Predictive modeling of pH on the transport of Co(II) Ions from aqueous solutions through supported ceramic polymer membrane.

Optimal pH is essential for efficient cobalt extraction from polymeric membrane systems, with D2EHPA used as an extractant for Co(II) at pH < 7, achieving 47% efficiency. The pH of piperazine as a stripping agent increases to a concentration of 0.48 M, and the extraction efficiency of Co(II) > 80%. Depending on the functional group of (C4H10N2), the optimal pH for separation was 9.8. The study revealed that pKa value was calculated to predict the ideal pH, and its value was 9.73, which is nearly to the pH, since the pH of the strip concentration and the properties of the membrane affect the extraction of cobalt at 30 °C. The partition ratio indicates the high distribution of the extract in supported ceramic polymer membrane (SCPM). The ceramic component provides mechanical strength and rigidity to the overall membrane structure, allowing it to withstand high pressures and temperatures during operation Study various factors such as the effect of pH on the ionization of the extract; effect of pH on band ionization; effect of pH on the temperature in the extract, effect of pH on the solute, effect of the band at different pH ranges and a comparison was made between the predictive model and experimental data that was proven through mathematical modeling using the MATLAB program.

Retraction: Urinary Bladder Hernia: A Rare Cause of Urinary Frequency.

[This retracts the article DOI: 10.7759/cureus.20993.].

Bullous pemphigoid in a previously healthy adolescent: a case report and literature review.

Introduction: Bullous pemphigoid (BP) is considered the most common bullous autoimmune disorder, characterized by autoantibodies directed against hemidesmosomes in the skin and mucous membranes. It usually affects elderly individuals in the sixth through eighth decades of life, with an average age at onset of 65 years. Only a few cases have been reported in children and teenagers. Case presentation: Herein, we report a 17-year-old boy who presented with a pruritic vesicular rash on his arms and legs accompanied by erythema. He was treated at the beginning with topical lotion and acyclovir, but the rash kept deteriorating and eventually bullae appeared, involving also his mouth. A dermatologist was consulted and diagnosed him with BP, and he was treated accordingly. Discussion: BP is the most prevalent autoimmune bullous illness, caused by autoantibodies against hemidesmosomes in the basement membrane of skin and mucosal surfaces, which in turn attract immune cells, including T-cells and neutrophils, and activate them, which causes damage to and separation of keratinocytes, resulting in the bullous formation. Diagnosis can be accomplished by recognizing clinical symptoms supported by histopathological and immunofluorescence testing. Steroids, whether topical or systemic, are the cornerstone treatment; depending on the extent of the disease, other immunosuppressant drugs can be used as a second line. Conclusion: BP manifestations are polymorphic; physicians should keep in mind that they may present with non-bullous, pruritic lesions, which may persist for some days to several months before bullae appear. Although this disease is rare in the young population, it should be considered in the differential diagnosis of bullous lesions.

Mutations in V-ATPase in follicular lymphoma activate autophagic flux creating a targetable dependency.

The recent discovery of recurrent gene mutations in chaperones or components of the vacuolar-type H+-translocating ATPase (V-ATPase) in follicular lymphoma (FL) was an unexpected finding. The application of whole exome sequencing and targeted gene re-sequencing has resulted in the identification of mutations in ATP6AP1, ATP6V1B2 and VMA21 in a combined 30% of FL, together constituting a major novel mutated pathway in this disease. Interestingly, no other human hematological malignancy carries these mutations at more than sporadic occurrences, implicating unique aspects of FL biology requiring these mutations. The mutations in ATP6V1B2 and VMA21 through separate mechanisms impair lysosomal V-ATPase activity resulting in an elevated lysosomal pH. The elevated lysosomal pH impairs protein and peptide hydrolysis and associates with reduced cytoplasmic amino acid concentrations resulting in compensatory activation of autophagic flux. The elevated autophagic flux constitutes a survival dependency for FL cells and can be targeted with inhibitors to ULK1 and multiple recently identified cyclin-dependent kinase inhibitors. Targeting autophagy alone or in combination with other targeted therapies constitutes a novel therapeutic opportunity for FL patients.

Follicular lymphoma-associated mutations in the V-ATPase chaperone VMA21 activate autophagy creating a targetable dependency.

The discovery of recurrent mutations in subunits and regulators of the vacuolar-type H+-translocating ATPase (V-ATPase) in follicular lymphoma (FL) highlights a role for macroautophagy/autophagy, amino-acid, and nutrient-sensing pathways in the pathogenesis of this disease. Here, we report on novel mutations in the ER-resident chaperone VMA21, which is involved in V-ATPase assembly in 12% of FL. Mutations in a novel VMA21 hotspot (p.93X) result in the removal of a C-terminal non-canonical ER retrieval signal thus causing VMA21 mislocalization to lysosomes. The resulting impairment in V-ATPase activity prevents full lysosomal acidification and function, including impaired pH-dependent protein degradation as shown via lysosomal metabolomics and ultimately causes a degree of amino acid depletion in the cytoplasm. These deficiencies result in compensatory autophagy activation, as measured using multiple complementary assays in human and yeast cells. Of translational significance, the compensatory activation of autophagy creates a dependency for survival for VMA21-mutated primary human FL as shown using inhibitors to ULK1, the proximal autophagy-regulating kinase. Using high-throughput microscopy-based screening assays for autophagy-inhibiting compounds, we identify multiple clinical grade cyclin-dependent kinase inhibitors as promising drugs and thus provide new rationale for innovative clinical trials in FL harboring aberrant V-ATPase.Abbreviations: ALs: autolysosomes; APs: autophagosomes; ER: endoplasmic reticulum; FL: follicular lymphoma; GFP: green fluorescent protein; IP: immunoprecipitation; LE/LY: late endosomes/lysosomes; Lyso-IP: lysosomal immunoprecipitation; OST: oligosaccharide transferase; prApe1: precursor aminopeptidase I; SEP: super ecliptic pHluorin; V-ATPase: vacuolar-type H+-translocating ATPase.

Urinary Bladder Hernia: A Rare Cause of Urinary Frequency.

Hernia repair is one of the most commonly performed surgical operations worldwide. Inguinal hernia is a common condition and has a high prevalence rate. Advanced age and male sex are the most important risk factors. Inguinal hernia usually presents with groin swelling with abdominal discomfort. We report the case of a 39-year-old man who presented to our urologic clinic with a complaint of urinary frequency for the last two months. This was associated with nocturia, feeling of incomplete emptying, and groin swelling. There was no history of hesitancy, intermittency, or weak stream. The patient was otherwise healthy with no significant previous medical or surgical history. Abdominal examination showed a right groin swelling with associated visible and palpable cough impulse in keeping with inguinal hernia. There was no abdominal guarding or rigidity, and the abdomen was non-tender. Examination of the genitalia was unremarkable. No abnormal findings were noted in the examination of other systems. Routine laboratory markers did not show any abnormalities. Urinalysis findings showed no leukocytes and had negative results for leukocyte esterase and nitrites. A computed tomography (CT) scan confirmed the presence of a right-sided inguinal hernia, with part of the urinary bladder seen herniating into the right inguinal canal. The patient underwent a laparoscopic surgery in which the herniated bladder was reduced and the defect was closed with a synthetic mesh. The patient recovered with no complications. Postoperatively, the patient reported significant improvement in his symptoms. Herniation of the bladder through the inguinal canal is an uncommon surgical condition. The case highlighted the importance of considering this diagnosis when they encounter a patient with unexplained lower urinary symptoms. Laparoscopic repair is a feasible and safe option if the surgical team was experienced with this approach.

Novel adsorbent based on carbon-modified zirconia/spinel ferrite nanostructures: Evaluation for the removal of cobalt and europium radionuclides from aqueous solutions.

Herein, a novel adsorbent based on carbon-modified zirconia/spinel ferrite (C@ ZrO2/Mn0.5Mg0.25Zn0.25Fe2O4) nanostructures were chemically prepared to remove 60Co and 152+154Eu radionuclides from liquid media using batch experiments. The XRD pattern confirms the successful preparation of the C@ZrO2/MnMgZnFe2O4 composite. Also, SEM and TEM images confirmed that the composite owns a heterogeneous morphology in the nanoscale range. The optical band gap value of Mn0.5Mg0.25Zn0.25Fe2O4, ZrO2, and the composite samples was 1.45, 2.38, and 1.54 eV, respectively. Many parameters have been studied as the effect of time, solution pH, and initial ion concentration. The kinetics models for the removal process of 152+154Eu and 60Co radionuclides were studied. The second-order kinetic equation could describe the sorption kinetics for both radionuclides. The Langmuir monolayer capacity for 60Co was 82.51 mg/g and for 152+154Eu was 136.98 mg/g. The thermodynamic parameters such as free energy ΔGo, the enthalpy ΔHo, and the entropy ΔSo were calculated. The results indicated that the sorption process has endothermic nature for both two radionuclides onto C@ZrO2/MnMgZnFe2O4 composite.

Sorbent extraction behavior of cesium and strontium from nitric acid solutions using a new high thermal stability material.

In this study a new low-cost carbonaceous material was prepared from husks of opuntia-ficus-indica as a starting material (precursor) which was accomplished by chemical activation route using H3PO4 impregnation. The material has been identified by different analytical tools. The sorption performance of Cs(I) and Sr(II) from HNO3 solutions was examined through batch system. Variations of the distribution coefficients (Kd) as a function of HNO3 concentration in the range 0.001-5.0 M were presented. Some of separation probabilities were suggested. The results attained signals that the Sr(II) selectivity is higher than that of Cs(I) at high molarities. The retention capacity (qe) of Cs(I) and Sr(II) ions increased with growing temperature. The capacities at 0.001 M HNO3 are 34 and 108 mg/g for Cs(I) and Sr(II), respectively. Whereas, at 2.0 M HNO3 capacities were about 4 and 37 mg/g for each of Cs(I) and Sr (II), respectively. This studies demonstrates that the prepared carbonaceous sorbent is an economically effective sorbent for retention of Cs(I) and Sr(II) species from HNO3 solutions. Cs(I) and Sr(II) removal potential was tested from simulated low- and intermediate-level radioactive waste samples.

Follicular Lymphoma-associated BTK Mutations are Inactivating Resulting in Augmented AKT Activation.

PURPOSE: On the basis of the recent discovery of mutations in Bruton tyrosine kinase (BTK) in follicular lymphoma, we studied their functional properties. EXPERIMENTAL DESIGN: We identified novel somatic BTK mutations in 7% of a combined total of 139 follicular lymphoma and 11 transformed follicular lymphoma cases, none of which had received prior treatment with B-cell receptor (BCR) targeted drugs. We reconstituted wild-type (WT) and mutant BTK into various engineered lymphoma cell lines. We measured BCR-induced signal transduction events in engineered cell lines and primary human follicular lymphoma B cells. RESULTS: We uncovered that all BTK mutants destabilized the BTK protein and some created BTK kinase-dead mutants. The phospholipase C gamma 2 (PLCγ2) is a substrate of BTK but the BTK mutants did not alter PLCγ2 phosphorylation. Instead, we discovered that BTK mutants induced an exaggerated AKT phosphorylation phenotype in anti-Ig-treated recombinant lymphoma cell lines. The short hairpin RNA-mediated knockdown of BTK expression in primary human nonmalignant lymph node-derived B cells resulted in strong anti-Ig-induced AKT activation, as did the degradation of BTK protein in cell lines using ibrutinib-based proteolysis targeting chimera. Finally, through analyses of primary human follicular lymphoma B cells carrying WT or mutant BTK, we detected elevated AKT phosphorylation following surface Ig crosslinking in all follicular lymphoma B cells, including all BTK-mutant follicular lymphoma. The augmented AKT phosphorylation following BCR crosslinking could be abrogated by pretreatment with a PI3Kδ inhibitor. CONCLUSIONS: Altogether, our data uncover novel unexpected properties of follicular lymphoma-associated BTK mutations with direct implications for targeted therapy development in follicular lymphoma.See related commentary by Afaghani and Taylor, p. 2123.

Virtual Texture Generated using Elastomeric Conductive Block Copolymer in Wireless Multimodal Haptic Glove.

Haptic devices are in general more adept at mimicking the bulk properties of materials than they are at mimicking the surface properties. This paper describes a haptic glove capable of producing sensations reminiscent of three types of near-surface properties: hardness, temperature, and roughness. To accomplish this mixed mode of stimulation, three types of haptic actuators were combined: vibrotactile motors, thermoelectric devices, and electrotactile electrodes made from a stretchable conductive polymer synthesized in our laboratory. This polymer consisted of a stretchable polyanion which served as a scaffold for the polymerization of poly(3,4-ethylenedioxythiophene) (PEDOT). The scaffold was synthesized using controlled radical polymerization to afford material of low dispersity, relatively high conductivity (0.1 S cm-1), and low impedance relative to metals. The glove was equipped with flex sensors to make it possible to control a robotic hand and a hand in virtual reality (VR). In psychophysical experiments, human participants were able to discern combinations of electrotactile, vibrotactile, and thermal stimulation in VR. Participants trained to associate these sensations with roughness, hardness, and temperature had an overall accuracy of 98%, while untrained participants had an accuracy of 85%. Sensations could similarly be conveyed using a robotic hand equipped with sensors for pressure and temperature.

Therapeutic targeting of TP53-mutated acute myeloid leukemia by inhibiting HIF-1α with echinomycin.

TP53 mutation in acute myeloid leukemia (AML) is associated with poor prognosis. Since no targeted therapy is available to restore p53 function, it is of great interest to test whether other pathways activated by TP53 mutations can be therapeutically targeted. Here, we showed HIF-1α target genes are enriched in TP53-mutated versus TP53-wild-type AML. To determine the role of this activation, we tested efficacy of HIF-1α inhibitor echinomycin in TP53-mutated AML samples in vitro and in vivo. Echinomycin was broadly effective against a panel of primary AML blast cells, with low nanomolar IC50s and, based on colony-forming unit assay, was tenfold more effective in eliminating AML stem cells. Echinomycin selectively eliminated CD34+CD38- AML cells. To test the therapeutic efficacy of echinomycin, we established a xenograft model of TP53-mutated AML. Echinomycin was broadly effective against xenografts from multiple AML samples in vivo, and more effective than cytarabine + daunorubicin chemotherapy. Importantly, while cytarabine + daunorubicin enriched for AML stem cells, echinomycin nearly eliminated this population. Using TP53-mutated AML cell line THP1 and patient-derived AML cells, we tested a new echinomycin formulation with longer half-life and significantly improved therapeutic effect. Our data suggest a novel approach to treat AML with TP53 mutations.

The Genomic Landscape of Centromeres in Cancers.

Centromere genomics remain poorly characterized in cancer, due to technologic limitations in sequencing and bioinformatics methodologies that make high-resolution delineation of centromeric loci difficult to achieve. We here leverage a highly specific and targeted rapid PCR methodology to quantitatively assess the genomic landscape of centromeres in cancer cell lines and primary tissue. PCR-based profiling of centromeres revealed widespread heterogeneity of centromeric and pericentromeric sequences in cancer cells and tissues as compared to healthy counterparts. Quantitative reductions in centromeric core and pericentromeric markers (α-satellite units and HERV-K copies) were observed in neoplastic samples as compared to healthy counterparts. Subsequent phylogenetic analysis of a pericentromeric endogenous retrovirus amplified by PCR revealed possible gene conversion events occurring at numerous pericentromeric loci in the setting of malignancy. Our findings collectively represent a more comprehensive evaluation of centromere genetics in the setting of malignancy, providing valuable insight into the evolution and reshuffling of centromeric sequences in cancer development and progression.

Follicular lymphoma-associated mutations in vacuolar ATPase ATP6V1B2 activate autophagic flux and mTOR.

The discovery of recurrent mutations in subunits of the vacuolar-type H+-translocating ATPase (v-ATPase) in follicular lymphoma (FL) highlights a role for the amino acid- and energy-sensing pathway to mTOR in the pathogenesis of this disease. Here, through the use of complementary experimental approaches involving mammalian cells and Saccharomyces cerevisiae, we have demonstrated that mutations in the human v-ATPase subunit ATP6V1B2 (also known as Vma2 in yeast) activate autophagic flux and maintain mTOR/TOR in an active state. Engineered lymphoma cell lines and primary FL B cells carrying mutated ATP6V1B2 demonstrated a remarkable ability to survive low leucine concentrations. The treatment of primary FL B cells with inhibitors of autophagy uncovered an addiction for survival for FL B cells harboring ATP6V1B2 mutations. These data support the idea of mutational activation of autophagic flux by recurrent hotspot mutations in ATP6V1B2 as an adaptive mechanism in FL pathogenesis and as a possible new therapeutically targetable pathway.

Assessment of iodine supplementation program on thyroid function in Sudan.

The aim of this Study is to investigate whether the Iodine Supplementation Programme is successful or not. This Programme was implemented in Nyala to treat the Iodine deficiency. In this Study Nyala was selected to act as (a study area), due to the history of Iodine deficiency of this region, while Khartoum was selected to act as (a control area). 2000 samples were collected from Khartoum versus 450 samples from Nyala. Thyroxine (T4) and triiodothyronine (T3) levels in two regions were measured and performed by using radioimmunoassay (RIA), also the immunoradiometric assay (IRMA) used for measurement of thyroid stimulating hormone (TSH). The obtained results analyzed by using Statistical Package for Social Sciences (SPSS). (Coherent retrospective) used to determine differences between the study groups. The results of this study showed, there was no significant difference between the mean serum concentrations of T3 and TSH for Khartoum and Nyala. T4of Khartoum (117.93 ±â€¯42.797) nmol/L and the mean serum T4 of Nyala (114.54 ±â€¯45.526) nmol/L, the (P-value = 0.133).T3for Khartoum (1.8040 ±â€¯0.99047) nmol/L and T3of Nyala (1.7307 ±â€¯0.96508) nmol/L, the (P-value = 0.153). TSH for Khartoum (1.4480 ±â€¯0.95807)mIU/Land the mean serum TSH of Nyala (1.4553 ±â€¯1.0244) mIU/L, the (P-value = 0.885). The study showed a clear observation of improvement of hypothyroidism cases in Nyala while the ratio decreased from 64.09% to 0.6%. All the results were carried out according to normal range of Sudanese. The conclusion from this study the iodine supplementation programme is successful. The study recommends rising the health awareness among people by explain the severity of iodine deficiency, and continue in iodine supplementation programme, also establishment of monitoring system including monitoring the presence of iodized diets (sugar, salt, oils, and bread) in the markets. Finally, further studies are needed in other parts of Sudan to assess the size of iodine deficiency problem.

CRISPR/Cas9-Based Gene Dropout Screens.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9-based technology enables efficient and precise perturbations of target genomic sites. Combining the endonuclease Cas9 and a pooled guide RNA library allows for systematic screenings of genes associated with a growth disadvantage or lethal phenotype under various conditions in organisms and tissues. Here, we describe a complete protocol for scalable CRISPR/Cas9-based dropout screening for essential genes from focused genomic regions to whole genomes.

Gene Disruption Using CRISPR-Cas9 Technology.

The emergence of the clustered, regularly interspaced, short palindromic repeat (CRISPR) technology provides tools for researchers to modify genomes in a specific and efficient manner. The Type II CRISPR-Cas9 system enables gene editing by directed DNA cleavage followed by either non-homologous end joining (NHEJ) or homology-directed repair (HDR). Here, we described the use of the Type II CRISPR-Cas9 system in detail from designing the guides to analyzing the desired gene disruption events.

Mitral Chordae Rupture as a Possible First-Time Presentation for Graves’ Disease.

Graves' disease is a common cause of hyperthyroidism that can lead to multiple cardiovascular complications. Herein is described the case of a 44-year-old male who presented with new-onset atrial fibrillation and mitral regurgitation secondary to flail anterior mitral leaflet with chordae tendineae rupture. This is a rare complication for Graves' disease, and has been reported only twice previously. It was hypothesized that this complication is secondary to Graves'-associated myxomatous degeneration of the mitral valve in the presence of a hyperdynamic circulation.

RAFT Polymerization of an Intrinsically Stretchable Water-Soluble Block Copolymer Scaffold for PEDOT.

Despite the common association of π-conjugated polymers with flexible and stretchable electronics, these materials can be rigid and brittle unless they are designed otherwise. For example, low modulus, high extensibility, and high toughness are treated as prerequisites for integration with soft and biological structures. One of the most successful and commercially available organic electronic materials is the conductive and brittle polyelectrolyte complex poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS). To make this material stretchable, additives such as ionic liquids must be used. These additives may render the composite incompatible with biological tissue. In this work, we describe the synthesis of an intrinsically stretchable variant of the conductive polymer PEDOT:PSS that is free of additives. The approach involves the synthesis of a block copolymer comprising soft segments of poly(polyethylene glycol methyl ether acrylate) (PPEGMEA) and hard segments of poly(styrene sulfonate) (PSS) using a reversible addition-fragmentation chain transfer (RAFT) polymerization. Subsequently, we used the newly synthesized ionic elastomer PSS-b-PPEGMEA as a matrix for the oxidative polymerization of EDOT. The resulting polyelectrolyte elastomer, PEDOT:PSS-b-PPEGMEA, can withstand elongations up to 128% and has a toughness up to 10.1 MJ m-3. While the polyelectrolyte elastomer is not as conductive as the commercial material, the toughness and extensibility are each more than an order of magnitude higher. Moreover, the electrical conductivity of the polyelectrolyte elastomer exhibits minimal decrease with strain within the elastic regime. We then compared the block copolymer to physical blends of PEDOT:PSS and PPEGMEA. The blend material had a much lower failure strain of only 38% and a maximum toughness of 4.9 MJ m-3. This approach thus emphasizes the importance of the covalent linking of the PSS and PPEGMEA blocks. Furthermore, we demonstrate that the conductivity of scratched films can be restored upon exposure to water.