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Introduction: Acyanotic congenital heart disease (ACHD) patients with pulmonary hypertension (PH) are prone to postoperative complications, and characterization of the risk profile continues to fail in identifying inflammatory predilection. Our objective is to investigate the role of platelet-leukocyte indices (neutrophil-lymphocyte ratio [NLR], platelet-lymphocyte ratio [PLR], and systemic immune-inflammation index [SII] [neutrophil × platelet/lymphocyte]) in predicting poor outcomes following cardiac surgery in ACHD cohort with preoperative PH. Methods: This single-center, retrospective risk-predictive study included ACHD patients undergoing surgical correction at our tertiary cardiac center between January 2015 and December 2019. Standard institutional perioperative management protocol was followed, and poor postoperative outcome was defined as ≥ 1 of: low cardiac output syndrome, new-onset renal failure, prolonged mechanical ventilation (MV > 24 hours), stroke, sepsis, and/or death. Results: One hundred eighty patients out of 1,040 (17.3%) presented poor outcome. On univariate analysis, preoperative factors including right ventricular systolic pressure (RVSP) (PH-severity marker), congestive heart failure, albumin, NLR, PLR, SII, and aortic cross-clamping (ACC) and cardiopulmonary bypass (CPB) times predicted poor outcome. However, on multivariate analysis, RVSP, NLR, SII, and ACC and CPB times emerged as independent predictors. An NLR, SII prognostic cutoff of 3.33 and 860.6×103/mm3 was derived (sensitivity: 77.8%, 78.9%; specificity: 91.7%, 82.2%; area under the curve: 0.871, 0.833). NLR and SII values significantly correlated with postoperative MV duration, mean vasoactive-inotropic scores, and length of intensive care unit and hospital stay (P

Water is one of the most important natural resource because existence of living organisms depends on water. Total amount of water on the earth is approximately 1.4 billion km3 out of which 97% is saline water and 3% is freshwater. Nowadays, water is polluted due to rapid industrialization, urbanization, use of pesticides, and fertilizers and wastewater disposal. Due to use of polluted water, human beings suffer from various waterborne diseases, so availability of good quality water is an essential requirement for prevention of diseases. Almost all lakes and ponds in India are adversely affected by water pollution. The main adverse effects of water pollution are death of aquatic organisms, waterborne diseases, eutrophication, bioaccumulation of contaminants, etc. In the present paper, water pollution, source of water pollution, and adverse effects of water pollution are discussed, and a summary of studies on water quality assessment is presented.

Background: Mediastinum is a “Pandora's box” with many neoplastic and nonneoplastic lesions. The purpose of this study was to analyze our institutional experience of mediastinal lesions on fine-needle aspiration cytology (FNAC) and/or biopsy. Materials and Methods: This study was an analysis of 144 patients who had undergone ultrasound-guided FNAC and/or core biopsy for mediastinal lesions. Results: A total of 144 cases of suspected mediastinal masses were seen, and in 139 cases, tissue diagnosis was attempted. Out of 139 cases, 93 cases were neoplastic in nature (67%), 32 were nonneoplastic (23%), and 14 remained inconclusive (10%). Among neoplastic mediastinal lesions, metastatic carcinoma (37.4%) was the most common neoplastic lesion, followed by non-Hodgkin's lymphoma (12.2%), Hodgkin's lymphoma (7.1%), thymic lesions (3.5%), etc. Among nonneoplastic conditions, tuberculosis was the most common lesion (20.1%). An accurate tissue diagnosis was made in 89.9% cases by FNAC or core biopsy of mediastinal lesions in this study. Procedure-related mortality was nil. Complications were mostly minor and included chest pain in 24.5%, small pneumothorax in 13.6% requiring closed tube thoracostomy in 1.4%, and scanty hemoptysis in 9.3% cases. Conclusion: Neoplastic mediastinal lesions are more common than nonneoplastic lesions, with metastatic carcinoma being the most common cause followed by tuberculosis. A wide variety of lesions observed in this study stress on the importance of cytohistological diagnosis in all cases of mediastinal lesions for the final diagnosis and management planning. A guided FNAC or core biopsy is still accurate, well tolerated, and devoid of major complications.

Background The knee joint is frequently involved in sports and other injuries with Anterior cruciate ligament being a very common ligament to be injured. The Lachman test, pivot-shift test, and instrumented knee laxity examination are frequently used and reported for evaluation of ACL reconstruction. The aim of this study is to examine and evaluate the relationships between the clinical assessment of ligament stability and subjective assessment of symptoms and function after ACL reconstruction. Methods A total of 50 young and middle aged patients with unilateral knee ACL injury treated with ACL reconstruction using hamstring graft were evaluated for a minimum period of 1 year. Clinical assessment of ligament stability was done through Lachman and pivot-shift examination. Subjective variables of symptoms at follow-up included pain, swelling, instability and locking of knee. Subjective function at follow up included satisfaction with outcome, squatting, ascending or descending stairs, jumping, twisting and Lysholm score. Results Lachman Examination at follow-up had no significant (P > .05) relationship with pain, swelling, instability, locking, squatting, ascending or descending stairs, jumping, twisting, satisfaction with outcome and Lysholm score. Pivot-shift examination at follow-up had significant associations with patient satisfaction (P = .04), instability of knee (P = .02), difficulty during twisting (P = .02) and Lysholm score (P = .01). Conclusion Pivot-shift examination is a better measure than Lachman examination or instrumented knee laxity as far as patients’ functional outcome and overall satisfaction is concerned.

Objective The aim of the present study was to determine and compare the expression pattern and localization of nestin, in an attempt to explore its role in oral carcinogenesis. Methods Western blot and immunohistochemistry analysis were performed to study the expression pattern of nestin in normal mucosa, leukoplakia, and oral squamous cell carcinoma samples. Nestin expression was evaluated in the keratinocytes and blood vessels of all the samples and compared with various clinico-pathological parameters. Results Nestin expression was increased in samples of leukoplakia and oral squamous cell carcinoma when compared with normal mucosa. Among leukoplakia samples, the expression was increased in cases without dysplasia compared to cases with dysplastic features. In cases of oral squamous cell carcinoma, the expression of nestin was found to be decreased with the loss of differentiation. Neoangiogenesis status determined by nestin expression showed an increasing expression from normal mucosa through leukoplakia, to oral squamous cell carcinoma. Conclusion This study has two major findings: (1) identification of nestin as an effective indicator of neoangiogenesis, and (2) nestin may be used as a marker in predicting the early changes in oral carcinogenesis.

Highlights • Rheumatoid Arthritis is an auto-immune disease that affects the cartilage and small joints of the body. Moreover, it complicates oral therapy due to the associated medication induced xerostomia, accompanying periodontitis and increasing bone-loss which may lead to peri-implantitis with surface treated implants. Hence treating these patients with conventional implants can often pose a challenge to the attending dentist, however making them excellent candidates for smooth surface single piece implants. • These bicortical smooth surface single piece implants engage into the cortical bone as well as preclude the use of bone grafts and hence can be safely placed in Rheumatoid Arthritis patients with atrophic jaws successfully. • The greatest advantages associated with these implants are that they are placed in a flapless manner with an immediate loading protocol of 72 h. This precludes the need for bone augmentation via additional surgeries as well as the increase costs associated with bone grafting procedures. It also reduces overall chairside appointments thereby making it a convenient treatment alternative for the patient., Introduction and importance The aim of this article is to report the long-term outcome of full mouth rehabilitation with single piece, smooth surface implants following immediate loading protocol on a patient suffering with RA and severe unilateral condylar resorption. Case presentation Here, we present a challenging case of a patient suffering from Rheumatoid Arthritis who was stabilized and completed successfully with a 4 year follow-up period. Prosthetic management optimized the inter-occlusal relationship to maintain both function and esthetic integrity. Single piece implants are designed to engage and take support from the cortical bone low in metabolic activities thus promoting the force transmission through apical threads that are engaged in the cortical bone. Discussion Rheumatoid Arthritis [RA] is an auto-immune inflammatory condition in which the inflamed and hypertrophic synovial membrane grows into the articulation surfaces. The Temporomandibular Joints [TM] are frequently involved in rheumatoid arthritis. According to the literature on RA, due to frequent periodontitis, decreased salivary secretion, medication, as well as decrease in bone regenerative potential, RA is often considered as a relative contraindication in the use of implants. Atrophic jaws and cases with comorbidities like osteoporosis, diabetes, rheumatoid arthritis, periodontally infected cases are restored with high success by single piece smooth surface. Conclusion To the best of our knowledge, this may be the first case of immediate functional loading by bi-cortical single piece implants.

Background: The objective of this study was to evaluate the early and mid-term outcome of total correction of tetralogy of Fallot (TOF) done through transatrial approach avoiding ventriculotomy with or without transannular patching.Methods: Of 210 patients undergoing total correction for TOF between January 2016 and January 2019, 180 patients were operated via transatrial approach. The ventricular septal defect closure, infundibular resection and pulmonary valvotomy were performed through the right atrium. Age ranged from 12 months to 44 years (mean, 2.6 years), 104 patients were male and 76 patients were females.Results: Three patients (1.67%) died in early post-operative period. Pulmonary complications were seen in 8 (4.44%), septicemia in 1 (0.55%), low output syndrome in 2 (1.10%) and temporary arrhythmias in 6 (3.33%) patients. Reintubation was needed in 3 (1.67%) patients. Early reoperation was needed in 3 (1.67%) patients in view of post-operative bleeding. There were no mediastinal or deep sternal wound infections. None of our patient had complete heart block. There were no late deaths or late reoperations. Echocardiography before discharge did not reveal significant residual VSD in any patient. The mean right ventricular outflow tract pressure gradient was 28 mmHg (range of 20 to 44 mmHg) which decreased on follow-up echocardiography to 16 mmHg (range of 14 to 24 mmHg) at mean follow up of 23 months. None of our patient had severe pulmonary or tricuspid regurgitation or severe right ventricular dysfunction on follow up.Conclusions: Transatrial repair of TOF is associated with remarkably low morbidity and mortality in our early experience.

Background: The aim of the study was to determine the incidence, risk factors, and outcomes for chylothorax in patients undergoing cardiothoracic surgery, with special emphasis on its management.Methods: Total of 24 patients with post-operative chylothorax, operated from September 2015 to December 2018, was included in the study. Medical records were maintained, including daily records of drainage volumes and management.Results: From September 2015 to December 2018, there were 24 cases of chylothorax in 600 congenital cardio-thoracic surgeries-an incidence of 4.0%. Overall mortality rate was similar, but cases had longer postoperative hospital stays (median, 22 versus 8 days). Incidence of chylothorax was significantly higher with congenital cardiac procedures. Diagnosis was made at a median of 6 days after surgery. Duration of drainage was a median of 15 days, with 11 patients draining more than 30 days. Longer duration of drainage was associated with cavopulmonary anastomosis procedure. Nutritional management included low fat diet, enteral feeds enriched with medium-chain triglycerides, and parenteral nutrition. Three patients were treated with octreotide, 4 with thoracic duct ligation, and 1 with pleurodesis. Octreotide was associated with a variable effect on drainage. Thoracic duct ligation reduced, but did not stop drainage.Conclusions: Chylothorax increases duration of hospitalization after cardiovascular surgery in children. Early diagnosis may reduce the duration of chylothorax. Nutritional strategies remain the cornerstone for management of postoperative chylothorax. The impact of octreotide and surgical intervention is limited when reserved for patients with severe or prolonged drainage.

Nerve sheath tumours arising from the sympathetic chain are extremely rare and are a diagnostic challenge. Schwannomas are benign nerve sheath tumours deriving from Schwann cells that occur in the head and neck region in 25-45% of cases. Cervical lesions originate from spinal nerves, the last four cranial nerve roots, or occasionally from the sympathetic chain. Carotid body tumour (CBT), the most common tumour of the carotid bifurcation, presents as a pulsatile mass. Cervical sympathetic chain (CSC) schwannomas are slow growing lesions and may appear pulsatile due to the displacement of vascular structures by the non-vascular mass and thus may mimic a CBT. We here in discuss a case of 22year old female, who underwent surgical resection of a mass at carotid bifurcation, presuming a CBT, but postoperative histopathological examination revealed it a schwannoma.

Spirometry is a widely used pulmonary function test to detect the airflow limitations associated with various obstructive lung diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and even obesity-related complications. These conditions arise due to the change in the airway resistance, alveolar compliance, and inductance values. Currently, zero-dimensional (0D) compartmental models are commonly used for calibrating these resistance, compliance, and inductance values, i.e., solving the inverse spirometry problem. However, 0D compartments cannot capture the flow physics or the spatial geometry effects, thereby generating a low fidelity prediction of the diseased lung. Computational fluid dynamics (CFD) models offer higher fidelity solutions but may be impractical for certain applications due to the duration of these simulations. Recently, a novel, fast-running and robust Quasi-3D (Q3D) wire model for simulating the airflow in the human lung airway was developed by CFD Research Corporation (CFDRC). This Q3D method preserved the 3D spatial nature of the airways and was favorably validated against CFD solutions. In the present study, the Q3D compartmental multi-scale combination is further improved to predict regional lung constriction of diseased lungs using spirometry data. The Q3D mesh is resolved up to the eighth lung airway generation. The remainder of the airways and the alveoli sections are modeled using a compartmental approach. The Q3D geometry is then split into different spatial sections and the resistance values in these regions are obtained using parameter inversion. Finally, the airway diameter values are then reduced to create the actual diseased lung model, corresponding to these resistance values. This diseased lung model can be used for patient-specific drug deposition predictions and the subsequent optimization of the orally inhaled drug products.

Tuberculosis is endemic in developing countries like India. However, calvarial tuberculosis is very rare. It was reported first time by Reid in 1942 and only a few cases have been reported till now. Most cases occur in first two decades secondary to haematogenous spread from a primary focus elsewhere in the body that may not always be evident. Calvarial tuberculosis in middle aged male with no evidence of tuberculosis elsewhere in body is very rare. Tuberculosis of the cranium is a rare entity, and can mimic tumors or multiple myeloma. A high index of suspicion and knowledge is required for an early diagnosis. We present a rare case of tuberculosis of calvaria in a middle-aged male who responded well to anti tubercular therapy.

Currently no effective vaccine is available for human visceral leishmaniasis(VL) caused by Leishmania donovani. Previously, we showed that centrin1 and p27gene deleted live attenuated Leishmania parasites (LdCen1−/− and Ldp27−/−) are safe, immunogenic and protective in animal models. Here, to assess the correlates of protection, we evaluated immune responses induced by LdCen1−/− and Ldp27−/− in human blood samples obtained from healthy, healed VL (HVL), post kala-azar dermal leishmaniasis(PKDL) and VL subjects. Both parasites infected human macrophages, as effectively as the wild type parasites. Further, LdCen1−/− and Ldp27−/− strongly stimulated production of pro-inflammatory cytokines including, IL-12, IFN-γ, TNF-α, IL-2, IL-6 and IL-17 in the PBMCs obtained from individuals with a prior exposure to Leishmania (HVL and PKDL). There was no significant stimulation of anti-inflammatory cytokines (IL-4 and IL-10). Induction of Th1 biased immune responses was supported by a remarkable increase in IFN-γ secreting CD4+ and CD8+ T cells and IL-17 secreting CD4+ cells in PBMCs from HVL cases with no increase in IL-10 secreting T cells. Hence, LdCen1−/− and Ldp27−/− are promising as live vaccine candidates against VL since they elicit strong protective immune response in human PBMCs from HVL, similar to the wild type parasite infection, mimicking a naturally acquired protection following cure.

Widespread antimonial resistance in anthroponotic visceral leishmaniasis (VL) makes it critical to monitor the susceptibility of prevailing field isolates to upcoming antileishmanials in order to frame the right treatment policies to protect these drugs against development of resistance. We aimed to generate the baseline data on natural in vitro susceptibility to paromomycin and sitamaquine in Leishmania donovani field isolates from VL patients ( n = 20) coming from zones of varying sodium antimony gluconate (SAG) resistance. We further monitored nitric oxide (NO) release in infected macrophages treated with these drugs. Field isolates exhibited variable sensitivity to paromomycin and sitamaquine with respective mean 50% effective dose (ED 50 ) values ± standard error of the mean (SEM) of 3.9 ± 0.3 μM and 2.1 ± 0.2 μM at the intracellular amastigote stage and 29.8 ± 2.5 μM and 17.7 ± 1.0 μM at the promastigote stage. Susceptibilities at the two parasite stages did not correlate for either drug. Isolates from high SAG resistance zones exhibited significantly lower susceptibility to sitamaquine than those from low SAG resistance zones, while isolates from different zones showed similar susceptibilities to paromomycin. NO release was promoted in L. donovani -infected macrophages upon treatment with paromomycin/sitamaquine. NO inhibitors significantly compromised amastigote killing by sitamaquine, but not by paromomycin. In conclusion, SAG-resistant/sensitive VL isolates were susceptible to both paromomycin and sitamaquine. Paromomycin, exhibiting higher efficacy against SAG-resistant parasites and having a distinct mechanism of action, appears to be a promising drug for combination therapy.

Aim: The aim of this study was to compare the efficiency of conventional and digital radiography in assessing alveolar bone loss. Materials and Methods: The study group comprised 50 participants (25 males and 25 females) between 25 and 45 years of age. The participants were screened for all clinical features of periodontitis. A series of conventional bitewing radiographs of right and left of both maxillary and mandibular posterior region (15,16,17,25,26,27,35,36,37,45,46,47) were taken for each of 50 patients by examiner 1. Similarly, a series of digital bitewing radiographs were taken by examiner 2 for each 50 patients by using RVG of Planmeca Dixi 2 B Series. In digital bitewing radiographs, the measurement was done by examiner 2, using Planmeca Dixi 2 B Digital Software, by dragging the cursor to make a line by joining the linear points. Bone level less than 2 mm from the cementoenamel junction (CEJ) was considered normal while above that was considered bone loss. In case of conventional bitewing radiographs, alveolar bone loss was measured by the same examiner by measuring the distance from the CEJ to the most apical level of crestal bone using a divider and transparent ruler. The above collected data of examiners 1 and 2 were handed over to examiner 3 for statistical evaluation. Results: Comparison of conventional and digital radiographic techniques in left maxilla, left and right mandible, and between maxilla and mandible in the total sample and in females aged 25–35 and 36–45 years yielded a significant correlation while comparison of the two techniques in the right maxilla and between maxilla and mandible in males yielded a nonsignificant correlation. Conclusion: Direct digital radiography provides an edge over conventional radiography in assessing the periodontal bone destruction.

A 28-year-old male patient presented with angina on exertion for 3 years, dyspnea on exertion for 2 years. On examination patient was average built, having slow rising pulse, with ejection systolic murmur over aortic area, radiating to carotids. Blood investigations were normal, ECG was suggestive of LV strain pattern, Chest X ray was suggestive of LV type apex with notching of inferior margins of ribs. 2D Echocardiography was done, and was suggestive of thickened calcified bicuspid aortic valve, aortic annulus 21 mm, ascending aorta 42 mm, Gradient across aortic valve Peak 100 mmHg, Mean 64 mmHg. Patient was referred for Aortic valve replacement. However, in view of borderline dilated ascending aorta, CT aortography was done, and was suggestive of membranous juxtaductal Coarctation of aorta with no antegrade contrast opacification suggesting total aortic occlusion with reformation of aorta through large systemic thoracic wall and mediastinal collaterals.

Primary intracardiac tumors are rare and approximately 50% are myxomas. Majority of myxomas are located in left atrium. Most of myxomas are attached to inter-atrial septum and have variable clinical presentation depending on size, location and mobility of the tumor. We report a case of large myxoma in the right atrium with atypical clinical presentation and location for this type of tumor.

Malignant pleural effusion (MPE) denotes an advanced malignant disease process. Most of the MPE are metastatic involvement of the pleura from primary malignancy at lung, breast, and other body sites apart from lymphomas. The diagnosis of MPE has been traditionally made on cytological examination of pleural fluid and/or histological examination of pleural biopsy tissue that still remains the initial approach in these cases. There has been tremendous advancement in the diagnosis of MPE now a day with techniques i.e. characteristic Ultrasound and computed tomography features, image guided biopsies, fluorodeoxyglucose-positron emission tomography imaging, thoracoscopy with direct biopsy under vision, tumor marker studies and immunocytochemical analysis etc., that have made possible an early diagnosis of MPE. The management of MPE still remains a challenge to pulmonologist and oncologist. Despite having various modalities with better tolerance such as pleurodesis and indwelling pleural catheters etc., for long-term control, all the management approaches remain palliative to improve the quality of life and reduce symptoms. While choosing an appropriate management intervention, one should consider the clinical status of the patient, life expectancy, overall cost, availability and comparative institutional outcomes, etc.

PSA (Promastigote Surface Antigen) belongs to a family of membrane-bound and secreted proteins present in several Leishmania (L.) species. PSA is recognized by human Th1 cells and provides a high degree of protection in vaccinated mice. We evaluated humoral and cellular immune responses induced by a L. amazonensis PSA protein (LaPSA-38S) produced in a L. tarentolae expression system. This was done in individuals cured of cutaneous leishmaniasis due to L. major (CCLm) or L. braziliensis (CCLb) or visceral leishmaniasis due to L. donovani (CVLd) and in healthy individuals. Healthy individuals were subdivided into immune (HHR-Lm and HHR-Li: Healthy High Responders living in an endemic area for L. major or L. infantum infection) or non immune/naive individuals (HLR: Healthy Low Responders), depending on whether they produce high or low levels of IFN-γ in response to Leishmania soluble antigen. Low levels of total IgG antibodies to LaPSA-38S were detected in sera from the studied groups. Interestingly, LaPSA-38S induced specific and significant levels of IFN-γ, granzyme B and IL-10 in CCLm, HHR-Lm and HHR-Li groups, with HHR-Li group producing TNF-α in more. No significant cytokine response was observed in individuals immune to L. braziliensis or L. donovani infection. Phenotypic analysis showed a significant increase in CD4+ T cells producing IFN-γ after LaPSA-38S stimulation, in CCLm. A high positive correlation was observed between the percentage of IFN-γ-producing CD4+ T cells and the released IFN-γ. We showed that the LaPSA-38S protein was able to induce a mixed Th1 and Th2/Treg cytokine response in individuals with immunity to L. major or L. infantum infection indicating that it may be exploited as a vaccine candidate. We also showed, to our knowledge for the first time, the capacity of Leishmania PSA protein to induce granzyme B production in humans with immunity to L. major and L. infantum infection. This study received financial support from EU's Seventh Framework Programme (FP7) (RAPSODI project, grant agreement number 223341). Sí

The aim of the current study was to investigate the oral antidiabetic activity of six structurally related flavonoids: flavone (1), 3-hydroxyflavone (2), 6-hydroxyflavone (3), 7-hydroxyflavone (4), chrysin (5) and quercetin (6). Normoglycemic and STZ-nicotinamide diabetic rats were treated with these flavonoids (50 mg/kg) and the hypoglycemic and antidiabetic effects in acute and sub acute (five days of treatment) experiments were determined. Compounds 1, 5 and 6 were found most active in both experiments in comparison with control group (p0.05). After five days of administration to STZ-nicotinamide diabetic rats, flavonoids induced a significantly diminishing of total cholesterol, TG and LDL and an augment of HDL compared with the control group (p0.05). The in vitro inhibitory activity of the compounds against 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) was also evaluated. Quercetin, the most active compound, was docked into the crystal structure of 11beta-HSD1. Docking results indicate potential hydrogen bond interactions with hydroxyl groups of catalytic amino acid residues.

Individuals with visceral leishmaniasis, or kala azar (KA) and individuals with post-KA dermal leishmaniasis (PKDL) are considered to be reservoirs of transmission of Leishmania donovani in India. When intracellular amastigotes were used to assess the natural susceptibility that PKDL isolates and KA isolates have to sodium antimony gluconate (SAG), the mean ED(50) was found to be 12.0+/-2.49 and 11.0+/-1.38 microg/mL, respectively; and there was a significant correlation with the clinical response (r rank=0.99). All KA isolates, as well as a significant proportion (55%) of PKDL isolates from high-endemicity zones, were resistant to SAG. The median ED(50) for SAG-resistant PKDL isolates (20.0 microg/mL) was significantly higher (P

An avulsed permanent tooth is one of the few real time dental emergencies, wherein a potential unscheduled diagnostic and treatment decision outside the regular practice experience of the dentist awaits him. Prognosis is dependent on the decisions taken in the "Golden Hour" aftermath the accident. Reimplantation is the treatment of choice as there are chances of successfully saving a tooth. The condition is compounded by the lack of public awareness and the presence of a proper avulsion management protocol that has been tested by prospective longitudinal studies. This article discusses an unusual case of total replacement resorption along with a comprehensive review of the etiology, pathology, clinical features, and the management of the condition.

In the future, we may be faced with the need to provide treatment for an emergent biological threat against which existing vaccines and drugs have limited efficacy or availability. To prepare for this eventuality, our objective was to use a metabolic network-based approach to rapidly identify potential drug targets and prospectively screen and validate novel small-molecule antimicrobials. Our target organism was the fully virulent Francisella tularensis subspecies tularensis Schu S4 strain, a highly infectious intracellular pathogen that is the causative agent of tularemia and is classified as a category A biological agent by the Centers for Disease Control and Prevention. We proceeded with a staggered computational and experimental workflow that used a strain-specific metabolic network model, homology modeling and X-ray crystallography of protein targets, and ligand- and structure-based drug design. Selected compounds were subsequently filtered based on physiological-based pharmacokinetic modeling, and we selected a final set of 40 compounds for experimental validation of antimicrobial activity. We began screening these compounds in whole bacterial cell-based assays in biosafety level 3 facilities in the 20th week of the study and completed the screens within 12 weeks. Six compounds showed significant growth inhibition of F. tularensis, and we determined their respective minimum inhibitory concentrations and mammalian cell cytotoxicities. The most promising compound had a low molecular weight, was non-toxic, and abolished bacterial growth at 13 µM, with putative activity against pantetheine-phosphate adenylyltransferase, an enzyme involved in the biosynthesis of coenzyme A, encoded by gene coaD. The novel antimicrobial compounds identified in this study serve as starting points for lead optimization, animal testing, and drug development against tularemia. Our integrated in silico/in vitro approach had an overall 15% success rate in terms of active versus tested compounds over an elapsed time period of 32 weeks, from pathogen strain identification to selection and validation of novel antimicrobial compounds.

Synovial sarcoma is highly malignant tumor of soft tissues, occurring chiefly in the extremities and limb girdle with a propensity for local recurrence and sometimes metastases to the lungs. Primary synovial sarcoma arising in the lungs is rare and brain metastasis as presentation is further uncommon. We report a case of primary monophasic synovial sarcoma lung presenting with brain metastasis in a 35-year-old male patient. The diagnosis was made on percutaneous transthoracic needle aspiration from left-sided pulmonary mass and later confirmed by immunohistochemistry. The utility of preoperative diagnosis by percutaneous aspiration cytology is also stressed.

A rapid and accurate method to detect and quantify Leishmania parasite is urgently needed to facilitate early diagnosis of leishmaniasis and monitoring of antileishmania therapy. In this study, real-time assay was applied to estimate parasite load in clinical samples of visceral leishmaniasis (VL) and post kala-azar dermal leishmaniasis (PKDL) patients. The mean parasite load in blood of VL patients (n = 31) was 8,372 parasites/ml, while the mean parasite load in bone marrow aspirate (BMA) was 194,962 parasites/million nucleated cells (n = 12). Parasite load was undetectable after treatment with amphotericin B (n = 9) in VL, while a residual parasite burden was detected in 2 of 6 patients following treatment with sodium antimony gluconate. Further, circulating levels of IFN-gamma, TNF-alpha, IL-10, IL-6, IL-4 and IL-2 were analysed in VL patients (n = 29) by Cytometric Bead Array to evaluate correlation with parasitic load. Interestingly, IL-10 levels correlated significantly with parasite load (r = 0.82, P