Steroid avoidance/withdrawal and maintenance immunosuppression in pediatric kidney transplantation.

BACKGROUND: Corticosteroids have been an integral part of maintenance immunosuppression for pediatric kidney transplantation. However, prolonged steroid therapy is associated with significant toxicities resulting in several SW/avoidance strategies in recent years. METHOD/OBJECTIVE: This comprehensive review aims to discuss steroid-related toxicities and the safety, efficacy, and benefit of steroid avoidance/withdrawal immunosuppression in pediatric kidney transplant recipients. RESULTS: Initial studies of SW/avoidance conducted in the setting of CSA and AZA showed an increased incidence of AR but no increase in graft loss or mortality with SW/avoidance maintenance immunosuppression. Studies performed under modern immunosuppression (induction therapy, Tac, and MMF) show no significant increase in AR or graft loss with SW/avoidance immunosuppression. Furthermore, SW/avoidance immunosuppression is associated with significant improvement in growth, BMI, BP control, and lipid profile in pediatric kidney transplant recipients. Despite these data, SW/avoidance remains controversial, and only 40% of pediatric kidney transplant recipients in the United States are currently on SW/avoidance maintenance immunosuppression. CONCLUSION: SW/avoidance maintenance immunosuppression is safe and associated with fewer side effects compared with steroid-inclusive maintenance immunosuppression in pediatric kidney transplant recipients.

Induction and maintenance immunosuppression in pediatric kidney transplantation-Advances and controversies.

Advances in immunosuppression have improved graft survival in pediatric kidney transplant recipients; however, treatment-related toxicities need to be balanced against the possibility of graft rejection. Several immunosuppressive agents are available for use in transplant recipients; however, the optimal combinations of agents remain unclear, resulting in variations in institutional protocols. Lymphocyte-depleting antibodies, specifically ATG, are the most common induction agent used for pediatric kidney transplantation in the US. Basiliximab may be used for induction in immunologically low-risk children; however, pediatric data are scarce. CNIs and antiproliferative agents (mostly Tac and mycophenolate in recent years) constitute the backbone of maintenance immunosuppression. Steroid-avoidance maintenance regimens remain controversial. Belatacept and mTOR inhibitors are used in children under specific circumstances such as non-adherence or CNI toxicity. This article reviews the indications, mechanism of action, efficacy, dosing, and side effect profiles of various immunosuppressive agents available for pediatric kidney transplantation.

Optical, Magnetic and Photocatalytic Activity Studies of Li, Mg and Sr Doped and Undoped Zinc Oxide Nanoparticles.

Nanoparticles of Li, Mg and Sr doped and undoped zinc oxide was prepared by simple precipitation method. The structural, optical, and magnetic properties of the samples were investigated by the Powder X-ray Diffraction (XRD), Scanning Electron Microscope (SEM), Transmission Electron Microscope (TEM), Fourier Transform Infrared (FTIR) spectroscopy, Ultra-violet Visible spectroscopy (UV-vis) spectra, Photoluminescence (PL) and Vibrational Sample Magnetometer (VSM). The Powder X-ray diffraction data confirm the formation of hexagonal wurtzite structure of all doped and undoped ZnO. The SEM photograph reveals that the pores availability and particles size in the range of 10 nm-50 nm. FTIR and UV-Visible spectra results confirm the incorporation of the dopant into the ZnO lattice nanostructure. The UV-Visible spectra indicate that the shift of blue region (lower wavelength) due to bandgap widening. Photoluminescence intensity varies with doping due to the increase of oxygen vacancies in prepared ZnO. The pure ZnO exist paramagnetic while doped (Li, Mg and Sr) ZnO exist ferromagnetic property. The photocatalytic activity of the prepared sample also carried out in detail.

Management of Intrauterine Contraception in Early Pregnancy.

OBJECTIVES: Women with rare intrauterine contraception (IUC) failures are advised to have their IUC removed because of the risk of poor obstetric outcomes with a retained IUC. Specifics regarding IUC removal in early pregnancy including techniques for removal, rates of success, and immediate pregnancy outcomes following removal are not well described, however. The objective of this study was to identify women with an IUC in early pregnancy examined at a tertiary care center with the primary objective of describing IUC removal attempts, IUC removal successes, and pregnancy outcomes at 20 weeks following IUC removal. METHODS: Case series of women with concurrent IUC and early pregnancy who presented to a tertiary care ultrasound center by 12 weeks' gestation. RESULTS: A total of 3116 women had an early pregnancy ultrasound during the study period. Nineteen (19/3116, 0.61%) women underwent ultrasounds that identified a pregnancy before 12 weeks and an IUC in the uterus. A copper IUC was identified in 11 women (11/19, 58%) on their first ultrasound, and a levonogestrel IUC was identified in 5 women (5/19, 26%). Seventeen (17/19, 88%) women attempted to remove their IUC; 11 of 69 (69%) were successfully removed on the first attempt. Fourteen (14/19; 74%) women with an IUC examined by 12 weeks' gestation had an ongoing pregnancy at 20 weeks compared with 1782 (1782/2678, 67%; P = 0.209) women without an IUC. CONCLUSIONS: Pregnancy with IUC is rare. Among the 19 women who were found to have an in situ IUC and early pregnancy, most had a successful IUC removal and had an ongoing pregnancy at 20 weeks' gestation. In our case series, IUC removal in the first trimester was a straightforward procedure and likely successful.

Prevention and management of CMV infection in pediatric solid organ transplant recipients.

Human cytomegalovirus (CMV) remains one of the most common opportunistic infections following solid organ transplantation in children. CMV causes morbidity and mortality through direct tissue-invasive disease and indirect immunomodulatory effects. In recent years, several new agents have emerged for the prevention and treatment of CMV disease in solid organ transplant recipients. However, pediatric data remain scarce, and many of the treatments are extrapolated from the adult literature. Controversies exist about the type and duration of prophylactic therapies and the optimal dosing of antiviral agents. This review provides an up-to-date overview of treatment modalities used to prevent and treat CMV disease in solid organ transplant (SOT) recipients.

BRAFV600E-mutated serrated colorectal neoplasia drives transcriptional activation of cholesterol metabolism.

BRAF mutations occur early in serrated colorectal cancers, but their long-term influence on tissue homeostasis is poorly characterized. We investigated the impact of short-term (3 days) and long-term (6 months) expression of BrafV600E in the intestinal tissue of an inducible mouse model. We show that BrafV600E perturbs the homeostasis of intestinal epithelial cells, with impaired differentiation of enterocytes emerging after prolonged expression of the oncogene. Moreover, BrafV600E leads to a persistent transcriptional reprogramming with enrichment of numerous gene signatures indicative of proliferation and tumorigenesis, and signatures suggestive of metabolic rewiring. We focused on the top-ranking cholesterol biosynthesis signature and confirmed its increased expression in human serrated lesions. Functionally, the cholesterol lowering drug atorvastatin prevents the establishment of intestinal crypt hyperplasia in BrafV600E-mutant mice. Overall, our work unveils the long-term impact of BrafV600E expression in intestinal tissue and suggests that colorectal cancers with mutations in BRAF might be prevented by statins.

Artificial intelligence applications in different imaging modalities for corneal topography.

Interpretation of topographical maps used to detect corneal ectasias requires a high level of expertise. Several artificial intelligence (AI) technologies have attempted to interpret topographic maps. The purpose of this study is to provide a review of AI algorithms in corneal topography from the perspectives of an eye care professional, a biomedical engineer, and a data scientist. A systematic literature review using Web of Science, Pubmed, and Google Scholar was performed from 2010 to 2020 on themes regarding imaging modalities, their parameters, purpose, and conclusions and their samples and performance related to AI in corneal topography. We provide a comprehensive summary of advances in corneal imaging and its applications in AI. Combined metrics from the Dual Scheimpflug and Placido device could be a good starting point to try AI models in corneal imaging systems. The range of area under the receiving operating curve for AI in keratoconus detection and classification was from 0.87 to 1, sensitivity was from 0.89 to 1, and specificity was from 0.82 to 1. A combination of different types of AI applications to corneal ectasia diagnosis is recommended.

An Artificial Intelligence-Based Bio-Medical Stroke Prediction and Analytical System Using a Machine Learning Approach.

Stroke-related disabilities can have a major negative effect on the economic well-being of the person. When left untreated, a stroke can be fatal. According to the findings of this study, people who have had strokes generally have abnormal biosignals. Patients will be able to obtain prompt therapy in this manner if they are carefully monitored; their biosignals will be precisely assessed and real-time analysis will be performed. On the contrary, most stroke diagnosis and prediction systems rely on image analysis technologies such as CT or MRI, which are not only expensive but also hard to use. In this study, we develop a machine learning algorithm for the prediction of stroke in the brain, and this prediction is carried out from the real-time samples of electromyography (EMG) data. The study uses synthetic samples for training the support vector machine (SVM) classifier and then the testing is conducted in real-time samples. To improve the accuracy of prediction, the samples are generated using the data augmentation principle, which supports training with vast data. The simulation is conducted to test the efficacy of the model, and the results show that the proposed classifier achieves a higher rate of classification accuracy than the existing methods. Furthermore, it is seen that the rate of precision, recall, and f-measure is higher in the proposed SVM than in other methods.

A study on the resting preference of mosquito species in wells in Vellore in Tamilnadu, South India.

The resting preferences of mosquito species was investigated in domestic wells. In addition to the routine adult surveys in human dwellings, adult collections were also made in domestic wells using an innovated equipment operating on the principles of spray sheet collections. Above the water surface, wells provide humid and dark microclimate along the inner walls. It has been observed that this microclimate provides very congenial resting place for few mosquito species; specially for the males and for the females between their gonotropic cycles. Larval collections in the wells did not reveal breeding of majority of the mosquito species collected by this technique. Investigations were conducted in 87 wells in 11 localities during 2005. A total of 4969 mosquitos were collected of which 69.1% (3441) were males and 30.9% (1528) were females. From among the mosquitos collected 96.5% were Cu. quinquifasciatus, 0.26% All stephensi, 3.0% Aedes agypti and 0.24% Armegeres sp. The results of the analysis of the physical and chemical parameter of water samples of the study wells before and after the surveys endorsed the utility of this technique for entomological investigations in outbreak situations, for monitoring the liquidation of outbreak foci and for other research purposes.

Interval Female Sterilization.

Female sterilization is relied on by nearly one in three women aged 35-44 years in the United States. Sterilization procedures are among the most common procedures that obstetrician-gynecologists perform. The most frequent sterilization procedures include postpartum tubal ligation, laparoscopic tubal disruption or salpingectomy, and hysteroscopic tubal occlusion. The informed consent process for sterilization is crucial and requires shared decision-making between the patient and the health care provider. Counseling should include the specific risks and benefits of the specific surgical approaches. Additionally, women should be counseled on the alternatives to sterilization, including intrauterine contraceptives and subdermal contraceptive implants. Complications, including unplanned pregnancy after successful female sterilization, are rare. The objectives of this Clinical Expert Series are to describe the epidemiology of female sterilization, access to postpartum sterilization, advances in interval sterilization techniques, and clinical considerations in caring for women requesting sterilization.

Resistance training performed at distinct angular velocities elicits velocity-specific alterations in muscle strength and mobility status in older adults.

BACKGROUND: The purpose of this study was to compare the effects of high and low velocity knee extension training on changes in muscle strength and mobility status in high-functioning older adults. METHODS: Twenty-six (16 female, 10 male) older adults (mean age of 65) were randomized to either 6weeks of low velocity resistance training (LVRT) performed at 75°/s or high velocity resistance training (HVRT) performed at 240°/s. Both groups performed 3 sets of knee extension exercises at maximal effort, 3 times a week. Muscle strength was assessed through a range of testing velocities on an isokinetic dynamometer. Mobility status was assessed with the short physical performance battery (SPPB) and myosin heavy chain (MyHC) transcript levels were quantified via qRT-PCR. RESULTS: From baseline to post-training, there were several significant (P<0.05) differences in muscle strength and functional characteristics in LVRT (n=13) and HVRT (n=13) groups. From baseline to post-training, MyHC-α mRNA and MyHC-IIa mRNA showed a significant (P<0.05) increase within HVRT but MyHC-IIx mRNA did not change significantly. Our results demonstrate HVRT provides a greater number of muscular enhancements when compared to LVRT, particularly under conditions of high velocity muscle contraction. CONCLUSION: HVRT is emerging as the optimal training stimulus for the older adult. The present study demonstrates, in addition to increased strength and functional outcomes, HVRT elicits a potentially therapeutic (i.e., slow to fast) transcriptional response in MyHC.

Three-dimensional ex vivo co-culture models of the leukaemic bone marrow niche for functional drug testing.

Acute myeloid leukaemia (AML) is a hierarchically structured malignancy in which aberrant leukemic stem cells drive the production of leukaemic blast cell clones. AML cells strictly depend on the bone marrow microenvironment (BMM) in which they reside. Classical AML cell cultures fail to mimic the BMM and, therefore, drug discovery studies are dominated by in vivo models. However, animal models are time consuming, labour intensive, provide limited mechanistic insight, and are unsuited for high-throughput studies, necessitating the development of novel AML models. The evolving ex vivo BMM-mimicking culture systems aim to fill this gap, with increasing success. Here, we discuss how AML-microenvironment co-culture models advance our understanding of this disease, and highlight their future potential for translational AML research.

Plectranthus amboinicus leaf extract mediated synthesis of zinc oxide nanoparticles and its control of methicillin resistant Staphylococcus aureus biofilm and blood sucking mosquito larvae.

In this study, zinc oxide nanoparticles were biologically synthesized using the leaf extract of Plectranthus amboinicus (Pam-ZnO NPs). The synthesized Pam-ZnO NPs were characterized by UV-Vis spectrophotometer, FTIR, TEM and XRD analysis. TEM analysis of Pam-ZnO NPs showed the average size of about 20-50 nm. Pam-ZnO NPs control the growth of methicillin-resistant Staphylococcus aureus biofilms (MRSA ATCC 33591) at the concentration of 8-10 µg/ml. Confocal laser scanning microscope (CLSM) images revealed that Pam-ZnO NPs strongly inhibited the biofilm forming ability of S. aureus. In addition, Pam-ZnO NPs showed 100% mortality of fourth instar mosquito larvae of Anopheles stephensi, Culex quinquefasciatus and Culex tritaeniorhynchus at the concentration of 8 and 10 µg/ml. The histopathological studies of Pam-ZnO NPs treated A. stephensi and C. quinquefasciatus larvae revealed the presence of damaged cells and tissues in the mid-gut. The damaged tissues suffered major changes including rupture and disintegration of epithelial layer and cellular vacuolization. The present study conclude that Pam-ZnO NPs showed effective control of S. aureus biofilms and mosquito larvae by damaging the mid gut cells.

Laser reflectance imaging of human organs and comparison with perfusion images.

Based on the principle of backscattering of laser radiation from tissues, a non-invasive PC-AT based reflectance imaging technique is developed. The laser beam from a semiconductor laser operating at 670 nm is guided to the tissue site by an optical fibre. The backscattered radiation is collected by another fibre placed in the same probe, and is detected by a photodiode-amplifier assembly. This probe is moved manually over the organs under observation, and the data after the ADC, interpolation and median filtering are displayed in the form of reflectance image of the organ along with grey scale. By this technique images of the human hands and forearms are obtained, which depend on the variations in their colour, composition and blood flow. A comparison is made with perfusion images, obtained by a Periflux laser Doppler flowmeter. These show that the reflectance images provide greater details of the tissue structure than the perfusion images.

Lung injury by furanoterpenoids isolated from Fusarium solani infected sweet potato, Ipomea batatas.

Intraperitoneal administration (1 mg/kg body/wt./day for 21 days) of crude extract of furanoterpenoids, isolated from F. solani damaged I. batatas caused pulmonary oedema in albino rats. The elevated broncho alveolar lavage (BAL) angiotensin converting enzyme (ACE), lactate dehydrogenase (LDH) and protein levels indicated lung damage. The estimation of pulmonary extracellular surfactant phospholipids showed an alteration in various phospholipid fractions.

Effect of chloroquine on rat liver mitochondria.

Chloroquine causes an increase in phospholipid and a decrease in cholesterol in liver mitochondria. A significant decrease in the activities of mitochondrial inner membrane enzymes such as NADH dehydrogenase, succinate dehydrogenase and cytochrome c oxidase is observed. Decrease in cytochrome contents and respiratory control ratio, shown by a decrease in state 3(+ADP) and an increase in state 4 (-ADP), implies decreased ATP synthesis following chloroquine administration. The results confirm drug-induced inhibition of mitochondrial respiration, thereby impairing availability and utilisation of energy.

Hypolipidemic activity of tincture of Crataegus in rats.

Tincture of Crataegus (TCR), an alcoholic extract of the berries of Crataegus oxyacantha, when administered to rats fed a hyperlipidemic diet (HLD), could prevent the elevation in plasma lipid levels. A significant decrease in lipid deposits in liver and aorta was also observed. Analysis of the plasma lipoprotein profile showed that TCR produced remarkable reduction in the increased levels of cholesterol, triglycerides and phospholipids in the low density lipoprotein (LDL) and very low density lipoprotein (VLDL) fractions in hyperlipidemic rats. Histological examination showed severe fatty vacuolation and degeneration of liver of HLD fed rats. TCR administration had an ameliorating effect on these changes. Agarose gel electrophoretic pattern of plasma lipoproteins also indicated that the drug brought down the raised levels of the atherogenic beta-lipoproteins in hyperlipidemic rats.

Quorum-quenching activity of the AHL-lactonase from Bacillus licheniformis DAHB1 inhibits Vibrio biofilm formation in vitro and reduces shrimp intestinal colonisation and mortality.

Vibrio parahaemolyticus is a significant cause of gastroenteritis resulting from the consumption of undercooked sea foods and often cause significant infections in shrimp aquaculture. Vibrio virulence is associated with biofilm formation and is regulated by N-acylated homoserine lactone (AHL)-mediated quorum sensing. In an attempt to reduce vibrio colonisation of shrimps and mortality, we screened native intestinal bacilli from Indian white shrimps (Fenneropenaeus indicus) for an isolate which showed biofilm-inhibitory activity (quorum quenching) against the pathogen V. parahaemolyticus DAHP1. The AHL-lactonase (AiiA) expressed by one of these, Bacillus licheniformis DAHB1, was characterised as having a broad-spectrum AHL substrate specificity and intrinsic resistance to the acid conditions of the shrimp intestine. Purified recombinant AiiA inhibited vibrio biofilm development in a cover slip assay and significantly attenuated infection and mortality in shrimps reared in a recirculation aquaculture system. Investigation of intestinal samples also showed that AiiA treatment also reduced vibrio viable counts and biofilm development as determined by confocal laser scanning microscopy (CLSM) imaging. These findings suggest that the B. licheniformis DAHB1 quorum-quenching AiiA might be developed for use as a prophylactic treatment to inhibit or reduce vibrio colonisation and mortality of shrimps in aquaculture.

cDNA cloning, characterization and expression analysis of a novel antimicrobial peptide gene penaeidin-3 (Fi-Pen3) from the haemocytes of Indian white shrimp Fenneropenaeus indicus.

A new member of antimicrobial peptide genes of the penaeidin family, penaeidin 3, was cloned from the haemocytes of Indian white shrimp Fenneropeneaus indicus (F. indicus), by reverse transcription PCR (RT-PCR) and rapid amplification of cDNA end (RACE-PCR) methods. The complete nucleotide sequence of cDNA clone of Indian white shrimp F. indicus Penaeidin 3 (Fi-Pen3) was 243bp long and has an open reading frame which encodes 80 amino acid peptide. The homology analysis of Fi-Pen3 sequence with other Penaeidins 3 shows higher similarity with Penaeus monodon (92%). The theoretical 3D structure generated through ab initio modelling indicated the presence of two-disulphide bridges in the alpha-helix. The signal peptide sequence of Fi-Pen3 is almost entirely homologous to that of other Penaeidin 3 of crustaceans, while differing relatively in the N-terminal domain of the mature peptide. The mature peptide has a predicted molecular weight of 84.9kDa, and a theoretical pI of 9.38. Phylogenetic analysis of Fi-Pen3 shows high resemblance with other Pen-3 from P. monodon, Litopenaeus stylirostris, Litopenaeus vannamei and Litopenaeus setiferus. Fi-Pen3 found to be expressed in haemocytes, heart, hepatopancreas, muscles, gills, intestine, and eyestalk with higher expression in haemocytes. Microbial challenge resulted in mRNA up-regulation, up to 6h post injection of Vibrio parahemolyticus. The Fi-Pen3 mRNA expression of F. indicus in the premolt stage (D(01) and D(02)) was significantly up-regulated than the postmolt (A and B) and intermolt stages (C). The findings of the present paper underline the involvement of Fi-Pen3 in innate immune system of F. indicus.

Pressurised air injury in a child.

We report the case of a 7 year old girl, who sustained accidental injury following injection of pressurized air from a bicycle tyre air nozzle. She presented with generalized subcutaneous emphysema along with pneumomediastinum, pneumothorax, pneumoperitoneum, pneumoretroperitoneum and pneumorra-chis. The child was recovered completely on conservative management.