Exploring the Influence of Nanocrystalline Structure and Aluminum Content on High-Temperature Oxidation Behavior of Fe-Cr-Al Alloys.

The present study examines the high-temperature (500-800 °C) oxidation behavior of Fe-10Cr-(3,5) Al alloys and studies the effect of nanocrystalline structure and Al content on their resistance to oxidation. The nanocrystalline (NC) alloy powder was synthesized via planetary ball milling. The prepared NC alloy powder was consolidated using spark plasma sintering to form NC alloys. Subsequently, an annealing of the NC alloys was performed to transform them into microcrystalline (MC) alloys. It was observed that the NC alloys exhibit superior resistance to oxidation compared to their MC counterparts at high temperatures. The superior resistance to oxidation of the NC alloys is attributed to their considerably finer grain size, which enhances the diffusion of those elements to the metal-oxide interface that forms the protective oxide layer. Conversely, the coarser grain size in MC alloys limits the diffusion of the oxide-forming components. Furthermore, the Fe-10Cr-5Al alloy showed greater resistance to oxidation than the Fe-10Cr-3Al alloy.

Outbreak of Ichthyophthirius multifiliis associated with Aeromonas hydrophila in Pangasianodon hypophthalmus: The role of turmeric oil in enhancing immunity and inducing resistance against co-infection.

Ichthyophthirius multifiliis, a ciliated parasite causing ichthyophthiriasis (white spot disease) in freshwater fishes, results in significant economic loss to the aquaculture sector. One of the important predisposing factors for ichthyophthiriasis is low water temperature (i.e., below 20°C), which affects the health and makes freshwater fishes more susceptible to parasitic infections. During ichthyophthiriasis, fishes are stressed and acute immune reactions are compromised, which enables the aquatic bacterial pathogens to simultaneously infect the host and increase the severity of disease. In the present work, we aimed to understand the parasite-bacteria co-infection mechanism in fish. Later, Curcuma longa (turmeric) essential oil was used as a promising management strategy to improve immunity and control co-infections in fish. A natural outbreak of I. multifiliis was reported (validated by 16S rRNA PCR and sequencing method) in Pangasianodon hypophthalmus from a culture facility of ICAR-CIFRI, India. The fish showed clinical signs including hemorrhage, ulcer, discoloration, and redness in the body surface. Further microbiological analysis revealed that Aeromonas hydrophila was associated (validated by 16S rRNA PCR and sequencing method) with the infection and mortality of P. hypophthalmus, confirmed by hemolysin and survival assay. This created a scenario of co-infections, where both infectious agents are active together, causing ichthyophthiriasis and motile Aeromonas septicemia (MAS) in P. hypophthalmus. Interestingly, turmeric oil supplementation induced protective immunity in P. hypophthalmus against the co-infection condition. The study showed that P. hypophthalmus fingerlings supplemented with turmeric oil, at an optimum concentration (10 ppm), exhibited significantly increased survival against co-infection. The optimum concentration induced anti-stress and antioxidative response in fingerlings, marked by a significant decrease in cortisol and elevated levels of superoxide dismutase (SOD) and catalase (CAT) in treated animals as compared with the controls. Furthermore, the study indicated that supplementation of turmeric oil increases both non-specific and specific immune response, and significantly higher values of immune genes (interleukin-1ß, transferrin, and C3), HSP70, HSP90, and IgM were observed in P. hypophthalmus treatment groups. Our findings suggest that C. longa (turmeric) oil modulates stress, antioxidant, and immunological responses, probably contributing to enhanced protection in P. hypophthalmus. Hence, the application of turmeric oil treatment in aquaculture might become a management strategy to control co-infections in fishes. However, this hypothesis needs further validation.

Elucidation of dominant energy metabolic pathways of methane, sulphur and nitrogen in respect to mangrove-degradation for climate change mitigation.

Mangroves play a key role in ecosystem balancing and climate change mitigation. It acts as a source and sink of methane (CH4), a major greenhouse gas responsible for climate change. Energy metabolic pathways of methane production (methanogenesis) and oxidation (methanotrophy) are directly driven by sulphur (S) and nitrogen (N) metabolism and salinity in coastal wetlands. To investigate, how mangrove-degradations, affect the source-sink behaviour of CH4; the pathways of CH4, S and N were studied through whole-genome metagenomic approach. Soil samples were collected from degraded and undisturbed mangrove systems in Sundarban, India. Structural and functional microbial diversities (KEGG pathways) of CH4, S and N metabolism were analysed and correlated with labile carbon pools and physico-chemical properties of soil. Overall, the acetoclastic pathway of methanogenesis was dominant. However, the relative proportion of conversion of CO2 to CH4 was more in degraded mangroves. Methane oxidation was higher in undisturbed mangroves and the serine pathway was dominant. After serine, the ribulose monophosphate pathway of CH4 oxidation was dominant in degraded mangrove, while the xylulose monophosphate pathway was dominant in undisturbed site as it is more tolerant to salinity and higher pH. The assimilatory pathway (AMP) of S-metabolism was dominant in both systems. But in AMP pathway, adenosine triphosphate sulfurylase enzyme reads were higher in degraded mangrove, while NADPH-sulfite reductase abundance was higher in undisturbed mangrove due to higher salinity, and pH. In N-metabolism, the denitrification pathway was predominant in degraded sites, whereas the dissimilatory nitrate reduction pathway was dominant in undisturbed mangroves. The relative ratios of sulphur reducing bacteria (SRB): methanogens were higher in degraded mangrove; however, methanotrophs:methanogens was higher in undisturbed mangrove indicated lower source and greater sink capacity of CH4 in the system. Microbial manipulation in mangrove-rhizosphere for regulating major energy metabolic pathways of methane could open-up a new window of climate change mitigation in coastal wetlands.

Detection of Bovine Antibodies against a Conserved Capsid Epitope as the Basis of a Novel Universal Serological Test for Foot-and-Mouth Disease.

Diagnostic tests for foot-and-mouth disease (FMD) include the detection of antibodies against either the viral nonstructural proteins or the capsid. The detection of antibodies against the structural proteins (SP) of the capsid can be used to monitor seroconversion in both infected and vaccinated animals. However, SP tests need to be tailored to the individual FMD virus (FMDV) serotype and their sensitivity may be affected by antigenic variability within each serotype and mismatching between test reagents. As a consequence, FMD reference laboratories are required to maintain multiple type-specific SP assays and reagents. A universal SP test would simplify frontline diagnostics and facilitate large-scale serological surveillance and postvaccination monitoring. In this study, a highly conserved region in the N terminus of FMDV capsid protein VP2 (VP2N) was characterized using a panel of intertype-reactive monoclonal antibodies. This revealed a universal epitope in VP2N which could be used as a peptide antigen to detect FMDV-specific antibodies against all types of the virus. A VP2-peptide enzyme-linked immunosorbent assay (VP2-ELISA) was optimized using experimental and reference antisera from immunized, convalescent, and naïve animals (n = 172). The VP2-ELISA is universal and simple and provided sensitive (99%) and specific (93%) detection of antibodies to all FMDV strains used in this study. We anticipate that this SP test could have utility for serosurveillance during virus incursions in FMD-free countries and as an additional screening tool to assess FMD virus circulation in countries where the disease is endemic.

Impact of heat stress on transcriptional abundance of HSP70 in cardiac cells of goat.

The present study was aimed to document the effect of heat stress on the transcriptional abundance of heat shock protein 70 (HSP70) mRNA in cultured cardiac cells of goat. The heart tissues (n = 6) from different goats were used for the culture study. The cardiac cells obtained from different heart tissues were cultured in 24 well cell culture plates and incubated in a humidified CO2 (5%) incubator at 37 °C. The cardiac cells were allowed to become 75-80% confluent after 72 h of incubation. Thereafter, the cardiac cells were subjected to heat exposure at 42 °C (heat exposed) for 0, 20, 60 and 100 min. The cardiac cells exposed to heat stress at 42 °C for 0 min was taken as control. The relative abundance of HSP70 mRNA was gradually up-regulated (p < .05) from 20 to 100 min of heat exposure and reached the zenith (p < .05) at 100 min of heat challenge. The present finding highlights that, HSP70 could possibly act as a cytoprotective factor and may promote cardiac cell survival against the detrimental effect of heat stress. Moreover, this study may serve as the harbinger to conduct further research work on expression kinetics of HSP70 in cardiac cells of goat including other livestock species.

TRPV4 activation in rat carotid artery in DOCA hypertension involves eNOS and endothelium-derived contractile factor (EDCF).

Aim: Role of TRPV4 channel in regulation of endothelial function in the carotid artery in deoxycorticosterone acetate (DOCA) model of hypertension in rat was studied. Methods: 8-10 weeks old albino Wistar rats divided into three groups namely Control, UNX and hypertensive animals. Vascular smooth muscle response was studied in isolated carotid artery of rat with acetylcholine, sodium nitroprusside, GSK1016790A (GSK) in presence and absence of L-NAME and indomethacin. Results: At the end of the 6th week, the mean systolic blood pressure was increased in DOCA-treated hypertensive rats (166 ± 8 mm Hg) compared to Control and UNX (125 ± 5 mm Hg). ACh (10-9 to 10-5 M) produced almost 100% relaxation in Control (Emax = 97.48 ± 1.06 %) and UNX animals (Emax = 93.16 ± 2.33 %) which was attenuated in DOCA-treated hypertensive animals (Emax = 70.85 ± 1.65 %). No significant changes seen in SNP (10-12 to 10-5 M) induced relaxation. GSK1016790A (10-12 to 10-7 M)-mediated relaxation was significantly attenuated in DOCA-treated hypertensive animals (Emax = 25.58 ± 13.60%) compared to the control (Emax = 80.59 ± 6.86%) and UNX (Emax = 87.32 ± 2.01%) animals. L-NAME (10-4 M) potently blocked GSK-induced relaxation, and a contractile response to GSK was observed in presence of L-NAME in all the three groups of animals which was sensitive to indomethacin (10-5 M). Conclusion: TRPV4 may regulate the vascular tone of rat carotid artery through an attenuated NO pathway and stimulation of the release of contractile prostanoids in the DOCA hypertensive rats.

A study of salivary opiorphin levels using different anesthetic drugs and techniques - A randomized controlled clinical study.

PURPOSE: This study aimed at assessing the change in salivary opiorphin levels before and after administration of local anesthesia, with the use of three different local anesthetic agents, and different anaesthetic techniques. METHODS: The investigators implemented a randomized controlled clinical study in 144 patients who required tooth extraction after administration of local anaesthesia. A total of 288 samples were collected in sterile containers before and after administration of local anesthetics. The salivary samples were centrifuged and salivary opiorphin levels were estimated using ELISA testing and spectrophotometric analysis. Statistical analysis was done using one way ANOVA and unpaired t test. RESULTS: There was a mean decrease in salivary opiorphin levels after administration of local anesthesia. There was no significant difference in the change in salivary opiorphin levels across different anesthetic techniques and different drug subgroups. CONCLUSION: The present study did not show much association between various local anesthetic agents and techniques and change in salivary opiorphin levels. The role of opiorphin as a biomarker for pain control and its effect on various pain control methods including local anesthesia must be evaluated in detail. Institutional review board number SRMDC/IRB/2014/MDS/No. 405.

Structural Evolution during Milling, Annealing, and Rapid Consolidation of Nanocrystalline Fe-10Cr-3Al Powder.

Structural changes during the deformation-induced synthesis of nanocrystalline Fe-10Cr-3Al alloy powder via high-energy ball milling followed by annealing and rapid consolidation by spark plasma sintering were investigated. Reduction in crystallite size was observed during the synthesis, which was associated with the lattice expansion and rise in dislocation density, reflecting the generation of the excess grain boundary interfacial energy and the excess free volume. Subsequent annealing led to the exponential growth of the crystallites with a concomitant drop in the dislocation density. The rapid consolidation of the as-synthesized nanocrystalline alloy powder by the spark plasma sintering, on the other hand, showed only a limited grain growth due to the reduction of processing time for the consolidation by about 95% when compared to annealing at the same temperature.

Neonatal sepsis in rural India: timing, microbiology and antibiotic resistance in a population-based prospective study in the community setting.

OBJECTIVE: To examine the timing and microbiology of neonatal sepsis in a population-based surveillance in the Indian community setting. STUDY DESIGN: All live born infants in 223 villages of Odisha state were followed at home for 60 days. Suspect sepsis cases were referred to study hospitals for further evaluation including blood culture. RESULTS: Of 12 622 births, 842 were admitted with suspected sepsis of whom 95% were 4 to 60 days old. Culture-confirmed incidence of sepsis was 6.7/1000 births with 51% Gram negatives (Klebsiella predominating) and 26% Gram positives (mostly Staphylococcus aureus). A very high level of resistance to penicillin and ampicillin, moderate resistance to cephalosporins and extremely low resistance to Gentamicin and Amikacin was observed. CONCLUSION: The bacterial burden of sepsis in the Indian community is not high. Judicious choice of empiric antibiotics, antibiotic stewardship and alternate modalities should be considered for the management or prevention of neonatal sepsis in India.

Serological Detection of Antibodies to Peste des Petits Ruminants Virus in Large Ruminants.

Peste des petits ruminants (PPR) is an economically important disease of small ruminants with a rapidly expanding geographical distribution. Peste des petits ruminants virus may manifest in a variety of ways with disease ranging from acute to subclinical. We investigated the exposure of large ruminants to PPRV in areas where the virus is endemic in the small ruminant population by assessing the serological status of groups of animals. This study focused on the Punjab province of Pakistan as an area where the virus is endemic and where mixed farming practices occur enabling close interactions between small and large ruminant populations. An overall PPR seropositivity was detected in 10.0% of cattle and 14.16% of buffaloes. Following an assessment of serological profiles in large ruminants within different age groups, a maximum seroprevalence was observed in cattle (17.5%) and buffaloes (22.5%) over 2 years of age indicating the potential utility of sampling large ruminant populations for PPR serosurveillance. The large ruminants sampled between one and two years of age had similar levels of seropositivity within populations with 11.2% and 16.2% of animals being seropositive, respectively. Current PPR vaccination strategies do not enable the differentiation between infected and vaccinated small ruminants, and as such, the serological surveillance of sheep and goats is of little value. When considering eradication programmes for PPRV, this factor is of great significance. However, where large and small ruminants are farmed together, serological surveillance of large ruminants may provide a snapshot of virus infection within populations where mild disease is present or where small ruminants are regularly vaccinated.

Re-emergence of Peste des Petits Ruminants virus in 2015 in Morocco: Molecular characterization and experimental infection in Alpine goats.

Peste des Petits Ruminants (PPR) is a transboundary viral disease of small ruminants that causes huge economic losses in Africa, The Middle East and Asia. In Morocco, the first PPR outbreak was notified in 2008. Since then no cases were reported for seven years, probably due to three successive vaccination campaigns during 2008-2011 and close surveillance at the border areas. In June 2015, the disease re-emerged in Morocco, raising questions about the origin of the virus. The PPR virus was confirmed by qRT-PCR and virus was isolated from clinical samples on VeroNectin-4 cells. The disease was experimentally reproduced in Alpine goats using both sheep and goat derived outbreak isolates. Molecular characterization of the 2015 Moroccan PPR isolate confirmed the identity of the virus as lineage IV, closely related to the 2012 Algerian (KP793696) and 2012 Tunisian (KM068121) isolates and significantly distinct from the previous PPRV Morocco 2008 strain (HQ131927). Therefore this study confirms a new incursion of PPR virus in Morocco during 2015 and highlights the urgency of implementation of a common control strategy to combat PPR in Maghreb region in North Africa.

GW627368X inhibits proliferation and induces apoptosis in cervical cancer by interfering with EP4/EGFR interactive signaling.

PGE2, the major product of cyclooxygenases implicated in carcinogenesis, is significantly upregulated in cervical cancer. PGE2 via prostanoid receptor EP4 stimulates proliferation and motility while inhibiting apoptosis and immune surveillance. It promotes angiogenesis by stimulating the production of pro-angiogenic factors. The present study demonstrates GW627368X, a highly selective competitive EP4 antagonist, which hinders cervical cancer progression by inhibiting EP4/epithelial growth factor receptor (EGFR) interactive signaling. GW627368X reduced protein kinase A (PKA) phosphorylation which in turn leads to decreased cAMP response element-binding protein (CREB) activation. Decreased PKA phosphorylation also directly enhanced Bax activity and in part reduced glycogen synthase kinase 3 (GSK3)ß phosphorylation. Owing to the interactive signaling between EP4 and EGFR, GW627368X lowered EGFR phosphorylation in turn reducing Akt, mitogen-activated protein kinase (MAPK) and GSK3ß activity significantly. Sublethal dose of GW627368X was found to reduce the nuclear translocation of ß-catenin in a time dependent manner along with time-dependent decrease in cytoplasmic as well as whole-cell ß-catenin. Decreased CREB and ß-catenin transcriptional activity restricts the aberrant transcription of key genes like EP4, cyclooxygenase (COX)-2, vascular endothelial growth factor and c-myc, which ultimately control cell survival, proliferation and angiogenesis. Reduced activity of EGFR resulted in enhanced expression of 15-hydroxyprostaglandin dehydrogenase increasing PGE2 degradation thereby blocking a positive feedback loop. In xenograft model, dose-dependent decrease in cancer proliferation was observed characterized by reduction in tumor mass and volume and a marked decrease in Ki67 expression. A diminished CD31 specific staining signified decreased tumor angiogenesis. Reduced expression of pAkt, pMAPK, pEGFR and COX-2 validated in vitro results. GW627368X therefore effectively inhibits tumor survival, motility, proliferation and angiogenesis by blocking EP4/EGFR interactive signaling. EP4 is a potent therapeutic target in cervical cancer and can be explored in combination with conventional therapies to attain superior outcomes and to overcome complications associated with organ toxicities, therapeutic resistance and disease relapse.

A fuzzy integral method based on the ensemble of neural networks to analyze fMRI data for cognitive state classification across multiple subjects.

The huge number of voxels in fMRI over time poses a major challenge to for effective analysis. Fast, accurate, and reliable classifiers are required for estimating the decoding accuracy of brain activities. Although machine-learning classifiers seem promising, individual classifiers have their own limitations. To address this limitation, the present paper proposes a method based on the ensemble of neural networks to analyze fMRI data for cognitive state classification for application across multiple subjects. Similarly, the fuzzy integral (FI) approach has been employed as an efficient tool for combining different classifiers. The FI approach led to the development of a classifiers ensemble technique that performs better than any of the single classifier by reducing the misclassification, the bias, and the variance. The proposed method successfully classified the different cognitive states for multiple subjects with high accuracy of classification. Comparison of the performance improvement, while applying ensemble neural networks method, vs. that of the individual neural network strongly points toward the usefulness of the proposed method.

Emergence of Lineage IV Peste des Petits Ruminants Virus in Ethiopia: Complete Genome Sequence of an Ethiopian Isolate 2010.

Isolates of peste des petits ruminants virus (PPRV) can be segregated genetically into four lineages. For decades, lineages I-III have been reported across Africa whilst lineage IV has predominantly circulated across Asia. However, the lineage distribution is currently changing in Africa. Importantly, full genome sequence data for African field isolates have been lacking. Here, we announce the first complete genome sequence of a field isolate of peste des petits ruminants virus (PPRV) from East Africa. This isolate was derived from the intestine of a goat suffering from severe clinical disease during the 2010 outbreak in Ethiopia. The full genome sequence of this isolate, PPRV Ethiopia/2010, clusters genetically with other lineage IV isolates of PPRV, sharing high levels of sequence identity across the genome. Further, we have carried out a phylogenetic analysis of all of the available African partial N gene and F gene PPRV sequences to investigate the epidemiology of PPRV with a focus on the emergence of different lineages of PPRV in Africa.

Peste des petits ruminants.

Peste des petits ruminants virus causes a highly infectious disease of small ruminants that is endemic across Africa, the Middle East and large regions of Asia. The virus is considered to be a major obstacle to the development of sustainable agriculture across the developing world and has recently been targeted by the World Organisation for Animal Health (OIE) and the Food and Agriculture Organisation (FAO) for eradication with the aim of global elimination of the disease by 2030. Fundamentally, the vaccines required to successfully achieve this goal are currently available, but the availability of novel vaccine preparations to also fulfill the requisite for differentiation between infected and vaccinated animals (DIVA) may reduce the time taken and the financial costs of serological surveillance in the later stages of any eradication campaign. Here, we overview what is currently known about the virus, with reference to its origin, updated global circulation, molecular evolution, diagnostic tools and vaccines currently available to combat the disease. Further, we comment on recent developments in our knowledge of various recombinant vaccines and on the potential for the development of novel multivalent vaccines for small ruminants.

A hybrid method for classifying cognitive states from fMRI data.

Functional magnetic resonance imaging (fMRI) makes it possible to detect brain activities in order to elucidate cognitive-states. The complex nature of fMRI data requires under-standing of the analyses applied to produce possible avenues for developing models of cognitive state classification and improving brain activity prediction. While many models of classification task of fMRI data analysis have been developed, in this paper, we present a novel hybrid technique through combining the best attributes of genetic algorithms (GAs) and ensemble decision tree technique that consistently outperforms all other methods which are being used for cognitive-state classification. Specifically, this paper illustrates the combined effort of decision-trees ensemble and GAs for feature selection through an extensive simulation study and discusses the classification performance with respect to fMRI data. We have shown that our proposed method exhibits significant reduction of the number of features with clear edge classification accuracy over ensemble of decision-trees.

Detection and Genetic Characterization of Lineage IV Peste Des Petits Ruminant Virus in Kazakhstan.

Peste des petits ruminant (PPR) is endemic in many Asian countries with expansion of the range in recent years including across China during 2013-2014 (OIE, 2014). Till the end of 2014, no cases of PPR virus (PPRV) were officially reported to the Office Internationale des Epizooties (OIE) from Kazakhstan. This study describes for the first time clinicopathological, epidemiological and genetic characterization of PPRV in 3 farm level outbreaks reported for the first time in Zhambyl region (oblast), southern Kazakhstan. Phylogenetic analysis based on partial N gene sequence data confirms the lineage IV PPRV circulation, similar to the virus that recently circulated in China. The isolated viruses are 99.5-99.7% identical to the PPRV isolated in 2014 from Heilongjiang Province in China and therefore providing evidence of transboundary spread of PPRV. There is a risk of further maintenance of virus in young stock despite vaccination of adult sheep and goats, along livestock trade and pastoral routes, threatening both small livestock and endangered susceptible wildlife populations throughout Kazakhstan.

Totally drug-resistant tuberculosis and adjunct therapies.

The first cases of totally drug-resistant (TDR) tuberculosis (TB) were reported in Italy 10 years ago; more recently, cases have also been reported in Iran, India and South Africa. Although there is no consensus on terminology, it is most commonly described as 'resistance to all first- and second-line drugs used to treat TB'. Mycobacterium tuberculosis (M.tb) acquires drug resistance mutations in a sequential fashion under suboptimal drug pressure due to monotherapy, inadequate dosing, treatment interruptions and drug interactions. The treatment of TDR-TB includes antibiotics with disputed or minimal effectiveness against M.tb, and the fatality rate is high. Comorbidities such as diabetes and infection with human immunodeficiency virus further impact on TB treatment options and survival rates. Several new drug candidates with novel modes of action are under late-stage clinical evaluation (e.g., delamanid, bedaquiline, SQ109 and sutezolid). 'Repurposed' antibiotics have also recently been included in the treatment of extensively drug resistant TB. However, because of mutations in M.tb, drugs will not provide a cure for TB in the long term. Adjunct TB therapies, including therapeutic vaccines, vitamin supplementation and/or repurposing of drugs targeting biologically and clinically relevant molecular pathways, may achieve better clinical outcomes in combination with standard chemotherapy. Here, we review broader perspectives of drug resistance in TB and potential adjunct treatment options.

Inflammation and tuberculosis: host-directed therapies.

Tuberculosis (TB) is an airborne infectious disease that kills almost two million individuals every year. Multidrug-resistant (MDR) TB is caused by strains of Mycobacterium tuberculosis (M. tb) resistant to isoniazid and rifampin, the backbone of first-line antitubercular treatment. MDR TB affects an estimated 500,000 new patients annually. Genetic analysis of drug-resistant MDR-TB showed that airborne transmission of undetected and untreated strains played a major role in disease outbreaks. The need for new TB vaccines and faster diagnostics, as well as the development of new drugs, has recently been highlighted. The major problem in terms of current TB research and clinical demands is the increasing number of cases of extensively drug-resistant and 'treatment-refractory' TB. An emerging scenario of adjunct host-directed therapies is intended to target pulmonary TB where inflammatory processes can be deleterious and lead to immune exhaustion. 'Target-organ-saving' strategies may be warranted to prevent damage to infected tissues and achieve focused, clinically relevant and long-lasting anti-M. tb cellular immune responses. Candidates for such interventions may be biological agents or already approved drugs that can be 're-purposed' to interfere with biologically relevant cellular checkpoints. Here, we review current concepts of inflammation in TB disease and discuss candidate pathways for host-directed therapies to achieve better clinical outcomes.