Temporo-Parieto-Occipital Disconnection by Robot-Assisted Magnetic Resonance Imaging-Guided Laser Interstitial Thermal Therapy for Refractory Epilepsy in a Pediatric Patient: Proof-of-Principle Case Report and Surgical Nuances.

OBJECTIVE: Magnetic resonance imaging-guided laser interstitial thermal therapy (MRIgLITT) has been proven safe and effective for the treatment of focal epilepsy of different etiologies. It has also been used to disconnect brain tissue in more extensive or diffuse epilepsy, such as corpus callosotomy and hemispherotomy. METHODS: In this study, we report a case of temporo-parieto-occipital disconnection surgery performed using MRIgLITT assisted by a robotic arm for refractory epilepsy of the posterior quadrant. A highly realistic cadaver simulation was performed before the actual surgery. RESULTS: The patient was a 14-year-old boy whose seizures began at the age of 8. The epilepsy was a result of a left perinatal ischemic event that caused a porencephalic cyst, and despite receiving multiple antiepileptic drugs, the patient continued to experience daily seizures which led to the recommendation of surgery. CONCLUSIONS: A Wada test lateralized language in the right hemisphere. Motor and sensory function was confirmed in the left hemisphere through magnetic resonance imaging functional studies and NexStim. The left MRIgLITT temporo-parieto-occipital disconnection disconnection was achieved using 5 laser fibers. The patient followed an excellent postoperative course and was seizure-free, with no additional neurological deficits 24 months after the surgery.

Facilitating Medical Care for Latinx Individuals at Risk for CKD: A Pilot Intervention.

Rationale and Objective: Latinx individuals are at a higher risk for kidney failure than non-Latinx White individuals; however, they are less likely to receive pre-kidney failure medical care. The objective of this study was to determine the feasibility and acceptability of a community health worker (CHW) intervention that facilitated access to medical care for Latinx individuals. Study Design: Single-arm prospective study. Setting and Participants: Latinx adults were found to have albuminuria or risk factors for kidney disease at community screening events in Austin, Texas. Intervention: A 6-month CHW intervention that facilitated the following: (1) obtaining medical insurance; (2) medical care coordination with primary and nephrology care; (3) kidney disease education; and (4) connection with local resources to address health-related social needs. Outcomes: Recruitment, retention, medical care linkage, and participant and CHW-reported satisfaction with the intervention. Results: Of the 173 individuals who attended the 2 community screening events, 49 agreed to participate in the study, of whom, 51% were men with a mean ± standard deviation (SD) age of 45 ± 14 years, and all self-identified as Mexican or Chicano. The mean ± SD estimated glomerular filtration rate (eGFR) was 110 ± 21 mL/min/1.73 m2 and 41% of the participants reported a urine albumin-creatinine ratio of ≥30 mg/g. Among those enrolled, 28 of the 49 (57%) completed at least 1 CHW visit, and 20 of 49 (41%) completed the intervention. 7 individuals who needed assistance with insurance obtained insurance, and 15 of 20 (75%) scheduled an appointment with a primary care physician within 180 days. Participants reported that the US health care previously seemed inaccessible but gained insurance, the ability to navigate the system, and the ability to help others in their community to access medical care because of the program. Limitations: Small sample size and a single community may limit generalizability. Conclusions: We reported the acceptability of a CHW intervention. We encountered challenges with feasibility and identified strategies to overcome them. Studies are needed to test the effect of CHW interventions on outcomes and kidney health disparities. Funding: National Kidney Foundation young investigator research grant to Dr Novick. Plain Language Summary: Latinx individuals are at a higher risk for kidney failure than non-Latinx White individuals; however, they are less likely to receive pre-kidney failure medical care. We piloted a community health worker intervention that connected people with risk factors or showed evidence of kidney dysfunction at community screening events with medical care. Our findings indicate the acceptability of the intervention. We encountered challenges with feasibility and identified strategies to overcome them.

Mitochondrial genomes of the land hermit crab Coenobita clypeatus (Anomura: Paguroidea) and the mole crab Emerita talpoida (Anomura: Hippoidea) with insights into phylogenetic relationships in the Anomura (Crustacea: Decapoda).

The infraorder Anomura is a species-rich clade of decapod crustaceans recognized by its remarkable disparity in terms of morphology, anatomy, ecology, physiology, and behavior. This study assembled and characterized the complete mitochondrial genomes of two anomuran species, the hermit crab Coenobita clypeatus and the mole crab Emerita talpoida. The AT-rich mitochondrial genomes of C. clypeatus and E. talpoida are 16,469 bp and 15,810 bp long, respectively, and are composed of 13 protein-coding genes (PCGs), two ribosomal RNA genes, and 22 transfer RNA genes. A 1,390 bp and 553 bp long intergenic space is assumed to be the D-loop in C. clypeatus and E. talpoida, respectively. Mitochondrial synteny in C. clypeatus is identical to that reported in other congeneric hermit crabs while synteny in E. talpoida is identical to that described for the confamilial mole crab Stemonopa insignis. No major differences occur between the studied species and their respective congeneric / cofamilial species in terms of nucleotide composition and codon usage profiles of PCGs. Selective pressure analysis in PCGs, rarely conducted in anomuran crabs, indicate that all these mitochondrial PCGs experience purifying selection and that this purifying selection is stronger in some (i.e., cox family genes and cob) compared to other PCGs (e.g., atp8). Most of the tRNA genes exhibited a typical 'cloverleaf' secondary structure with few exceptions in the two studied species. In C. clypeatus, tRNA-Ser1 lacks the thymine pseudouracil cytosine (TΨC) loop while tRNA-Phe and tRNA-Tyr each exhibit a deletion of the dihydroxyuridine (DHU) loop but not the arm. In turn, in E. talpoida, tRNA-Phe and tRNA-Arg exhibit a deletion of the DHU loop but not the arm while tRNA-Ser1 lacks the TΨC arm. A phylogenomic analysis based on translated PCGs confirms the monophyly of the infraorder Anomura and retrieves most/all relationships at the superfamily and family level previously reported for anomurans. The analysis supports the monophyletic status of the families Albuneidae, Lithodidae, Coenobitidae, and Porcellanidae. In turn, the superfamily Paguroidea, and the families Paguridae and Diogenidae are polyphyletic.

Changes in fatty acid in Tecoma stans grown in mine residues after compost amendment.

Amendment tailing heaps with compost may deplete metal(loid)s concentration and improve the conditions for plant development. This research aimed to compare the Tecoma stans ability to grow on soil from the Sonora desert and mining waste (MW) after amendment with compost. Amendment the MW, with compost, decreased soluble As, Cd, Cu, Mn, Pb, and Zn up to 47, 33, 11, 34, 69, and 34%, respectively; increased ten times the leaves weight, and thirteen times the leaf area of the plants. Arsenic, Cd, Pb, Cu, and Zn in plants tissues decreased 27, 28, 27, 12, and 11%, respectively. The bioaccumulation and translocation factors were lower than one, so T. stans do not accumulate these elements. Polyunsaturated fatty acids 18:2ω6 and 18:3ω3 were increased, suggesting lower alteration of thylakoidal membrane integrity due to compost treatment. But, the amendment to the tailing was not enough to deplete the abiotic stress.

Amendment mine tailing with vermicompost depletes changes in polyunsaturated fatty acid of Tecoma stans.

Sterol Composition of Sponges, Cnidarians, Arthropods, Mollusks, and Echinoderms from the Deep Northwest Atlantic: A Comparison with Shallow Coastal Gulf of Mexico.

Triterpenoid biosynthesis is generally anaerobic in bacteria and aerobic in Eukarya. The major class of triterpenoids in bacteria, the hopanoids, is different to that in Eukarya, the lanostanoids, and their 4,4,14-demethylated derivatives, sterols. In the deep sea, the prokaryotic contribution to primary productivity has been suggested to be higher because local environmental conditions prevent classic photosynthetic processes from occurring. Sterols have been used as trophic biomarkers because primary producers have different compositions, and they are incorporated in primary consumer tissues. In the present study, we inferred food supply to deep sea, sponges, cnidarians, mollusks, crustaceans, and echinoderms from euphotic zone production which is driven by phytoplankton eukaryotic autotrophy. Sterol composition was obtained by gas chromatography and mass spectrometry. Moreover, we compared the sterol composition of three phyla (i.e., Porifera, Cnidaria, and Echinodermata) collected between a deep and cold-water region and a shallow tropical area. We hypothesized that the sterol composition of shallow tropical benthic organisms would better reflect their photoautotrophic sources independently of the taxonomy. Shallow tropical sponges and cnidarians from environments showed plant and zooxanthellae sterols in their tissues, while their deep-sea counterparts showed phytoplankton and zooplankton sterols. In contrast, echinoids, a class of echinoderms, the most complex phylum along with hemichordates and chordates (deuterostomes), did not show significant differences in their sterol profile, suggesting that cholesterol synthesis is present in deuterostomes other than chordates.

A Phase 1 Study of IRX195183, a RARα-Selective CYP26 Resistant Retinoid, in Patients With Relapsed or Refractory AML.

Subsets of non-acute promyelocytic leukemia (APL) acute myelogenous leukemia (AML) exhibit aberrant retinoid signaling and demonstrate sensitivity to retinoids in vitro. We present the results of a phase 1 dose-escalation study that evaluated the safety, pharmacodynamics, and efficacy of IRX195183, a novel retinoic acid receptor α agonist, in patients with relapsed or refractory myelodysplastic syndrome (MDS) or AML. In this single center, single arm study, eleven patients with relapsed or refractory MDS/AML were enrolled and treated. Oral IRX195183 was administered at two dose levels: 50 mg daily or 75 mg daily for a total of two 28-day cycles. Patients with stable disease or better were allowed to continue on the drug for four additional 28-day cycles. Common adverse events included hypertriglyceridemia, fatigue, dyspnea, and edema. Three patients at the first dose level developed asymptomatic Grade 3 hypertriglyceridemia. The maximally tolerated dose was not reached. Four of the eleven patients had (36%) stable disease or better. One had a morphological complete remission with incomplete hematologic recovery while on the study drug. Two patients had evidence of in vivo leukemic blast maturation, as reflected by increased CD38 expression. In a pharmacodynamics study, plasma samples from four patients treated at the lowest dose level demonstrated the capacity to differentiate leukemic cells from the NB4 cell line in vitro. These results suggest that IRX195183 is safe, achieves biologically meaningful plasma concentrations and may be efficacious in a subset of patients with MDS/AML. Clinical Trial Registration: clinicaltrials.gov, identifier NCT02749708.

Knockout of Cyp26a1 and Cyp26b1 during postnatal life causes reduced lifespan, dermatitis, splenomegaly, and systemic inflammation in mice.

All-trans-retinoic acid (atRA), the active metabolite of vitamin A, is an essential signaling molecule in all chordates. Global knockouts of the atRA clearing enzymes Cyp26a1 or Cyp26b1 are embryonic lethal. In adult rodents, inhibition of Cyp26a1 and Cyp26b1 increases atRA concentrations and signaling. However, postnatal knockout of Cyp26a1 does not cause a severe phenotype. We hypothesized that Cyp26b1 is the main atRA clearing Cyp in postnatal mammals. This hypothesis was tested by generating tamoxifen-inducible knockout mouse models of Cyp26b1 alone or with Cyp26a1. Both mouse models showed dermatitis, blepharitis, and splenomegaly. Histology showed infiltration of inflammatory cells including neutrophils and T lymphocytes into the skin and hyperkeratosis/hyperplasia of the nonglandular stomach. The mice lacking both Cyp26a1 and Cyp26b1 also had a reduced lifespan, failed to gain weight, and showed fat atrophy. There were significant changes in vitamin A homeostasis. Postnatal knockout of Cyp26b1 resulted in increased atRA concentrations in the skin while the postnatal knockout of both Cyp26a1 and Cyp26b1 resulted in increased atRA concentrations in the liver, serum, skin, spleen, and intestines. This study demonstrates the paramount role of Cyp26b1 in regulating retinoid homeostasis in postnatal life.

The retinoic acid hydroxylase Cyp26a1 has minor effects on postnatal vitamin A homeostasis, but is required for exogenous atRA clearance.

The all-trans-retinoic acid (atRA) hydroxylase Cyp26a1 is essential for embryonic development and may play a key role in regulating atRA clearance also in adults. We hypothesized that loss of Cyp26a1 activity via inducible knockout in juvenile or adult mice would result in decreased atRA clearance and increased tissue atRA concentrations and atRA-related adverse effects. To test these hypotheses, Cyp26a1 was knocked out in juvenile and adult male and female Cyp26a1 floxed mice using standard Cre-Lox technology and tamoxifen injections. Biochemical and histological methods were used to study the effects of global Cyp26a1 knockout. The Cyp26a1 knockout did not result in consistent histopathological changes in any major organs. Cyp26a1-/- mice gained weight normally and exhibited no adverse phenotypes for up to 1 year after loss of Cyp26a1 expression. Similarly, atRA concentrations were not increased in the liver, testes, spleen, or serum of these mice, and the Cyp26a1 knockout did not cause compensatory induction of lecithin:retinol acetyltransferase (Lrat) or retinol dehydrogenase 11 (Rdh11) mRNA or a decrease in aldehyde dehydrogenase 1a1 (Aldh1a1) mRNA in the liver compared with tamoxifen-treated controls. However, the Cyp26a1-/- mice showed increased bone marrow cellularity and decreased frequency of erythroid progenitor cells in the bone marrow consistent with a retinoid-induced myeloid skewing of hematopoiesis. In addition, the Cyp26a1 knockout decreased clearance of exogenous atRA by 70% and increased atRA half-life 6-fold. These findings demonstrate that despite lacking a major impact on endogenous atRA signaling, Cyp26a1 critically contributes as a barrier for exogenous atRA exposure.

Involvement of OpsLTP1 from Opuntia streptacantha in abiotic stress adaptation and lipid metabolism.

Plant lipid transfer proteins (LTPs) exhibit the ability to transfer lipids between membranes in vitro, and have been implicated in diverse physiological processes associated to plant growth, reproduction, development, biotic and abiotic stress responses. However, their mode of action is not yet fully understood. To explore the functions of the OpsLTP1 gene encoding a LTP from cactus pear Opuntia streptacantha Lem., we generated transgenic Arabidopsis thaliana (L.) Heynh. plants to overexpress OpsLTP1 and contrasted our results with the loss-of-function mutant ltp3 from A. thaliana under abiotic stress conditions. The ltp3 mutant seeds showed impaired germination under salt and osmotic treatments, in contrast to OpsLTP1 overexpressing lines that displayed significant increases in germination rate. Moreover, stress recovery assays showed that ltp3 mutant seedlings were more sensitive to salt and osmotic treatments than wild-type plants suggesting that AtLTP3 is required for stress-induced responses, while the OpsLTP1 overexpressing line showed no significant differences. In addition, OpsLTP1 overexpressing and ltp3 mutant seeds stored lower amount of total lipids compared with wild-type seeds, showing changes primarily on 16C and 18C fatty acids. However, ltp3 mutant also lead changes in lipid profile and no over concrete lipids which may suggest a compensatory activation of other LTPs. Interestingly, linoleic acid (18:2ω6) was consistently increased in neutral, galactoglycerolipids and phosphoglycerolipids of OpsLTP1 overexpressing line indicating a role of OpsLTP1 in the modulation of lipid composition in A. thaliana.

HIV-associated nephropathy: links, risks and management.

Despite the decreased incidence of human immunodeficiency virus (HIV)-associated nephropathy due to the widespread use of combined active antiretroviral therapy, it remains one of the leading causes of end-stage renal disease (ESRD) in HIV-1 seropositive patients. Patients usually present with low CD4 count, high viral load and heavy proteinuria, with the pathologic findings of collapsing focal segmental glomerulosclerosis. Increased susceptibility exists in individuals with African descent, largely due to polymorphism in APOL1 gene. Other clinical risk factors include high viral load and low CD4 count. Advanced kidney disease and nephrotic range proteinuria have been associated with progression to ESRD. Improvement in kidney function has been observed after initiation of combined active antiretroviral therapy. Other treatment options, when clinically indicated, are inhibition of the renin-angiotensin system and corticosteroids. Further routine management approaches for patients with chronic kidney disease should be implemented. In patients with progression to ESRD, kidney transplant should be pursued, provided that viral load control is adequate. Screening for the presence of kidney disease upon detection of HIV-1 seropositivity in high-risk populations is recommended.

Urban sewage lipids in the suspended particulate matter of a coral reef under river influence in the South West Gulf of Mexico.

Nutritional quality of suspended particulate matter (SPM) and the degree of human fecal pollution in the largest coral reef system in the southwest Gulf of Mexico were evaluated using lipid classes, fatty acids (FA) and sterols in the dry and rainy seasons. High proportions of triacylglycerols and saturated and monounsaturated FA were detected in the SPM however it was considered poor quality because it had low proportions of highly unsaturated FA which can be used to determine production of marine biogenic material of dietary value to pelagic and benthic organisms. Urban sewage organic carbon was traced with coprostanol. The reference value of coprostanol from the point source of pollution was set using two samples from a sewage treatment plant processing waste from >140,000 people near the coral reef system, and it was contrasted with one river station and nine marine stations including six coral reefs. The concentration of coprostanol in the SPM was 3621 ± 98 ng L-1 comprising 26% of total sterols. During the dry season, the river was contaminated upstream with human feces as evidenced by coprostanol at 1823 ng L-1, the 5ß-coprostanol: cholesterol ratio at 0.5, and 5ß-coprostanol: [5α-cholestanol+5ß-coprostanol] at 0.7. In contrast, marine stations had concentrations of coprostanol lower than a suggested regulation limit for tropical marine coastal waters (30 ng L-1), ranging between 6 and 28 ng L-1. During the rainy season a dilution effect was detected in the river, however significantly higher concentrations of coprostanol in the marine stations were detected ranging between 15 and 215 ng L-1, higher than the tentative tropical regulation range (30-100 ng L-1). Among the reefs, the nearshore one, 14.3 km from the treatment plant, was more exposed to human-fecal pollution, and offshore reefs, >17.3 km from the plant, had a lower degree of contamination. Finally, only three stations were clearly uncontaminated during both seasons including two reefs in the south located 21.8 and 35.6 km from the plant, with no presence of coprostanol. Contamination in the rainy season likely comes from a village with untreated sewage located 9.3-32 km from the reefs, and from the second largest Mexican river flowing into the Gulf of Mexico which has a watershed covering three states with lower than average sewage treatment. Inclusion of coprostanol monitoring could be a key factor in the management of this coral reef system.