Impact of occurrence of cardiac arrest in the donor on long-term outcomes of pediatric heart transplantation.

OBJECTIVE: The impact of cardiac arrest in the donor on long-term outcomes of pediatric heart transplantation has not been studied. METHODS: The UNOS database was queried for primary pediatric heart transplantation (1999-2020). The cohort was divided into recipients who received a cardiac allograft from a donor who had a cardiac arrest (CA) versus a donor who did not (NCA). Univariable and multivariable analysis was done to compare recipient outcomes, followed by survival analysis using the Kaplan-Meier method. RESULTS: A total of 7300 patients underwent heart transplantation, of which 579 (7.9%) patients belonged to the CA group. The CA group was younger (median 3 vs. 5 years, p < .001), male (51% vs. 47%, p = .03), and smaller in weight (13 vs. 17 kg, p < .001) and height (101 vs. 109 cm, p < .001) than the NCA group. The groups were similar in recipient heart failure diagnosis and blood type. The CA donors were younger (3 vs. 6 years, p < .001) versus nonwhite (48% vs. 45%, p = .003) and died from drowning and asphyxiation compared to blunt injury and intracranial hemorrhage in the NCA group. The left-ventricular ejection fraction was similar between the groups. There was no difference in VAD and ECMO use before the transplant. The listing status, waitlist days, and allograft ischemic times were similar. Posttransplant morbidity such as stroke, dialysis, pacemaker implantation, and treated rejection were similar. Donor cardiac arrest (hazard ratio = 0.93, p = .5) was not an independent predictor of mortality on multivariable analysis. There was no survival difference even beyond 20 years of follow-up between the groups (p = .88). CONCLUSION: The occurrence of donor cardiac arrest has no impact on long-term survival in pediatric heart transplant recipients.

National Fontan Operation short-term outcomes at or below 2-years-of-age compared to older than 2-years-of-age.

INTRODUCTION: Opinion is divided about optimal early timing of the Fontan Operation (FO). While some studies have suggested 3 years-of-age, others have shown good outcomes below 2 years-of-age. We analyzed the impact of age ≤2 years as compared age >2 years on short-term outcome of the FO using a large national database. METHODS: A retrospective analysis of the Kids Inpatient Database (2009-16) for the FO was done. The groups were divided into those who underwent FO at age ≤2 years (Early FO [EF]) as compared to age >2 years (Late FO [LF]). The data was abstracted for demographics, clinical characteristics, and operative outcomes. Standard statistical tests were used. RESULTS: A total of 3381 patients underwent FO during this period of which 1482 (44%) were EF. The mean ages of the EF and LF were 1.6 and 4.3, respectively (p < .001). LF were more likely to be non-White, female, and have Heterotaxy syndrome. HLHS was more common in EF. There was no difference in the discharge mortality, length of stay, disposition (majority went home), and mean total charges incurred. The overall discharge mortality was low at 0.7% (24/3381). In multivariate analysis: cardiac arrest, acute kidney injury, mechanical ventilation >96 h, endocardial cushion defect and non-White ethnicity were predictors of a mortality and not age. CONCLUSION: Contemporary outcomes for FO are excellent with equivalent short-term outcomes in both the age groups. Occurrence of postoperative complications, non-White ethnicity and endocardial cushion defect diagnosis were predictive of a negative outcome.

National outcomes of the Fontan operation with endocardial cushion defect.

BACKGROUND: The traditional outcomes of the Fontan operation (FO) in endocardial cushion defect (ECD) patients have been suboptimal. Previous studies have been limited by the smaller number of ECD patients, longer study period with an era effect, and do not directly compare short-term outcomes of FO in ECD patients with non-ECD patients. Our study aims to address these shortcomings. METHODS: A retrospective analysis of the Kids Inpatient Database (2009, 2012, and 2016) for the FO was done. The groups were divided into those who underwent FO with ECD as compared to non-ECD diagnosis. The data were abstracted for demographics, clinical characteristics, and operative outcomes. Standard statistical tests were used. RESULTS: Three thousand three hundred eighty patients underwent the FO of which 360 patients (11%) were FO-ECD. ECD patients were more likely to have Down syndrome, Heterotaxy syndrome, transposition/DORV, and TAPVR as compared to non-ECD patients. FO-ECD had a higher discharge-mortality (2.84% vs. 0.45%, p = .04). The length of stay (16 vs. 13 days, p = .05) and total charges incurred ($283, 280 vs. $234, 106, p = .03) for the admission were higher in the FO-ECD as compared to non-ECD patients. In multivariable analysis, ECD diagnosis, cardiac arrest, acute kidney injury, and postoperative hemorrhage were predictors of mortality. CONCLUSION: Contemporary outcomes for FO are excellent with very low overall operative mortality. However, the outcomes in ECD patients are inferior with higher operative mortality than in non-ECD patients. The occurrence of postoperation complications and a diagnosis of ECD were predictive of a negative outcome.

A High-Fidelity Percutaneous Model Used to Demonstrate ECMO Cannulation.

Medical simulation provides a realistic environment for practitioners to experience a planned clinical event in a controlled educational setting. We established a simulation model composed of synthetic ballistic gelatin that provided an inexpensive high-fidelity model for our extracorporeal membrane oxygenation (ECMO) team members to develop, master, and maintain clinical skills necessary for percutaneous cervical or femoral cannulation. The simulation component includes a cervical torso or femoral percutaneous synthetic gelatin model that is attached to either a static fluid model or to the high-fidelity perfusion simulator. Either model can be accessed with ultrasound guidance, cannulated with appropriately sized cannula, and connected to an in situ ECMO circuit. This article explains how the model is made and connected to the simulator with the purpose of re-creating this high-fidelity experience at any institution.

Important role of annexin A2 (ANXA2) in new blood vessel development in vivo and human triple negative breast cancer (TNBC) growth.

Development of new blood vessels in the tumor microenvironment is an essential component of tumor progression during which newly formed blood vessels nourish tumor cells and play a critical role in rapid tumor growth, invasion and metastasis. Nevertheless, how tumor cells develop new blood vessels in the tumor microenvironment (TME) have been enigmatic. Previously, we have shown specific overexpression of ANX A2 in TNBC cells regulates plasmin generation and suspected a role in neoangiogenesis. In this report, we used Matrigel plug model of in vivo angiogenesis and confirmed its role in new blood vessel development. Next, we tested if blocking of ANX A2 in aggressive human breast TME can inhibit angiogenesis and tumor growth in vivo. We showed that aggressive human breast tumor cells growing in nude mice can induce intense neoangiogenesis in the tumor mass. Blocking of ANXA2 significantly inhibited neoangiogenesis and resulted in inhibition of tumor growth. Interestingly, we identified that blocking of ANXA2 significantly inhibited tyrosine phosphorylation (Tyr-P) of ANXA2 implying its involvement in tyrosine signaling pathway and suggesting it may regulate angiogenesis. Taken together, our experimental evidence suggests that ANX A2 could be a novel strategy for disruption of tyrosine signaling and inhibition of neoangiogenesis in breast tumor.

Bioactive Oxylipins in Infants and Children With Congenital Heart Disease Undergoing Pediatric Cardiopulmonary Bypass.

OBJECTIVES: To determine the production of 9-hydroxyoctadecadienoic acid and 13-hydroxyoctadecadienoic acid during cardiopulmonary bypass in infants and children undergoing cardiac surgery, evaluate their relationship with increase in cell-free plasma hemoglobin, provide evidence of bioactivity through markers of inflammation and vasoactivity (WBC count, milrinone use, vasoactive-inotropic score), and examine their association with overall clinical burden (ICU/hospital length of stay and mechanical ventilation duration). DESIGN: Prospective observational study. SETTING: Twelve-bed cardiac ICU in a university-affiliated children's hospital. PATIENTS: Children were prospectively enrolled during their preoperative clinic appointments with the following criteria: greater than 1 month to less than 18 years old, procedures requiring cardiopulmonary bypass INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS: Plasma was collected at the start and end of cardiopulmonary bypass in 34 patients. 9-hydroxyoctadecadienoic acid, 13-hydroxyoctadecadienoic acid, plasma hemoglobin, and WBC increased. 9:13-hydroxyoctadecadienoic acid at the start of cardiopulmonary bypass was associated with vasoactive-inotropic score at 2-24 hours postcardiopulmonary bypass (R = 0.25; p < 0.01), milrinone use (R = 0.17; p < 0.05), and WBC (R = 0.12; p < 0.05). 9:13-hydroxyoctadecadienoic acid at the end of cardiopulmonary bypass was associated with vasoactive-inotropic score at 2-24 hours (R = 0.17; p < 0.05), 24-48 hours postcardiopulmonary bypass (R = 0.12; p < 0.05), and milrinone use (R = 0.19; p < 0.05). 9:13-hydroxyoctadecadienoic acid at the start and end of cardiopulmonary bypass were associated with the changes in plasma hemoglobin (R = 0.21 and R = 0.23; p < 0.01). The changes in plasma hemoglobin was associated with milrinone use (R = 0.36; p < 0.001) and vasoactive-inotropic score less than 2 hours (R = 0.22; p < 0.01), 2-24 hours (R = 0.24; p < 0.01), and 24-48 hours (R = 0.48; p < 0.001) postcardiopulmonary bypass. Cardiopulmonary bypass duration, 9:13-hydroxyoctadecadienoic acid at start of cardiopulmonary bypass, and plasma hemoglobin may be risk factors for high vasoactive-inotropic score. Cardiopulmonary bypass duration, changes in plasma hemoglobin, 9:13-hydroxyoctadecadienoic acid, and vasoactive-inotropic score correlate with ICU and hospital length of stay and/mechanical ventilation days. CONCLUSIONS: In low-risk pediatric patients undergoing cardiopulmonary bypass, 9:13-hydroxyoctadecadienoic acid was associated with changes in plasma hemoglobin, vasoactive-inotropic score, and WBC count, and may be a risk factor for high vasoactive-inotropic score, indicating possible inflammatory and vasoactive effects. Further studies are warranted to delineate the role of hydroxyoctadecadienoic acids and plasma hemoglobin in cardiopulmonary bypass-related dysfunction and to explore hydroxyoctadecadienoic acid production as a potential therapeutic target.

Annexin A2 (ANX A2): An emerging biomarker and potential therapeutic target for aggressive cancers.

ANX A2 is an important member of annexin family of proteins expressed on surface of endothelial cells (ECs), macrophages, mononuclear cells and various types of cancer cells. It exhibits high affinity binding for calcium (Ca++ ) and phospholipids. ANX A2 plays an important role in many biological processes such as endocytosis, exocytosis, autophagy, cell-cell communications and biochemical activation of plasminogen. On the cell surface ANX A2 organizes the assembly of plasminogen (PLG) and tissue plasminogen activator (tPA) for efficient conversion of PLG to plasmin, a serine protease. Proteolytic activity of plasmin is required for activation of inactive pro-metalloproteases (pro-MMPs) and latent growth factors for their biological actions. These activation steps are critical for degradation of extracellular matrix (ECM) and basement proteins (BM) for cancer cell invasion and metastasis. Increased expression of ANX A2 protein/gene has been correlated with invasion and metastasis in a variety of human cancers. Moreover, clinical studies have positively correlated ANX A2 protein expression with aggressive cancers and with resistance to anticancer drugs, shorter disease-free survival (DFS), and worse overall survival (OS). The mechanism(s) by which ANX A2 regulates cancer invasion and metastasis are beginning to emerge. Investigators used various technologies to target ANX A2 in preclinical model of human cancers and demonstrated exciting results. In this review article, we analyzed existing literature concurrent with our own findings and provided a critical overview of ANX A2-dependent mechanism(s) of cancer invasion and metastasis.

Highly atom-economical, catalyst-free, and solvent-free phosphorylation of chalcogenides.

Silica gel promoted, catalyst-free and solvent-free S-P, Se-P and Te-P bond formations are described. A variety of disulfides coupled with diarylphosphine oxides provide the corresponding phosphinothioates in excellent yields. For the first time, diselenides and ditellurides reacted with dialkyl phosphites under catalyst-free conditions to provide the corresponding phosphoroselenoates and phosphorotelluroates, respectively, in good to excellent yields.

Associations of Perioperative Renal Oximetry Via Near-Infrared Spectroscopy, Urinary Biomarkers, and Postoperative Acute Kidney Injury in Infants After Congenital Heart Surgery: Should Creatinine Continue to Be the Gold Standard?

OBJECTIVES: Examine the relationship between perioperative renal regional tissue oximetry, urinary biomarkers, and acute kidney injury in infants after congenital cardiac surgery with cardiopulmonary bypass. DESIGN: Prospective, observational. SETTING: Cardiac operating room and cardiac ICU. PATIENTS: Neonates and infants without history of kidney injury or anatomic renal abnormality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Renal regional tissue oximetry was measured intraoperatively and for 48 hours postoperatively. Urinary levels of neutrophil gelatinase-associated lipocalin and tissue inhibitor of metalloproteinases 2 together with insulin-like growth factor-binding protein 7 were measured preoperatively, 2, 12, and 24 hours postoperatively. Patients were categorized as no acute kidney injury, stage 1, or Stage 2-3 acute kidney injury using the Kidney Disease: Improving Global Outcomes criteria with 43 of 70 (61%) meeting criteria for any stage acute kidney injury. Stage 2-3 acute kidney injury patients had higher tissue inhibitor of metalloproteinases 2, insulin-like growth factor-binding protein 7 at 2 hours (0.3 vs 0.14 for stage 1 acute kidney injury and 0.05 for no acute kidney injury; p = 0.052) and 24 hours postoperatively (1.71 vs 0.27 for stage 1 acute kidney injury and 0.19 for no acute kidney injury, p = 0.027) and higher neutrophil gelatinase-associated lipocalin levels at 24 hours postoperatively (10.3 vs 3.4 for stage 1 acute kidney injury and 6.2 for no acute kidney injury, p = 0.019). Stage 2-3 acute kidney injury patients had lower mean cardiac ICU renal regional tissue oximetry (66% vs 79% for stage 1 acute kidney injury and 84% for no acute kidney injury, p = 0.038). Regression analyses showed that tissue inhibitor of metalloproteinases 2, insulin-like growth factor-binding protein 7 at 2 hours postoperatively and nadir intraoperative renal regional tissue oximetry to be independent predictors of postoperative kidney damage as measured by urinary neutrophil gelatinase-associated lipocalin. CONCLUSIONS: We observed modest differences in perioperative renal regional tissue oximetry and urinary biomarker levels compared between acute kidney injury groups classified by creatinine-dependent Kidney Disease: Improving Global Outcomes criteria, but there were significant correlations between renal regional tissue oximetry, tissue inhibitor of metalloproteinases 2, insulin-like growth factor-binding protein 7, and postoperative neutrophil gelatinase-associated lipocalin levels. Kidney injury after infant cardiac surgery may be undetectable by functional assessment (creatinine) alone, and continuous monitoring of renal regional tissue oximetry may be more sensitive to important subclinical acute kidney injury.

Heart Transplantation from Biventricular Support in Infant with Novel SMYD1 Mutation.

SET and MYND domain-containing protein 1 (SMYD1) has been shown to be responsible for the development of fast twitch and cardiac muscle. Mutations in SMYD1 have been shown to be uniformly fatal in laboratory studies, and not previously described in living humans. We describe here the care of an infant suffering from cardiac failure due to an SMYD1 mutation requiring biventricular assist devices as a bridge to successful heart transplantation. The patient is now doing well 2 years post-transplant and represents a known survivor of a suspected uniformly fatal genetic mutation.

A High-Fidelity Surgical Model and Perfusion Simulator Used to Demonstrate ECMO Cannulation, Initiation, and Stabilization.

Our high-fidelity simulation model provides a realistic example for health-care professionals to experience cannulation, initiation, and hemodynamic stabilization during extracorporeal membrane oxygenation (ECMO) therapy. This educational experience brings a variety of critical care specialties together, in a controlled simulation setting, to develop, master, and maintain clinical skills. This may include perfusionists, ECMO specialists, surgical technicians, registered nurses, physicians, and students. The simulation component includes a unique vascular access pad that is attached to either a static fluid model or to the Califia perfusion simulator system (Biomed Simulation, Inc., San Diego, CA). This collective high-fidelity simulation model can be surgically cannulated via a cutdown technique using an appropriately sized cannula and connected to an in situ ECMO circuit. This article explains the educational strategy, how the surgical pad is made, and the simulator connections so that any hospital can re-create this experience.

Survival and Long-Term Functional Outcomes for Children With Cardiac Arrest Treated With Extracorporeal Cardiopulmonary Resuscitation.

OBJECTIVES: To identify patient- and disease-related factors related to survival and favorable outcomes for children who underwent extracorporeal cardiopulmonary resuscitation after a refractory cardiac arrest. DESIGN: Retrospective observational study with prospective assessment of long-term functional outcome. PATIENTS: Fifty-six consecutive children undergoing extracorporeal cardiopulmonary resuscitation at our institution from 2007 to 2015. Median age at arrest was 3.5 months (interquartile range, 1-53). SETTING: Tertiary pediatric university hospital with a referral heart center. INTERVENTIONS: Health-related quality of life and family functioning assessment with the Pediatric Quality of Life Inventory and the McMaster Family Assessment Device. MEASUREMENTS AND MAIN RESULTS: Fifty-eight consecutive extracorporeal cardiopulmonary resuscitation episodes were included, with 46 (79.3%) related to primary cardiac conditions. Initial cannulation site was central in 19 (32.8%) and peripheral in 39 (67.2%). Survival to decannulation was 77.6% with survival at hospital discharge and at the end of the follow-up period being 65.5% and 62.1%, respectively. Time to follow-up was 38 months (interquartile range, 19-52). Patients who survived tended to be younger (3.5 mo [1 mo to 2 yr] vs 7 mo [1.25 mo to 17 yr]; p = 0.3) with decreased extracorporeal cardiopulmonary resuscitation times (28 min [15-47 min] vs 37.5 min [28.5-55 min]; p = 0.04). Those who received therapeutic hypothermia tended to have higher hospital survival (21/28 [75%] vs 16/29 [55%]; p = 0.08). Follow-up assessments of survivors demonstrated good quality of life and family functioning (Pediatric Quality of Life Inventory, 84 [76-89.5]; McMaster Family Assessment Device, 1.62 [1.33-1.83]). CONCLUSIONS: In this series, extracorporeal cardiopulmonary resuscitation was associated with relatively high survival rates and a good health-related quality of life and family functioning. Larger series are needed to assess whether this technique should be more broadly available in the pediatric critical care community.

Telemedicine in Pediatric Critical Care: A Retrospective Study in an International Extracorporeal Membrane Oxygenation Program.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is an invaluable rescue technique for critically ill children with imminent or present cardiopulmonary collapse. However, medical team expertise to optimize results and decrease complications is scarce. Telemedicine can be used to enhance the delivery of quality interventions. MATERIALS AND METHODS: This is a retrospective review of pediatric patients assisted with ECMO in the cardiac intensive care unit (CICU) at Fundación Cardiovascular de Colombia from July 2011 to June 2015 (telemedicine) compared with similar patients from a previous period (pretelemedicine). Collected information included demographic data, cardiac diagnosis, risk adjustment for congenital heart surgery (RACHS-1), hospital mortality, CICU and hospital length of stay (LOS), ECMO type, and ECMO run hours as well as specific telemedicine information. RESULTS: Fifty-seven patients in the pretelemedicine and 109 in the telemedicine periods were included in the analysis. Forty-nine teleconsulted patients received 218 teleconsultations, with a recommendation for diagnostic or interventional catheterization in 38 patients (77.5%). A surgical procedure for significant residual lesions was recommended in 30 patients (61.2%). Patients in the telemedicine period were older (4.7 months vs. 1.6 months, p = 0.006), more likely to receive operating room ECMO (43.1% vs. 24.6%, p = 0.02), and had a higher proportion of patients with two-ventricle physiology (73.4% vs. 54.4%, p = 0.013). Hospital survival was higher during the telemedicine period (54.1% vs. 29.8%, p = 0.002), with a longer hospital LOS (67 days vs. 28 days, p < 0.001). CONCLUSION: The implementation of telemedicine-assisted interventions in a pediatric ECMO program delivered valuable diagnostic and therapeutic advice, was associated with significant changes in selection criteria and model of care, and an increased hospital survival.

Cell-Free Plasma Hemoglobin and Male Gender Are Risk Factors for Acute Kidney Injury in Low Risk Children Undergoing Cardiopulmonary Bypass.

OBJECTIVES: To determine the relationship between the production of cell-free plasma hemoglobin and acute kidney injury in infants and children undergoing cardiopulmonary bypass for cardiac surgery. DESIGN: Prospective observational study. SETTING: Twelve-bed cardiac ICU in a university-affiliated children's hospital. PATIENTS: Children were prospectively enrolled during their preoperative outpatient appointment with the following criteria: greater than 1 month to less than 18 years old, procedures requiring cardiopulmonary bypass, no preexisting renal dysfunction. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma and urine were collected at baseline (in a subset), the beginning and end of cardiopulmonary bypass, and 2 hours and 24 hours after cardiopulmonary bypass in 60 subjects. Levels of plasma hemoglobin increased during cardiopulmonary bypass and were associated (p < 0.01) with cardiopulmonary bypass duration (R = 0.22), depletion of haptoglobin at end and 24 hours after cardiopulmonary bypass (R = 0.12 and 0.15, respectively), lactate dehydrogenase levels at end cardiopulmonary bypass (R = 0.27), and change in creatinine (R = 0.12). Forty-three percent of patients developed acute kidney injury. There was an association between plasma hemoglobin level and change in creatinine that varied by age (overall [R = 0.12; p < 0.01]; in age > 2 yr [R = 0.22; p < 0.01]; and in < 2 yr [R = 0.03; p = 0.42]). Change in plasma hemoglobin and male gender were found to be risk factors for acute kidney injury (odds ratio, 1.02 and 3.78, respectively; p < 0.05). CONCLUSIONS: Generation of plasma hemoglobin during cardiopulmonary bypass and male gender are associated with subsequent renal dysfunction in low-risk pediatric patients, especially in those older than 2 years. Further studies are needed to determine whether specific subgroups of pediatric patients undergoing cardiopulmonary bypass would benefit from potential treatments for hemolysis and plasma hemoglobin-associated renal dysfunction.

Selective Fusion of Heterogeneous Classifiers for Predicting Substrates of Membrane Transporters.

Membrane transporters play a crucial role in determining fate of administered drugs in a biological system. Early identification of plausible transporters for a drug molecule can provide insights into its therapeutic, pharmacokinetic, and toxicological profiles. In the present study, predictive models for classifying small molecules into substrates and nonsubstrates of various pharmaceutically important membrane transporters were developed using quantitative structure-activity relationship (QSAR) and proteochemometric (PCM) approaches. For this purpose, 4575 substrate interactions for these transporters were collected from the Metabolism and Transport Database (Metrabase) and the literature. The transporters selected for this study include (i) six efflux transporters, viz., breast cancer resistance protein (BCRP/ABCG2), P-glycoprotein (P-gp/MDR1), and multidrug resistance proteins (MRP1, MRP2, MRP3, and MRP4), and (ii) seven influx transporters, viz., organic cation transporter (OCT1/SO22A1), peptide transporter (PEPT1/SO15A1), apical sodium-bile acid transporter (ASBT/NTCP2), and organic anion transporting peptides (OATP1A2/SO1A2, OATP1B/SO1B1, OATP1B3/SO1B3, and OATP2B1/SO2B1). Various types of descriptors and machine learning methods (classifiers) were evaluated for the development of robust predictive models. Additionally, ensemble models were developed by bagging of homogeneous classifiers and selective fusion of heterogeneous classifiers. It was observed that the latter approach improves the accuracy of substrate/nonsubstrate prediction for transporters (average correct classification rate of more than 0.80 for external validation). Moreover, structural fragments important in determining the substrate specificity across the various transporters were identified. To demonstrate these fragments on the query molecule, contour maps were generated. The prediction efficacy of the developed models was illustrated by a good correlation between the reported logBB value of a molecule and its predicted substrate propensity for blood-brain barrier transporters. Conclusively, this comprehensive modeling analysis can be efficiently employed for the prediction of membrane transporters of a drug, thereby providing insights into its pharmacological profile.

Morphological and topographical anatomy of nutrient foramens in human metacarpals and their surgical importance.

PURPOSE: Trauma to the hand is extremely common, often resulting in metacarpal fractures and dislocations. The surgical intervention may be required for restoration of function and appearance. The preoperative, topographical knowledge of the nutrient foramens is valuable in such operative procedures to preserve the circulation for healing and good postoperative results. METHODS: The topographic and morphometric analysis of 250 non-pathological metacarpals (fifty each from first to fifth) was performed and the foraminal index of each metacarpal was evaluated. RESULTS: All the metacarpals were having single nutrient foramen except the second metacarpal which showed double nutrient foramens in two cases. The nutrient foramen was situated on the medial surface of first and second metacarpals and on lateral surface in third, fourth and fifth metacarpals in majority of the cases; however, their presence on anterior border (2.8%) was also noticed. The direction of the foramen was always away from the growing end. In 88, 98.1, 90, 94 and 100% of first to fifth consecutive metacarpals, foraminal index ranged between 33.3 and 66.6, indicating their presence on middle third of the shaft. CONCLUSIONS: Though the majority (94%) of foramens were present on the middle third of the shaft, their presence on the proximal (2.8%) and distal third (3.2%) of the shaft cannot be ruled out. The presence of nutrient foramens on the anterior border of third metacarpal has not been classically reported. This information may be important for radiologists to avoid misdiagnosing them as pathology.

Elicitation of Diosgenin Production in Trigonella foenum-graecum (Fenugreek) Seedlings by Methyl Jasmonate.

The effects of methyl jasmonate (MeJA), an elicitor of plant defense mechanisms, on the biosynthesis of diosgenin, a steroidal saponin, were investigated in six fenugreek (Trigonella foenum-graecum) varieties (Gujarat Methi-2, Kasuri-1, Kasuri-2, Pusa Early Branching, Rajasthan Methi and Maharashtra Methi-5). Treatment with 0.01% MeJA increased diosgenin levels, in 12 days old seedlings, from 0.5%-0.9% to 1.1%-1.8%. In addition, MeJA upregulated the expression of two pivotal genes of the mevalonate pathway, the metabolic route leading to diosgenin: 3-hydroxy-3-methylglutaryl-CoA reductase (HMG) and sterol-3-ß-glucosyl transferase (STRL). In particular, MeJA increased the expression of HMG and STRL genes by 3.2- and 22.2-fold, respectively, in the Gujarat Methi-2 variety, and by 25.4- and 28.4-fold, respectively, in the Kasuri-2 variety. Therefore, MeJA may be considered a promising elicitor for diosgenin production by fenugreek plants.

Butanolides from methanolic extract of Litsea glutinosa.

Phytochemical investigations of a MeOH extract obtained from the heartwoods of the Litsea glutinosa (Lauraceae) led to the isolation and characterization of four new butenolides, (3R,4S,5S)-2-hexadecyl-3-hydroxy-4-methylbutanolide 1, litsealactone C (2), and litsealactone D (4), litsealactone G (5), and a new benzoic acid derivative named eusmoside C (3). The structures of these compounds were elucidated on the basis of spectral studies.