Safety and efficacy of convalescent plasma for severe COVID-19: a randomized, single blinded, parallel, controlled clinical study.

BACKGROUND: Convalescent plasma (CP) has been widely used to treat COVID-19 and is under study. However, the variability in the current clinical trials has averted its wide use in the current pandemic. We aimed to evaluate the safety and efficacy of CP in severe coronavirus disease 2019 (COVID-19) in the early stages of the disease. METHODS: A randomized controlled clinical study was conducted on 101 patients admitted to the hospital with confirmed severe COVID-19. Most participants had less than 14 days from symptoms onset and less than seven days from hospitalization. Fifty patients were assigned to receive CP plus standard therapy (ST), and 51 were assigned to receive ST alone. Participants in the CP arm received two doses of 250 mL each, transfused 24 h apart. All transfused plasma was obtained from "super donors" that fulfilled the following criteria: titers of anti-SARS-CoV-2 S1 IgG ≥ 1:3200 and IgA ≥ 1:800 antibodies. The effect of transfused anti-IFN antibodies and the SARS-CoV-2 variants at the entry of the study on the overall CP efficacy was evaluated. The primary outcomes were the reduction in viral load and the increase in IgG and IgA antibodies at 28 days of follow-up. The per-protocol analysis included 91 patients. RESULTS: An early but transient increase in IgG anti-S1-SARS-CoV-2 antibody levels at day 4 post-transfusion was observed (Estimated difference [ED], - 1.36; 95% CI, - 2.33 to - 0.39; P = 0.04). However, CP was not associated with viral load reduction in any of the points evaluated. Analysis of secondary outcomes revealed that those patients in the CP arm disclosed a shorter time to discharge (ED adjusted for mortality, 3.1 days; 95% CI, 0.20 to 5.94; P = 0.0361) or a reduction of 2 points on the WHO scale when compared with the ST group (HR adjusted for mortality, 1.6; 95% CI, 1.03 to 2.5; P = 0.0376). There were no benefits from CP on the rates of intensive care unit admission (HR, 0.82; 95% CI, 0.35 to 1.9; P = 0.6399), mechanical ventilation (HR, 0.66; 95% CI, 0.25 to 1.7; P = 0.4039), or mortality (HR, 3.2; 95% CI, 0.64 to 16; P = 0.1584). Anti-IFN antibodies and SARS-CoV-2 variants did not influence these results. CONCLUSION: CP was not associated with viral load reduction, despite the early increase in IgG anti-SARS-CoV-2 antibodies. However, CP is safe and could be a therapeutic option to reduce the hospital length of stay. Trial registration NCT04332835.

[Association between ulcerative colitis and primary esclerosing cholangitis]. / Asociación entre colitis ulcerativa y colangitis esclerosante primaria.

Ulcerative Colitis (UC) is associated to Primary Sclerosing Cholangitis (PSC) in 80% of cases, and this association is more common than the one with Crohn’s disease. Nevertheless, the prevalence of PSC in patients with UC is only 2.9% in Latin America. We present the case of a female patient who presents a clinical history characterized for chronic diarrhea of one year of evolution, associated to fever, oral ulcers and loss of weight. In the laboratory results there is an elevation in the following: alkaline phosphatase, GGT, ALT and AST, for that reason we decide to do an abdominal ultrasound finding a hepatomegaly. In the colonoscopy we found an ulcerative colitis. Later, we do a magnetic resonance cholangiopancreatography, because of the diagnosis of UC and the abnormalities at the liver function tests, diagnosing PSC associated to UC. At that moment, the patient starts treatment with sulfasalazine that is stopped because of an adverse effect, starting prednisone and azathioprine. The patient then is discharged with the medication already mentioned and has a favorable clinical outcome. We decide to report the case because is the second reported case in Peru, being this association not commonly found in the South hemispheric.

Phenazine antibiotic inspired discovery of potent bromophenazine antibacterial agents against Staphylococcus aureus and Staphylococcus epidermidis.

Nearly all clinically used antibiotics have been (1) discovered from microorganisms (2) using phenotype screens to identify inhibitors of bacterial growth. The effectiveness of these antibiotics is attributed to their endogenous roles as bacterial warfare agents against competing microorganisms. Unfortunately, every class of clinically used antibiotic has been met with drug resistant bacteria. In fact, the emergence of resistant bacterial infections coupled to the dismal pipeline of new antibacterial agents has resulted in a global health care crisis. There is an urgent need for innovative antibacterial strategies and treatment options to effectively combat drug resistant bacterial pathogens. Here, we describe the implementation of a Pseudomonas competition strategy, using redox-active phenazines, to identify novel antibacterial leads against Staphylococcus aureus and Staphylococcus epidermidis. In this report, we describe the chemical synthesis and evaluation of a diverse 27-membered phenazine library. Using this microbial warfare inspired approach, we have identified several bromophenazines with potent antibacterial activities against S. aureus and S. epidermidis. The most potent bromophenazine analogue from this focused library demonstrated a minimum inhibitory concentration (MIC) of 0.78-1.56 µM, or 0.31-0.62 µg mL(-1), against S. aureus and S. epidermidis and proved to be 32- to 64-fold more potent than the phenazine antibiotic pyocyanin in head-to-head MIC experiments. In addition to the discovery of potent antibacterial agents against S. aureus and S. epidermidis, we also report a detailed structure-activity relationship for this class of bromophenazine small molecules.

[Detection of toxigenic genes nheA, nheB and nheC in Bacillus cereus strains isolated from powdered milk samples in Costa Rica]. / Presencia de los genes de toxigenicidad nheA, nheBy nheC en cepas de Bacillus cereus aisladas de leches deshidratadas en Costa Rica.

Powdered milk is a frequently consumed product that does not need to be kept under cold conditions. Nevertheless, different microorganisms may contaminate it. Powdered milk is a highly consumed product by Costa Rican population, and Bacillus cereus is a potentially pathogenic bacteria associated to it, with the ability to develop toxins depending on the presence of the respective codifying genes. The aim of this study was to determine the presence of the toxigenic genes nheA, nheB and nheC from B. cereus strains, found in powdered milk sold at the Costa Rican national market. Five different lots of ten brands of powdered milk, distributed in the metropolitan area of San José, Costa Rica were analyzed. B cereus load was quantified using the Most Probable Number technique and identified using the Vitek system. The presence of the toxigenic genes was determined using the PCR technique. The isolation frequency of this bacteria in the powdered milk samples analyzed reached 50%, with populations ranging from 3 to > 100 MPN/g. Five out from nineteen strains were found positive for the three toxigenic genes, indicating contamination with potentially toxigenic B. cereus in powdered milk distributed in the national market, and an important risk for public. health.

A new lizard of the Phymaturus genus (Squamata: Liolaemidae) from Sierra Grande, northeastern Patagonia, Argentina.

A new species of lizard of the saxicolous and viviparous genus Phymaturus from Patagonia is described. The new species is a member of the Phymaturus patagonicus species group distributed on volcanic plateaus, mountains or rocky outcrops of southern Argentina. Phymaturus yachanana sp. nov. differs from the other members of the patagonicus group by a dorsal pattern of small and medium-sized white spots on a brown background, the number of scales around the midbody, genetic differences in mitochondrial and nuclear markers, and allopatric geographic distribution in an isolated group of hills. As other species of the group, the new species is viviparous and herbivorous. 

Clinical presentation and microbiological characteristics of community-acquired Staphylococcus aureus bacteraemia at a tertiary hospital in Costa Rica.

Introduction. Staphylococcus aureus is a leading agent in community-acquired bacteraemia (CAB) and has been linked to elevated mortality rates and methicillin resistance in Costa Rica.Gap statement and aim. To update and enhance previous data obtained in this country, we analysed the clinical manifestations of 54 S. aureus CAB cases in a tertiary hospital and delineated the sequence types (STs), virulome, and resistome of the implicated isolates.Methodology. Clinical information was retrieved from patient files. Antibiotic susceptibility profiles were obtained with disc diffusion and automated phenotypic tests. Genomic data were exploited to type the isolates and for detection of resistance and virulence genes.Results. Primary infections predominantly manifested as bone and joint infections, followed by skin and soft tissue infections. Alarmingly, 70% of patients continued to exhibit positive haemocultures beyond 48 h of treatment modification, with nearly a quarter requiring mechanical ventilation or developing septic shock. The 30-day mortality rate reached an alarming 40%. More than 60% of the patients were found to have received suboptimal or inappropriate antibiotic treatment, and there was an alarming tendency towards the overuse of third-generation cephalosporins as empirical treatment. Laboratory tests indicated elevated creatinine levels, leukocytosis, and bandaemia within the first 24 h of hospitalization. However, most showed improvement after 48 h. The isolates were categorized into 13 STs, with a predominance of representatives from the clonal complexes CC72 (ST72), CC8 (ST8), CC5 (ST5, ST6), and CC1 (ST188). Twenty-four isolates tested positive for mecA, with ST72 strains accounting for 20. In addition, we detected genes conferring acquired resistance to aminoglycosides, MLSB antibiotics, trimethoprim/sulfamethoxazole, and mutations for fluoroquinolone resistance in the isolate collection. Genes associated with biofilm formation, capsule synthesis, and exotoxin production were prevalent, in contrast to the infrequent detection of enterotoxins or exfoliative toxin genes.Conclusions. Our findings broaden our understanding of S. aureus infections in a largely understudied region and can enhance patient management and treatment strategies.

DAF-16/FOXO and HLH-30/TFEB comprise a cooperative regulatory axis controlling tubular lysosome induction in C. elegans.

Although life expectancy has increased, longer lifespans do not always align with prolonged healthspans and, as a result, the occurrence of age-related degenerative diseases continues to increase. Thus, biomedical research has been shifting focus to strategies that enhance both lifespan and healthspan concurrently. Two major transcription factors that have been heavily studied in the context of aging and longevity are DAF-16/FOXO and HLH-30/TFEB; however, how these two factors coordinate to promote longevity is still not fully understood. In this study, we reveal a new facet of their cooperation that supports healthier aging in C. elegans. Namely, we demonstrate that the combinatorial effect of daf-16 and hlh-30 is required to trigger robust lysosomal tubulation, which contributes to systemic health benefits in late age by enhancing cross-tissue proteostasis mechanisms. Remarkably, this change in lysosomal morphology can be artificially induced via overexpression of SVIP, a previously characterized tubular lysosome stimulator, even when one of the key transcription factors, DAF-16, is absent. This adds to growing evidence that SVIP could be utilized to employ tubular lysosome activity in adverse conditions or disease states. Mechanistically, intestinal overexpression of SVIP leads to nuclear accumulation of HLH-30 in gut and non-gut tissues and triggers global gene expression changes that promotes systemic health benefits. Collectively, our work reveals a new cellular process that is under the control of DAF-16 and HLH-30 and provides further insight into how these two transcription factors may be exerting their pro-health effects.

Spin canting and slow magnetic relaxation in mononuclear cobalt(II) sulfadiazine ternary complexes.

Monomeric [Co(SDZ)2phen] (1) and [Co(SDZ)(bq)Cl] (2) complexes (SDZ = sulfadiazine, phen = 1,10-phenanthroline, and bq = 2,2'-biquinoline) have been synthesized and characterized. X-ray diffraction studies indicate that SDZ acts as a bidentate ligand coordinating through the sulfonamide and the pyrimidine N atoms in both compounds. In complex 1, the coordination sphere consists of two SDZ ligands and a bis-chelating phen ligand, giving rise to a CoN6 coordination sphere. On the other hand, 2 has a CoN4Cl core, with two N-atoms from SDZ and two from the bq ligand. Both compounds have been studied by dc and ac magnetometry and shown to display slow magnetic relaxation under an optimum external dc field (1 kOe) at low temperatures. Moreover, compound 2 displays long range magnetic ordering provided by spin-canted antiferromagnetism, which has been characterized by further field-dependent magnetic susceptibility measurements, FC/ZFC curves, hysteresis loops and frequency-independent ac curves. The signs of the calculated D parameters, positive in 1 and negative in 2, have been rationalized according to the two lowest-lying transitions in the orbital energy diagrams derived from ab initio ligand field theory (AILFT). In a subsequent attempt to reveal the possible hidden zero-field SMM behaviour, Ni(II)-based 3 and Co(II)-doped Ni(II)-based (with a Ni : Co ratio of 0.9 : 0.1) heterometallic compound 2Ni were synthesized.

A molecular phylogeny of the lizard genus Phymaturus (Squamata, Liolaemini): implications for species diversity and historical biogeography of southern South America.

The lizard genus Phymaturus is widely distributed in Argentina and along the eastern edge of Chile between 25° and 45° south. We sampled 27 of the 38 currently recognized species plus 22 candidate species using two mitochondrial genes (cytb and 12S), four protein coding nuclear genes and seven anonymous nuclear loci, and present the first comprehensive molecular phylogenetic hypothesis for the clade. We recovered two large clades (the palluma or northern group and patagonicus or southern group) previously recognized on the basis of morphological and mitochondrial sequence evidence, and compared results obtained from concatenated-gene analyses with results of a coalescent-based species-tree approach (BEST). With both methods we identified four main clades within the palluma group (mallimaccii, roigorum, verdugo, and vociferator) and five main clades within the patagonicus group (calcogaster, indistinctus, payuniae, somuncurensis, and spurcus). We found several instances of non-monophyly with cytb and cases of incongruence between mitochondrial vs nuclear data for which we discuss alternative hypotheses. Although with lower support values, combined BEST results are more congruent with concatenated nuclear data than with combined concatenated analyses, suggesting that BEST is less influenced by demographic processes than combined concatenated analyses. We discuss the taxonomic, biogeographic and conservation implications of these results and how the future integration of phylogeographic and morphological approaches will allow the further testing of demographic and biogeographic hypotheses.

Identification of neuronal subpopulations that project from hypothalamus to both liver and adipose tissue polysynaptically.

The autonomic nervous system regulates fuel availability and energy storage in the liver, adipose tissue, and other organs; however, the molecular components of this neural circuit are poorly understood. We sought to identify neural populations that project from the CNS indirectly through multisynaptic pathways to liver and epididymal white fat in mice using pseudorabies virus strains expressing different reporters together with BAC transgenesis and immunohistochemistry. Neurons common to both circuits were identified in subpopulations of the paraventricular nucleus of the hypothalamus (PVH) by double labeling with markers expressed in viruses injected in both sites. The lateral hypothalamus and arcuate nucleus of the hypothalamus and brainstem regions (nucleus of the solitary tract and A5 region) also project to both tissues but are labeled at later times. Connections from these same sites to the PVH were evident after direct injection of virus into the PVH, suggesting that these regions lie upstream of the PVH in a common pathway to liver and adipose tissue (two metabolically active organs). These common populations of brainstem and hypothalamic neurons express neuropeptide Y and proopiomelanocortin in the arcuate nucleus, melanin-concentrating hormone, and orexin in the lateral hypothalamus and in the corticotrophin-releasing hormone and oxytocin in the PVH. The delineation of this circuitry will facilitate a functional analysis of the possible role of these potential command-like neurons to modulate autonomic outflow and coordinate metabolic responses in liver and adipose tissue.

Molecular phylogenetic relationships of the Liolaemus rothi complex and a new species of lizard from Auca Mahuida Volcano (Squamata: Liolaemini).

A new species of lizard of the genus Liolaemus from Neuquén Province, western Argentina, is described. The new species is a member of the Liolaemus rothi species complex, and mitochondrial and nuclear molecular data show it as sister taxon of the clade composed of (L. hermannunezi (L. tromen + L. loboi)), differing in size, squamation, coloration, and sexual dimorphism from the other species of this group. Liolaemus sitesi sp. nov. has a dark body coloration with series of notched blotches on the dorsum, with bright spots, and a very iridescent yellow-green coloration in natural light. Liolaemus sitesi sp. nov. is found only in the Auca Mahuida volcano and is terrestrial, dwelling on the stony slopes with sandy soil between 1300 m and the volcano summit.

[Basophil activation test to follow-up of patients treated with hymenoptera venom immunotherapy: a review of current evidence]. / Prueba de activación de basófilos en el seguimiento de pacientes que reciben inmunoterapia con veneno de himenópteros: revisión de la evidencia actual.

Hymenoptera venom immunotherapy (HVI) is a long-term effective treatment to avoid new systemic reactions in patients with Hymenoptera allergy. The sting challenge test is considered the gold standard to confirm the tolerance. However, the use of this technique is not generalized in clinical practice, being the basophil activation test (BAT), which functionally explores allergen response, an alternative that does not entail any of the provocation risks associated with the sting challenge test. This study reviews the publications that used the BAT to follow up and evaluate the success of the HVI. Studies assessing the changes between a baseline BAT before the start and BATs performed between the starting and maintenance phases of the HVI were selected. Ten articles were found, comprising information from 167 patients, of which 29% used the sting challenge test. The studies concluded the importance of evaluating the responses with submaximal allergen concentrations, which reflect basophil sensitivity, to monitor the HVI using the BAT. It was also observed that changes in the maximum response (reactivity) could not reflect the clinical status of tolerance, particularly in the initial phases of HVI.

La inmunoterapia con veneno de himenópteros (IVH) es, a largo plazo, un tratamiento eficaz para evitar nuevas reacciones sistémicas en pacientes con alergia a este tipo de insectos. La prueba de repicadura controlada es el estudio de referencia para confirmar la tolerancia del individuo. Sin embargo, no se ha generalizado su indicación clínica, por lo que la prueba de activación de basófilos (TAB) resulta una buena alternativa, pues valora de manera funcional la respuesta al alérgeno y está exenta de los riesgos asociados con la provocación. En esta revisión se explora la utilidad de la TAB en el seguimiento y valoración del éxito de la IVH. Se seleccionaron estudios que evalúan los cambios entre una TAB basal y en otro momento de la fase de inicio o mantenimiento de la IVH. Se incluyeron 10 estudios con datos de 167 pacientes, de los que el 29% había tenido prueba de repicadura controlada. Para vigilar la eficacia de la IVH debe explorarse la respuesta del basófilo, con la determinación de las concentraciones submáximas del alérgeno, que reflejan la sensibilidad del basófilo. Los cambios en la respuesta máxima (reactividad) no pueden aportar información del estado de tolerancia, especialmente en las fases iniciales de la IVH.

Tubular lysosome induction couples animal starvation to healthy aging.

Dietary restriction promotes longevity in several species via autophagy activation. However, changes to lysosomes underlying this effect remain unclear. Here using the nematode Caenorhabditis elegans, we show that the induction of autophagic tubular lysosomes (TLs), which occurs upon dietary restriction or mechanistic target of rapamycin inhibition, is a critical event linking reduced food intake to lifespan extension. We find that starvation induces TLs not only in affected individuals but also in well-fed descendants, and the presence of gut TLs in well-fed progeny is predictive of enhanced lifespan. Furthermore, we demonstrate that expression of Drosophila small VCP-interacting protein, a TL activator in flies, artificially induces TLs in well-fed worms and improves C. elegans health in old age. These findings identify TLs as a new class of lysosomes that couples starvation to healthy aging.

A new species of Liolaemus (Reptilia: Squamata) of the Liolaemus capillitas clade (Squamata, Liolaemini, Liolaemus elongatus-kriegi group) from Sierra de Velasco, La Rioja Province, Argentina.

A new species of the Liolaemus capillitas clade is described. Liolaemus galactostictos sp. nov. differs from other members of its group by a combination of morphological and molecular traits, in particular its black dorsal coloration pattern not found in any other Liolaemus species. Liolaemus galactostictos sp. nov. is only known from its type locality. This new species is found in rocky fields surrounded by grasslands on the top of the Velasco Mountains, a ¨sky island environment¨, in northwestern Argentina. As well as other members of its clade this species seems to be strictly saxicolous, viviparous and feeds on insects.

Genome-informed loop-mediated isothermal amplification assay for specific detection of Pectobacterium parmentieri in infected potato tissues and soil.

Pectobacterium parmentieri (formerly Pectobacterium wasabiae), which causes soft rot disease in potatoes, is a newly established species of pectinolytic bacteria within the family Pectobacteriaceae. Despite serious damage caused to the potato industry worldwide, no field-deployable diagnostic tests are available to detect the pathogen in plant samples. In this study, we aimed to develop a reliable, rapid, field-deployable loop-mediated isothermal amplification (LAMP) assay for the specific detection of P. parmentieri. Specific LAMP primers targeting the petF1 gene region, found in P. parmentieri but no other Pectobacterium spp., were designed and validated in silico and in vitro using extensive inclusivity (15 strains of P. parmentieri) and exclusivity (94 strains including all other species in the genus Pectobacterium and host DNA) panels. No false positives or negatives were detected when the assay was tested directly with bacterial colonies, and with infected plant and soil samples. Sensitivity (analytical) assays using serially diluted bacterial cell lysate and purified genomic DNA established the detection limit at 10 CFU/mL and 100 fg (18-20 genome copies), respectively, even in the presence of host crude DNA. Consistent results obtained by multiple users/operators and field tests suggest the assay's applicability to routine diagnostics, seed certification programs, biosecurity, and epidemiological studies.

Tocilizumab reduces COVID-19 mortality and pathology in a dose and timing-dependent fashion: a multi-centric study.

Life-threatening COVID-19 is associated with strong inflammation, where an IL-6-driven cytokine storm appears to be a cornerstone for enhanced pathology. Nonetheless, the specific inhibition of such pathway has shown mixed outcomes. This could be due to variations in the dose of tocilizumab used, the stage in which the drug is administered or the severity of disease presentation. Thus, we performed a retrospective multicentric study in 140 patients with moderate to critical COVID-19, 79 of which received tocilizumab in variable standard doses (< 400 mg, 400-800 mg or > 800 mg), either at the viral (1-7 days post-symptom onset), early inflammatory (8-15) or late inflammatory (16 or more) stages, and compared it with standard treated patients. Mortality, reduced respiratory support requirements and pathology markers were measured. Tocilizumab significantly reduced the respiratory support requirements (OR 2.71, CI 1.37-4.85 at 95%) and inflammatory markers (OR 4.82, CI 1.4-15.8) of all patients, but mortality was only reduced (4.1% vs 25.7%, p = 0.03) when the drug was administered at the early inflammatory stage and in doses ranging 400-800 mg in severely-ill patients. Despite the apparent inability of Tocilizumab to prevent the progression of COVID-19 into a critical presentation, severely-ill patients may be benefited by its use in the early inflammatory stage and moderate doses.

Definition of estrogen receptor pathway critical for estrogen positive feedback to gonadotropin-releasing hormone neurons and fertility.

The mechanisms through which estrogen regulates gonadotropin-releasing hormone (GnRH) neurons to control mammalian ovulation are unknown. We found that estrogen positive feedback to generate the preovulatory gonadotropin surge was normal in estrogen receptor beta knockout (ERbeta) mutant mice, but absent in ERalpha mutant mice. An ERalpha-selective compound was sufficient to generate positive feedback in wild-type mice. As GnRH neurons do not express ERalpha, estrogen positive feedback upon GnRH neurons must be indirect in nature. To establish the cell type responsible, we generated a neuron-specific ERalpha mutant mouse line. These mice failed to exhibit estrogen positive feedback, demonstrating that neurons expressing ERalpha are critical. We then used a GnRH neuron-specific Pseudorabies virus (PRV) tracing approach to show that the ERalpha-expressing neurons innervating GnRH neurons are located within rostral periventricular regions of the hypothalamus. These studies demonstrate that ovulation is driven by estrogen actions upon ERalpha-expressing neuronal afferents to GnRH neurons.

Presbyopia Treatment With Eye Drops: An Eight Year Retrospective Study.

Purpose: The purpose of this study was to evaluate the safety and efficacy across time, of patients topically treated with Benozzi's method for presbyopia. Methods: A nonrandomized case series retrospective study was developed, including patients with emmetropia with binocular uncorrected distance visual acuity (UDVA) of 25/20 or better, and with uncorrected near visual acuity (UNVA) at least Jaeger 2 or worse. The study was set in Buenos Aires, Argentina, from January 2011 to June 2018, with at least 1-year follow-up. Patients were treated with pilocarpine and diclofenac preservative-free eye drops (Benozzi Method; US 8.524.758 B2, EP1.938.839 B1), and the main outcome measured was binocular UNVA at different follow-up times. Other parameters, as the UDVA and presence of side effects, were evaluated. Results: A total of 910 patients were included with a mean age at baseline of 48.67 ± 3.72 years old (range, 40-59 years). The baseline UNVA was 4.74 ± 1.53 and at 8 years of follow-up was decreased to 1.36 ± 0.48 (Jaeger scale). The mean binocular UDVA at baseline was 0.00 ± 0.01 logarithm of the minimum angle of resolution (logMAR) and after 8 years of follow-up was 0.03 ± 0.04 logMAR. All side effects reported (decrease of light perception, headaches, symptoms of ocular surface dryness, and dizziness) were spontaneously resolved in patients who continued with the treatment. Conclusions: The efficacy of the pharmacological treatment of presbyopia to improve the UNVA without affecting the UDVA is shown. Side effects were well tolerated and resolved before 1 year of treatment. Translational Relevance: This is a nonsurgical option for patients with emmetropic presbyopia who do not wish to wear glasses, which is a pharmacological treatment with eye drops.

Metalloid and Metal Oxide Nanoparticles Suppress Sudden Death Syndrome of Soybean.

Soybeans (Glycine max) (V3 stage) were sprayed once with nanoparticles (NPs) of AgO, B, CeO, CuO, MnO, MoO3, SiO, TiO, or ZnO and exposed to Fusarium virguliforme, the cause of sudden death syndrome. Up to 80% root rot was observed in greenhouse experiments. However, NP CuO, B, MoO3, or ZnO reduced the root rot severity by 17-25%. Infected roots and shoots had significant changes in B, Mg, P, S, Si, and Zn, but NP treatment restored levels to that of the healthy control. For example, the increased root Mg and Mn contents induced by disease were reversed by NP B and Mn amendments. In vitro assays found that the NPs did not inhibit the pathogen. This, along with the restoration of altered nutrient levels in the plant tissue, suggests that modulated plant nutrition increased disease defense. Treatment of seedlings with nanoscale micronutrients may be a new tool in promoting soybean health.

Gastric Electrical Stimulation Has an Effect on Gastric Interstitial cells of Cajal (ICC) That is Associated With Mast Cells.

Introduction Gastric electrical stimulation (GES) is an emerging therapy for gastric motility disorders, showing improvement of gastroparesis related symptoms in previous studies. Interstitial cells of Cajal (ICC) and mast cells have been shown to have a relevant role in gastroparesis pathogenesis. However, the exact effects of GES in those cells is relatively unknown. Methods Full thickness biopsies (FTBx) of 20 patients with refractory gastroparesis were obtained at the time of GES placement and repeated when the device was exchanged (mean of 22.5 months between biopsies). A patient-reported outcomes survey was obtained during each office visit during this period. All biopsies were stained with cluster of differentiation 117 (CD117), S100, and mast cell tryptase antibodies and were analyzed. Results Half of the patients had a significant increase of ICC during the repeated biopsy compared with baseline (p=0.01) and the other half had significant decrease in ICC levels (p=0.006) but there was no noticeable difference in mast cells counts at baseline between groups. Mast cells analysis was performed in two different groups depending on ICC change from the baseline biopsy (CD117 increase vs CD117 decrease). There was only a significant increase of mast cells count within the CD117 worsened ICC group (p=0.007). Conclusion No significant increase in the number of mast cells count seen in patients who received a GES may indicate an improvement in overall inflammation in patients with refractory gastroparesis after GES placement.