Functional Outcome Analysis of Autologous Stromal Vascular Fraction (SVF) (Sahaj Therapy®) Using Direct Sonication in Osteonecrosis of the Femoral Head (ONFH): A 6-Year Follow-Up Study.

Introduction: We investigated the safety, efficacy, functional, and clinical outcomes of intra-osseous implantation of mechanically isolated, autologous stromal vascular fraction (SVF), an Australian patented direct ultrasonication technology (Sahaj Therapy®) in osteonecrosis of the femoral head (ONFH). Materials and Methods: A total of 32 cases of ONFH were enrolled in the study after confirming with an MRI of the affected hip. All cases were treated with an intra-osseous autologous SVF implantation [4-5 cc with the cellular dosage of 8.0 × 107 cells with a viability of > 85% SVF cells] on the same surgical sitting. All the cases were followed up clinically, functionally, and radiologically at regular intervals. A comparison of mean HOOS scores at different follow-ups was done using Paired 't'-test. A P value of < 0.05 was considered significant. Results: In our study, male preponderance was seen (53.1%). According to the modified Ficat and Arlet classification, the most common grade of ONFH was grade 2 [right: 25 hips and left: 25 hips]. There was a statistically significant improvement in the mean HOOS score of the right hip (n = 10) and left hip (n = 9) from preoperative time till 72 months (P < 0.05). The follow-up MRI of the affected hips shows improved osteogenesis without any further worsening of the contour of the femoral head. No adverse effects were seen in any of the study participants. Conclusion: For individuals with ONFH, treated with intra-osseous autologous SVF implantation in the same surgical procedure is an innovative and promising treatment modality. Even after 6 years of follow-up, the study participants with ONFH have shown good clinical and functional outcomes with autologous SVF.

Prevalence of drug resistant Enterobacteriaceae in a Nepalese tertiary care hospital.

Antimicrobial resistance in Enterobacteriaceae is an emerging global public health problem. Numerous studies have reported community-acquired AmpC beta-lactamase and extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae in Nepal. However, there are limited data on community-acquired Metallo-beta-lactamase (MBL) producing Enterobacteriaceae. A hospital-based descriptive cross-sectional study was conducted using 294 Enterobacteriaceae isolates from a total of 2,345 different clinical specimens collected from patients attending a tertiary care hospital in Nepal. Bacteria were isolated using standard microbiological growth media and identified using biochemical tests. For antimicrobial susceptibility testing, Kirby-Bauer disc diffusion technique was used. AmpC, ESBL, and MBL productions were detected by using combined disc method. AmpC, ESBL, and MBL productions were detected in 19.4%, 29.6%, and 8.5% of total Enterobacteriaceae isolates respectively. Higher rates of beta-lactamases production were seen among the isolates from in-patients in comparison with those from out-patients. However, 11.6%, 25%, and 3.7% of the total isolates from out-patients were AmpC, ESBL, and MBL producers respectively. The co-production of the beta-lactamases was also detected, with two Klebsiella pneumoniae isolates producing all three beta-lactamases. One MBL producing Proteus vulgaris isolate that was pan-resistant with no remaining treatment options was also isolated. Prevalence of drug resistant Enterobacteriaceae in our study was very high. Detection of AmpC, ESBL, and MBL positive isolates from out-patients, who did not have recent history of hospital visit, indicated the community dissemination of the drug resistant bacteria. This is a matter of great concern and an immediate attention to formulate strategies to prevent further development and spread of antibiotic resistance is required.

Underwater Adhesives from Redox-Responsive Polyplexes of Thiolated Polyamide Polyelectrolytes.

We report the fabrication of optically clear underwater adhesives using polyplexes of oppositely charged partially-thiolated polyamide polyelectrolytes (TPEs). The thiol content of the constituent PEs was varied to assess its influence on the adhesive properties of the resulting glues. These catechol-free, redox-responsive TPE-adhesives were formulated in aquo and exhibited high optical transparency and strong adhesion even on submerged or moist surfaces of diverse polar substrates such as glass, aluminium, wood, and bone pieces. The adhesives could be cured under water through oxidative disulphide crosslinking of the constituent TPEs. The polyamide backbone provided multi-site H-bonding interactions with the substrates while the disulphide crosslinking provided the cohesive strength to the glue. Strong adhesion of mammalian bones (load bearing capacity upto 7 kg/cm2 ) was achieved using the adhesive containing 30 mol % thiol residues. Higher pH and use of oxidants such as povidone-iodine solution enhanced the curing rate of the adhesives, and so did the use of Tris buffer instead of Phosphate buffer. The porous architecture of the adhesive and its progressive degradation in aqueous medium over the course of three weeks bode well for diverse biomedical applications where temporary adhesion of tissues is required.

An Observational Study Comparing the Effects of Chloroquine and Artemisinin-Based Combination Therapy on Hematological Recovery in Patients With Plasmodium vivax Malaria.

Introduction Malaria, a common parasitic disease in tropical regions, produces hematological changes in patients. In the present study, we compare hematologic recovery between the chloroquine and artemether-lumefantrine treatment groups of patients with Plasmodium vivax malaria. Methodology This was a cross-sectional observational study comparing hematological parameters, including total and differential white blood cell counts, and platelet counts between two patient groups: one group with 48 patients receiving chloroquine, and the other with 47 patients receiving the artemether-lumefantrine combination. Both groups received primaquine to combat the hypnozoite stage. Results The rate of platelet count recovery was significantly faster in patients treated with the artemether-lumefantrine combination (p-value 0.002). Rates of recovery of the total white blood cell count and neutrophil count were faster with the artemether-lumefantrine combination, while the recovery of the lymphocyte count was faster in patients treated with chloroquine. However, these changes were statistically insignificant (p-values = 0.69, 0.42, and 0.65, respectively). Conclusion Based on hematological recovery, artemisinin combination therapy may be preferred over treatment with chloroquine in cases of P. vivax malaria. However, factors such as the adverse effect profile, cost-effectiveness, and chloroquine resistance need to be considered for the practical applicability of the same.

Combating the Progression of Novel Coronavirus SARS-CoV-2 Infectious Disease: Current State and Future Prospects in Molecular Diagnostics and Drug Discovery.

A highly infectious and life-threatening virus was first reported in Wuhan, China, in late 2019, and it rapidly spread all over the world. This novel virus belongs to the coronavirus family and is associated with severe acute respiratory syndrome (SARS), causing respiratory disease known as COVID-19. In March 2020, WHO has declared the COVID-19 outbreak a global pandemic. Its morbidity and mortality rates are swiftly rising day by day, with the situation becoming more severe and fatal for the comorbid population. Many COVID-19 patients are asymptomatic, but they silently spread the infection. There is a need for proper screening of infected patients to prevent the epidemic transmission of disease and for early curative interventions to reduce the risk of developing severe complications from COVID-19. To date, the diagnostic assays are of two categories, molecular detection of viral genetic material by real-time RTpolymerase chain reaction and serological test, which relies on detecting antiviral antibodies. Unfortunately, there are no effective prophylactics and therapeutics available against COVID-19. However, a few drugs have shown promising antiviral activity against it, and these presently are being referred for clinical trials, albeit FDA has issued an Emergency Use Authorization (EUA) for the emergency use of a few drugs for SARSCoV- 2 infection. This review provides an insight into current progress, challenges and future prospects of laboratory detection methods of COVID-19, and highlights the clinical stage of the major evidence-based drugs/vaccines recommended against the novel SARS-CoV-2 pandemic virus.

Plant-derived immuno-adjuvants in vaccines formulation: a promising avenue for improving vaccines efficacy against SARS-CoV-2 virus.

The SARS-CoV-2 outbreak has posed a plethora of problems for the global healthcare system and socioeconomic burden. Despite valiant efforts to contain the COVID-19 outbreak, the situation has deteriorated to the point that there are no viable preventive therapies to treat this disease. The case count has skyrocketed globally due to the newly evolved variants. Despite vaccination drives, the re-occurrence of recent pandemic waves has reinforced the importance of innovation/utilization of immune-booster to achieve appropriate long-term vaccine protection. Plant-derived immuno-adjuvants, which have multifaceted functions, can impede infections by boosting the immune system. Many previous studies have shown that formulation of vaccines using plant-derived adjuvant results in long-lasting immunity may overcome the natural tendency of coronavirus immunity to wane quickly. Plant polysaccharides, glycosides, and glycoprotein extracts have reportedly been utilized as enticing adjuvants in experimental vaccines, such as Advax, Matrix-M, and Mistletoe lectin, which have been shown to be highly immunogenic and safe. When employed in vaccine formulation, Advax and Matrix-M generate long-lasting antibodies, a balanced robust Th1/Th2 cytokine profile, and the stimulation of cytotoxic T cells. Thus, the use of adjuvants derived from plants may increase the effectiveness of vaccines, resulting in the proper immunological response required to combat COVID-19. A few have been widely used in epidemic outbreaks, including SARS and H1N1 influenza, and their use could also improve the efficacy of COVID-19 vaccines. In this review, the immunological adjuvant properties of plant compounds as well as their potential application in anti-COVID-19 therapy are thoroughly discussed.

Transcript analysis and expression of the glbO gene, encoding truncated hemoglobin,O, of M. Smegmatis implicate its role under hypoxia and oxidative stress.

Although truncated hemoglobin O, (trHbO), is ubiquitous among mycobacteria, its physiological function is not very obvious and may be diverse. In an attempt to understand role of trHbO in cellular metabolism of a non-pathogenic mycobacterium, we analysed expression profile of the glbO gene, encoding trHbO, in M. smegmatis and studied implications of its overexpression on physiology of its host under different environmental conditions. Quantitative RT-PCR indicated that transcript level of the glbO gene remains low at a basal level under aerobic growth cycle of M. smegmatis but its level gets induced significantly during low oxygen, oxidative stress and macrophage infection. Overexpression of the glbO gene enhanced growth of M. smegmatis under hypoxia, promoted pellicle biofilm formation and provided resistance towards oxidative stress. Additionally, glbO gene overexpressing M. smegmatis exhibited enhanced cell survival over isogenic control cells and altered the level of pro- and anti- inflammatory cytokines during intracellular infection. These results suggested important role of trHbO, in supporting the cellular metabolism and survival of M, smegmatis both under low oxygen and oxidative stress.

A Phagosomally Expressed Gene, rv0428c, of Mycobacterium tuberculosis Demonstrates Acetyl Transferase Activity and Plays a Protective Role Under Stress Conditions.

Mycobacterium tuberculosis genome is composed of several hypothetical gene products that need to be characterized for understanding the physiology of bacteria. Rv0428c was one of the 11 proteins exclusively identified within the phagosomal compartment of macrophages infected with mycobacteria and marked as hypothetical. The expression of rv0428c gene was upregulated under acidic and nutritive stress conditions in M. tuberculosis H37Ra, which was supported by potential sigma factor binding sites in the region upstream to the rv0428c gene. The bioinformatics analysis predicted it to be a GCN5- acetyl transferase, belonging to the Histone acetyl transferase (HAT) family. The docking analysis predicted formation of hydrogen bonds and hydrophobic interactions between donor acetyl-co-A and histone H3 tail region. rv0428c gene was cloned and expressed in E. coli. The protein was purified to homogeneity and was fairly stable over a wide range of pH 5.0-9.0 and temperature up to 40 °C. The HAT activity of purified Rv0428c was confirmed by in vitro acetylation assay using recombinant H3 histone expressed in bacteria as substrate, which increased in time dependent manner. The results suggested that it is the second confirmed acetyl transferase in M. tuberculosis H37Rv. Furthermore, rv0428c was over expressed in surrogate host M. smegmatis, which led to enhanced growth rate and altered colony morphology. The expression of rv0428c in M. smegmatis promoted the survival of bacteria under acidic and nutritive stress conditions. In conclusion, Rv0428c, a phagosomal acetyl transferase of M. tuberculosis, might be involved in survival under stress conditions.

Pharmaco-immunomodulatory interventions for averting cytokine storm-linked disease severity in SARS-CoV-2 infection.

The year 2020 is characterised by the COVID-19 pandemic that has quelled more than half a million lives in recent months. We are still coping with the negative repercussions of COVID-19 pandemic in 2021, in which the 2nd wave in India resulted in a high fatality rate. Regardless of emergency vaccine approvals and subsequent meteoric global vaccination drives in some countries, hospitalisations for COVID-19 will continue to occur due to the propensity of mutation in SARS-CoV-2 virus. The immune response plays a vital role in the control and resolution of infectious diseases. However, an impaired immune response is responsible for the severity of the respiratory distress in many diseases. The severe COVID-19 infection persuaded cytokine storm that has been linked with acute respiratory distress syndrome (ARDS), culminates into vital organ failures and eventual death. Thus, safe and effective therapeutics to treat hospitalised patients remains a significant unmet clinical need. In that state, any clue of possible treatments, which save patients life, can be treasured for this time point. Many cohorts and clinical trial studies demonstrated that timely administration of immunomodulatory drugs on severe COVID-19 patients may mitigate the disease severity, hospital stay and mortality. This article addresses the severity and risk factors of hypercytokinemia in COVID-19 patients, with special emphasis on prospective immunomodulatory therapies.

Effect of Particle Morphology on Stiffness, Strength and Volumetric Behavior of Rounded and Angular Natural Sand.

Stress-strain and volume change behavior for clean sands which have distinct particle shape (rounded and angular) with very similar chemical (mineralogical) composition, size, and texture in one-dimensional (1D) compression and drained triaxial compression are presented. The effect of particle morphology on the crushing behavior in one-dimensional loading is explored using laser light diffraction technique which is suitable for particle crushing because of its high resolution and small specimen volume capability. Particle size distribution in both volume/mass and number distributions are considered for improved understanding associated with the process of comminution. Number distributions present a clearer picture of particle crushing. It is argued that particle crushing in granular assemblies initiates in larger particles, rather than in smaller particle. It was found that rounded sand specimens showed greater crushing than angular sand specimens with higher uniformity coefficient. In 1D compression, loose specimens compress approximately 10% more than dense specimens irrespective of particle shape. Densification of angular sand results in improvement in stiffness (approximately 40%) and is comparable to that of loose rounded sand. In general, density has a greater influence on the behavior of granular materials than particle morphology. The effect of particle shape was found to be greater in loose specimens than in dense specimens. The effect of grain shape on critical state friction angle is also quantified.

Nano-Neurotherapeutics (NNTs): An Emergent and Multifaceted Tool for CNS Disorders.

Impressive research steps have been taken for the treatment of neurological disorders in the last few decades. Still, effective treatments of brain related disorders are very less due to problems associated with crossing the blood-brain barrier (BBB), non-specific therapies, and delay in functional recovery of the central nervous system (CNS) after treatment. Striving for novel treatment options for neurological disorders, nanotechnology- derived materials, and devices have gained ground due to inherent features of derivatization/encapsulation with drugs as per the neurological ailments and pharmacological targets. Facile developments/syntheses of the nanomaterials-drug conjugates have also been the driving force for researchers to get into this field. Moreover, the tunable size and hydro/lipophilicity of these nanomaterials are the added advantages that make these materials more acceptable for CNS disorders. These nano-neurotherapeutics (NNTs) systems provide the platform for diagnosis, theranostics, treatments, restoration of CNS disorders, and encourage the translation of NNTs from "bench to bedside". Still, these techniques are in the primary stages of medical development. This review describes the latest advancements and future scenarios of developmental and clinical aspects of polymeric NNTs.

Emerging biomedical applications of polyaspartic acid-derived biodegradable polyelectrolytes and polyelectrolyte complexes.

Polyelectrolytes (PELs) - polymers with charged repeat units - have emerged as a useful class of polymers for biomedical applications due to their high aqueous solubility, low aggregation propensity and the opportunity they afford for polyvalent interactions with surfaces. Biodegradability and biocompatibility of PELs are important prerequisites for their utilization in in vivo applications. PELs that can be chemically functionalized with ease prove advantageous for creating diverse biomaterials. Polyaspartic acid (PASA) is a modular and biocompatible synthetic PEL that has all these features. It also shows many positive biomedical attributes such as bone-tissue targeting, muco-adhesive behavior and extended blood circulation time. Cationic PELs derived from PASA are rapidly internalized by mammalian and bacterial cells, and hence have immense utility in therapeutic delivery applications. Polyelectrolyte complexes (PECs) and multilayers (PEMs) formed from PASA PELs have further expanded their biomedical utility. This mini-review highlights some recent literature examples of unique biomedical applications of PELs, PECs and PEMs prepared through the molecular engineering of PASA. It discusses biomineralization modulators, anti-mycobacterial agents, underwater adhesives, mucoadhesive drug and gene delivery agents, and cell encapsulants fabricated using PASA derived PELs.

Persistent decrease of renal functional reserve in patients after cardiac surgery-associated acute kidney injury despite clinical recovery.

Background: Cardiac surgery is a leading cause of acute kidney injury (AKI). Such AKI patients may develop progressive chronic kidney disease (CKD). Others, who appear to have sustained no permanent loss of function (normal serum creatinine), may still lose renal functional reserve (RFR). Methods: We extended the follow-up in the observational 'Preoperative RFR Predicts Risk of AKI after Cardiac Surgery' study from hospital discharge to 3 months after surgery for 86 (78.2%) patients with normal baseline estimated glomerular filtration rate (eGFR), and re-measured RFR with a high oral protein load. The primary study endpoint was change in RFR. Study registration at clinicaltrials.gov Identifier: NCT03092947, ISRCTN Registry: ISRCTN16109759. Results: At 3 months, three patients developed new CKD. All remaining patients continued to have a normal eGFR (93.3 ± 15.1 mL/min/1.73 m2). However, when stratified by post-operative AKI and cell cycle arrest (CCA) biomarkers, AKI patients displayed a significant decrease in RFR {from 14.4 [interquartile range (IQR) 9.5 - 24.3] to 9.1 (IQR 7.1 - 12.5) mL/min/1.73 m2; P < 0.001} and patients without AKI but with positive post-operative CCA biomarkers also experienced a similar decrease of RFR [from 26.7 (IQR 22.9 - 31.5) to 19.7 (IQR 15.8 - 22.8) mL/min/1.73 m2; P < 0.001]. In contrast, patients with neither clinical AKI nor positive biomarkers had no such decrease of RFR. Finally, of the three patients who developed new CKD, two sustained AKI and one had positive CCA biomarkers but without AKI. Conclusions: Among elective cardiac surgery patients, AKI or elevated post-operative CCA biomarkers were associated with decreased RFR at 3 months despite normalization of serum creatinine. Larger prospective studies to validate the use of RFR to assess renal recovery in combination with biochemical biomarkers are warranted.

Clinical and Etiological Profile of Fever with Thrombocytopenia - A Tertiary Care Hospital Based Study.

Objectives: Febrile thrombocytopenia is a condition commonly caused by infections. The present study is intended to know the underlying etiology of fever with thrombocytopenia, the various presentations and complications in our community. Material and Methods: A cross-sectional epidemiological study was conducted including 1217 patients aged more than 14 years with fever and thrombocytopenia admitted in the medical wards from October 2013 to September 2014. Detailed clinical examination and routine investigations were done; specific investigations like blood culture, widal test, antigen test for malaria, IgM ELISA leptospira, IgM ELISA dengue, bone marrow aspiration/biopsy etc. were done as and when indicated. The data are presented as percentage and numbers. Rates and ratios are computed. Results: Infection was the commonest cause of thrombocytopenia and dengue was the commonest of the infections followed by malaria. Bleeding manifestations were seen in 42.7% of patients. 91.40% of patients with bleeding tendencies had petechiae/purpura as the commonest bleeding manifestation, followed by spontaneous bleeding in 57%. Spontaneous bleeding was noted when platelet counts were less than 20,000. Petechiae/Purpura were seen more commonly when platelet count was in the range of less than or equal to 50,000. Good recovery was noted in 95%, while 5% had mortality. Septicemia accounted for 85.24% of deaths followed by malaria (6.55%) and dengue (5%). Conclusion: Fever with thrombocytopenia is an important clinical condition commonly caused by infections, particularly dengue and malaria. In majority of patients thrombocytopenia was transient and asymptomatic, but in significant number of cases there were bleeding manifestations. On treating the specific cause drastic improvement in platelet count was noted. Mortality in febrile thrombocytopenia is not directly associated with degree of thrombocytopenia but with concomitant involvement of other organs leading to multiorgan dysfunction.

Preoperative Renal Functional Reserve Predicts Risk of Acute Kidney Injury After Cardiac Operation.

BACKGROUND: Although acute kidney injury (AKI) frequently complicates cardiac operations, methods to determine AKI risk in patients without underlying kidney disease are lacking. Renal functional reserve (RFR) can be used to measure the capacity of the kidney to increase glomerular filtration rate under conditions of physiologic stress and may serve as a functional marker that assesses susceptibility to injury. We sought to determine whether preoperative RFR predicts postoperative AKI. METHODS: We enrolled 110 patients with normal resting glomerular filtration rates undergoing elective cardiac operation. Preoperative RFR was measured by using a high oral protein load test. The primary end point was the ability of preoperative RFR to predict AKI within 7 days of operation. Secondary end points included the ability of a risk prediction model, including demographic and comorbidity covariates, RFR, and intraoperative variables to predict AKI, and the ability of postoperative cell cycle arrest markers at various times to predict AKI. RESULTS: AKI occurred in 15 patients (13.6%). Preoperative RFR was lower in patients who experienced AKI (p < 0.001) and predicted AKI with an area under the receiver operating characteristic curve (AUC) of 0.83 (95% confidence interval [CI]: 0.70 to 0.96). Patients with preoperative RFRs not greater than 15 mL · min-1 · 1.73 m-2 were 11.8 times more likely to experience AKI (95% CI: 4.62 to 29.89 times, p < 0.001). In addition, immediate postoperative cell cycle arrest biomarkers predicted AKI with an AUC of 0.87. CONCLUSIONS: Among elective cardiac surgical patients with normal resting glomerular filtration rates, preoperative RFR was highly predictive of AKI. A reduced RFR appears to be a novel risk factor for AKI, and measurement of RFR preoperatively can identify patients who are likely to benefit from preventive measures or to select for use of biomarkers for early detection. Larger prospective studies to validate the use of RFR in strategies to prevent AKI are warranted. ClinicalTrials.gov identifier: NCT03092947, ISRCTN Registry: ISRCTN16109759.

Characterization of ML0314c of Mycobacterium leprae and deciphering its role in the immune response in leprosy patients.

Mycobacterium leprae has a reduced genome size due to the reductive evolution over a long period of time. Lipid metabolism plays an important role in the life cycle and pathogenesis of this bacterium. In comparison to 26 lip genes (Lip A-Z) of M. tuberculosis, M. leprae retained only three orthologs indicating their importance in its life cycle. ML0314c (LipU) is one of them. It is conserved throughout the mycobacterium species. Bioinformatics analysis showed the presence of an α/ß hydrolase fold and 'GXSXG' characteristic of the esterases/lipases. The gene was expressed in E. coli and purified to homogeneity. It showed preference towards short chain esters with pNP-acetate as the preferred substrate. The enzyme showed optimal activity at 45°C and pH8.0. ML0314c protein was stable between temperatures ranging from 20 to 60°C and pH5.0-8.0, i.e., relatively acidic and neutral conditions. The active site residues predicted bioinformatically were confirmed to be Ser168, Glu267, and His297 by site directed mutagenesis. E-serine, DEPC and Tetrahydrolipstatin (THL) completely inhibited the activity of ML0314c. The protein was localized in cell wall and extracellular medium. Several antigenic epitopes were predicted in ML0314c. Protein elicited strong humoral immune response in leprosy patients, whereas, a reduced immune response was observed in the relapsed cases. No humoral response was observed in treatment completed patients. Overexpression of ml0314c in the surrogate host M. smegmatis showed marked difference in the colony morphology and growth rate. In conclusion, ML0314c is a secretary carboxyl esterase that could modulate the immune response in leprosy patients.

[Fabry's disease: an example of cardiorenal syndrome type 5].

Fabry's disease (FD) is a severe congenital metabolic disorder characterized by the deficient activity of lysosomal exoglycohydrolase alpha-galactosidase, characterized by glycosphingolipid deposition in several cells, such as capillary endothelial cells, renal, cardiac, and nerve cells. As a systemic disease leading to a contemporaneous myocardial and renal dysfunction, FD might be an example of cardiorenal syndrome type 5 (CRS-5). Kidney damage is commonly characterized by proteinuria, isosthenuria and altered tubular function when occurs at the second-third decade, azotemia and end-stage renal disease in third-fifth decade. Beyond the irreversible glomerular, tubular and vascular damages, the podocytes foot process effacement is the major cause of kidney dysfunction. Myocardial damage is usually observed with right and left ventricular hypertrophy, arrhythmias (due to sinus node and conduction system impairment), diastolic dysfunction, congestive heart failure, myocardial ischemia, fibrosis and cardiac death. The enzymatic replacement therapy is essential for the management of FD, as well as the control of renal (with anti-proteinuric agents such as angiotensin-converting enzyme inhibitors- and/or angiotensin II receptor blockers), brain (coated aspirin, clopidogrel and statins to prevent strokes) and heart complications (calcium channel blockers for ischemic cardiomyopathy, warfarin and amiodarone or cardioverter device for arrhythmias).

mesT, a unique epoxide hydrolase, is essential for optimal growth of Mycobacterium tuberculosis in the presence of styrene oxide.

AIM: mesT of Mycobacterium tuberculosis, a hypothetical/putative epoxide hydrolase, is predicted to convert toxic epoxides to the more water-soluble and less toxic diols. Detailed characterization of the protein was carried out. RESULTS: mesT demonstrated esterase as well as epoxide hydrolase activity. It was membrane bound and was upregulated under hypoxic conditions. The enzyme was able to degrade styrene oxide. The presence of antisense against this gene resulted in the inhibition of in vitro bacterial growth/survival in the presence of styrene oxide. Conclusion & future perspective: We demonstrated that mesT possessed epoxide hydrolase activity and styrene oxide might be its physiological substrate. Inhibition of mesT reduced the growth of the bacteria in presence of styrene oxide and its expression under hypoxic condition suggested its role in intracellular survival of bacteria.

Ex vivo biomechanical evaluation of pigeon (Columba livia) cadaver intact humeri and ostectomized humeri stabilized with caudally applied titanium locking plate or stainless steel nonlocking plate constructs.

OBJECTIVE To evaluate mechanical properties of pigeon (Columba livia) cadaver intact humeri versus ostectomized humeri stabilized with a locking or nonlocking plate. SAMPLE 30 humeri from pigeon cadavers. PROCEDURES Specimens were allocated into 3 groups and tested in bending and torsion. Results for intact pigeon humeri were compared with results for ostectomized humeri repaired with a titanium 1.6-mm screw locking plate or a stainless steel 1.5-mm dynamic compression plate; the ostectomized humeri mimicked a fracture in a thin cortical bone. Locking plates were secured with locking screws (2 bicortical and 4 monocortical), and nonlocking plates were secured with bicortical nonlocking screws. Constructs were cyclically tested nondestructively in 4-point bending and then tested to failure in bending. A second set of constructs were cyclically tested non-destructively and then to failure in torsion. Stiffness, strength, and strain energy of each construct were compared. RESULTS Intact specimens were stiffer and stronger than the repair groups for all testing methods, except for nonlocking constructs, which were significantly stiffer than intact specimens under cyclic bending. Intact bones had significantly higher strain energies than locking plates in both bending and torsion. Locking and nonlocking plates were of equal strength and strain energy, but not stiffness, in bending and were of equal strength, stiffness, and strain energy in torsion. CONCLUSIONS AND CLINICAL RELEVANCE Results for this study suggested that increased torsional strength may be needed before bone plate repair can be considered as the sole fixation method for avian species.

Rationale for the Evaluation of Renal Functional Reserve in Living Kidney Donors and Recipients: A Pilot Study.

BACKGROUND: In living kidney transplantation, preoperative donors' renal functional reserve (RFR) may correlate with postoperative residual renal function in both donors and recipients. The aim of this study was to evaluate the donors' RFR before transplantation and to compare basal and stress renal function before and after transplantation in both donors and recipients. METHODS: Seven pairs of living kidney donors and recipients were considered for this observational study. RFR was measured with a renal stress test (RST) before and after the kidney transplantation through an oral protein loading test (1 g/kg of body weight). RFR was defined as the difference between the maximum value of creatinine clearance after protein load (stress glomerular filtration rate, sGFR) and baseline creatinine clearance (basal GFR, bGFR). RESULTS: Before transplantation, a significant difference between sGFR and bGFR (p = 0.04) was observed in donors, with an RFR = 30.6 (11.9-41.5) mL/min/1.73 m2. After kidney transplantation, sGFR was similar to bGFR for both donors and recipients (p = 0.13), with a limited RFR (7.9 [6.70-19.25] and 14.90 [-6.67 to 25.53] mL/min/1.73 m2, respectively). The sum of the donor's and recipient's post-transplant sGFR was similar to the pre-transplant donor's sGFR (p = 0.73). CONCLUSION: RST is a safe, feasible, easy, and an inexpensive tool that is able to quantify RFR. In living kidney transplantation, it can be used in clinical practice to measure the original global filtration capacity of the donor's kidneys (sGFR) and to quantify the susceptibility of donors and recipients in developing postoperative kidney dysfunction. However, further studies with an adequate sample size and follow-up period are needed to test this hypothesis.