Overview of the rules of the microbial engagement in the gut microbiome: a step towards microbiome therapeutics.

Human gut microbiome is a diversified, resilient, immuno-stabilized, metabolically active and physiologically essential component of the human body. Scientific explorations have been made to seek in-depth information about human gut microbiome establishment, microbiome functioning, microbiome succession, factors influencing microbial community dynamics and the role of gut microbiome in health and diseases. Extensive investigations have proposed the microbiome therapeutics as a futuristic medicine for various physiological and metabolic disorders. A comprehensive outlook of microbial colonization, host-microbe interactions, microbial adaptation, commensal selection and immuno-survivability is still required to catalogue the essential genetic and physiological features for the commensal engagement. Evolution of a structured human gut microbiome relies on the microbial flexibility towards genetic, immunological and physiological adaptation in the human gut. Key features for commensalism could be utilized in developing tailor-made microbiome-based therapy to overcome various physiological and metabolic disorders. This review describes the key genetics and physiological traits required for host-microbe interaction and successful commensalism to institute a human gut microbiome.

Inferior right hepatic vein on routine contrast-enhanced CT of the abdomen: prevalence and correlation with right hepatic vein size.

AIM: To determine the prevalence of the inferior right hepatic vein (IRHV) in patients undergoing routine contrast-enhanced computed tomography (CECT) of the abdomen and to compare it with the size of the right hepatic vein (RHV). MATERIALS AND METHODS: Two hundred and twenty-four consecutive patients who underwent routine CECT abdomen, with adequate venous opacification, were included in the study. The number and diameter of IRHVs and the diameter of the RHV was noted in each case. RESULTS: A total of 214 IRHVs were detected in 126 cases (56.2%) with a mean diameter of 4.15±1.44 mm. The number of IRHVs ranged from one to four (more than one IRHV was present in 39.7% [50/126] of cases). In approximately one-third of cases (46/126), an IRHV ≥5 mm was found. A weak negative correlation was found between size of the RHV and IRHV (Pearson's correlation coefficient -0.222; p=0.01). The RHV was smaller in size in patients with an IRHV (7.34±1.88 mm) than in patients without an IRHV (8.47±1.99 mm) on CECT abdomen. A larger IRHV was associated with a smaller RHV (6.91±2.05 mm). CONCLUSION: The presence of IRHV on routine CECT abdomen is frequent, and it is not uncommon to encounter more than one IRHV. The diameter of the IRHV has a weak negative correlation with the diameter of the RHV, and a smaller RHV is found in patients with an IRHV.

Assessing the impact of a program for late surgical intervention in early-blind children.

OBJECTIVE: Many blind children in the developing world are unable to obtain timely treatment due to lack of financial and medical resources. Can public health programs that identify and treat such children several years after the onset of blindness enhance their quality of life? The notion that visual development is subject to an early 'critical period' argues against this possibility. However, there are inadequate empirical data from humans on this issue. To address this need, we examined the quality of life of children living in India and who were treated for early-onset blindness (before one year of age), due to cataracts or corneal opacities. STUDY DESIGN: Survey study. METHODS: As part of an ongoing scientific effort named Project Prakash, we screened over 40,000 children in rural northern India to identify those suffering from early-onset blindness. They were provided eye surgeries in a tertiary care ophthalmic center in New Delhi. We subsequently surveyed 64 Prakash children, ranging in age from 5 to 22 years and obtained their responses on a multi-dimensional quality of life questionnaire. RESULTS: Nearly all of the subjects indicated that their quality of life had improved after treatment. Children reported marked enhancement in their mobility, independence, and safety, and also in social integration. Surprisingly, we found no significant correlations between quality of life metrics and factors such as age at treatment, gender, time since treatment, and pre-surgery and post-surgery acuity. CONCLUSIONS: A key question for public health policy makers is whether a program of surgical intervention for older blind children is likely to be beneficial, or if the resources are better spent on rehabilitation via vocational training and assistive devices. The marked improvements in quality of life we find in our data strongly argue for the provision of surgical care regardless of a child's age.

Tuning the carrier concentration using Zintl chemistry in Mg3Sb2, and its implications for thermoelectric figure-of-merit.

Zintl compounds are potential candidates for efficient thermoelectric materials, because typically they are small band gap semiconductors. In addition, such compounds allow fine tuning of the carrier concentration by chemical doping for the optimization of thermoelectric performance. Herein, such tunability is demonstrated in Mg3Sb2-based Zintl compounds via Zn(2+) doping at the Mg(2+) site of the anionic framework (Mg2Sb2)(2-), in the series Mg3-xZnxSb2 (0 ≤ x ≤ 0.1). The materials have been successfully synthesized using the spark plasma sintering (SPS) technique. X-ray diffraction (XRD) analysis confirms a single solid solution phase of Mg3-xZnxSb2 (0 ≤ x ≤ 0.1). The thermoelectric properties are characterized by the Seebeck coefficient, electrical conductivity, and thermal conductivity measurements from 323 K to 773 K. Isoelectronic Zn substitution at the Mg site presents the controlled variation in the carrier concentration for optimizing the high power factor and reduced thermal conductivity. These results lead to a substantial increase in ZT of 0.37 at 773 K for a composition with x = 0.10 which is ∼42% higher than undoped Mg3Sb2. The electronic transport data for the Mg3-xZnxSb2 (0 ≤ x ≤ 0.1) compound are analyzed using a single parabolic band model predicting that Mg2.9Zn0.1Sb2 exhibits a near-optimal carrier concentration for high ZT. The electronic structure of transport properties of these disordered Mg3-xZnxSb2 (0 ≤ x ≤ 0.1) is also studied using density functional theory and the results obtained are in good agreement with experimental results. The low cost, lightness and non-toxicity of the constituent elements make these materials ideal for mid-temperature thermoelectric applications.

Panoscopically optimized thermoelectric performance of a half-Heusler/full-Heusler based in situ bulk composite Zr(0.7)Hf(0.3)Ni(1+x)Sn: an energy and time efficient way.

All scale hierarchical architecturing, matrix/inclusion band alignment and intra-matrix electronic structure engineering, the so called panoscopic approach for thermoelectric materials has been demonstrated to be an effective paradigm for optimizing high ZT. To achieve such hierarchically organized microstructures, composition engineering has been considered to be an efficient strategy. In this work, such a panoscopic concept has been extended to demonstrate for the first time in the case of half-Heusler based thermoelectric materials via a composition engineering route. A series of new off-stoichiometric n-type Zr0.7Hf0.3Ni1+xSn (0 ≤x≤ 0.10) HH compositions have been modified to derive HH(1 -x)/full-Heusler (FH)(x) composite with an all scale hierarchically modified microstructure with FH inclusions within the matrix to study the temperature dependent thermoelectric properties. The structural analysis employing XRD, FE-SEM and HR-TEM of these materials reveal a composite of HH and FH, with hierarchically organized microstructures. In such a submicron/nano-composite, the electronic properties are observed to be well optimized yielding a large power factor; α(2)σ (∼30.7 × 10(-4) W m(-1) K(-2) for Zr0.7Hf0.3Ni1.03Sn) and reduced thermal conductivity (∼2.4 W m(-1) K(-1) for Zr0.7Hf0.3Ni1.03Sn) yielding a high ZT∼ 0.96 at 773 K for composition Zr0.7Hf0.3Ni1.03Sn which is ∼250% larger than the normal HH Zr0.7Hf0.3NiSn (ZT∼ 0.27 at 773 K). The enhancement in ZT of these composites has been discussed in terms of primary electron filtering, electron injection and several phonon scattering mechanisms such as alloy scattering, point defect scattering, and grain boundary scattering. The Bergman and Fel model is used to calculate effective thermoelectric parameters of these composites for comparing the experimental results.

A young healthy male with syncope and complete heart block.

INTRODUCTION: It is rare to see heart block as the first-and-only presentation of Lyme disease, the reported incidence being just 1% in untreated patients. CASE PRESENTATION: We report a patient who presented with syncope secondary to a fluctuating heart block. He had no previous manifestations of Lyme disease. Lyme carditis was suspected after the other usual etiologies of heart block were ruled out. Later, serologies came positive and patient's heart block resolved on ceftriaxone therapy. CONCLUSION: In at-risk individuals, clinicians should rule out this readily-treatable cause of heart block before proceeding with permanent pacemaker implantation due to enormous clinical and cost implications involved. Missing the diagnosis also exposes the patient to the risk of developing the late complications of Lyme disease. Diagnosis of isolated Lyme carditis is a challenge because the clinician does not have the diagnostic-clues that can usually be gleaned from the more common stigmata of Lyme disease.

Amperometric choline biosensor based on multiwalled carbon nanotubes/zirconium oxide nanoparticles electrodeposited on glassy carbon electrode.

A bienzymatic choline biosensor was constructed by coimmobilizing acetylcholinesterase (AChE) and choline oxidase (ChO) onto nanocomposite of carboxylated multiwalled carbon nanotubes (c-MWCNTs) and zirconium oxide nanoparticles (ZrO(2)NPs) electrodeposited on the surface of a glassy carbon electrode (GCE) and using it (AChE-ChO/c-MWCNT/ZrO(2)NPs/GCE) as working electrode, Ag/AgCl as reference electrode, and Pt wire as auxiliary electrode connected through a potentiostat. The enzyme electrode was characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and cyclic voltammetry (CV) studies, optimized, and evaluated. The biosensor exhibited optimum response within 4 s at +0.2V, pH 7.4, and 25 °C. The detection limit and working range of the biosensor were 0.01 µM and 0.05 to 200 µM, respectively. The half-life of the enzyme electrode was 60 days at 4 °C. The serum choline level, as measured by the biosensor, was 9.0 to 12.8 µmol/L (with a mean of 10.81 µmol/L) in apparently healthy persons and 5.0 to 8.4 µmol/L (with a mean of 6.53 µmol/L) in persons suffering from Alzheimer's disease. The enzyme electrode was unaffected by a number of serum substances.

Synthesis, antitubercular evaluation and 3D-QSAR study of N-phenyl-3-(4-fluorophenyl)-4-substituted pyrazole derivatives.

As a part of our ongoing research to develop novel antitubercular agents, a series of N-phenyl-3-(4-fluorophenyl)-4-substituted pyrazoles have been synthesized and tested for antimycobacterial activity in vitro against Mycobacterium tuberculosis H37Rv strain using the BACTEC 460 radiometric system. A 3D-QSAR study based on CoMFA and CoMSIA was performed on these pyrazole derivatives to correlate their chemical structures with the observed activity against M. tuberculosis. The CoMFA model provided a significant correlation of steric and electrostatic fields with the biological activity while the CoMSIA model could additionally shed light on the role of hydrogen bonding and hydrophobic features. The important features identified in the 3D-QSAR models have been used to propose new molecules whose activities are predicted higher than the existing systems. This study provides valuable directions to our ongoing endeavor of rationally designing more potent antitubercular agents.

Assessing the optimal imaging modality in the diagnosis of jaw osteomyelitis. A meta-analysis.

Osteomyelitis is an inflammatory infectious disease that affects bone and bone marrow. Histopathology remains the gold standard method for diagnosis, but imaging modalities also play an important role. We systematically reviewed five articles with comparative studies on plain films, computed tomography (CT) scan, magnetic resonance imaging (MRI), cone beam computed tomography (CBCT), positron emission tomography (PET), single photon-emission computed tomography (SPECT), scintigraphy, and SPECT/CT. Scintigraphy and SPECT/CT has the highest sensitivity of 100%. PET is only to be used in cases of follow up. Orthopantomography (OPG) is the most common initial diagnostic tool despite its low sensitivity. CT provides the necessary specificity needed for radionuclide imaging, which has the highest negative predictive value of 100% and a positive predictive value >95%. SPECT/CT with 100% sensitivity and 85% specificity can be considered as the imaging modality of choice for initial diagnosis and follow up.

Bleomycin sclerotherapy in lymphangiomas of the head and neck region: a prospective study.

Intralesional sclerotherapy for lymphatic malformations (LMs) has become a modality of choice because of the high morbidity and recurrence rates with surgical excision. Traditionally, the macrocystic variant has shown good results with sclerotherapy. This prospective study was performed to evaluate the role of bleomycin sclerotherapy in the management of different radiological variants of LM. A total of 142 patients were included in this study. The lesions were classified as macrocystic, microcystic, or mixed LMs on the basis of ultrasonography. All patients were managed by intralesional injection of bleomycin and were recalled after 4 weeks for evaluation. Colour photographs of the patients were taken before the onset of treatment and at each monthly visit, and were utilized to assess the response. Following the second, third, and fourth doses, the response was better in patients with the macrocystic variant than in those with the other two variants. However, after the completion of six doses, 80.3% of patients with the macrocystic variant, 67.4% with the microcystic variant, and 71.4% with the mixed type had a complete response. There was no difference in the overall response between the three types (P=0.28). Oedema, erythema, and local induration with fever were the most common adverse effects and were more common in younger children.

Role of immune activation in CD4+ T-cell depletion in HIV-1 infected Indian patients.

OBJECTIVES: The correlation of immune activation with CD4(+) depletion and HIV-1 disease progression has been evidenced by several studies involving mainly clade B virus. However, this needs to be investigated in developing countries such as India predominately infected with clade C virus. MATERIALS AND METHODS: In a cross-sectional study of 68 antiretroviral treatment naïve, HIV-1 infected Indian patients, we studied the association between CD4(+) T cells, plasma HIV-1 RNA levels, and immune activation markers using unadjusted and adjusted correlative analyses. RESULTS: Significant negative correlations of higher magnitude were observed between the CD4(+) T cell percentages and plasma HIV-1 RNA levels in the study population when adjusted for the effects of immune activation markers. However, the negative association of CD4(+) T cells with immune activation markers remained unaffected when controlled for the effects of plasma HIV-1 RNA levels. CONCLUSIONS: Our results support the important role of immune activation in CD4(+) T cell depletion and disease progression during untreated HIV-1 infection.

Effect of Curculigo orchioides rhizomes on sexual behaviour of male rats.

The rhizomes of Curculigo orchioides have been traditionally used as aphrodisiac. In the present study ethanolic extract of rhizomes was evaluated for its effect on sexual behavior in rats. Administration of 100 mg/kg of extract change significantly the sexual behavior as assessed by determining parameters such as penile erection, mating performance, mount frequency and mount latency. Moreover a pronounced anabolic and spermatogenic effect was evidenced by weight gains of reproductive organs. The treatment also markedly affected sexual behavior of animals as reflected in reduction of mount latency, an increase in mount frequency and enhanced attractability towards female. Penile erection index was also incremented in treated group.

"Low platelet usage" haematology laboratories: To store or not to store?

In the UK, hospitals with annual platelet use of less than 500 pools, like our institution, usually do not store platelets on-site and these are only ordered from the national blood service (NBS) when a transfusion is required. In 2016, we piloted routine on-site storage of one pool of A RhD negative PLT. Data were collected retrospectively on units of PLTs ordered from NBS, units transfused to patients, wastage, requirements for emergency deliveries from NBS and overall cost. These were compared to corresponding data from the four preceding years (2012-2015). There was a 39% reduction in the PLT ordered from NBS in 2016 compared to previous years and a 50% reduction in transfused PLT. Annual wastage for 2016 increased by 23% even though the absolute number of wasted PLT did not alter significantly. Annual cost reduced by 36% in 2016 resulting from reduction in the total amount of PLTs ordered as well as reduction in emergency deliveries.

Neuroprotection and neurogenesis: modulation of cornus ammonis 1 neuronal survival after transient forebrain ischemia by prior fimbria-fornix deafferentation.

Severe transient forebrain ischemia causes selective neuronal death in the hippocampal cornus ammonis 1 region. We tested the hypothesis that fimbria-fornix deafferentation can provide long-term protection to cornus ammonis 1 neurons and modulate neurogenesis following ischemia. Fimbria-fornix lesion or sham-fimbria-fornix lesion was performed on Wistar rats 13 days prior to 10 min forebrain ischemia or sham ischemia. Temperature was regulated and rats survived for 7, 14 or 28 days. Immunofluorescent bromodeoxyuridine and neuron specific nuclear protein staining and immunochemistry terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling staining were performed. At 7 days after ischemia, 73%+/-14% of cornus ammonis 1 neurons were damaged, while deafferentation reduced the injury to 36%+/-17% of cornus ammonis 1 neurons. This protection persisted for at least 28 days. Ischemia significantly increased the number of bromodeoxyuridine-positive cells (85-90 cells/section in stroke group vs. 6 to 11 cells/section in normal or sham stroke group), with very few terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-stained cells adjacent to the hippocampal cornus ammonis 1. Fimbria-fornix lesioning followed by ischemia increased the percentage of new neurons 13-fold over ischemia alone and 6.5-fold over sham lesion plus ischemia. The results indicate that fimbria-fornix deafferentation provides long-term neuroprotection in cornus ammonis 1 following forebrain ischemia and promotes neurogenesis after ischemic insults.

Radiation therapy outcomes in muscle invasive urinary bladder cancer: A single institution experience.

INTRODUCTION: To audit the survival outcomes and loco-regional control in muscle invasive urinary bladder cancer patients treated with external beam radiation therapy (RT). MATERIALS AND METHODS: From November 2008 through December 2011, 50 consecutively diagnosed muscle invasive urinary bladder carcinoma (T2-4a N0-2, M0) patients were included in this retrospective study. All these patients received external beam RT to a median dose of 60 Gy (range 30-66 Gy), and were not suitable for radical surgery due to patients' preference or medical comorbidities. A stepwise procedure using proportional hazard regression was used to identify prognostic factors with respect to survival. RESULTS: Completion trans-urethral resection of bladder tumor was done in 38 (76%) patients of the cohort and 47 (94%) had transitional cell carcinoma on histopathology. Clinical stage T2 was diagnosed in 40 (80%) patients. The median follow-up for the entire cohort was 14 ± 8.9 months (range 1-36 months). In conclusion, 24 patients (48%) were free of disease, 5 patients (10%) had residual disease, and 13 patients (26%) had died of disease. Two-year and 3 year overall survival of intact bladder for the entire cohort was 58% and 43.6%, respectively. Cox regression modeling strongly suggested clinical stage (P = 0.01) and RT dose (P = 0.001) as being predictors for overall survival. CONCLUSION: RT shows reliable outcomes and excellent compliance in this advanced disease. Prescribing a higher RT dose could potentially correlate to better intact bladder control rates while maintaining good quality of life in selected patients.

European Concerted Action on Anticoagulation. A multicentre calibration study of WHO international reference preparations for thromboplastin, rabbit (RBT/90) and human (rTF/95).

A 10 centre calibration was performed after six years to determine the international sensitivity index (ISI) of rTF/95 relative to RBT/90, and to assess any international normalised ratio (INR) bias compared with the original multicentre calibration. After exclusion of one outlying centre, the follow up calibration gave a mean ISI for rTF/95 of 0.99, which although a small difference, is significantly greater than the mean ISI of 0.94 obtained previously. The change in ISI for international reference preparation (IRP) rTF/95 relative to RBT/90 would lead to a slight bias in INR for human compared with rabbit thromboplastins. At a theoretical INR of 3.0, the INR bias is 6.0%, and this is below the accepted 10% level of clinical relevance. Ongoing stability monitoring of World Health Organisation thromboplastin IRP is advised.

Multiplicity of garlic health effects and Alzheimer's disease.

The epidemiological, clinical and laboratory data have shown that garlic contains many biologically active compounds which are beneficial to human health in general. Among all, one garlic-preparation called aged garlic extract, is proven to be safer. Although additional studies are warranted in humans, compelling evidence supports the health effects attributed to aged garlic extract and its implications in preventing or reducing the risk of cardiovascular ailments, stroke and cancer. Recently, the beneficial effects of garlic and its constituents on neuronal physiology and brain functions are beginning to emerge. However, this field is still in infancy and not yet fully explored. This review encompasses multiple health effects of garlic and its constituents with reference to neuroprotection. Possible potential of dietary garlic as an alternative herbal pharmacotherapy for Alzheimer's disease is discussed.

Synthesis and characterization of nanocrystalline forsterite coated poly(L-lactide-co-ß-malic acid) scaffolds for bone tissue engineering applications.

In this research, after synthesizing poly(L-lactide-co-ß-malic acid) (PLMA) copolymer, hybrid particles of ice and nanocrystalline forsterite (NF) as coating carriers were used to prepare NF-coated PLMA scaffolds. The porous NF-coated scaffolds were directly fabricated by a combined technique using porogen leaching and freeze-drying methods. The obtained results indicate that the scaffolds were structurally porous with NF particles on their surfaces. When compared to the uncoated scaffolds, the NF coating improved both mechanical properties as well as enhanced bioactivity of the scaffolds. In addition, in vitro biological response of the rat bone marrow stromal cells indicated that NF significantly increased the biocompatibility of NF-coated scaffolds compared with PLMA.

A systematic study on the use of ultrasound energy for the synthesis of nickel-metal organic framework compounds.

A nickel metal-organic framework (Ni-MOF) was successfully synthesized using ultrasound irradiation. Further to this, X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FT-IR), Thermo-Gravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC) and nitrogen adsorption [i.e. Brunauer-Emmett-Teller (BET) Surface Area Analysis] techniques were used to characterize the synthesized Ni-MOF. In addition, the effect of sonication on the surface area, pore diameter and pore volume of the final product was systematically studied using Taguchi technique. The experiments ascertained that manufacturing of the Ni-MOF by means of the ultrasonic-assisted technique is feasible at a relatively shorter time compare to the conventional methods. The final product showed more uniform shape distribution and improved BET properties. The obtained results offered that the synthesized Ni-MOF samples could be used in several applications.

European Concerted Action on Anticoagulation (ECAA): an assessment of a method for ISI calibration of two whole blood point-of-care PT monitor systems based on lyophilized plasmas using whole blood equivalent PT.

Previously, the attempt to simplify the International Sensitivity Index (ISI) calibration of the CoaguChek Mini whole blood point-of-care test prothrombin time (PT) monitor system was successful using lyophilized plasmas from coumarin-treated patients but not with lyophilized artificially depleted plasmas. With the TAS PT-NC monitor system, both types of plasma failed to provide reliable calibrations. The present study assesses a procedure for the ISI calibration of a TAS PT-NC and CoaguChek Mini whole blood point-of-care test PT monitor systems using lyophilized plasmas. Using lyophilized artificially depleted and coumarin plasma calibrations, we have evaluated a correction for the monitor displayed PT. This was based on a 'line of equivalence' derived from the relationship between whole blood and fresh plasma PT with both types of monitor system. With the TAS PT-NC, the use of this 'line of equivalence' resulted in reliable ISI with both lyophilized coumarin and artificially depleted plasmas. There was no significant difference between mean monitor and mean reference International Normalized Ratio (INR) with the artificially depleted plasmas. With the lyophilized coumarin plasma calibrations there was only a small INR difference. Correction with the 'line of equivalence' therefore facilitates calibration of the TAS PT-NC with lyophilized plasmas. With the CoaguChek Mini, the correction based on the 'line of equivalence' did not improve results but was not required with this system.