction in global TB diagnosis by 3 months and TB mortality will increase by 13% and this brings us back to the level of TB mortality we had 5 years ago. Between 2020 and 2025, 1.4 million TB deaths could be recorded as a direct consequence of COVID-19. Therefore, ensuring the continuation of basic services and operations to deal with long-standing health problems like tuberculosis or other similar diseases to protect the lives of people is very important.

Methods:

This study is a case series has been performed in three hospital centers in Tehran where respiratory and infectious patients were treated. We report on eleven cases of patients who were either unaware of their tuberculosis or of their COVID-19 and after visiting a medical center, they found out that they have both of them.

Results:

Of the eleven patients in this study, seven were male and four were female, with a mean age of 56.6 years (minimum age 27 years and maximum age 91 years). Five patients were previously diagnosed with tuberculosis and six patients were initially admitted with a diagnosis of COVID-19. Seven were Afghans and four were Iranians. Ten patients had respiratory tuberculosis and one had both pulmonary and spinal tuberculosis. Fever, productive cough, and hemoptysis were present in all of them.

Conclusions:

Tuberculosis and COVID-19 are both common infections of the respiratory system and have common signs and symptoms and these similarities may cause overlapping the two diseases. While experience with COVID-19 infection in TB patients is still limited, it is predicted that people with TB and COVID-19 may have poorer treatment outcomes, especially if TB treatment is postponed.
Tuberculosis and diabetes
Authors: chema Marouane , sana kammoun , mariem Frikha , salma Hachicha , asma Ghorbel , salma Smaoui , neila Zalila , férièle Messadi Akrout
Published: January 2021

Aims and objectives:

Diabetic patients are considered at increased risk of infections, including tuberculosis. The purpose of this work was to analyze the epidemiological, clinical, diagnostic, therapeutic characteristics, aggravating factors and evolution in patients with pulmonary tuberculosis and diabetes.

Methods:

This retrospective study included 42 patients with pulmonary tuberculosis and diabetes, followed in Farhat Hached health center of Sfax and whose bacteriological diagnosis was confirmed in the hygiene laboratory of Hedi Chaker university hospital between 2009 and 2015.

Results:

Diabetes affects 10.8% of patients with pulmonary tuberculosis. The mean age was 55.5 years and the sex ratio were 1.2. Diabetes occurs before tuberculosis in 88% of cases. The majority of patients had type 2 diabetes, of which 23.8% required insulin treatment. Anti-diabetic treatment was modified in 21.4% of cases due to poor glycemic control. The diagnosis of pulmonary tuberculosis was based on clinical, radiological, histological data and microbiological analysis. Cough was the most frequent symptom (88.1%). Pulmonary tuberculosis patients with diabetes were more likely to have pulmonary cavities (66.7%) and apical lesions (76.1%). Smear was positive in 85.7%. After 2 months of treatment, only 50% of the positive smears became negative. Tuberculosis treatment lasted more than 6 months in 66.7%. Most of patients had a favorable evolution (90.5%), 4.7% of cases had relapsed and one patient died. Smoking (52%), family history of pulmonary tuberculosis (47.6%) and high blood pressure (30.9%) were the most frequent risk factors in these patients.

Conclusion:

The bidirectional association between pulmonary tuberculosis and diabetes due to the modification of the clinical presentation and evolution under treatment makes patients more fragile requiring a better medical care.
DNA vaccine against tuberculosis by using five mycobacterium specific genes
Authors: Shahzad Mirza Imran
Published: January 2021

Aim and Objective:

In this study, five genes of Mycobacterium tuberculosis were used as DNA vaccine. Each gene was cloned in pcDNA3.1 Topo and later in pND mammalian expression vectors.

Methods:

All the clones were tested through animal cell lines. In animal trial studies, endotoxin-free DNA were used to inoculate eight week old female Balb/c mice in quadriceps muscles with 50 μg DNA/leg and 25 μg DNA intradermally at the base of tail. No boosters were given.

Result:

The best humoral response was observed by hspx-pND vaccinated group. Similar but quantitatively less positive response was observed in case of equally mixed ag85a, b and c-pND vaccine group, whereas, cfp10-pND vaccinated animals showed poor immune response.

Conclusion:

The study concludes that all M. tb gene constructs were good in expression under in vitro and in vivo conditions and produced significant level of antibodies except cfp10-pND construct. The study proved that subunit based DNA vaccines alone or in combination with each or with BCG, can provide breakthrough in vaccines against TB.
Treatment Outcomes of Non-tuberculous mycobacteriosis (NTM) in children with Cystic Fibrosis
Authors: Mir F , Nathwani AA , Shakoor S
Published: January 2021

Aim and objectives:

To describe presentation and treatment course of children with cystic fibrosis and pulmonary NTM disease at Aga khan University in last 5 years

Methods:

A retrospective chart review of children diagnosed with cystic fibrosis at the Aga Khan University, Karachi and NTM Pulmonary disease between January 2015 to Dec 2019 will be conducted. We will evaluate clinical and laboratory profile of these children and present descriptive demographic and treatment-related statistics. Results will be presented as median age at diagnosis (IQR), median weight for age z scores at presentation and after treatment, sputum/PFTs/radiological findings as proportions (percentages) and treatment outcomes (sputum clearance, improvement in weight and PFTs, death).

Conclusions:

We will present clinical profiles of children with CF and NTM managed at Aga Khan University in the last 5 years and highlight challenges encountered in diagnosis and management of NTM in this population
Cloning and Expression of virulent proteins CFP-10 and ESAT-6 of Mycobacterium bovis AN5 for diagnosis of bovine tuberculosis
Authors: Reza Arefpajoohi , Tagi Zahraei Salehi , Nader Mosavari , Ramak Yahya raeyat
Published: January 2021

Aims and objects:

Bovine tuberculosis caused by Mycobacterium bovis is an important disease that has negative effects in public health and economic losses. Traditional controlling program in cattle is based on test and slaughter strategy, but false positive is disadvantage of tuberculin skin test. To overcome the limitation, there is a need of using proteins with high specificity. The objective of this study was to clone and express of virulent protein CFP-10 and ESAT-6 of Mycobacterium bovis AN5 for diagnosis of bovine tuberculosis.

Methods:

Briefly, full-length genes of cfp-10 and esat-6 were amplified by PCR technique. In parallel pET23a (+) and PCR product has been double digested by EcoRI and HindIII. After Ligation, transformation was done into competent E.coli DH5α. Then the cloned vector was transformed into E.coli BL21. Induction was performed by isopropyl-β-D-thiogalactopyranoside (IPTG). The expressed proteins almost entirely in the inclusion body form. To dissolution of expressed protein, urea 8M was used. Purification of recombinant proteins was done by Nickle-Resin. Urea eliminated by decreasing gradient. Delayed hyper sensitivity of two proteins beside bovine tuberculin, avian tuberculin and human tuberculin studied in guinea-pig model.

Results:

Protein expression was confirmed by Western Blotting (WB) using 6X His-tag antibodies. The results showed that CFP-10 and ESAT-6 molecules has been successfully cloned and expressed in prokaryotic system. Results showed that CFP-10 has satisfactory relative potency but it is not in range about ESAT-6.

Conclusion:

The recombinant CFP-10 can play a significant role in reducing the false positive in diagnosis of bovine tuberculosis by improving the specificity of the tuberculin skin test
A Potent Inhibitor of IL-10/STAT3 Axis Signaling Modulates Anti-Inflammatory Responses and Boosts Anti-Tuberculosis Immunity in rBCG30 Immunized Mice
Authors: Ahmad Faraz , Umar Mohd Saad , Khan Nazoora , Gupta Pushpa , Gupta Umesh Datta , Owais Mohammad
Published: January 2021

Aims and Objectives:

In the present study we tried to improve anti-TB immunity offered by 2nd generation rBCG30 vaccine. We attempted to bolster rBCG30 invoked anti-TB immunity in mice through modulation of the IL-10/STAT3 interaction mediated anti-inflammatory program. The study was aimed towards generating optimum activated APCs, early either after vaccination (with rBCG30) or infection (with Mtb), which can process and present mycobacterial antigens more efficiently to T cells. It was envisage that downmodulating IL-10/STAT3 signaling may improve immunity and protection offered by rBCG30 vaccine.

Methods:

A small molecule immunomodulator aimed at disrupting anti-inflammatory signaling orchestrated by IL-10/STAT3 axis was administered in rBCG30 immunized mice. The comparative expansion of pathogen permissive Alternatively Activated Monocytes/Macrophages/DCs (AAMs/AADCs) and Classically Activated Monocytes/Macrophages/DCs (CAMs/CADCs), the cells that resist establishment of successful Mtb infection, was profiled in both peritoneal and splenic compartment. To assess innate and adaptive T cell responses, splenocytes cytokine production was checked ex vivo using sandwich ELISA. We also checked polyfunctional T cell response, T cell memory response and comparative Th17/Treg cells expansion using flow cytometry. Finally, to assess the real time efficacy of the employed immunotherapeutic strategy, in vivo protection study was undertaken in BALB/c mice challenge with aerosolized Mtb (H37 Rv).

Results:

The small molecule mediated inhibition of IL-10/STAT3 signaling was resulted in improved pro inflammatory immune responses in both post-vaccination and post-infection immunotherapy schedules. The improved immune profile in rBCG30 vaccinated and immunotherapy administered mice was accompanied with enhanced expansion of CAMs/CADCs, elevated production of polyfunctional T cells producing signature Th1 cytokines, long lasting CD4+ and CD8+ memory T cell response and balanced Th17/Treg cells ratio. Interestingly, post-infection, and not post-vaccination immunotherapy, was able to significantly reduce mycobacterial loads in spleen and lungs of experimentally infected mice.

Conclusions:

Small molecule mediated transient disruption of anti-inflammatory effectors, such as IL-10/STAT3, during vaccination or post infection with Mtb, may serve to enhance the efficacy of existing and forthcoming TB vaccines. The strategy can also be tested concomitantly with standard chemotherapy (either in vaccinated or unvaccinated host) to enhance the efficacy of therapeutic regimen and to reduce the treatment length.
Use of whole genome sequencing to identify transmission of resistant tuberculosis strains in italy
Authors: Tagliani Elisa , Borroni Emanuele , Cirillo Daniela Maria
Published: January 2021

Aims and objectives:

In the present study, we report on the cross-border clusters involving Italian MDR-TB strains collected in the framework of the ECDC supported EUSeqMyTB project. This pilot study was conducted as retrospective/prospectic WGS-based surveillance project to monitor possible cross-border TB transmission involving strains isolated in Europe.

Methods:

Within the EUSeqMyTB study period (approximately 24 months) 2218 RR/MDR-TB strains from 25 EU countries were collected, including a total of 127 strains from Italy. Additional RR/MDR-TB strains were collected and sequenced in Italy as part of the national WGS-based surveillance. All strains were subjected to WGS according to standard protocol for the Ion torrent or Illumina platform. Sequencing of Italian strains was performed by Illumina. WGS data were subjected to quality check (See Tagliani et al ERJ 2020) and analysis was performed by SNP based pipeline and Core Genome MSLT (SeqSphere+ Redom GmbH, Germany)

Results:

The Euroamerican superlineage was the most represented in Italy (64% of cases). The Italian strains were included in the 3 major cross-border clusters identified in the study. The largest cluster comprised a total of 30 patients from 3 different countries, including 22 individuals born in the same European country. Italy contributed to this cluster with 12 cases isolated during the study period and with additional two cases after the end of the study in 2019. The clustered strains isolated in Italy were from both Italian born and foreign born TB cases, the majority of which were from another EU country. For the majority of the clustered cases isolated in Italy the epidemiological link was identified and the cluster was linked to a pub located in Milan, Italy. A subgroup of the MDR-TB cases showed additional resistance to 2nd line anti TB drugs as well as resistance to bedaquiline (linked to a large deletion in the rv0678 gene). One clustered case showed also a minimum inhibitory concentration for delamanid close to the drug critical concentration. For the additional two large cross-border clusters identified in the EUSeqMyTB pilot study, Italy contributed with respectively 2 and 5 cases. All of them were linked to migration from sub-Saharan Africa countries and no case of transmission to Italian born population was identified neither during the study timeframe nor afterwards.

Conclusions:

We documented that WGS-based surveillance of RR/MDR-TB strains highly support contact tracing investigation. The implementation of WGS in routine should require the performance of WGS as soon as the strain become available and not in batches with delay. Information exchange with neighboring countries should be facilitate. We report on an ongoing transmission of a pre-XDR strain linked to a larger EU cluster and that the transmitted strain is highly resistant to therapy with the current MDR recommended treatment.
Animal Models of Tuberculosis
Authors: Gupta U. D. , Gupta Pushpa
Published: January 2021

Aims and objectives:

Tuberculosis (TB) remain a leading cause of death globally among among infectious diseases that has killed more number of people than any other infectious diseases. It was Robert Koch who recognized the spectrum of pathology of tuberculosis (TB) in different animal species.

Methods:

The examination of clinical specimens from infected humans and animals confirmed the variable patterns of pathological reactions in different animal species. Guinea pigs are innately susceptible while humans, mice and rabbits show different level of resistance depending upon their genotype. The studies of TB in laboratory animals like mice, rabbits and guinea pigs have significantly increased the understanding of the aetiology, viurulence, and pathogenesis of the disease. By introducing less than five virulence organisms into guinea pigs by the respiratory route can produce lung lesions, bacteraemia and fatal diseases, which has helped the extrapolation of results of such experiments to humans beings. The similarities in the course of course of clinical infection between guinea pigs and humans allow us to model different models of TB and to evaluate the protective efficacy of candidate in such systems. The only limitation of this model is a dearth of immunogical reagents required for the qualitative and quantitative evaluation of the immune responses, special reference to cytokines and cell phenotypes. Further limitation is the higher cost of the guinea pigs as compared with the mice.

Results:

The rabbit is relatively resistant to M TB infection, however following infection with virulent Mycobacterium bovis, the rabbit produces pulmonary cavities like humans. The rabbit model, however, is also limited by the lack of immunological reagents. Mice are the animal choice of studying the immunology of Mycobacterial infections and contributed much to our current understanding of the roles of various immunological mechanisms of resistance. The resistance of mice to the development of classic TB disease, however, represents a significant disadvantage to the mouse model. Although non-human primates are closely related to humans, owing to high cost and handing difficulties they have not been exploited to a large extent.

Conclusions:

As all existing animal models fall to mimic the human disease perfectly, efforts should be focused on the development of the non-human primate (s) as the alternative animal model for TB.
Use of linezolid to replace kanamycin in the shorter MDR-TB regimen in case of hearing loss
Authors: Souleymane Mahamadou Bassirou , Piubello Alberto , Maman-Lawan Ibrahim , Morou Soumaila , Boukary Ibrahim , Assao-Neino Mourtala Mohamed
Published: January 2021

Aims and objectives:

The standardized short treatment regimen (STR) is implemented in Niger to treat multidrug-resistant tuberculosis (MDR-TB) since 2008 with excellent outcomes. However, ototoxicity secondary to injectable is a concern and data on modified oral STR are limited. The aim of this study is to test if linezolid can replace the injectable. Both drugs have a similar mechanism of action and the use of linezolid in replacement of SLI may preserve bedaquiline as core-drug in a salvage regimen to treat possible failures and relapses. Linezolid is used only in the intensive phase to reduce the risk of peripheral neuropathy and optic neuritis.

Methods:

A prospective longitudinal study was conducted on a modified STR replacing kanamycin with linezolid (600 mg/d) in case of hearing loss (grade 1) at baseline or during treatment. WHO definitions were used for outcomes and adverse events were assessed according to French National Agency for Research on AIDS. Audiometry was performed bimonthly from 2016 to 2017 and monthly from 2018 onwards.

Results:

A total of 173 patients were treated with the STR for pulmonary MDR-TB from 2016 to June 2018. Among them, 22 (12.7%) had a modified STR, switching from kanamycin to linezolid during treatment (14) or starting with linezolid (8) because of hearing loss. Fourteen (63.6%) were males, 2 (9.1%) were HIV positive, the median age was 37.5 years (range 21-71) and the median BMI was 16.5 kg/m2 (range 13-24.2). No patients had strains resistant to fluoroquinolones and/or injectables. The median time from treatment start to switch kanamycin to linezolid was 2 months (range 0-3) and the median duration of treatment with linezolid was 2 months (range 1-5). All patients had smear and culture conversion with a median and range of 1 month (1-6) and 2 months (2-4) respectively.

Conclusions:

A modified STR with linezolid may achieve high cure rates with manageable adverse events.
Antimycobacterial activity of total extracts from Solanum torvum Swartz. (Solanaceae)
Authors: Nguta Joseph Mwanzia
Published: January 2021

Aims and objectives:

Tuberculosis (TB) caused by Mycobacterium tuberculosis complex remains a leading cause of morbidity and mortality worldwide. The zoonotic infectious condition represents a never-ending challenge towards which drug discovery efforts are needed. The current study was designed to evaluate the in vitro antimycobacterial activity of ethanolic extracts from roots, stem bark, leaves and unripe fruits derived from Solanum torvum, a shrub traditionally used against respiratory tract illnesses, including tuberculosis.

Methods:

The phenotypic colorimetric micro plate alamar blue assay (MABA) was used to study the antimycobacterial activity of the ethanolic extracts against six mycobacterial strains. Each experiment was run in triplicate. Data generated was analyzed using descriptive statistics to obtain mean minimum inhibitory concentration values.

Results:

The roots, stem bark, leaves and unripe fruits exhibited minimum inhibitory concentration values of 1.250 mg/mL, 0.078 mg/mL, 1.250 mg/mL and 0.625 mg/mL against the pathogenic mycobacterial strain, M. tuberculosis H37Rv (ATCC 27294) respectively.

Conclusions:

In conclusion, Solanum torvum stem bark has demonstrated moderate activity against the pathogenic Mycobacterium tuberculosis strain. This observation validates the ethno pharmacological use of the plant species against tuberculosis. Further studies are required to isolate, elucidate the structure and characterize the antimycobacterial compounds responsible for the observed activity. These will potentially contribute towards bioprospecting for a new class of ligands with activity against sensitive and drug resistant strains of M. tuberculosis.
Assessment of line probe assay for rapid detection of extensively drug-resistant Mycobacterium tuberculosis isolates
Authors: Kardan-Yamchi Jalil , Kazemian Hossein , Abtahi HamidReza , Amini Sirus , Feizabadi Mohammad Mehdi
Published: January 2021

Aims and objectives:

Molecular techniques have considerable advantages for rapid detection, a reduction of infectiousness, prevention of further resistance development and surveillance of drug-resistant TB. MTBDRsl VER 2.0 was used to detect resistance to second-line anti-tuberculosis drugs on rifampicin-resistant M. tuberculosis (RR-MTB) isolates compared to the minimum inhibitory concentrations (MICs) and whole genome sequencing (WGS).

Methods:

The MTBDRsl VER 2.0 (Hain Life Science, Nehren, Germany) and WGS (San Diego, CA, USA) was performed for tracing mutations in resistant-related genes involved in resistance to fluoroquinolone (FLQs) and second-line injectable drugs (SLIDs). The broth microdilution method using 7H9 Middlebrook media supplemented with OADC was used to determine the MICs.

Results:

The MTBDRsl VER 2.0 correctly detected 5/6 (83.3%) of FLQ-resistant strains having gyrA mutations. The MUT1 A1401G (7 strains) and MUT2 G1484T (1 strain) mutations in rrs gene were detected in 8 AMK/KAN/CAP-resistant strains. Four low-level KAN-resistant strains with the G-10A/C-12T (3 strains) and C-14T (1 strain) mutations in eis gene was diagnosed using MTBDRsl VER 2.0.

Conclusions:

Five error results were found in detecting resistance to kanamycin and capreomycin compared to the phenotypic drug susceptibility testing and WGS. Failing wild type-bands without improved mutant-bands did not indicate a reliable resistance. WGS could efficiently resolve the discrepancies of the results. MTBDRsl showed better performance in detecting extensively drug-resistant strains.
Sex differences in haemostatic and other haematological parameters of tuberculosis patients at pre-treatment, post-intensive and post-continuation phase anti-tuberculosis therapy
Authors: Okeke  , Okechukwu Chizoba , Ifeanyichukwu  , Ositadimma Martin , Amilo  , Grace  , Okeke  , Makuachukwu Chisom
Published: January 2021

Aims &Objective:

Gender variations are common features of many physiological parameters. Thus sex differences in haemostatic and haematological parameters are expected, but how anti-tuberculosis therapy modulates these differences is unclear. We hypothesized that anti-tuberculosis therapy will induce further changes in the level of these parameters when compared between male and female tuberculosis (TB) subjects.

Aims and Objectives:

This comparative follow-up study was designed to compare the levels of haemostatic and other haematological parameters between male and female TB subjects at pre-treatment, and followed up with a repeat comparison at post-intensive phase treatment and post-continuation phase treatment, to ascertain the differences at each phase of treatment.

Methods:

A total of sixty TB subjects of both genders (35 males and 25 females) were enlisted in this study. They were recruited before initiation of therapy and followed up post-intensive phase and post-continuation phase treatment and samples collected and analysed.

Results:

At pre-treatment, P-selectin (ng/ml), PCV (l/l), neutrophil-lymphocyte ratio (NLR) and platelet count (x109 /l) were significantly higher in male compared to female TB subject (P=0.044, 0.022, 0.040 and 0.039). At post-intensive phase treatment, P-selectin (ng/ml), TPO (pg/ml), total white blood cell count (x109 /l), neutrophil count (x109 /l), lymphocyte count (x109 /l), monocyte count (x109 /l), eosinophil count (x109 /l) and monocyte lymphocyte ratio (MLR) was significantly higher in male compared to female TB subjects (P=0.046, 0.030, 0.022, 0.044, 0.029, 0.036, 0.042 and 0.036). Conversely, the mean platelet count (x109 /l) was significantly higher in females than males (P=0.022). At post-continuation phase treatment, the median P-selectin (ng/ml) was significantly higher in male compared with female TB subjects (P=0.028).

Conclusion:

Sex differences in haemostatic and haematological parameters vary with different phases of anti-tuberculosis treatment. But P-selectin displays a consistent higher level in male TB subjects at all phases of treatment.
The Risk of TB Laboratory Personals That Received Specimens from Patients Having Both Tuberculosis & COVID-19
Authors: Farnia Parissa , Farnia Poopak , Ghanavi Jalaledin , Velayati Ali Akbar
Published: January 2021

Aims and Objective:

The SAR COVID2 virus devastated the world in the very short time. The virus not only effected the individuals, but also the economy and infrastructure of laboratories working in other infectious diseases. The synergy between patients with other air borne diseases like tuberculosis and COVID-19 is not very clear, but it have been shown that few patients expired having two diseases at the same time. Now the question comes out for safety of laboratory personal and necessary precaution for those that handle the specimens from patients who got both infection (tuberculosis &COVID-19).

Results:

The investigation should that most of peripheral TB laboratories (85%) in Iran are using biological safety cabinet type 1 or 2; therefore they are not using open bench for making smear. Small number of general hospital (30%) use the open bench for smear preparation at the peripheral levels. It is advisable that after smearing they kept the smear for drying in the cabinet with using UV light for 1-2 hours; then they proceed with fixation and staining. May be it is also advisable to handle the specimens, with proper clothing also.

Conclusion:

It looks that with pandemic of COVID-19, even TB laboratories need re-vision of their protocol as far as safety of personal is concerned. Also, the open benching for smearing should be avoided in all other countries.
High frequency of bedaquiline resistance in programmatically treated drug-resistant TB patients with sustained culture-positivity in Cape Town, South Africa
Authors: Derendinger Brigitta , Dippenaar Anzaan , de Vos Margaretha , Alberts Rudi , Sirgel Frederick , Dolby Tania , Spies Claudia , Rigouts Leen , Metcalfe John , Engelthaler David , Warren Rob , Cox Helen , Theron Grant
Published: January 2021

Aims & objectives:

Potentially transformative new tuberculosis (TB) drugs like bedaquiline are undergoing roll-out, however, this is largely in the absence of programmatic drug susceptibility testing (DST). We lack information on how susceptibility changes during treatment in patients on bedaquiline-containing regimens, especially in at risk patients who have complex treatment histories, are in programmatic rather than trial environments, and have a delayed treatment response (defined here as sustained culture-positivity).

Methods:

Serial isolates from 51 patients with drug resistant (DR-)TB who were culture-positive after ≥4 months of a programmatically administered bedaquiline-containing regimen, were collected. Bedaquiline phenotypic DST in MGIT 960 (1μg/ml), targeted deep sequencing (Rv0678, atpE, pepQ) and whole genome sequencing was done on paired isolates (pre-bedaquiline initiation, post-four-month).

Results:

24/51 (47%) patients were phenotypically and genotypically resistant (39% acquired resistance). Excluding one patient with an unknown history, prior clofazimine exposure was associated with bedaquiline-resistance [21/24 (88%) bedaquiline resistant cases had prior clofazimine vs. 12/26 (46%) susceptibles; p=0.002]. Diverse combinations of single nucleotide polymorphisms (SNPs) and indels were in the Rv0678 promoter region and the Rv0678 and atpE genes. Examples of newly described resistance associated variants (RAVs) include Rv0678 -8 T/G and atpE 223 C/T. RAVs were not in defined hotspots and sometimes occurred concurrently with atpE RAVs.

Discussion:

The rate of bedaquiline resistance acquisition in this population is alarmingly high and associated with prior clofazimine exposure. The diverse RAVs pose challenges to molecular test development. This study highlights the existence of a potentially infectious pool of bedaquiline-resistant patients present under programmatic conditions in a resource-constrained setting and illustrates the danger of starting patients with complex histories on a novel drug without routinely available DST.
Recent advances and future directions on the use of optical coherence tomography in neuro-ophthalmology
Authors: Lo Cody , Vuong Laurel N. , Micieli Jonathan A.
Published: January 2021

Optical coherence tomography (OCT) is a noninvasive imaging technique used to qualitatively and quantitatively analyze various layers of the retina. OCT of the retinal nerve fiber layer (RNFL) and ganglion cell–inner plexiform layer (GCIPL) is particularly useful in neuro-ophthalmology for the evaluation of patients with optic neuropathies and retrochiasmal visual pathway disorders. OCT allows for an objective quantification of edema and atrophy of the RNFL and GCIPL, which may be evident before obvious clinical signs and visual dysfunction develop. Enhanced depth imaging OCT allows for visualization of deep structures of the optic nerve and has emerged as the gold standard for the detection of optic disc drusen. In the evaluation of compressive optic neuropathies, OCT RNFL and GCIPL thicknesses have been established as the most important visual prognostic factor. There is increasing evidence that inclusion of OCT as part of the diagnostic criteria for multiple sclerosis (MS) increases its sensitivity. Moreover, OCT of the RNFL and GCIPL may be helpful in the early detection and monitoring the treatment of conditions such as MS and Alzheimer's disease. OCT is an important aspect of the neuro-ophthalmologic assessment and its use is likely to increase moving forward.
Survei Kualitas Air Danau Pandan yang Terletak di Kecamatan Pinangsori Kabupaten Tapanuli Tengah
Authors: Fitria M Dian , Rosmasita Rosmasita , Yanti Emma Suri , Bagariang Ramona Indah
Published: January 2021

Danau pandan memiliki luas ± 103 Ha yang terletak di desa Parjalihotan Baru kecamatan Pinangsori kabupaten Tapanuli Tengah. Status keberadaan danau pandan masih jarang diketahui oleh masyarakat Tapanuli Tengah maupun masyarakat luar dari kabupaten Tapanuli Tengah, sehingga penelitian mengenai danau pandan masih jarang dilakukan. Tujuan penelitian ini adalah untuk mengetahui kualitas air danau pandan yang diamati dari parameter fisika yaitu suhu dan kedalaman, sedangkan parameter kimianya mengamati kandungan pH (Potensial Hidrogen) dan DO (Dissolved Oxygen) perairan, serta mengetahui kondisi hidrologi dari danau pandan tersebut. Hasil pengukuran suhu air danau pandan selama penelitian memperlihatkan bahwa suhu air pada 10 titik stasiun berkisar antara 32,0 ºC – 36,0 ºC, sedangkan kedalaman danau berkisar 0,8 m – 1,7 m. Nilai DO atau kandungan oksigen terlarut perairan danau pandan kisaran dari 4,91 mg/l – 9,03 mg/l. pH air danau Pandan berkisar antara 6,8 – 9,02. Kondisi hidrologi Danau Pandan dibentuk oleh aliran parit-parit dan sungai yang yang bermuara ke Danau Pandan antara lain: Sungai Aek Kemuning dan Aek Lobu. Sedangkan outlet Danau Pandan secara alami mengalir ke arah utara melalui Sungai Aek Kemuning dan bermuara ke Desa Sitardas, Badiri Tapanuli Tengah.
Famili Rhizophoraceae di Hutan Mangrove KKPD Rupat Utara Provinsi Riau Bagian I, Deskripsi Anggota
Authors: Syahrial Syahrial , Erlangga Erlangga , Sembiring Rini Tri Lestari , Syahrin Alfi
Published: January 2021

Pemantauan kekayaan spesies mangrove sangat diperlukan dalam merumuskan suatu pengelolaan dan konservasi mangrove, sehingga kajian deskripsi angota-anggota famili Rhizophoraceae dilakukan pada bulan Juli 2018 di hutan mangrove KKPD Rupat Utara. Kajian ini bertujuan untuk mengeksplorasi anggota famili Rhizophoraceae yang menyusun hutan mangrove KKPD Rupat Utara dan juga bertujuan sebagai data dasar dalam mengevaluasi ekosistem mangrove KKPD Rupat Utara dikemudian harinya. Metode yang digunakan adalah transek garis dan jelajah. Hal ini bermaksud agar spesimen yang dikumpulkan menjadi lebih lengkap. Sebanyak 5 spesies anggota Rhizophoraceae teridentifikasi sebagai penyusun hutan mangrove KKPD Rupat Utara yaitu Bruguiera gymnorrhiza, B. sexangula, Ceriops tagal, Rhizophora apiculata dan R. mucronata.