Does Liposuction for Lymphedema Worsen Lymphatic Injury?

Liposuction for treatment of lymphedema is an effective and time-tested treatment. However, as there is a fear regarding further lymphatic damage caused by liposuction, we objectively compared lymphatic function pre- and post-liposuction. All patients with solid-predominant lymphedema who were treated during the study period of June 2014 and November 2018 were included. Patients were assessed using patient-reported baselines/outcomes, lymphedema- specific quality of life scale (LYMQOL), limb circumference/volume measurements, and indocyanine green lymphography (ICGL) preoperatively and at predefined postoperative time intervals. Fifty-seven limbs from 41 patients were included. Mean lipoaspirate volumes were 2035 mL, 5385 mL, and 3106 mL for the arm, thigh, and leg, respectively with a mean adipose fraction of the lipoaspirate of 71%. All patients underwent redundant skin excision with the "flying squirrel" technique. The mean follow-up was 10.7 months (range 3 - 48 months) with a mean limb volume reduction of 32.2% and all patients reporting satisfactory relief of symptoms. All showed statistically significant improvement in LYMQOL in symptoms, appearance, and function. On ICGL, none showed worsened lymphatic drainage, rather, all showed improved lymph drainage. Furthermore, the improved lymph drainage was found to be progressive during the study period in all patients. Our study results demonstrate that treating extremity lymphedema with liposuction does not worsen lymphatic function and in fact, paradoxically, it induces progressive improvement in lymph drainage.

Recent Advances in Sugarcane Genomics, Physiology, and Phenomics for Superior Agronomic Traits.

Advances in sugarcane breeding have contributed significantly to improvements in agronomic traits and crop yield. However, the growing global demand for sugar and biofuel in the context of climate change requires further improvements in cane and sugar yields. Attempts to achieve the desired rates of genetic gain in sugarcane by conventional breeding means are difficult as many agronomic traits are genetically complex and polygenic, with each gene exerting small effects. Unlike those of many other crops, the sugarcane genome is highly heterozygous due to its autopolyploid nature, which further hinders the development of a comprehensive genetic map. Despite these limitations, many superior agronomic traits/genes for higher cane yield, sugar production, and disease/pest resistance have been identified through the mapping of quantitative trait loci, genome-wide association studies, and transcriptome approaches. Improvements in traits controlled by one or two loci are relatively easy to achieve; however, this is not the case for traits governed by many genes. Many desirable phenotypic traits are controlled by quantitative trait nucleotides (QTNs) with small and variable effects. Assembling these desired QTNs by conventional breeding methods is time consuming and inefficient due to genetic drift. However, recent developments in genomics selection (GS) have allowed sugarcane researchers to select and accumulate desirable alleles imparting superior traits as GS is based on genomic estimated breeding values, which substantially increases the selection efficiency and genetic gain in sugarcane breeding programs. Next-generation sequencing techniques coupled with genome-editing technologies have provided new vistas in harnessing the sugarcane genome to look for desirable agronomic traits such as erect canopy, leaf angle, prolonged greening, high biomass, deep root system, and the non-flowering nature of the crop. Many desirable cane-yielding traits, such as single cane weight, numbers of tillers, numbers of millable canes, as well as cane quality traits, such as sucrose and sugar yield, have been explored using these recent biotechnological tools. This review will focus on the recent advances in sugarcane genomics related to genetic gain and the identification of favorable alleles for superior agronomic traits for further utilization in sugarcane breeding programs.

Probing the Electronic Structure of Hybrid Perovskites in the Orientationally Disordered Cubic Phase.

Hybrid organic-inorganic lead halide perovskites are projected as new generation photovoltaic and optoelectronic materials with improved efficiencies. However, their electronic structure so far remains poorly understood, particularly in the orientationally disordered cubic phase. We performed electronic structure investigations using angle-resolved photoemission spectroscopy on two prototypical samples (MAPbBr3 and MAPbCl3) in their cubic phase, and the results are compared with the calculations within two theoretical models where MA+ is orientationally (1) disordered (MA+ ion is replaced by spherically symmetric Cs+ ion) and (2) ordered (MA oriented along (100) direction) but keeping the symmetry of the unit cell cubic. Degeneracy of the valence bands and behavior of constant energy contours are consistent with model 1, which supports strongly the disordered nature of the orientation of the MA+ ions in the cubic phase. Band structure calculations also reveal that spin-orbit coupling induced Rashba splitting is suppressed by the orientational disorder.

The Interpeduncular Angle: A Practical and Objective Marker for the Detection and Diagnosis of Intracranial Hypotension on Brain MRI.

BACKGROUND AND PURPOSE: Classic findings of intracranial hypotension on MR imaging, such as brain stem slumping, can be variably present and, at times, subjective, potentially making the diagnosis difficult. We hypothesize that the angle between the cerebral peduncles correlates with the volume of interpeduncular cistern fluid and is decreased in cases of intracranial hypotension. We aimed to investigate its use as an objective assessment for intracranial hypotension. MATERIALS AND METHODS: Brain MRIs of 30 patients with intracranial hypotension and 30 age-matched controls were evaluated by 2 fellowship-trained neuroradiologists for classic findings of intracranial hypotension and the interpeduncular angle. Group analysis was performed with a Student t test, and receiver operating characteristic analysis was used to identify an ideal angle threshold to maximize sensitivity and specificity. Interobserver reliability was assessed for classic findings of intracranial hypotension using the Cohen κ value, and the interpeduncular angle, using the intraclass correlation. RESULTS: The interpeduncular angle had excellent interobserver reliability (intraclass correlation coefficient value = 0.833) and was significantly lower in the intracranial hypotension group compared with the control group (25.3° versus 56.3°; P < .001). There was significant correlation between the interpeduncular angle and the presence of brain stem slumping (P < .001) and in cases with ≥3 classic features of intracranial hypotension (P = .01). With a threshold of 40.5°, sensitivity and specificity were 80% and 96.7%, respectively. CONCLUSIONS: The interpeduncular angle is a sensitive and specific measure of intracranial hypotension and is a reliably reproducible parameter on routine clinical MR imaging.

Evaluation of effectiveness of Mass Vaccination Campaign against Peste des petits ruminants in Chhattisgarh state, India.

The study evaluated the effectiveness of 'Mass Vaccination Campaign (MVC)' implemented against the contagious transboundary OIE notified Peste des petits ruminants (PPR) in sheep and goats on the lines of 'pulse polio campaign' for humans in Chhattisgarh state, India. The effectiveness was evaluated on the axes of adequacy, financial viability under with and without MVC through differencing under various scenarios and options and programme impact from a farmer's perspective. The adequacy evaluation revealed that the reported outbreaks, diagnosed and death cases declined under PPR-MVC inconsonance with increased vaccination coverage. Furthermore, the seroconversion increased during post PPR-MVC implies elevated immunity levels in the sheep and goat population. The estimated mean mortality loss was USD 45.2 and USD 16.5 per animal in goats and sheep, respectively, whereas the treatment and opportunity cost of labour was USD 1.9 and USD 2.5 per animal respectively. Under the low PPR incidence scenario, benefit: cost ratio, net present value and internal rate of return were 4.9:1, 48.9 million USD and 146.6%, whereas it was 12.4:1,142.7 million USD and 430.4% and 13.5:1,156.7 million USD and 430.4% under medium and high incidence scenarios. Furthermore, the option of vaccinating 100% risk population during the first year followed by 30% during subsequent years to cover naïve population will maximize benefits than 100% coverage every year; nevertheless, benefits outweighs cost manifolds in both of these options. The farmers had a positive opinion on the overall services provided under PPR-MVC and the results provide the empirical evidence on effectiveness of 'mass vaccination' for its replication in other states of India or countries with similar socio-economic and rearing environments.

Adoption of potato varieties and their role for climate change adaptation in India.

Adoption of improved varieties is an important strategy to adapt to the negative implication associated with climate change and variability. However, incomplete data on varietal release and adoption is often the reality in many countries hindering informed decision-making on breeding and varietal dissemination strategies to effectively adapt to climate change. In taking the example of potatoes in India, we analyze the extent to which the potato sector is resilient to climate change. We do so by comparing state-level climate change projections with adoption of high resistant and tolerant potato varieties to major abiotic and biotic stresses. Release and adoption data was collected in 2016 in six expert elicitation workshops conducted with 130 experts from the potato value chain in Bihar, Gujarat, Karnataka, Punjab, Uttar Pradesh, and West Bengal. We found that from the total of 81 releases, 45 improved varieties are adopted in India and that in each state high resistant and tolerant varieties are cultivated providing some degree of varietal resilience. Early maturity has been the most important and heat tolerance is the least important trait. Comparing climate projections with adoption rates of high resistant and tolerant varieties, we found that Gujarat is relatively most resilient. In other states we found some mismatches between climate projections and adopted specific varietal traits. Our results allow policy-makers and breeders to better prioritize investments into breeding for specific traits and dissemination strategies.

Role of HAMP Genetic Variants on Pathophysiology of Iron Deficiency Anemia.

Hepcidin is a 25-amino acid peptide hormone produced by hepatocytes and plays a key role in body iron metabolism. Hepcidin deficiency is the cause of iron overload in hereditary hemochromatosis, iron-loading anemia, and its excess is associated with anemia of inflammation, chronic disease and iron deficiency anemia (IDA). The aims of this study was to evaluate HAMP gene mutation, namely IVS2 + 1(-G) (c.148-150 + 1del) and Gly71 Asp (c.212G > A (rs104894696) association with iron status in IDA conditions. Our study participants were 500 IDA patients and 550 age and sex-matched healthy controls. Hepcidin, ferritin and CRP analysis was done by ELISA method while ESR analysis was done according to Wintrobe method. CBC analysis was done by auto-analyzer. Two mutations in the HAMP genes were analysed by PCR RFLP method. Among the IDA patients, 7 were heterozygous for Met50del IVS2 + 1(-G) mutation. Nine IDA patients were heterozygous for G71D G-A mutation and homozygous were not identified in both mutations.Controls were showing heterozygous frequency 1.8 and 2.1% of Met50del IVS2 + 1(-G) and G71D G-A mutations respectively. Mutation of HAMP (Met50del IVS2 + 1(-G) and G71D G-A) were clinically associated with IDA and act as modulator of disease.

Prevalence of Factor V Leiden-G1691A and MTHFR-C677T Thrombosis Gene Modifier in Iron Deficiency Anemia: A Pathophysiological Effect in Indian Isolates.

Normal iron levels are required to prevent thrombocytosis by inhibiting thrombopoiesis. Thrombocytosis is usually associated with a mild iron deficiency and is the result of a lack of inhibition of thrombopoiesis. Study participants were 430 iron deficiency anemia (IDA) patients. Ten (10) mL of venous blood were collected for the subjects. Ferritin analysis was done by ELISA method while Hemogram analysis was done by auto-analyzer. Factor V Leiden, PRTG20210A, and MTHFR C677T genotype analysis was performed by PCR-RFLP method. Among the patients, 9 were heterozygous (G>A) and 2 were homozygous (A>A) carrier of FV Leiden; while 20 were heterozygous (C>T) and 3 were homozygous (T>T) for MTHFR polymorphism. None of the patient was identified with PT mutation. Patients with thrombosis gene marker had lower hemoglobin, mean corpuscular volume, mean corpuscular haemoglobin levels, and mean corpuscular hemoglobin concentration than patients without thrombosis gene marker. Serum ferritin was elevated in subject with the absence of thrombosis gene markers. Our data suggest a high impact of inherited hypercoagulability risk factors in the pathogenesis of IDA and its complications.

SPINK1 promotes colorectal cancer progression by downregulating Metallothioneins expression.

Colorectal cancer (CRC) is the third most common cancer in the world, and second leading cause of cancer deaths in the US. Although, anti-EGFR therapy is commonly prescribed for CRC, patients harboring mutations in KRAS or BRAF show poor treatment response, indicating an ardent demand for new therapeutic targets discovery. SPINK1 (serine peptidase inhibitor, Kazal type 1) overexpression has been identified in many cancers including the colon, lung, breast and prostate. Our study demonstrates the functional significance of SPINK1 in CRC progression and metastases. Stable knockdown of SPINK1 significantly decreases cell proliferation, invasion and soft agar colony formation in the colon adenocarcinoma WiDr cells. Conversely, an increase in these oncogenic phenotypes was observed on stimulation with SPINK1-enriched conditioned media (CM) in multiple benign models such as murine colonic epithelial cell lines, MSIE and YAMC (SPINK3-negative). Mechanistically, SPINK1 promotes tumorigenic phenotype by activating phosphatidylinositol 3-kinase (PI3K/AKT) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathways, and the SPINK1-positive WiDr cells are sensitive to AKT and MEK inhibitors. Importantly, SPINK1 silencing mediated upregulation of various Metallothionein isoforms, considered as tumor suppressors in CRC, confer sensitivity to doxorubicin, which strengthens the rationale for using the combinatorial treatment approach for the SPINK1-positive CRC patients. Furthermore, in vivo studies using chicken chorioallantoic membrane assay, murine xenograft studies and metastasis models further suggest a pivotal role of SPINK1 in CRC progression and metastasis. Taken together, our study demonstrates an important role for the overexpressed SPINK1 in CRC disease progression, a phenomenon that needs careful evaluation towards effective therapeutic target development.

Clarithromycin enhances the antimalarial efficacy of mefloquine via its increased bioavailability and disrupting P. falciparum apicoplast.

AIM: Many important drugs like mefloquine are not being used because of the development of resistance and other related issues. In the present study, we aimed to control drug resistance by using combination therapy and tried to understand the mechanism involved. MATERIAL AND METHODS: We have explored in vitro interaction of clarithromycin (CLTR), and mefloquine (MQ) against Pf3D7 and PfK1 strains. Bioavailability of MQ in parasitized RBC lysate was checked in the presence/absence of CLTR using HPLC method. Further tufA mRNA/protein expression was investigated to know the effect of both drugs on apicoplast by using qPCR and Western blotting. KEY FINDINGS: MQ and CLTR inhibited growth of Pf3D7 and PfK1. CLTR showed its delayed antimalarial effect by its low IC50 values in the second cycle which indicates its effect on apicoplast. Downregulation of tufA expression on both mRNA and protein level supports this hypothesis. MQ and CLTR showed synergism/additiveness (mean ∑FICs = 0.89 and 1.26) against Pf3D7 and PfK1 respectively. It is evidenced from HPLC data that CLTR might have reduced metabolism of MQ in Plasmodium falciparum, leading to increased levels of MQ to produce enhanced antimalarial activity. The metabolism of CLTR is also reduced may be due to competitive metabolism of MQ via CYP3A4. SIGNIFICANCE: The present study reveals that broad spectrum biological activities (i.e. antimalarial and antiviral) of MQ can be saved by using suitable partner drug like CLTR. This study also shows that CLTR increases the concentration of MQ and disrupts the apicoplast.

Synthesis, spectroscopic, thermal and antimicrobial studies of neodymium(III) and samarium(III) complexes derived from tetradentate ligands containing N and S donor atoms.

Trivalent lanthanide complexes of the type [Ln(L)Cl(H2O)2] (where Ln=Nd(III) or Sm(III) and LH2=Schiff bases derived by the condensation of 3-(phenyl/substitutedphenyl)-4-amino-5-mercapto-1,2,4-triazole with diacetyl/benzil) have been synthesized by the reactions of anhydrous lanthanide(III) chloride with Schiff bases in methanol. The structures of the complexes have been proposed on the basis of elemental analysis, electrical conductance, magnetic moment, spectroscopic measurements (IR, 1H, 13C NMR and UV-vis spectra) and X-ray diffraction studies. The spectral data reveal that the Schiff base ligands behave as dibasic tetradentate chelating agents having coordination sites at two thiol sulfur atoms and two azomethine nitrogen atoms. The presence of coordinated water in metal complexes was confirmed by thermal and IR data of the complexes. All the Schiff bases and their metal complexes have also been screened for their antibacterial activity against Bacillus subtilis, Staphylococcus aureus and antifungal activities against Aspergillus niger, Curvularia pallescens and Colletotrichum capsici.

Flow Characteristics of Distinctly Viscous Multilayered Intestinal Fluid Motion.

The goal of this investigation is to study the three layered (core layer, intermediate layer, and peripheral layer) tubular flow of power law fluids with variable viscosity by peristalsis in order to investigate the strength of the role played by an artificially generated intermediate layer to ease constipation. The solution is carried out under the long wavelength and low Reynolds number approximations in the wave frame of reference as the flow is creeping one. The stream functions for each layer such as core layer, intermediate layer, and peripheral layer are determined. The expressions for axial pressure gradient, interfaces, trapping, and reflux limits are obtained. The effects of power law index and viscosities on pressure across one wavelength, mechanical efficiency, and trapping are discussed numerically. It is found that the pressure required to restrain flow rates and the mechanical efficiency increase with the viscosities of the intermediate and peripheral layers as well as with the flow behaviour index. It is observed that the axisymmetric flow in intestines is less prone to constipation than two-dimensional flow and may be more easily overcome with introducing a viscous intermediate layer.

Investigation of thermoelectric properties of half-metallic Co2MnGe by using first principles calculations.

By combining the electronic structures obtained from first principles calculations with Boltzmann transport theory we have investigated the electronic, magnetic and transport properties of the Co2MnGe Heusler compound. The density of state plots, dispersion curves and the total energy of paramagnetic and ferromagnetic (FM) phases clearly show the half-metallic FM ground state for the compound, with an indirect band gap of about 400 meV in the minority spin channel. It has an integer value of the magnetic moment equal to 5 µ(B). In the FM phase a very large value (∼ 550 µV K(-1)) of the Seebeck coefficient (S) is obtained for down-spin electrons due to the existence of an almost flat conduction band along X in the Γ direction. The two-current model has been used to find the total S and the obtained value is about 10 µV K(-1). The calculated values of the Seebeck coefficient, resistivity and electronic thermal conductivity show nice agreement with the experimental results.

Non-steady peristaltic propulsion with exponential variable viscosity: a study of transport through the digestive system.

A theoretical study is presented for transient peristaltic flow of an incompressible fluid with variable viscosity in a finite length cylindrical tube as a simulation of transport in physiological vessels and biomimetic peristaltic pumps. The current axisymmetric analysis is qualitatively similar to two-dimensional analysis but exhibits quantitative variations. The current analysis is motivated towards further elucidating the physiological migration of gastric suspensions (food bolus) in the human digestive system. It also applies to variable viscosity industrial fluid (waste) peristaltic pumping systems. First, an axisymmetric model is analysed in the limit of large wavelength ([Formula: see text]) and low Reynolds number ([Formula: see text]) for axial velocity, radial velocity, pressure, hydromechanical efficiency and stream function in terms of radial vibration of the wall ([Formula: see text]), amplitude of the wave ([Formula: see text]), averaged flow rate ([Formula: see text]) and variable viscosity ([Formula: see text]). Subsequently, the peristaltic flow of a fluid with an exponential viscosity model is examined, which is based on the analytical solutions for pressure, wall shear stress, hydromechanical efficiency and streamline patterns in the finite length tube. The results are found to correlate well with earlier studies using a constant viscosity formulation. This study reveals some important features in the flow characteristics including the observation that pressure as well as both number and size of lower trapped bolus increases. Furthermore, the study indicates that hydromechanical efficiency reduces with increasing magnitude of viscosity parameter.

Association of HLA-G promoter and 14-bp insertion-deletion variants with acute allograft rejection and end-stage renal disease.

The aim of this study was to investigate the HLA-G 14-bp insertion/deletion (I/D) polymorphism among end-stage renal disease (ESRD) patients. Cytomegalovirus (CMV) infection, acute allograft rejection (AR) and overall survival after renal transplantation was investigated in 300 ESRD patients and 302 age, sex and ethnicity-matched controls. Sequencing was performed to evaluate the impact of HLA-G promoter region single-nucleotide polymorphisms (SNPs) whereas semi-quantitative PCR method was used to determine the probable HLA-G expression pattern among ESRD and AR cases. Further, soluble human leukocyte antigen (HLA)-G (sHLA-G) expression levels were compared in AR vs non-AR cases in the light of HLA-G 14-bp I/D polymorphism. Increased risk was found for 14-bp D/D (deletion-DD) genotype and 14-bp D allele [DD: odds ratio (OR) = 1.46, 95% confidence interval (CI) = 1.03-2.06, P value = 0.0358; D: OR = 1.29, 95% CI = 1.03-1.62, P value = 0.0277], respectively for ESRD and CMV infection (DD: OR = 2.70, 95% CI = 1.45-5.05, P value = 0.0021; D: OR = 1.94, 95% CI = 1.22-3.08, P value = 0.0052). Nearly fourfold (OR = 3.62, 95%CI = 1.61-8.14, p = 0.0039) risk was observed for 14-bp I/I (insertion-II) genotype for AR. Survival analysis showed increased overall survival (OS) (AR or death) for 14-bp D/D genotype. HLA-G promoter region sequencing was carried out among 60 ESRD patients and 100 normal controls which showed increased risk for -964 G>A, -725 C>G/T and -486 A>C SNPs. -964 G>A and -725 C>G/T SNPs showed risk association for AR patients. High level of HLA-G transcripts was observed among non-AR patients. Further soluble HLA-G (sHLA-G) showed increased levels in ESRD patients (mean ± SEM; 62.16 ± 2.43 U/ml) as compared to controls (mean ± SEM; 21.06 ± 3.89 U/ml) (P = <0.0001). The 14-bp I/I, 14-bp I/D and 14-bp D/D genotypes showed significantly higher levels of sHLA-G among non-AR as compared to AR patients.